PCSK9 Inhibitor with Statin Therapy for Intracranial Artery Stenosis ( PISTIAS): Rationale and design of a multicenter randomized controlled trial.

RATIONALE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors enable an additional 54-75% reduction in low-density lipoprotein cholesterol (LDL-C) in statin-treated patients, demonstrating plaque regression in coronary artery disease. However, the impact of achieving an extremely low level of LDL-C with PCSK9 inhibitors (e.g. Evolocumab) on symptomatic intracranial atherosclerosis remains unexplored. AIM AND HYPOTHESIS: To determine whether combining Evolocumab and statins achieves a more significant symptomatic intracranial plaque regression than statin therapy alone. SAMPLE SIZE ESTIMATES: With a sample size of 1000 subjects, a two-sided α of 0.05, and 20% lost to follow-up, the study will have 83.3% power to detect the difference in intracranial plaque burden. METHODS AND DESIGN: This is an investigator-initiated multicenter, randomized, open-label, outcome assessor-blinded trial, evaluating the impact of combining Evolocumab and statins on intracranial plaque burden assessed by high-resolution magnetic resonance imaging at baseline in patients undergoing a clinically indicated acute stroke or transient ischemic attack due to intracranial artery stenosis, and after 24 weeks of treatment. Subjects (n = 1000) were randomized 1:1 into two groups to receive either Evolocumab 140 mg every 2 weeks with statin therapy or statin therapy alone. STUDY OUTCOMES: The primary endpoint is the change in intracranial plaque burden assessed by high-resolution magnetic resonance imaging, performed at baseline and at the end of the 24-week treatment period. DISCUSSION: This trial will explore whether more significant intracranial plaque regression is achievable with the treatment of combining Evolocumab and statins, providing information about efficacy and safety data. TRIAL REGISTRATION NUMBER: ChiCTR2300068868; https://www.chictr.org.cn/.

Cell Membrane-Camouflaged Chitosan-Polypyrrole Nanogels Co-Deliver Drug and Gene for Targeted Chemotherapy and Bone Metastasis Inhibition of Prostate Cancer.

The development of functional nanoplatforms to improve the chemotherapy outcome and inhibit distal cancer cell metastasis remains an extreme challenge in cancer management. In this work, a human-derived PC-3 cancer cell membrane-camouflaged chitosan-polypyrrole nanogel (CH-PPy NG) platform, which can be loaded with chemotherapeutic drug docetaxel (DTX) and RANK siRNA for targeted chemotherapy and gene silencing-mediated metastasis inhibition of late-stage prostate cancer in a mouse model, is reported. The prepared NGs with a size of 155.8 nm show good biocompatibility, pH-responsive drug release profile, and homologous targeting specificity to cancer cells, allowing for efficient and precise drug/gene co-delivery. Through in-vivo antitumor treatment in a xenografted PC-3 mouse tumor model, it is shown that such a CH-PPy NG-facilitated co-delivery system allows for effective chemotherapy to slow down the tumor growth rate, and effectively inhibits the metastasis of prostate cancer to the bone via downregulation of the RANK/RANKL signaling pathway. The created CH-Ppy NGs may be utilized as a promising platform for enhanced chemotherapy and anti-metastasis treatment of prostate cancer.

Efficient removal of Cd(II) and Pb(II) from aqueous solution using biochars derived from food waste.

Massive amount of food waste has been generated annually, posing a threat to ecological sustainability and the social economy due to current disposal methods. Urgent action is needed worldwide to convert the traditional pathway for treating food waste into a sustainable bioeconomy, as this will significantly benefit food chain management. This study explores the use of pyrolysis to produce different types of food waste biochars and investigates their adsorption capabilities for removing Cd2+ and Pb2+ in aqueous solution. The results indicated that co-pyrolysis biochar from fresh food waste and rice husk (FWRB) exhibited superior adsorption performance for Cd2+ (61.84 mg·g-1) and Pb2+ (245.52 mg·g-1), respectively. Pseudo-second-order kinetics (0.74 ≤ R2 ≤ 0.98) and Langmuir isotherms (0.87 ≤ R2 ≤ 0.98) indicated that the immobilized Cd2+ and Pb2+ on biochars were mainly attributed to the chemisorption, including precipitation with minerals (e.g., carbonates, silicates, and phosphate), complexation with functional groups (-OH), cation exchange (-COO-), and coordination with π-electrons. Furthermore, FWRB demonstrated reduced EC and Na content in comparison to food waste digestate biochar (FWDB) and food waste digestate co-pyrolysis with sawdust biochar (FWSB), with levels of Cd and Pb falling below China's current guideline thresholds. These findings suggested that co-pyrolysis of fresh food waste with rice husk could be applicable to the recycling of food waste into biochar products for heavy metal stabilization in contaminated water and soils.

Diagnosis and differential diagnosis of tertiary androgenetic alopecia with severe alopecia areata based on high-resolution MRI.

BACKGROUND AND AIM: No previous study investigated the anatomical changes of the scalp and hair follicles between tertiary androgenetic alopecia and severe alopecia areata using high-resolution magnetic resonance imaging (HR-MRI). This study aimed to explore the value of HR-MRI in assessing alopecia. MATERIALS AND METHODS: Forty-eight people were included in this study. The imaging indicators of the vertex and occipital scalp were recorded and compared. The logistic regression model was developed for the indicators that differed between tertiary androgenetic alopecia and severe alopecia areata. The receiver-operating characteristic (ROC) curve was used to assess the diagnostic efficacy of the model for tertiary androgenetic alopecia and severe alopecia areata. RESULTS: At the vertex, the thickness of the subcutaneous tissue layer, follicle depth, relative follicle depth, total number of follicles within a 2-cm distance, and number of strands reaching the middle and upper third of the subcutaneous fat layer within a 2-cm distance were statistically different between patients with tertiary androgenetic alopecia, those with severe alopecia areata, and healthy volunteers (p < 0.05). The logistic regression model suggested that the subcutaneous tissue layer thickness was important in discriminating tertiary androgenetic alopecia from severe alopecia areata. The ROC curve showed that the area under the curve, sensitivity, specificity, and best cutoff values of the subcutaneous tissue layer were 0.886, 94.4%, 70%, and 4.31 mm, respectively. CONCLUSIONS: HR-MRI can observe the changes in anatomical structures of the scalp and hair follicles in patients with alopecia. HR-MRI can be applied to the differential diagnosis of tertiary androgenetic alopecia and severe alopecia areata.

Preparation and application of biochar from co-pyrolysis of different feedstocks for immobilization of heavy metals in contaminated soil.

Co-pyrolysis is a potentially effective method for both biomass waste management and multi-functional biochar-based product design. It involves the thermochemical decomposition of biomass waste under anoxic conditions, which can reduce the cost of disposal and produce biochar with beneficial properties. Herein, this study aimed to investigate the properties and environmental applications of biochar from single- and mixed- feedstocks of wheat straw, rice husk, pig manure, and oyster shell at 450 ℃, respectively. A pot experiment with Chinese cabbage was carried out to compare the effects of biochars with limestone on soil Cd and Pb immobilization at two harvest periods. The results indicated that co-pyrolysis of various biomasses exhibited synthetic effects on promoting the calorific value of syngas and enhancing the quality of produced biochar. The pot experiment revealed a significant promotion on soil pH, soil organic matter, cation exchange capacity, and soluble Ca, which consequently reduced Cd and Pb availability. In contrast with limestone treatment, soil amendment with single biomass-derived and co-pyrolysis-derived (COPB) biochars had a significant positive impact on soil fertility and microbial biomass. Application of COPB at a 0.5% dosage consistently and most effectively enhanced the shoot biomass, increased leaf Vitamin C content but reduced leaf content of nitrate and heavy metals in both harvests. Using COPB for soil remediation would be financially visible due to the enhancement of crop yield. Therefore, this study proposes a strategy for targeted enhancement of the functions of biochar derived from co-pyrolysis of selected biomass waste for soil remediation and agricultural production.

Effect of Proprietary Chinese Medicine on Coronary Microvascular Dysfunction in Patients with Microvascular Angina: A Systematic Review and Meta-Analysis.

Background: Microvascular angina (MVA) has received increasing attention and interest in recent years, but there are still some shortcomings in the diagnosis and treatments at current stage. In recent years, several studies have confirmed the efficacy of proprietary Chinese medicines (PCMs) in improving MVA symptoms; however, there is no systematic review and meta-analysis to comprehensively assess the efficacy of PCMs in this area. Objective: Investigating the clinical efficacy of proprietary Chinese medicines for treating MVA and coronary microvascular function. Methods: We looked up articles from January 1, 2012, to the present from eight databases. Then, we screened the literature and followed the 2019 version 2 of Cochrane risk of bias tool for systematic review. The Stata/SE 15.0 software was used for the meta-analysis. Results: There are 21 studies, including 1,641 patients who were included in this review. According to the results, the combination of PCMs and conventional MVA treatment was able to further enhance clinical efficacy [RR = 1.28, 95% CI (1.20, 1.36), p < 0.001], prolong the time of duration on the treadmill exercise testing (TET) [SMD = 1.49, 95% CI (0.63, 2.36), p = 0.001] and improve levels of NO [SMD = -1.77 95% CI (-2.11, -1.43), p < 0.001]. At the same time, PCMs could also decrease the microvascular resistance index (IMR) [SMD = -1.79, 95% CI (-2.58, -1.00), p < 0.001)], serum level of hs-CRP [SMD = -1.21, 95% CI (-1.84, -0.58), p < 0.001] and ET-1 [SMD = -1.77 95% CI (-2.11, -1.43), p < 0.001]. Regards to medication safety, a total of 27 adverse events occurred, including 10 cases in the intervention group and 17 cases in the control group. Conclusion: The study suggests that the combination of PCMs and conventional MVA treatment enhances clinical efficacy and could better improve coronary microvascular function. In the future, we expect more high-quality, randomized, double-blind clinical studies to validate the safety, and efficacy of PCMs to provide valuable evidence-based medicine (EBM) for the treatment of MVA with PCMs.

A fluorescent probe based on a phenylalanine derivative is capable of sequential detection of Zn2+ and Cys/His.

A facile and dual fluorescent chemosensor (named 7-IDF) based on a phenylalanine derivative with an indole group was designed and synthesized. 7-IDF can selectively and sensitively detect Zn2+ via obvious fluorescence enhancement in an aqueous solution. Remarkably, the 7-IDF-Zn complex with blue luminescence has higher selectivity toward cysteine (Cys) and histidine (His) than for other amino acids. Intriguingly, 7-IDF can also be used as an excellent probe to detect Zn2+ in real water samples. Moreover, 7-IDF and 7-IDF-Zn possess excellent biocompatibility and cell permeability, and 7-IDF can consecutively detect Zn2+ and Cys/His in Hela cells through fluorescence imaging experiments. This study suggests that the phenylalanine-based chemosensor possesses great potential applications for the sequential detection of Zn2+ and Cys/His in biosystems.

Recurrent hypoglycemia increases hepatic gluconeogenesis without affecting glycogen metabolism or systemic lipolysis in rat.

INTRODUCTION: Recurrent hypoglycemia (RH) impairs secretion of counterregulatory hormones. Whether and how RH affects responses within metabolically important peripheral organs to counterregulatory hormones are poorly understood. OBJECTIVE: To study the effects of RH on metabolic pathways associated with glucose counterregulation within liver, white adipose tissue and skeletal muscle. METHODS: Using a widely adopted rodent model of 3-day recurrent hypoglycemia, we first checked expression of counterregulatory hormone G-protein coupled receptors (GPCRs), their inhibitory regulators and downstream enzymes catalyzing glycogen metabolism, gluconeogenesis and lipolysis by qPCR and western blot. Then, we examined epinephrine-induced phosphorylation of PKA substrates to validate adrenergic sensitivity in each organ. Next, we measured hepatic and skeletal glycogen content, degree of breakdown by epinephrine and abundance of phosphorylated glycogen phosphorylase under hypoglycemia and that of phosphorylated glycogen synthase during recovery to evaluate glycogen turnover. Further, we performed pyruvate and lactate tolerance tests to assess gluconeogenesis. Additionally, we measured circulating FFA and glycerol to check lipolysis. The abovementioned studies were repeated in streptozotocin-induced diabetic rat model. Finally, we conducted epinephrine tolerance test to investigate systemic glycemic excursions to counterregulatory hormones. Saline-injected rats served as controls. RESULTS: RH increased counterregulatory hormone GPCR signaling in liver and epidydimal white adipose tissue (eWAT), but not in skeletal muscle. For glycogen metabolism, RH did not affect total content or epinephrine-stimulated breakdown in liver and skeletal muscle. Although RH decreased expression of phosphorylated glycogen synthase 2, it did not affect hepatic glycogen biosynthesis during recovery from hypoglycemia or after fasting-refeeding. For gluconeogenesis, RH upregulated fructose 1,6-bisphosphatase 1 and monocarboxylic acid transporter 1 that imports lactate as precursor, resulting in a lower blood lactate profile during hypoglycemia. In agreement, RH elevated fasting blood glucose and caused higher glycemic excursions during pyruvate tolerance test. For lipolysis, RH did not affect circulating levels of FFA and glycerol after overnight fasting or upon epinephrine stimulation. Interestingly, RH upregulated the trophic fatty acid transporter FATP1 and glucose transporter GLUT4 to increase lipogenesis in eWAT. These aforementioned changes of gluconeogenesis, lipolysis and lipogenesis were validated in streptozotocin-diabetic rats. Finally, RH increased insulin sensitivity to accelerate glucose disposal, which was attributable to upregulated visceral adipose GLUT4. CONCLUSIONS: RH caused metabolic adaptations related to counterregulation within peripheral organs. Specifically, adrenergic signaling was enhanced in liver and visceral fat, but not in skeletal muscle. Glycogen metabolism remained unchanged. Hepatic gluconeogenesis was augmented. Systemic lipolysis was unaffected, but visceral lipogenesis was enhanced. Insulin sensitivity was increased. These findings provided insights into mechanisms underlying clinical problems associated with intensive insulin therapy, such as high gluconeogenic flux and body weight gain.

Diagnosis and differential diagnosis of dermatofibrosarcoma protuberans: Utility of high-resolution dynamic contrast-enhanced (DCE) MRI.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a kind of low-grade malignant spindle cell neoplasm, the diagnosis, and treatment, which have markedly attracted clinicians' attention for its repeated recurrence. High-resolution magnetic resonance imaging (HR-MRI) has shown unique capabilities in diagnosis of various cutaneous tumors. MATERIALS AND METHODS: Data of 29 patients with clinically suspected DFSPs and undergoing dynamic contrast-enhanced (DCE) HR-MRI preoperatively were prospectively collected. The HR-MRI qualitative features were evaluated and compared. The DCE-associated quantitative parameters and the time-signal intensity curve (TIC) types were provided using DCE sequences. RESULTS: A total of 7 DFSPs, nine dermatofibromas (DF, including four cases of cellular variant [CDF]), 12 keloids, and one nodular fasciitis were enrolled. DFSP showed the largest major diameter and the deepest depth. Five DFSPs (71.4%) showed ill-defined margins as well as infiltration of peripheral adipose. All DFSPs showed irregular shape. Most DFSPs presented hyperintensity on T2 WI (71.4%) and iso-intensity on T1 WI (85.7%). Six cases (85.7%) had significant enhancement, and six cases (85.7%) had homogeneous enhancement. There were significant differences of Ktrans , Kep , Ve and iAUC values among DFSPs, DFs, and keloids, and DFSP had the highest values for these parameters. Six DFSPs (85.7%) and four CDFs (100%) showed type-III TICs, while the other lesions showed type-Ⅰor type-Ⅱ TICs. CONCLUSIONS: DCE-HR-MRI could show the growth characteristics of DFSPs, which was of great value for the diagnosis and differential diagnosis of DFSPs and was helpful for the determination of treatment options, thereby to improve the prognosis of patients.

Propargyl Chalcones' Radical Annulation/Sulfonation Reaction: Efficient Synthesis of Benzo[b]oxepin-5(2H)-one and Chromane Derivatives.

A novel and facile methodology for the synthesis of sulfonated benzo[b]oxepinone and chromane derivatives was reported by the reaction of propargyl chalcones with arylsulfonyl chloride via radical cascade annulation/sulfonation under laboratory conditions. Readily available propargyl chalcones, commercialized arylsulfonyl chloride, and simple reaction conditions make this six(seven)-membered oxygen-containing heterocycles' synthetic strategy more attractive and with significant application values.

Reduced-Dose Full-Body CT in Lymphoma Follow-up: A Pilot Study.

BACKGROUND: How to reduce the radiation dose received from full-body CT scans during the follow-up of lymphoma patients is a concern. OBJECTIVE: The aim of the study was to investigate the image quality and radiation dose of reduced-dose full-body computerized tomography (CT) in lymphoma patients during the follow-up. METHODS: 121 patients were included and divided into conventional CT group (group 1, 120-kVp, n = 61) or reduced-dose CT group (group 2, 100-kVp combined dual-energy CT (DECT), n = 60). 140-kVp polychromatic images and 70-keV monochromatic images were reconstructed from DECT. The abdominal virtual non-enhanced (VNE) images were reconstructed from monochromatic images. Two radiologists rated the overall image quality with a five-point scale and graded the depiction of lesions using a four-point scale. The objective image quality was evaluated using image noise, signal-to-noise ratio, and contrast-to-noise ratio. The radiation dose and image quality were compared between the groups. RESULTS: The comparable subjective image quality was observed between 70-keV and 120-kVp images in the neck, while 120-kVp images showed better objective image quality. 70-keV images showed better objective image quality in the chest. While the subjective image quality of abdominal VNE images was inferior to that of true non-enhanced images, the improved objective image quality was observed in VNE images. In the abdominal arterial phase, similar subjective image quality was observed between the groups. Abdominal 70-keV images in the arterial phase showed improved objective image quality. Similar image quality was obtained in the abdominal venous phase between the groups. The effective radiation dose in group 2 showed a significant reduction. CONCLUSION: The application of reduced-dose full-body CT can significantly reduce the radiation dose for lymphoma patients during the follow-up while maintaining or improving the image quality.

Comparison of monoplanar and polyaxial screw fixation systems in percutaneous intermediate fixation for thoracolumbar fractures.

BACKGROUND: The newly developed monoplanar pedicle screws (MPPSs) can mobile in axial plane but fixed in the sagittal plane, which holds potential to combine ease of rod placement with sagittal plane strength theoretically. So far, few clinical studies focused on the outcomes of MPPSs for treatment of thoracolumbar fractures (TLFs). The aim of this study was to compare the efficacy of MPPSs to polyaxial pedicle screws (PAPSs) in percutaneous intermediate fixation of TLFs. METHODS: Seventy-eight patients who sustained TLFs without neurological deficits and underwent percutaneous intermediate fixation using MPPSs (40 patients) or PAPSs (38 patients) with a minimum 1-year follow-up were included in this study. The operation time, blood loss, local Cobb angle (LCA), vertebral wedge angle (VWA), anterior body height ratio (ABHR), visual analogue scale (VAS) and Oswestry Disability Index (ODI) were collected. RESULTS: No significant differences were observed in baseline demographics, clinical characteristics, operation time or blood loss between the two groups (P > 0.05). The postoperative LCA, VWA and ABHR were significantly corrected compared to these parameters preoperatively in both groups (#P < 0.05). The postoperative LCA, VWA and ABHR in the MPPS group were significantly better corrected than those in the PAPS group (*P < 0.05). Furthermore, the correction loss of LCA, VWA and ABHR in the MPPS group was significantly lower than that in the PAPS group (*P < 0.05). However, no significant difference in VAS and ODI scores was observed between the two groups. CONCLUSIONS: MPPSs showed similar efficiency as PAPSs in percutaneous intermediate fixation surgical procedures. More importantly, MPPSs achieved better radiological performance than PAPSs in the correction of TLFs and the prevention of correction loss.

Can Clinical and Functional Outcomes Be Improved with an Intelligent "Internet Plus"-Based Full Disease Cycle Remote Ischemic Conditioning Program in Acute ST-elevation Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention? Rationale and Design of the i-RIC Trial.

BACKGROUND: Acute ST-elevation myocardial infarction (STEMI) is associated with a high incidence of complications as well as a considerable hospitalization rate and economic burden. Preliminary evidence suggests that remote ischemic conditioning (RIC) is a promising non-invasive intervention that may effectively and safely reduce myocardial infarct size, subsequent cardiac events and complications, and mortality. However, RIC's cardio-protective effect remains under debate, especially for single timepoint RIC programs. Adequately powered large-scale randomized controlled trials investigating clinical outcomes are thus needed to clarify the role of full disease cycle RIC programs. METHODS: The intelligent "Internet Plus"-based full disease cycle remote ischemic conditioning (i-RIC) trial is a pragmatic, multicenter, randomized controlled, parallel group, clinical trial. The term, intelligent "Internet Plus"-based full disease cycle, refers to smart devices aided automatic and real-time monitoring of remote ischemic pre-, per- or post-conditioning intervention for patients with STEMI undergoing percutaneous coronary intervention (PCI). Based on this perspective, 4700 STEMI patients from five hospitals in China will be randomized to a control and an intervention group. The control group will receive PCI and usual care, including pharmacotherapy, before and after PCI. The intervention group will receive pre-, per-, and post-operative RIC combined with long-term i-RIC over a one-month period in addition. A smartphone application, an automated cuff inflation/deflation device and "Internet Plus"-based administration will be used in the long-term phase. The primary outcome is the combined cardiac death or hospitalization for heart failure rate. Secondary outcomes include clinical and functional outcomes: major adverse cardiac and cerebrovascular events rate, all-cause mortality, myocardial reinfarction rate, readmission rate for heart failure and ischemic stroke rate, unplanned revascularization rate, plasma concentration of myocardial infarction-related key biomarkers, infarct size, cardiac function, cardiopulmonary endurance, health-related quality of life, total hospital length of stay, total medical cost, and compliance with treatment regime. DISCUSSION: The i-RIC trial is designed to test the hypothesis that clinical and functional outcomes can be improved with the i-RIC program in STEMI patients undergoing PCI. The concept of RIC is expected to be enhanced with this intelligent "Internet Plus"-based program focusing on the full disease cycle. If the i-RIC program results in superior improvement in primary and secondary outcomes, it will offer an innovative treatment option for STEMI patients and form the basis of future recommendations. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ): ChiCTR2000031550, 04 April 2020.

Effects of different external cooling placements prior to and during exercise on athletic performance in the heat: A systematic review and meta-analysis.

Background: Nowadays, many high-profile international sport events are often held in warm or hot environments, hence, it is inevitable for these elite athletes to be prepared for the challenges from the heat. Owing to internal cooling may cause gastrointestinal discomfort to athletes, external cooling technique seems to be a more applicable method to deal with thermal stress. Central cooling mainly refers to head, face, neck and torso cooling, can help to reduce skin temperature and relieve thermal perception. Peripheral cooling mainly refers to four limbs cooling, can help to mitigate metabolic heat from muscular contrac to effectively prevent the accumulation of body heat. Hence, we performed a meta-analysis to assess the effectiveness of different external cooling placements on athletic performance in the heat Methods: A literatures search was conducted using Web of Science, MEDLINE and SPORTDiscus until September 2022. The quality and risk of bias in the studies were independently assessed by two researchers. Results: 1,430 articles were initially identified (Web of Science = 775; MEDLINE = 358; SPORTDiscus = 271; Additional records identified through other sources = 26), 60 articles (82 experiments) met the inclusion criteria and were included in the final analysis, with overall article quality being deemed moderate. Central cooling (SMD = 0.43, 95% CI 0.27 to 0.58, p < 0.001) was most effective in improving athletic performance in the heat, followed by central and peripheral cooling (SMD = 0.38, 95% CI 0.23 to 0.54, p < 0.001), AND peripheral cooling (SMD = 0.32, 95% CI 0.07 to 0.57, p = 0.013). For the cooling-promotion effects on different sports types, the ranking order in central cooling was ETE (exercise to exhaustion), TT (time-trial), EWT (exercise within the fixed time or sets), IS (intermittent sprint); the ranking order in peripheral cooling was EWT, TT, ETE and IS; the ranking order in central and peripheral cooling was ETE, IS, EWT and TT. Conclusion: Central cooling appears to be an more effective intervention to enhance performance in hot conditions through improvements of skin temperature and thermal sensation, compared to other external cooling strategies. The enhancement effects of peripheral cooling require sufficient re-warming, otherwise it will be trivial. Although, central and peripheral cooling seems to retain advantages from central cooling, as many factors may influence the effects of peripheral cooling to offset the positive effects from central cooling, the question about whether central and peripheral cooling method is better than an isolated cooling technique is still uncertain and needs more researchs to explore it.

Distinctive Gut Microbiota Alteration Is Associated with Poststroke Functional Recovery: Results from a Prospective Cohort Study.

Objectives: Functional prognosis is potentially correlated with gut microbiota alterations following the dysregulation of the gut-microbiota-brain axis after stroke. This study was designed to explore the poststroke alterations of gut microbiota and potential correlations between gut microbiota and global functions. Methods: A total of thirty-eight patients with stroke and thirty-five healthy demographics-matched controls were recruited. Their fecal DNAs were extracted, and the V3-V4 regions of the conserved bacterial 16S RNA were amplified and sequenced on the Illumina MiSeq platform. Microbial composition, diversity indices, and species cooccurrence were compared between groups. Random forest and receiver operating characteristic analysis were used to identify potential diagnostic biomarkers. Relationships between discriminant bacteria and poststroke functional outcomes were estimated. Results: Higher alpha diversity of gut microbiota was observed in poststroke patients as compared to the healthy controls (p < 0.05). Beta diversity showed that microbiota composition in the poststroke group was significantly different from that in the control group. Relative abundance of nine genera increased significantly in poststroke patients, while 82 genera significantly decreased (p < 0.05). The accuracy, specificity, and susceptibility of the optimal model consisted of the top 10 discriminant species were 93%, 100%, and 86%, respectively. Subgroup analysis showed that bacterial taxa abundant between subacute and chronic stroke patients were overall different (p < 0.05). The modified Rankin scale (mRS) (r = -0.370, p < 0.05), Fugl-Meyer assessment (FMA) score (r = 0.364, p < 0.05), water swallow test (WST) (r = 0.340, p < 0.05), and Barthel index (BI) (r = 0.349, p < 0.05) were significantly associated with alterations of distinctive gut microbiota. Conclusions: The gut microbiota in patients with stroke was significantly changed in terms of richness and composition. Significant associations were detected between alterations of distinctive gut microbiota and global functional prognosis. It would facilitate novel treatment target selection in the context of stroke while the causal relationships between distinctive gut microbiota alterations and functional variations need to be further verified with well-designed studies.

Comparative transcriptome analysis of abnormal cap and healthy fruiting bodies of the edible mushroom Lentinula edodes.

Lentinula edodes, a commercially important mushroom, is cultivated worldwide. Artificially cultivated L. edodes often present with abnormal symptoms in the fruiting body, which affect their commercial value and reduce production efficiency. In this study, we carried out a comparative transcriptome analysis of normal fruiting body pileus (LeNP), normal margin in abnormal fruiting body pileus (LeAPNM), and abnormal margin in abnormal fruiting body pileus (LeAPAM). Metabolic pathways such as those involved in transmembrane transport, ribosome production, tryptophan metabolism, arginine and proline metabolism, and the metabolism of other amino acids were significantly enriched in LeAPAM. F-box, short-chain dehydrogenases/reductases, the major facilitator superfamily, and the FMN_red superfamily are related to malformation in L. edodes. Genes encoding heat shock proteins, G protein, and ß-1,3-glucanase in the GH5 family showed different expression patterns, suggesting that these genes are involved in the development of L. edodes fruiting bodies. In particular, CAZymes, which are involved in the development of cell walls in L. edodes, were highly expressed in LeAPAM. According to TEM observation, the cell wall of LeAPAM samples showed significant thickening compared to the other samples. These results suggested that cell wall anabolism in LeAPAM samples was more active than that in normal fruiting bodies, enhancing the environmental adaptability of the fungus. This study provides preliminary data for future research aimed at solving the phenomenon of abnormal fruiting bodies of L. edodes.

Electrochemical Radical δ-H Sulfonylation Reaction for the Synthesis of 4-((Aryl,Arylsul fonyl)methylene)-2,5-Cyclohexadiene Derivatives.

A novel and efficient electrochemical radical δ-H sulfonylation reaction of para-quinone methides (p-QMs) and sodium sulfinates has been achieved under common laboratory conditions. In this strategy, a new C(sp2)-S bond was constructed for the synthesis of 4-((aryl,arylsulfonyl)methylene)-2,5-cyclohexadiene derivatives with a broad substrate scope, good functional group tolerance, and mild conditions. Further studies showed that the reaction had an excellent regional selectivity.

Effects of robot-assisted training on balance function in patients with stroke: A systematic review and meta-analysis.

OBJECTIVE: To investigate the effectiveness of robot-assisted therapy on balance function in stroke survivors. DATA SOURCES: PubMed, the Cochrane Library, Embase and China National Knowledge Infrastructure databases were searched systematically for relevant studies. STUDY SELECTION: Randomized controlled trials reporting robot-assisted therapy on balance function in patients after stroke were included. DATA EXTRACTION: Information on study characteristics, demographics, interventions strategies and outcome measures were extracted by 2 reviewers. DATA SYNTHESIS: A total of 19 randomized trials fulfilled the inclusion criteria and 13 out of 19 were included in the meta-analysis. Analysis revealed that robot-assisted therapy significantly improved balance function assessed by berg balance scale (weighted mean difference (WMD) 3.58, 95% confidence interval (95% CI) 1.89-5.28, p < 0.001) compared with conventional therapy. Secondary analysis indicated that there was a significant difference in balance recovery between the conventional therapy and robot-assisted therapy groups in the acute/subacute stages of stroke (WMD 5.40, 95% CI 3.94-6.86, p < 0.001), while it was not significant in the chronic stages. With exoskeleton devices, the balance recovery in robot-assisted therapy groups was significantly better than in the conventional therapy groups (WMD 3.73, 95% CI 1.83-5.63, p < 0.001). Analysis further revealed that a total training time of more than 10 h can significantly improve balance function (WMD 4.53, 95% CI 2.31-6.75, p < 0.001). No publication bias or small study effects were observed according to the Cochrane Collaboration tool. CONCLUSION: These results suggest that robot-assisted therapy is an effective intervention for improving balance function in stroke survivors.

Metal-Free Radical Annulation of Oxygen-Containing 1,7-Enynes: Configuration-Selective Synthesis of (E)-3-((Arylsulfonyl)methyl)-4-Substituted Arylidenechromene Derivatives.

A novel strategy for the synthesis of (E)-3-((arylsulfonyl)methyl)-4-substituted benzylidenechromene derivatives via a metal-free radical annulation reaction of oxygen-containing 1,7-enynes with thiosulfonates has been developed. The reaction shows broad substrate scope, wide functional group tolerance, and moderate to excellent yields. Moreover, thiosulfonates were well driven to achieve the bifunctionalization reaction of oxo-1,7-enynes which derived from aliphatic alkynes. In addition, the (E)-configuration of the products was highly controlled by the structure of 1,7-enyne.

Bibliometric analysis of the 100 most-cited articles in the field of hepatology / Análisis bibliométrico de los 100 artículos más citados en el ámbito hepatológico

OBJECTIVE: Bibliometric search of citation classics can function as a tool to identify extraordinary landmark articles and advanced research studies. We aimed to examine and characterize the 100 most-cited published articles in the field of hepatology. PATIENTS AND METHODS: A comprehensive list of the 100 most-cited articles published from 1950 to 2017 in the field of hepatology was compiled after searching the Web of Science with relevant terms, including "liver," "hepatitis," "hepatic," "hepatocellular," "hepatology," "cirrhosis," and "steatohepatitis." The articles were ranked according to their citation counts and were evaluated for characteristics including country, institution, authorship, publication year, subspecialty and others. RESULTS: The database search returned 323,291 articles associated with liver disease published between 1950 and 2017. The 100 most-cited articles were from 21 major journals, with the highest number of articles being published in Hepatology (n = 20). The average number of citations of the 100 most-cited articles was 1946.8; among these articles, the most frequently cited article received 5515 citations, and the least frequently cited article received 1155 citations. In total, 60 were original articles among the 100 most-cited articles. The most frequently represented specialties were hepatitis, hepatocellular carcinoma, and nonalcoholic fatty liver disease, which accounted for 53.3%, 23.3%, and 11.7% of these articles, respectively. DISCUSSION: Our study identified citation classics and provided a review of the most advanced studies in the field of hepatology. This can help to guide clinical treatment and future academic research resulting in advancements in hepatology

OBJETIVO: La búsqueda bibliométrica de clásicos en materia de citaciones puede funcionar como una herramienta para identificar artículos extraordinarios de interés y estudios de investigación avanzada. Nos propusimos examinar y caracterizar los 100 artículos publicados más citados en el ámbito de la hepatología. PACIENTES Y MÉTODOS: Se recabó una lista exhaustiva de los 100 artículos más citados en el ámbito de la hepatología publicados entre 1950 y 2017, tras realizar una búsqueda en la Web of Science con términos relevantes, como «hígado», «hepatitis», «hepático», «hepatocelular», «hepatología», «cirrosis» y «esteatohepatitis». Los artículos se clasificaron de acuerdo con el número de citas y se evaluaron en función de características como el país, la institución, la autoría, el año de publicación, la subespecialidad y otras. RESULTADOS: La búsqueda en la base de datos dio como resultado 323.291 artículos relacionados con enfermedades hepáticas publicados entre 1950 y 2017. Los 100 artículos más citados procedían de 21 revistas importantes, y el mayor número de artículos se había publicado en Hepatology (n=20). El promedio de citaciones de los 100 artículos más citados fue de 1.946,8; entre estos artículos, el artículo citado con más frecuencia se citó en 5.515 ocasiones, y el artículo citado con menor frecuencia recibió 1.155 citas. En total se encontraron 60 artículos originales entre los 100 artículos más citados. Las especialidades representadas con mayor frecuencia fueron hepatitis, carcinoma hepatocelular y esteatosis no alcohólica, que representaban el 53,3, el 23,3 y el 11,7% de estos artículos, respectivamente. DISCUSIÓN: En nuestro estudio se identificaron los clásicos en materia de citaciones y se proporcionó una revisión de los estudios más avanzados en el campo de la hepatología. Esto puede ayudar a guiar el tratamiento clínico y las futuras investigaciones académicas y derivar en avances en la hepatología