[Effects of "brain-gut coherence" method of acupuncture on motor function and intestinal microflora in the patients with cerebral ischemic stroke].

OBJECTIVE: To observe the clinical effect of "brain-gut coherence" method of acupuncture on cerebral ischemic stroke (CIS) and explore its action mechanism. METHODS: A total of 82 patients with CIS were randomly divided into an observation group (41 cases, 3 cases dropped out, 2 cases discontinued) and a control group (41 cases, 4 cases dropped out, 2 cases excluded). The conventional basic treatment was administered in the two groups. Additionally, in the observation group, "brain-gut coherence" method of acupuncture was delivered. The stimulating points included the parietal and temporal anterior oblique line on the affected side, Zhongwan (CV 12), Guanyuan (CV 4), and bilateral Tianshu (ST 25), Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39). In the control group, the routine acupuncture was operated at Baihui (GV 20), Yintang (GV 24+), bilateral Fengchi (GB 20) and Zusanli (ST 36), and Hegu (LI 4), Jianyu (LI 15), Quchi (LI 11), Waiguan (TE 5), Futu (ST 32), Sanyinjiao (SP 6) and Taichong (LR 3) on the affected side. Acupuncture stimulation lasted 30 min each time, once daily, and for 5 days a week. The intervention for 4 weeks was required. The scores of Fugl-Meyer assessment scale (FMA), Berg balance scale (BBS) and the modified Barthel index (MBI), as well as the score of gastrointestinal symptoms were compared before and after treatment in the two groups. The neutrophil count (NUE) and the content of the serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) were detected before and after treatment in the two groups. Using 16S rRNA gene sequencing, the structure and relative abundance of intestinal microflora was detected before and after treatment; and with the enzyme linked immunosorbent assay (ELISA) adopted, the levels of intestinal fatty acid-binding protein (iFABP), D-lactate (D-LA), lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP), tumor necrosis factor-α(TNF-α), interleukin (IL)-1ß and IL-6 in the serum were detected before and after treatment in the two groups. RESULTS: After treatment, the scores of FMA, BBS and MBI were increased (P<0.05), and the scores of gastrointestinal symptoms were decreased (P<0.05) compared with those before treatment in the two groups. Compared with the control group, the scores of FMA, BBS and MBI were higher (P<0.05) and the score of gastrointestinal symptoms was lower (P<0.05) in the observation group after treatment. NEU and the content of serum NT-proBNP were reduced in the two groups (P<0.05), and the content of serum NT-proBNP in the observation group was lower than that of the control group (P<0.05) after treatment. Chao1, Ace, Sobs and Shannon indexes were increased after treatment compared with those before treatment in the two groups (P<0.05); and these indexes in the observation group were higher when compared with the control group (P<0.05). After treatment, the relative abundance of Bacteroidaceae, Enterobacteriaceae, Oscillospiraceae, Streptococcaceae and Sutterellaceae was reduced in comparison with that before treatment in the two groups (P<0.05); and the relative abundance of these microflora was lower in the observation group when compared with the control group (P<0.05). After treatment, the relative abundance of Lachnospiraceae, Ruminococcaceae, Bifidobacteriaceae and Coriobacteriaceae was increased in comparison with that before treatment in the two groups (P<0.05); and the relative abundance of these microflora was elevated in the observation group when compared with the control group (P<0.05). After treatment, the levels of iFABP, D-LA, LPS, LBP, TNF-α, IL-1ß and IL-6 were reduced when compared with those before treatment in the two groups (P<0.05), and these levels of the observation group were lower than those of the control group (P<0.05). CONCLUSION: "Brain-gut coherence" method of acupuncture can improve the motor function and gastrointestinal function of the patients with cerebral ischemic stroke, which may be related to modulating the structure of intestinal microflora, alleviating inflammatory reactions and accelerating the intestinal barrier repair.

Association of serum ferritin and all-cause mortality in AKI patients: a retrospective cohort study.

Background: Serum ferritin (SF) is clinically found to be elevated in many disease conditions, and our research examines serum ferritin in patients with acute kidney injury (AKI) and its implication on the risk of short-term mortality in AKI. Methods: Data were extracted from the Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV 2.2) database. Adult patients with AKI who had serum ferritin tested on the first day of ICU admission were included. The primary outcome was 28-day mortality. Kaplan-Meier survival curves and Cox proportional hazards models were used to test the relationship between SF and clinical outcomes. Subgroup analyses based on the Cox model were further conducted. Results: Kaplan-Meier survival curves showed that a higher SF value was significantly associated with an enhanced risk of 28-day mortality, 90-day mortality, ICU mortality and hospital mortality (log-rank test: p < 0.001 for all clinical outcomes). In multivariate Cox regression analysis, high level of SF with mortality was significantly positive in all four outcome events (all p < 0.001). This result remains robust after adjusting for all variables. Subgroup analysis of SF with 28-day mortality based on Cox model-4 showed that high level of SF was associated with high risk of 28-day mortality in patients regardless of the presence or absence of sepsis (p for interaction = 0.730). Positive correlations of SF and 28-day mortality were confirmed in all other subgroups (p for interaction>0.05). Conclusion: High level of SF is an independent prognostic predictor of 28-day mortality in patients with AKI.

Preventive Effects of Melatonin on Delirium in Intensive Care Unit Patients: A Meta-Analysis of Randomized Controlled Trials.

Aims: To investigate the preventive efficacy of melatonin on the incidence of delirium and other clinical outcomes of subjects in the intensive care unit (ICU). Methods: Randomized controlled trials concerning the effects of melatonin on delirium published from inception to July 2022 were identified from PubMed, Embase, and the Cochrane Library. The primary outcome was delirium incidence. The secondary outcome was the length of ICU stay, the duration of mechanical ventilation, and the mortality in ICU. A meta-analysis was performed. Estimates were presented as risk ratio (RR) or standard mean difference (SMD) with 95% confidence interval (CI). Results: Eleven RCTs with 2002 patients were included. The forest plots showed that the delirium incidence did not significantly decrease after melatonin administration (RR 0.85; 95% CI, 0.61~1.18, P = .32, I2=60%, P for heterogeneity = .01). The subgroup analyses confirmed that melatonin significantly reduced the incidence of delirium (RR 0.70; 95% CI, 0.56~0.89, P = .003, I2 = 32%, P for heterogeneity = .22) for the special ICU patients. Also, for ICU patients, the length of ICU stays, duration of mechanical ventilation, and mortality were not significantly decreased after melatonin treatment (all P > .05). Conclusion: Melatonin may decrease the incidence of delirium for special ICU patients. PROSPERO registration number: CRD42022354874.

LL-37 improves sepsis-induced acute lung injury by suppressing pyroptosis in alveolar epithelial cells.

BACKGROUND: LL-37 (also known as murine CRAMP) is a human antimicrobial peptide that plays a crucial role in innate immune defence against sepsis through various mechanisms. However, its involvement in sepsis-induced lung injury remains unclear. OBJECTIVES: This work investigates the impact of LL-37 on pyroptosis generated by LPS in alveolar epithelial cells. The research utilizes both in vivo and in vitro sepsis-associated acute lung injury (ALI) models to understand the underlying molecular pathways. METHODS: In vivo, an acute lung injury model induced by sepsis was established by intratracheal administration of LPS in C57BL/6J mice, which were subsequently treated with low-dose CRAMP (recombinant murine cathelicidin, 2.5 mg.kg-1) and high-dose CRAMP (5.0 mg.kg-1). In vitro, pyroptosis was induced in a human alveolar epithelial cell line (A549) by stimulation with LPS and ATP. Treatment was carried out with recombinant human LL-37, or LL-37 was knocked out in A549 cells using small interfering RNA (siRNA). Subsequently, haematoxylin and eosin staining was performed to observe the histopathological changes in lung tissues in the control group and sepsis-induced lung injury group. TUNEL and PI staining were used to observe DNA fragmentation and pyroptosis in mouse lung tissues and cells in the different groups. An lactate dehydrogenase (LDH) assay was performed to measure the cell death rate. The expression levels of NLRP3, caspase1, caspase 1 p20, GSDMD, NT-GSDMD, and CRAMP were detected in mice and cells using Western blotting, qPCR, and immunohistochemistry. ELISA was used to assess the levels of interleukin (IL)-1ß and IL-18 in mouse serum, bronchoalveolar lavage fluid (BALF) and lung tissue and cell culture supernatants. RESULTS: The expression of NLRP3, caspase1 p20, NT-GSDMD, IL 18 and IL1ß in the lung tissue of mice with septic lung injury was increased, which indicated activation of the canonical pyroptosis pathway and coincided with an increase in CRAMP expression. Treatment with recombinant CRAMP improved pyroptosis in mice with lung injury. In vitro, treatment with LPS and ATP upregulated these classic pyroptosis molecules, LL-37 knockdown exacerbated pyroptosis, and recombinant human LL-37 treatment alleviated pyroptosis in alveolar epithelial cells. CONCLUSION: These findings indicate that LL-37 protects against septic lung injury by modulating the expression of classic pyroptotic pathway components, including NLRP3, caspase1, and GSDMD and downstream inflammatory factors in alveolar epithelial cells.

Prognostic Value of Neutrophils-to-Lymphocytes Ratio and Platelets-to-Lymphocytes Ratio in Sepsis Patients With Lymphopenia.

Background: Inflammation plays a critical role in sepsis. The integration of neutrophil-to-lymphocyte ratio (NLR) and platelets-to-lymphocytes ratio (PLR) from multiple cell types offers a novel approach to rapidly assess inflammation status. However, the predictive role of NLR and PLR in sepsis with lymphopenia remains uncertain. Objectives: The purpose of this study was to explore the prognostic value of NLR and PLR in sepsis patients with lymphopenia. Design and methods: In this observational retrospective study, we included 172 sepsis patients with lymphopenia and collected clinical characteristics for analysis. Through binary logistic regression analysis, we identified independent factors. Receiver-operating characteristic curves (ROC) and areas under the curves (AUC) were employed to assess the ability to predict hospital mortality risk. Results: Our results showed a total hospital mortality rate of 53.49%. Multivariate analysis demonstrated that NLR (OR = 1.11, P < .001) and PLR (OR = 1.01, P = .003) were independent predictors associated with hospital mortality in sepsis patients with lymphopenia. The AUCs of NLR and PLR were 0.750 (95% CI: 0.634-0.788, P < .001) and 0.662 (95% CI: 0.580-0.743, P < .001), respectively. Notably, an optimal cut-off value of 18.93 for NLR displayed a sensitivity of 75.0% and specificity of 63.0% in discriminating hospital mortality in sepsis patients with lymphopenia, while the optimal cut-off value for PLR was 377.50, with a sensitivity of 67.5% and specificity of 64.1%. Conclusion: NLR and PLR serve as independent predictors of hospital mortality in sepsis patients with lymphopenia.

Facile fabrication of adenosine triphosphate/chitosan/polyethyleneimine coating for high flame-retardant lyocell fabrics with outstanding antibacteria.

Addressing highly flammable and easily breeding bacteria property via environmentally friendly approach was critical for the large-scale application of lyocell fibers. Herein, a bio-based coating constructed by layer-by-layer deposition of adenosine triphosphate (ATP), chitosan (CS), and polyethyleneimine (PEI) was successfully fabricated to obtain excellent fire-resistant and antimicrobial lyocell fabrics (LBL/Lyocell). The resulted fabrics with add-on of 11.5 wt% achieved the limiting oxygen index (LOI) of 32.0 %. Meanwhile, compared with the pure lyocell fabrics, the peak of heat release rate (PHRR), total heat release (THR), and fire growth rate (FIGRA) of LBL/Lyocell fabrics decreased by 75.2 %, 61.0 % and 69.8 % in cone calorimetric test (CCT), respectively. By characterizing the gaseous products and solid residues, the presence of the ATP/CS/PEI coating could not only quickly form the dense expanded carbon layer by itself, but also promote the conversion of cellulose into thermal-stability residues, thus reducing the release of combustible substances during combustion and protecting the lyocell fabrics. In addition, LBL/Lyocell showed excellent antimicrobial properties with 99.99 % antibacterial rates against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). This bio-based coating was a promising candidate for efficiently flame-retardant cellulose fibers with excellent antibacteria.

Bioactive ambuic acid congeners from endophytic fungus Pestalotiopsis trachicarpicola SC-J551.

New ambuic acid derivatives, pestallic acids R-V (1-5), together with ambuic acid (6), were isolated from the endophytic fungus Pestalotiopsis trachicarpicola SC-J551 derived from the fern Blechnum orientale L., of which compound 2, being racemic, was separated to two optically pure enantiomers (+)-2 and (-)-2. The structures including absolute configurations of these new compounds were elucidated by extensive spectroscopic analysis and theoretical simulations of their ECD spectra and 13C NMR chemical shifts. Compounds 1 and 3 exhibited cytotoxicity against human carcinoma A549, HeLa, HepG2, and MCF-7 cells (IC50: 3.6-12.5 µM) and compound 3 was also active against Staphylococcus aureus and MRSA (MIC = 20 µg ml-1). Compound (±)-2 showed inhibitory activity against LPS-induced NO release (IC50 = 21.1 µM) and t-BHP-induced ROS production (IC50 = 8.5 µM) in RAW264.7 macrophages.

Eco-friendly phosphorus-free flame-retardant coating for microfiber synthetic leather via alginate-based layer-by-layer technology.

The excellent comprehensive properties of microfiber synthetic leathers have led to their wide application in various aspects of our lives. However, the issue of flammability remains a significant challenge that needs to be addressed. Nowadays, the bio-based chemicals used in the flame-retardant materials have extremely grabbed our eyes. Herein, we developed an ecologically friendly flame-retardant microfiber synthetic leather using phosphorus-free layer-by-layer assembly technology (LBL) based on natural polysaccharide alginate (SA) coupled with polyethyleneimine (PEI) and 3-aminopropyltriethoxysilane (APTES). The effect of different LBL coating systems on the flame retardancy of microfiber synthetic leather was investigated. The results demonstrated that the introduction of APTES can completely inhibit the melt-dripping by enhancing char formation through silica elements. Furthermore, the trinary coating system consisting of SA/APTES/PEI exhibited excellent flame retardancy by combining gas-phase action from PEI and condensed-phase function from APTES. This modified microfiber synthetic leather showed a significantly higher limiting oxygen index (LOI) value of 33.0 % with no molten droplet. Additionally, the SA-based coating slightly suppressed the heat release, resulting in a 20 % reduction in total heat release during the combustion test. Overall, this work presents a facile and environmentally-friendly approach for achieving flame-retardant and anti-dripping microfiber synthetic leather.

Preparation and Characterization of a Novel Morphosis of Dextran and Its Derivatization with Polyethyleneimine.

Dextran, a variant of α-glucan with a significant proportion of α-(1,6) bonds, exhibits remarkable solubility in water. Nonetheless, the precipitation of dextran has been observed in injection vials during storage. The present study aimed to establish a technique for generating insoluble dextran and analyze its structural properties. Additionally, the potential for positively ionizing IS-dextran with polyethyleneimine was explored, with the ultimate objective of utilizing IS-dextran-PEI as a promising support for enzyme immobilization. As a result, IS-dextran was obtained by the process of slow evaporation with an average molecular weight of 6555 Da and a yield exceeding 60%. The calculated crystallinity of IS-dextran, which reaches 93.62%, is indicative of its irregular and dense structure, thereby accounting for its water insolubility. Furthermore, positive charge modification of IS-dextran, coupled with the incorporation of epichlorohydrin, resulted in all zeta potentials of IS-dextran-PEIs exceeding 30 mV, making it a promising supporting factor for enzyme immobilization.

Candidate Oligo Therapeutic Target, miR-330-3p, Induces Tamoxifen Resistance in Estrogen Receptor-Positive Breast Cancer Cells via HDAC4.

Tamoxifen is a drug used for treating breast cancer (BC), especially for individuals diagnosed with estrogen receptor-positive (ER+) BC. Its prolonged use could reduce the risk of recurrence and significantly lengthen the survival rate of BC patients. However, an increasing number of patients developed resistance to tamoxifen treatment, which reduced therapeutic efficiency and caused substandard prognosis. Therefore, the exploration of the molecular processes involved in tamoxifen resistance (TR) is urgently required. This investigation aimed to elucidate the relationship of microRNA-330 (miR-330-3p) with the TR of BC. There is little information on miR-330-3p's link with drug-resistant BC, although it is well known to regulate cell proliferation and apoptosis. Primarily, miR-330-3p expression in parental BC (MCF7/T47D), TR (MCF7-TR), and T47D/TR cell lines was detected by qRT-PCR. Then, the impact of miR-330-3p on the TR of BC cells was assessed by a cell proliferation assay. Lastly, dual-luciferase reporter, qRT-PCR, and western blot assessments were carried out to identify histone deacetylase 4 (HDAC4) as the potential miR-330-3p target gene. The data indicated that miRNA-330 was overexpressed in TR ER+ BC cells and its overexpression could induce TR. Furthermore, miRNA-330 could also reduce the expression of HDAC4, which is closely linked to TR, and overexpression of HDAC4 could reverse miRNA-330-induced drug resistance. In summary, miR-330-3p could induce TR of ER+ BC cells by downregulating HDAC4 expression, which might be a novel marker of TR and a possible treatment target against BC patients who are tamoxifen-resistant.

Durable multifunctional cotton fabric with superior biocidal efficacy and flame retardancy based on an ammonium phosphate N-halamine.

Multifunctional textiles have become the mainstreams along with development of textile industry and the increased need of public. But a facile fabrication method with well-balance of multiple functions is still a challenge. In this work, an ammonium salt of tris(methylphosphonate)aminomethane (TAMPU), which can directly react with cellulose molecules and transform to N-halamine antibacterial structure, was easily synthesized and used to achieve multifunctional cotton fabric. As a result, the modified cotton fabric of 15.8 % weight gain exhibited excellent fire resistance with LOI value of 33.8 % and self-extinguishing behavior. Due to the good char-forming capacity of TAMPU, strong heat suppression was achieved and the peak of heat release rate (PHRR) and total heat release (THR) were decreased by 87.6 % and 60.8 %, respectively. Besides, the modified samples presented outstanding bactericidal effects, and all of S. aureus and E. coli could be inactivated within 5 min without dissolution phenomenon. Furthermore, the TAMPU-modified cotton fabric owned good washing durability and LOI value was remained at 29.8 % after 50 washing cycles. This TAMPU multifunctional modification had slight influence on the mechanical property and air permeability of cotton fabric. Thus, this work provides a convenient and friendly way to fabricate multifunctional flame-retardant and antibacterial cotton fabric.

Cofactor Metabolic Engineering of Escherichia coli for Aerobic L-Malate Production with Lower CO2 Emissions.

Escherichia coli has been engineered for L-malate production via aerobic cultivation. However, the maximum yield obtained through this mode is inferior to that of anaerobic fermentation due to massive amounts of CO2 emissions. Here, we aim to address this issue by reducing CO2 emissions of recombinant E. coli during aerobic L-malate production. Our findings indicated that NADH oxidation and ATP-synthesis-related genes were down-regulated with 2 g/L of YE during aerobic cultivations of E. coli E23, as compared to 5 g/L of YE. Then, E23 was engineered via the knockout of nuoA and the introduction of the nonoxidative glycolysis (NOG) pathway, resulting in a reduction of NAD+ and ATP supplies. The results demonstrate that E23 (ΔnuoA, NOG) exhibited decreased CO2 emissions, and it produced 21.3 g/L of L-malate from glucose aerobically with the improved yield of 0.43 g/g. This study suggests that a restricted NAD+ and ATP supply can prompt E. coli to engage in incomplete oxidization of glucose, leading to the accumulation of metabolites instead of utilizing them in cellular respiration.

Comorbidity of Anxiety and Hypertension: Common Risk Factors and Potential Mechanisms.

Anxiety is more common in patients with hypertension, and these two conditions frequently coexist. Recently, more emphasis has been placed on determining etiology in patients with comorbid hypertension and anxiety. This review focuses on the common risk factors and potential mechanisms of comorbid hypertension and anxiety. Firstly, we analyze the common risk factors of comorbid hypertension and anxiety including age, smoking, alcohol abuse, obesity, lead, and traffic noise. The specific mechanisms underlying hypertension and anxiety were subsequently discussed, including interleukin (IL)-6 (IL-6), IL-17, reactive oxygen species (ROS), and gut dysbiosis. Increased IL-6, IL-17, and ROS accelerate the development of hypertension and anxiety. Gut dysbiosis leads to hypertension and anxiety by reducing short-chain fatty acids, vitamin D, and 5-hydroxytryptamine (5-HT), and increasing trimethylamine N-oxide (TAMO) and MYC. These shared risk factors and potential mechanisms may provide an effective strategy for treating and preventing hypertension and comorbid anxiety.

[Electroacupuncture improves ischemic myocardial injury by activating Nrf2/HO-1 signaling pathway to inhibit ferroptosis in rats].

OBJECTIVE: To explore the role of nuclear factor E2 related factor 2 (Nrf2) / heme oxygenase (HO-1) signal pathway in electroacupuncture (EA) induced improvement of acute myocardial ischemia (AMI) and its relationship with ferroptosis in rats. METHODS: Male SD rats were randomly and equally divided into sham operation, model, EA and EA+ML385 (inhibitor of Nrf2) groups (n=8). The rat model of AMI was established by ligating the descending anterior branch of the left coronary artery. EA (2 Hz/100 Hz) was applied to bilateral "Shenmen"(HT7) and "Tongli"(HT5) for 20 min, once daily for 7 days. The electrocardiogram (ECG) of standard Ⅱ (ECG ST) lead and heart rate (HR) in each group was recorded and analyzed before and after modeling and after treatment by using PowerLab physiological recorder system. Histopathological changes of myocardial tissue were observed by H.E. staining, and the ultrastructure of myocardiocytes of cardiac apical tissue was observed under transmission electron microscope. The contents of Fe2+ and glutathione (GSH) in the myocardial tissue were measured by chromato-metry. The protein expression levels of Nrf2, HO-1, glutathione peroxidase 4 (GPX4), ferritin heavy chain polypeptide 1 (FTH1) and long chain acyl CoA synthase 4 (ACSL4) in the myocardial tissue were detected by Western blot. RESULTS: Compared with the sham operation group, the HR, ECG ST, Fe2+ content, expression levels of Nrf2, HO-1, FTH1 and ACSL4 proteins in myocardial tissues were significantly increased (P<0.01), while GSH content and GPX4 protein expression considerably decreased (P<0.01) in the model group. Compared with the model group, both EA and EA+ML385 groups had an obvious decrease in HR, Fe2+ content, and ACSL4 levels (P<0.01), and an increase in the expression levels of GPX4 and FTH1 proteins (P<0.01), EA (rather than EA+ML385) effectively down-regulated ECG ST, and up-regulated GSH, Nrf2 and HO-1 (P<0.01), whereas EA+ML385 apparently down-regulated expression levels of Nrf2 and HO-1 (P<0.01). It shows that ML385 pronouncedly weaken the effects of EA in slowing down ECG ST and HR, down-regulating Fe2+ content and ACSL4 expression (P<0.01), up-regulating GSH content, Nrf2, HO-1, GPX4 and FTH1 expressions (P<0.01). H.E. staining showed disordered arrangement and hyperplasia of myocardiocytes, enlarged myocardial fiber gap, agglomerated and deeply stained myoplasma, and some broken myocardial fibers with irregular mass and local tissue fibrosis in the model group, which was relatively milder in both EA and EA+ML385 groups. Compared with the sham operation group, the model group showed decreased mitochondrial atrophy, increased membrane density, and disappearance or reduction of cristae in myocardial cells，which was improved in the EA group. CONCLUSION: EA of HT7 and HT5 has a protective effect on ischemic myocardium in rats, which may be related to its effects in reducing oxidative stress by regulating Nrf2/HO-1 signaling pathway, and inhibiting "iron death" of myocardial cells.

Ischemic Stroke and Dysbiosis of Gut Microbiota: Changes to LPS Levels and Effects on Functional Outcomes.

Context: The intestinal microbiota and their metabolites play an important role in acute ischemic stroke (AIS) and modulate brain functions directly or indirectly through immune, endocrine, vagal, and other humoral pathways. However, relatively few investigations have evaluated the gut microbiome and its levels of inflammatory factors or the potential associations of those factors with stroke outcomes in patients who have had acute ischemic stroke (AIS), with different stroke severities. Objective: The study intended to determine if AIS patients would have different gut microbiota and inflammatory-factor levels than healthy individuals and if those levels would be associated with the stroke's severity and the patient's prognosis. Design: The research team performed a prospective observational study. Setting: The study took place in the Department of Rehabilitation at the General Hospital of Wanbei Coal and Electricity Group, which is the Third Affiliated Hospital of Bengbu Medical College in Suzhou, Anhui, China. Participants: Participants were 90 patients who had received a diagnosis and treatment of AIS within 48 hours of the stroke's onset at the hospital, between October 2021 and March 2022. Groups: The research team performed multiple comparisons of the baseline demographic and clinical characteristics, the gut microbiota, and levels of inflammatory factors of a number of groups: (1) the AIS patients, the AIS group, to the healthy controls, the control group; (2) the AIS participants who had had a mild or moderate stroke, the mild-moderate group, and those who had had a severe stroke, the severe group; (3) the AIS participants who had had a good primary outcome, the good outcome group, and those who had had a poor primary outcome, the poor outcome group; (4) the mild-moderate and severe groups to the control group; and (5) the good outcome and poor outcome groups to the control group. Outcome Measures: The research team: (1) obtained participants' fecal samples within 72 hours of admission; (2) collected baseline data for the included AIS patients and controls; (3) used 16S rRNA gene sequencing and an enzyme-linked immunosorbent assay (ELISA) to compare the fecal microbial compositions, lipopolysaccharide (LPS) contents, and inflammatory-factor levels between groups; and (4) evaluated the associations of the fecal microbial compositions with severity of stroke and 90-day functional outcomes, using logistic-regression models. Results: The gut microflora distinguished AIS patients from healthy controls. The LPS and inflammatory-factor levels were associated with an increased risk of poor functional outcomes at day 90. Conclusions: Dysbiosis of gut microbiota and LPS and inflammatory-factor levels can increase AIS patients' subsequent risks for poor functional outcomes, indicating that the dysbiosis and levels could be potential prognostic markers and therapeutic targets for stroke.

Cardiovascular Outcomes Observed with Ticagrelor versus Clopidogrel in Type 2 Diabetes Mellitus Patients with Acute Coronary Syndrome: A Meta-analysis.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is often associated with macrovascular complications including cardiovascular diseases (CVDs), resulting in acute coronary syndrome (ACS). Newer potent antiplatelet agents have recently been approved for use in clinical practice. In this analysis, we aimed to systematically compare the cardiovascular outcomes observed with ticagrelor versus clopidogrel in T2DM patients with ACS. METHODS: From August to September 2022, electronic databases were searched for publications that compared cardiovascular outcomes observed with ticagrelor versus clopidogrel in patients with T2DM. The statistical analysis was carried out using RevMan 5.4 software. A random effect statistical model was used to analyze the data. Risk ratios (RR) with 95% confidence intervals (CIs) were used to represent the data post analysis. RESULTS: A total of 5868 participants with T2DM were included in this analysis, of which 1944 participants were assigned to the ticagrelor group and 3924 participants were assigned to the clopidogrel group. Our analysis showed that ticagrelor was associated with a significantly lower risk of major adverse cardiac events (MACEs) (RR: 0.64, 95% CI: 0.49-0.84; P = 0.001), all-cause mortality (RR: 0.65, 95% CI: 0.51-0.83; P = 0.0004), and cardiac death (RR: 0.60, 95% CI: 0.43-0.84; P = 0.003) in comparison to clopidogrel. However, the risks of repeated revascularization (RR: 1.48, 95% CI: 0.44-4.99; P = 0.53), stent thrombosis (RR: 0.70, 95% CI: 0.18-2.71; P = 0.60), reinfarction (RR: 0.85, 95% CI: 0.58-1.23; P = 0.39), and stroke (RR: 0.56, 95% CI: 0.14-2.21; P = 0.41) were similar. Ticagrelor was associated with a significantly higher risk of minor bleeding (RR: 1.53, 95% CI: 1.07-2.19; P = 0.02), whereas the risk for major bleeding (RR: 1.08, 95% CI: 0.55-2.10; P = 0.82) was not significantly different. CONCLUSIONS: In these T2DM patients with ACS, a significantly lower risk of major adverse cardiovascular events including all-cause mortality was observed in the ticagrelor group compared with the clopidogrel group. However, T2DM patients who were assigned to ticagrelor showed a significantly higher minor bleeding risk. Larger clinical trials should be able to confirm these hypotheses.

Type 2 diabetes mellitus (T2DM) is increasing all over the world, and is often associated with macrovascular complications including cardiovascular diseases (CVDs), leading to acute coronary syndrome (ACS).Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is recommended in these patients.However, due to clopidogrel hyporesponsiveness, especially in patients with T2DM, a more potent antiplatelet is needed.Recently, newer, more potent antiplatelet agents have been approved for use in clinical practice.A significantly lower risk of major adverse cardiovascular outcomes including all-cause mortality was observed with ticagrelor compared with clopidogrel in these patients with T2DM.However, ticagrelor was associated with a significantly higher minor bleeding risk.

IDH Mutations Are Potentially the Intrinsic Genetic Link among the Multiple Neoplastic Lesions in Ollier Disease and Maffucci Syndrome: A Clinicopathologic Analysis from a Single Institute in Shanghai, China.

BACKGROUND: This study aims to investigate isocitrate dehydrogenase gene mutations in patients with the non-hereditary skeletal disorders of Ollier disease and Maffucci syndrome, particularly in the extraosseous tumours. METHODS: A total of 16 tumours from three patients with Ollier disease and three patients with Maffucci syndrome were collected. Sanger sequencing was applied to determine the hotspot mutations of IDH1 and IDH2 genes in multiple neoplastic tissues. RESULTS: A majority of the tumours displayed an IDH1 mutation (p.R132C in 11 tumours including the paediatric ovarian tumour from one patient with Ollier disease, 4 cutaneous haemangiomas from three patients with Maffucci syndrome, 5 enchondromas and 1 chondrosarcoma; p.R132H in 2 cartilaginous tumours from one patient). CONCLUSIONS: IDH1 mutations were demonstrated in multiple cartilaginous tumours and extraskeletal neoplasms in this case series. Specifically, identical IDH1 mutations were confirmed in the separate lesions of each patient. These results are in concordance with findings that have been reported. However, here, we additionally reported the first case of Ollier disease with an ovarian tumour, which harboured the identical IDH1 mutation with the corresponding cartilaginous tumour. We further provided evidence that IDH mutations are the potential genetic links among the multiple neoplastic lesions of Ollier disease and Maffucci syndrome.

Feasibility study of personalized speed adaptation method based on mental state for teleoperated robots.

The teleoperated robotic system can support humans to complete tasks in high-risk, high-precision and difficult special environments. Because this kind of special working environment is easy to cause stress, high mental workload, fatigue and other mental states of the operator, which will reduce the quality of operation and even cause safety accidents, so the mental state of the people in this system has received extensive attention. However, the existence of individual differences and mental state diversity is often ignored, so that most of the existing adjustment strategy is out of a match between mental state and adaptive decision, which cannot effectively improve operational quality and safety. Therefore, a personalized speed adaptation (PSA) method based on policy gradient reinforcement learning was proposed in this paper. It can use electroencephalogram and electro-oculogram to accurately perceive the operator's mental state, and adjust the speed of the robot individually according to the mental state of different operators, in order to perform teleoperation tasks efficiently and safely. The experimental results showed that the PSA method learns the mapping between the mental state and the robot's speed regulation action by means of rewards and punishments, and can adjust the speed of the robot individually according to the mental state of different operators, thereby improving the operating quality of the system. And the feasibility and superiority of this method were proved. It is worth noting that the PSA method was validated on 6 real subjects rather than a simulation model. To the best of our knowledge, the PSA method is the first implementation of online reinforcement learning control of teleoperated robots involving human subjects.

Multiclass Arrhythmia Detection and Classification From Photoplethysmography Signals Using a Deep Convolutional Neural Network.

Background Studies have reported the use of photoplethysmography signals to detect atrial fibrillation; however, the use of photoplethysmography signals in classifying multiclass arrhythmias has rarely been reported. Our study investigated the feasibility of using photoplethysmography signals and a deep convolutional neural network to classify multiclass arrhythmia types. Methods and Results ECG and photoplethysmography signals were collected simultaneously from a group of patients who underwent radiofrequency ablation for arrhythmias. A deep convolutional neural network was developed to classify multiple rhythms based on 10-second photoplethysmography waveforms. Classification performance was evaluated by calculating the area under the microaverage receiver operating characteristic curve, overall accuracy, sensitivity, specificity, and positive and negative predictive values against annotations on the rhythm of arrhythmias provided by 2 cardiologists consulting the ECG results. A total of 228 patients were included; 118 217 pairs of 10-second photoplethysmography and ECG waveforms were used. When validated against an independent test data set (23 384 photoplethysmography waveforms from 45 patients), the DCNN achieved an overall accuracy of 85.0% for 6 rhythm types (sinus rhythm, premature ventricular contraction, premature atrial contraction, ventricular tachycardia, supraventricular tachycardia, and atrial fibrillation); the microaverage area under the microaverage receiver operating characteristic curve was 0.978; the average sensitivity, specificity, and positive and negative predictive values were 75.8%, 96.9%, 75.2%, and 97.0%, respectively. Conclusions This study demonstrated the feasibility of classifying multiclass arrhythmias from photoplethysmography signals using deep learning techniques. The approach is attractive for population-based screening and may hold promise for the long-term surveillance and management of arrhythmia. Registration URL: www.chictr.org.cn. Identifier: ChiCTR2000031170.