Extraocular muscle volume on time-of-flight magnetic resonance angiography in patients with myasthenia gravis.

INTRODUCTION/AIMS: Despite being a prominent feature of myasthenia gravis (MG), extraocular muscle (EOM) has received little attention in clinical research. The aim of this study was to examine EOM volume in patients with MG and controls using time-of-flight magnetic resonance angiography (TOF-MRA). METHODS: EOM volumes (overall and individual rectus muscles) were calculated using TOF-MRA images and compared between MG patients (including subgroups) and controls. The correlation between EOM volume and disease duration was examined. Predictive equations for the selected parameters were developed using multiple linear regression analysis. RESULTS: EOM volume was lower in MG patients than controls, especially in MG patients with ophthalmoparesis (MG-O). MG-O exhibited a moderate negative correlation between EOM volume and disease duration. Multiple linear regression showed that disease duration and EOM status (ophthalmoparesis or not) account for 48.4% of EOM volume. DISCUSSION: Patients with MG show atrophy of the EOMs, especially those with ophthalmoparesis and long disease duration.

Facile Friedel-Crafts alkylation of arenes under solvent-free conditions.

The Friedel-Crafts alkylation of arenes is an important part of electrophilic aromatic substitution reactions. However, the reactivity of arenes is weakened by electron-withdrawing substituents, leading to limited substrate scopes and applications. Herein, we developed an efficient HOTf-promoted Friedel-Crafts alkylation reaction of broad arenes with α-aryl-α-diazoesters under metal-free and solvent-free conditions.

Astrocytes in ischemic stroke: Crosstalk in central nervous system and therapeutic potential.

In the central nervous system (CNS), a large group of glial cells called astrocytes play important roles in both physiological and disease conditions. Astrocytes participate in the formation of neurovascular units and interact closely with other cells of the CNS, such as microglia and neurons. Stroke is a global disease with high mortality and disability rate, most of which are ischemic stroke. Significant strides in understanding astrocytes have been made over the past few decades. Astrocytes respond strongly to ischemic stroke through a process known as activation or reactivity. Given the important role played by reactive astrocytes (RAs) in different spatial and temporal aspects of ischemic stroke, there is a growing interest in the potential therapeutic role of astrocytes. Currently, interventions targeting astrocytes, such as mediating astrocyte polarization, reducing edema, regulating glial scar formation, and reprogramming astrocytes, have been proven in modulating the progression of ischemic stroke. The aforementioned potential interventions on astrocytes and the crosstalk between astrocytes and other cells of the CNS will be summarized in this review.

Quality of systematic reviews with meta-analyses of resveratrol: A methodological systematic review.

Recently, several meta-analyses (MAs) have focused on the health effects of resveratrol. However, the methodological and reporting quality of these MAs has not yet been fully evaluated so far. Therefore, the present study evaluated the quality of these MAs through a methodological systematic review. Systematic searches were conducted in PubMed, Embase, Web of Science, and Cochrane Library from inception until May 20, 2022, and PubMed was used to update the search until September 6, 2023. The methodological and reporting quality of the selected MAs was evaluated using AMSTAR-2 and PRISMA 2009. Fifty-one MAs published during 2013-2023 were included. In each review, the number of primary studies ranged from 3 to 37, and the number of participants ranged from 50 to 2114. Among the first-listed primary outcomes, only 23 (45.10%) were "positive." As for the methodological quality, most MAs (44, 86.27%) on resveratrol were rated critically low. Inadequate reporting of the included MAs mainly involved items 2 ("Structured summary"), 5 ("Protocol and registration"), 8 ("Search"), 9 ("Study selection"), 10 ("Data collection process"), 12 ("Risk of bias in individual studies"), and 24 ("Summary of evidence") based on the PRISMA 2009. Additionally, journal's impact factor, number of authors, and funding support were positively associated with the overall methodological quality but were not statistically significant (p > 0.05). Future MAs on resveratrol require better design, implementation, and reporting by following the Cochrane Handbook, AMSTAR-2, and PRISMA.

Peptide hydrogel based electrochemical biosensor for simultaneous monitoring of H2O2 and NO released from three-dimensional cultured breast cancer cells.

An antifouling peptide hydrogel-based electrochemical biosensor was developed for real-time monitoring of hydrogen peroxide (H2O2) and nitric oxide (NO) released by 3D cultured breast cancer cells upon drug stimulation. Platinum nanoparticles (Pt NPs) were electrodeposited on titanium mesh (Pt NPs/TM) to enhance sensitivity and shown to possess excellent electrocatalytic ability toward H2O2 and NO. The composite hydrogel formed by co-assembling of N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) and a fluorine methoxycarbonyl group-functionalized Lys-(Fmoc)-Asp was coated on Pt NPs/TM electrode surface to provide cellular scaffolding. Their favorable biocompatibility promoted cell adhesion and growth, while good hydrophilicity endowed the sensor with greatly enhanced antifouling capability in complex cell culture environments. The biosensor successfully determined H2O2 and NO secretion from both non-metastatic and metastatic breast cancer cells in real time. Our results demonstrated robust associations between reactive oxygen species (ROS) and reactive nitrogen species (RNS) production and cell malignancy, with the main difference in oxidative stress between the two subtypes of cells being NO release, particularly emphasizing RNS's critical leading in driving cancer metastasis and invasion progression. This sensor holds great potential for cell-release research under the in vivo-like microenvironment and could reveal RNS as an attractive therapeutic target for treating breast cancer.

Quantity and Distribution of Muscle Spindles in Animal and Human Muscles.

Muscle spindles have unique anatomical characteristics that can be directly affected by the surrounding tissues under physiological and pathological conditions. Understanding their spatial distribution and density in different muscles is imperative to unravel the complexity of motor function. In the present study, the distribution and number/density of muscle spindles in human and animal muscles were reviewed. We identified 56 articles focusing on muscle spindle distribution; 13 articles focused on human muscles and 43 focused on animal muscles. The results demonstrate that spindles are located at the nerve entry points and along distributed vessels and they relate to the intramuscular connective tissue. Muscles' deep layers and middle segments are the main topographic distribution areas. Eleven articles on humans and thirty-three articles on animals (totaling forty-four articles) focusing on muscle spindle quantity and density were identified. Hand and head muscles, such as the pronator teres/medial pterygoid muscle/masseter/flexor digitorum, were most commonly studied in the human studies. For animals, whole-body musculature was studied. The present study summarized the spindle quantity in 77 human and 189 animal muscles. We identified well-studied muscles and any as-yet unfound data. The current data fail to clarify the relationship between quantity/density and muscle characteristics. The intricate distribution of the muscle spindles and their density and quantity throughout the body present some unique patterns or correlations, according to the current data. However, it remains unclear whether muscles with fine motor control have more muscle spindles since the study standards are inconsistent and data on numerous muscles are missing. This study provides a comprehensive and exhaustive approach for clinicians and researchers to determine muscle spindle status.

The Impact of Sciatic Nerve Injury on Extracellular Matrix of Lower Limb Muscle and Thoracolumbar Fascia: An Observational Study.

Peripheral nerve injury (PNI) is a complex clinical challenge resulting in functional disability. Neurological recovery does not always ensure functional recovery, as extracellular matrix (ECM) alterations affect muscle function. This study evaluates hyaluronan (HA) and collagen concentration in the gastrocnemius muscle and thoracolumbar fascia (TLF) in unilateral lower limb PNI rats to explore systemic ECM alterations following PNI and their impacts on functional recovery. Eighteen 8-week-old male Sprague-Dawley rats were divided into experimental (n = 12 left sciatic nerve injury) and control (n = 6) groups. After six weeks, motor function was evaluated. Muscle and TLF samples were analysed for HA and collagen distribution and concentrations. SFI and gait analysis confirmed a functional deficit in PNI rats 6 weeks after surgery. HA concentration in both sides of the muscles decreased by approximately one-third; both sides showed significantly higher collagen concentration than healthy rats (12.74 ± 4.83 µg/g), with the left (32.92 ± 11.34 µg/g) significantly higher than the right (20.15 ± 7.03 µg/g). PNI rats also showed significantly lower HA (left: 66.95 ± 20.08 µg/g; right: 112.66 ± 30.53 µg/g) and higher collagen (left: 115.89 ± 28.18 µg/g; right: 90.43 ± 20.83 µg/g) concentrations in both TLF samples compared to healthy rats (HA: 167.18 ± 31.13 µg/g; collagen: 47.51 ± 7.82 µg/g), with the left TLF more affected. Unilateral lower limb PNI induced HA reduction and collagen accumulation in both the lower limb muscles and the TLF, potentially exacerbating motor function impairment and increasing the risk of low back dysfunctions.

The genome of Eleocharis vivipara elucidates the genetics of C3-C4 photosynthetic plasticity and karyotype evolution in the Cyperaceae.

Eleocharis vivipara, an amphibious sedge in the Cyperaceae family, has several remarkable properties, most notably its alternate use of C3 photosynthesis underwater and C4 photosynthesis on land. However, the absence of genomic data has hindered its utility for evolutionary and genetic research. Here, we present a high-quality genome for E. vivipara, representing the first chromosome-level genome for the Eleocharis genus, with an approximate size of 965.22 Mb mainly distributed across 10 chromosomes. Its Hi-C pattern, chromosome clustering results, and one-to-one genome synteny across two subgroups indicates a tetraploid structure with chromosome count 2n = 4x = 20. Phylogenetic analysis suggests that E. vivipara diverged from Cyperus esculentus approximately 32.96 million years ago (Mya), and underwent a whole-genome duplication (WGD) about 3.5 Mya. Numerous fusion and fission events were identified between the chromosomes of E. vivipara and its close relatives. We demonstrate that E. vivipara has holocentromeres, a chromosomal feature which can maintain the stability of such chromosomal rearrangements. Experimental transplantation and cross-section studies showed its terrestrial culms developed C4 Kranz anatomy with increased number of chloroplasts in the bundle sheath (BS) cells. Gene expression and weighted gene co-expression network analysis (WGCNA) showed overall elevated expression of core genes associated with the C4 pathway, and significant enrichment of genes related to modified culm anatomy and photosynthesis efficiency. We found evidence of mixed nicotinamide adenine dinucleotide - malic enzyme and phosphoenolpyruvate carboxykinase type C4 photosynthesis in E. vivipara, and hypothesize that the evolution of C4 photosynthesis predates the WGD event. The mixed type is dominated by subgenome A and supplemented by subgenome B. Collectively, our findings not only shed light on the evolution of E. vivipara and karyotype within the Cyperaceae family, but also provide valuable insights into the transition between C3 and C4 photosynthesis, offering promising avenues for crop improvement and breeding.

Effects of comprehensive exercise training on frailty, negative emotions and physical functions of elderly patients with diabetes.

Objective: To evaluate the effects of comprehensive exercise training on frailty, negative emotions and physical functions of elderly patients with diabetes. Methods: This is a retrospective study. A total of 140 elderly patients with T2DM in The No.2 Hospital of Baoding were selected from December, 2021 to June, 2023 and randomly divided into two groups, with 70 patients in each group. The control group was given routine nursing and routine exercise education, and the study group was additionally given comprehensive exercise training. Tilburg frailty indicator (TFI), emotional status, physical functions, grip strength, fasting blood glucose and patient satisfaction were compared and analyzed between the two groups. Results: Before the intervention, TFI showed no significant differences between the two groups (p>0.05). After the intervention, physical, psychological and social frailty in the study group were significantly lower than those in the control group, with statistically significant differences (p= 0.00). SAS and SDS scores reduced significantly in the study group compared with those in the control group after the intervention, with statistically significant differences (p=0.00). After the intervention, the grip strength was significantly larger while the fasting blood glucose was significantly lower in the study group compared with those in the control group, with statistically significant differences (p=0.00). Patient satisfaction in the study group was higher than in the control group, with a statistically significant difference(p=0.03). Conclusion: Comprehensive exercise training for elderly patients with diabetes is beneficial to improving their frail state, negative emotions, blood glucose levels and physical functions. It has significant clinical application value.

The effects of dietary intervention combined with comprehensive exercise instruction on somatic function and quality of life in elderly patients with diabetes mellitus.

Objective: To assess the effects of dietary intervention combined with comprehensive exercise instruction on somatic function and quality of life in elderly patients with diabetes mellitus (DM). Methods: This was application research. A total of 120 elderly patients with type-2 diabetes mellitus (T2DM) admitted to The No.2 Hospital of Baoding from March 10, 2022 to March 10, 2023 were included and randomly divided into the control group and the experimental group(n=60). Patients in the control group received conventional treatment and nursing regimen, while those in the experimental group were given dietary intervention combined with comprehensive exercise instruction based on the control group. The differences before and after treatment between the two groups were compared and analyzed. Results: After the intervention, the experimental group had remarkably lower levels of fasting blood glucose (FBG), 2h postprandial blood glucose(2hPG) and glycated hemoglobin (HbA1c) than the control group (p=0.00), while significantly improved somatic function, psychological function, social function and material life status compared to the control group (p=0.00). The levels of SAS and SDS in the experimental group were significantly decreased compared with those in the control group (p=0.00). The levels of SOD, MDA and CAT in the experimental group were obviously superior to those in the control group, with statistically significant differences (p=0.00). Conclusion: Dietary intervention combined with comprehensive exercise instruction is an effective treatment for elderly patients with DM, boasting a variety of benefits such as regulating patients' blood glucose levels, improving patient satisfaction, and ameliorating the level of oxidative stress in the body, which is worthy of clinical promotion.

[Guidelines for construction of traditional Chinese medicine pharmacovigilance system in medical institutions].

The group standard Guidelines for construction of traditional Chinese medicine(TCM) pharmacovigilance system in medical institutions, managed by Chinese Association of Chinese Medicine and led by the Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences and Dongfang Hospital of Beijing University of Chinese Medicine, was announced on National Group Standard Information Platform on January 16, 2024, with the standard number T/CACM 1563. 2-2024. According to EU pharmacovigilance regulations and the second-level guidance principles of International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH), the unique characteristics of TCM were fully considered, and the relevant systems and procedures for constructing TCM pharmacovigilance systems in medical institutions were clearly defined. This included establishing TCM pharmacovigilance information platforms, arranging staff, formulating various regulations, and monitoring adverse reactions of TCM(including TCM decoction pieces, granules, Chinese patent medicines, in-hospital preparations, and pre-marketed Chinese patent medicines). It aimed to develop a TCM pharmacovigilance system in medical institutions that was tailored to the characteristics of TCM. The system could be appropriately adjusted according to the scope of practice and actual circumstances of medical institutions at different levels. This will enhance the implementation of TCM pharmacovigilance work and safeguard medication safety. The group standard underwent multiple rounds of consultations with internal and external experts and has ultimately evolved into a guiding document applicable to medical institutions and related entities engaged in pharmacovigilance activities.

[Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines].

Oral Chinese patent medicine is the essence of effective prescriptions created and summarized by Chinese medical scientists through thousands of years of medical practice. It is portable and convenient, with an obvious curative effect and other characteristics. However, at present, oral Chinese patent medicine is rich in dosage forms, various in types, complex in mechanism of action, and broad in clinical positioning. In clinical application, there are often cases of drug use without reference to instructions,repeated drug use, and prolonged drug use, which highlights safety problems such as adverse reactions and hepatorenal toxicity. Oral Chinese patent medicine pharmacovigilance is facing challenges. World Health Organization(WHO) has issued the WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems, and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH) has issued the ICH E2 pharmacovigilance guidelines. The United States has issued the Pharmacovigilance management standards and pharmacoepidemiological assessment guidelines, and the European Union has issued the Guidelines on good pharmacovigilance practices. Japan, South Korea, and other countries in the Asia Pacific region have established their own pharmacovigilance systems, but currently, there are no pharmacovigilance guidelines related to oral Chinese patent medicine in China. Therefore, experts from many disciplines and fields in China were invited to jointly develop the Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines, which aims to develop pharmacovigilance guidelines for clinical application that are consistent with China's national conditions and highlight the characteristics of oral Chinese patent medicine, and provide guidance for clinically safe and rational drug application in medical institutions.

[Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use].

There are many kinds and dosage forms of Chinese patent medicines for external use on the market, which are widely used in clinical departments. The common adverse reactions of Chinese patent medicines for external use are skin reactions, and those for the rare severe diseases include palpitation, chest tightness, dyspnea, and anaphylactic shock. At present, World Health Organization(WHO), International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH),the United States, the European Union, and Asia-Pacific countries(such as Japan and South Korea) have not issued any pharmacovigilance guideline of Chinese patent medicines for external use. China has not issued any pharmacovigilance guideline for these medicines, only releasing the standard Evaluation of skin adverse reactions caused by Chinese patent medicines for external use(T/CACM 005-2017). To standardize the safe and reasonable use of Chinese patent medicines for external use, Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use was developed with the joint efforts of experts in diverse disciplines. The guideline provides guidance on the monitoring and reporting of adverse reactions/events, identification and assessment of risk signals, and risk control measures in the clinical application of Chinese patent medicines for external use to guide the rational use of these medicines in clinical practice. At the same time, the possible risks and risk control measures in clinical application of Chinese patent medicines for external use are listed for clinical reference. In addition, the guideline provides guidance for risk minimization plans and the standardization of activities related to pharmacovigilance of Chinese patent medicines for external use in China.

[Pharmacovigilance guidelines of Chinese patent medicines].

Drug administration law of the People's Republic of China(2019 revised edition), which came into effect on December 1, 2019, proposed that " the state shall establish a pharmacovigilance system". Pharmacovigilance work of Chinese patent medicines is more difficult, and it is necessary to carry out Pharmacovigilance activities that are in line with the characteristics of Chinese patent medicines. Pharmacovigilance guidelines of Chinese patent medicines(T/CACM 1563. 1-2024), based on the principles of Drug Administration Law of the People's Republic of China(2019 revised edition) and Pharmacovigilance quality management standards(No. 65 of 2021) of the National Medical Products Administration, draws on the EU Pharmacovigilance regulation and the secondary guidelines of International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH), and it is drafted in accordance with the provisions of Guidelines for standardization work part 1: structure and drafting rules of standardization documents(GB/T1. 1-2020) based on the characteristics of Chinese patent medicines. It serves as a general document for a series of pharmacovigilance guidelines of Chinese patent medicines, such as Guidelines for construction of traditional Chinese medicine pharmacovigilance system in medical institutions(T/CACM 1563. 2-2024), Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines(T/CACM 1563. 3-2024), Pharmacovigilance guidelines for clinical application of traditional Chinese medicine injections(T/CACM 1563. 4-2024), Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use(T/CACM 1563. 5-2024), and Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration(T/CACM 1563. 6-2024), including four major elements of pharmacovigilance monitoring and reporting of Chinese patent medicines, signal identification, risk evaluation, and risk control, as well as pharmacovigilance activities for Chinese patent medicines, ensuring the safety of public drug use.

[Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration].

The group standard Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration was released on January 16, 2024, on the national group standards information platform by the Institute of Basic Research in Clinical Medicine of China Academy of Chinese Medical Sciences and School and Hospital of Stomatology of Peking University, under the centralized management by the China Association of Chinese Medicine. The standard number is T/CACM 1563.6-2024. It aims to propose key elements and specify technical methods for safety monitoring and reporting, signal identification, risk assessment, and risk control based on the Drug administration law of the People's Republic of China(revised in 2019), which establishes normative pharmacovigilance guideline of Chinese patent medicine for mucosal administration that is in line with the characteristics of traditional Chinese Medicine(TCM) based on the pharmacovigilance content for clinical application of Chinese patent medicine for mucosal administration. The group standard has been discussed by internal and external experts through multiple rounds of consultation. It serves as a guiding document for stakeholders involved in pharmacovigilance activities, including pharmaceutical license holders, drug manufacturers, medical institutions, research institutes, and pharmaceutical trading enterprises.

Prognostic significance of serial N-terminal pro-B-type natriuretic peptide levels in patients with acute myocardial infarction: A prospective study.

OBJECTS: This study aimed to investigate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at different sampling times and prognosis in patients with acute myocardial infarction (AMI) undergoing emergency percutaneous coronary intervention (PCI). METHODS AND RESULTS: Between March 2017 and January 2020, 1,105 patients with AMI who underwent emergency PCI were included. NT-proBNP levels were measured on days 0, 1, 2, 3, and 7. A composite of all-cause death, MI recurrence (reMI), and rehospitalization due to heart failure, known as major adverse cardiovascular events (MACE), was recorded. During the 36.8-month follow-up, 175 patients (15.8%) experienced MACEs. When patients were grouped based on quartiles of NT-proBNP levels on days 0 and 7, the results demonstrated that patients in quartile 4 showed a substantially increased MACE risk compared to those in quartile 1 (hazard ratio [HR] 2.27, 95% confidence interval [CI]:1.27-4.08, P = .006; HR 2.20, 95%CI:1.23-3.94, P = .008). There were U-shaped relationships between the HR for MACE and NT-proBNP levels on days 2, 3, and 7, as well as peak NT-proBNP (P for nonlinearity = .007, .006, .004, and .009, respectively). A similar relationship was observed in the HR for reMI and NT-proBNP levels on days 2 and 3. For MACE at 3 years, serial NT-proBNP levels improved the predictive accuracy of the Global Registry of Acute Coronary Events (GRACE) risk score (concordance index [C-index]: 0.711; continuous net reclassification improvement [NRI]: 0.192, 95% CI: 0.022-0.445; integrated discrimination improvement [IDI]: 0.034, 95% CI: 0.016-0.064). For all-cause death at 3 years, the combination of NT-proBNP and GRACE score showed excellent performance, with C-index, continuous NRI, and IDI values of 0.801, 0.373 (95%CI: 0.072-0.853), and 0.051 (95%CI: 0.025-0.091), respectively. CONCLUSIONS: Early and sequential measurement of NT-proBNP levels could assist in predicting MACE risk. Moreover, the relationship between MACE risk and NT-proBNP levels was U-shaped. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT: 03593928.

Prognostic impacts of diabetes status and lipoprotein(a) levels in patients with ST-segment elevation myocardial infarction: a prospective cohort study.

OBJECTS: This study aimed to investigate the impact of lipoprotein(a) [Lp(a)] levels on the prognosis of Chinese patients with ST-segment elevation myocardial infarction (STEMI), and to explore if the impact may differ in the diabetes mellitus (DM) and nonDM groups. METHODS: Between March 2017 and January 2020, 1543 patients with STEMI who underwent emergency percutaneous coronary intervention (PCI) were prospectively recruited. The primary outcome was a composite of all-cause death, MI recurrence (reMI), and stroke, known as major adverse cardiovascular events (MACE). Analyses involving the Kaplan-Meier curve, Cox regression, and restricted cubic spline (RCS) were conducted. RESULTS: During the 1446-day follow-up period, 275 patients (17.8%) experienced MACEs, including 141 with DM (20.8%) and 134 (15.5%) without DM. As for the DM group, patients with Lp(a) ≥ 50 mg/dL showed an apparently higher MACE risk compared to those with Lp(a) < 10 mg/dL (adjusted hazard ratio [HR]: 1.85, 95% confidence interval [CI]:1.10-3.11, P = 0.021). The RCS curve indicates that the HR for MACE appeared to increase linearly with Lp(a) levels exceeding 16.9 mg/dL. However, no similar associations were obtained in the nonDM group, with an adjusted HR value of 0.57 (Lp(a) ≥ 50 mg/dL vs. < 10 mg/dL: 95% CI 0.32-1.05, P = 0.071). Besides, compared to patients without DM and Lp(a) ≥ 30 mg/dL, the MACE risk of patients in the other three groups (nonDM with Lp(a) < 30 mg/dL, DM with Lp(a) < 30 mg/dL, and DM with Lp(a) ≥ 30 mg/dL) increased to 1.67-fold (95% CI 1.11-2.50, P = 0.013), 1.53-fold (95% CI 1.02-2.31, P = 0.041), and 2.08-fold (95% CI 1.33-3.26, P = 0.001), respectively. CONCLUSIONS: In this contemporary STEMI population, high Lp(a) levels were linked to an increased MACE risk, and very high Lp(a) levels (≥ 50 mg/dL) significantly indicated poor outcomes in patients with DM, while not for those without DM. TRIAL REGISTRATION: clinicaltrials.gov NCT: 03593928.

Cryptosporidium infection induced the dropping of SCFAS and dysbiosis in intestinal microbiome of Tibetan pigs.

The infection of Cryptosporidium in pigs causes digestive system ailments, diarrhea and weight loss serving as an economic burden, especially in newborn animals. The bacterial fermentation products of short-chain fatty acids have important roles in immune function, microbiota regulation, osmotic balance and metabolism. However, till now little knowledge is available about the effect of Cryptosporidium infection on microbiota and SCFAs in plateau pigs. Hence, we performed this study to explore the response of microbiota and SCFAs in the natural infection of Cryptosporidium in Tibetan pigs. Cryptosporidium positive (infected, G) and negative samples (healthy, J) in our previous study were used for high throughputsequencing and Gas Chromatography-Mass Spectrometer analysis. Over 81 000 and 74 000 filtered sequences were detected in healthy and infected Tibetan pigs, respectively. Lower sample richness and evenness were observed in Cryptosporidium infection, as alpha diversity analysis found that chao1 (p < 0.05), faith_pd (p < 0.05), and observed_features in group G were significantly lower than pigs in group J. A total of 4 and 27 significant different phyla and genera were found between group G and J. The changed genera were Psychrobacter, Desemzia, Succiniclasticum, Treponema, Campylobacter, Atopobium, Olsenella, Pediococcus, Peptococcus, Sharpea, Desulfovibrio, Acinetobacter, Rhodococcus, Anaerostipes, Turicibacter, Lactobacillus, RFN20, Phascolarctobacterium, Roseburia, Megasphaera, Streptococcus, Blautia, Lachnospira, rc4_4, Gemmiger, Dorea, Oribacterium and Prevotella, which affected the microbiota functions with 360 abundance changed enzymes, and pathways in L1, L2 and L3 levels of KEGG. The concentration of acetic acid (p < 0.01), butyric acid (p < 0.05) and caproic acid (p < 0.01) were lower in group G. In conclusion, the present study herein uncovered that the host responses to Cryptosporidium infection in Tibetan pigs with 27 of significantly changed genera decreased SCFAs in pigs, which may provide insights in further developing novel therapy against this protozoan.

Associations of Culprit Vessel Size and Plaque Characteristics in Patients with ST-Segment Elevation Myocardial Infarction.

Background: Small vessel disease (SVD) widely exists in patients with acute coronary syndrome. However, the plaque characteristic of SVD has not been investigated. Methods: Optical coherence tomography (OCT) of culprit lesion was examined in 576 patients with ST-segment elevation myocardial infarction (STEMI) and finally 404 patients with qualified images were analysed of plaque phenotypes and microstructure. The cohort was divided into three groups according to vessel diameters of culprit lesion which were measured by OCT. Major adverse cardiac events (MACEs) were recorded of each patient and compared among patients with different vessel diameters and plaque phenotypes. Results: Gender, age and body mass index (BMI) were significantly different among patients with different diameters of culprit vessels (98.4% vs. 85.7% vs.71.4%, p < 0.001; 40.0 ± 7.0 vs. 54.9 ± 6.6 vs. 68.9 ± 5.8, p < 0.001; 28.4 ± 4.0 vs. 25.8 ± 2.9 vs. 25.2 ± 3.0, p < 0.001, respectively). Moreover, patients with diameters of culprit lesion > 3 mm presented with more incidence of plaque rupture and macrophage (57.7% vs. 42.1% vs. 46.2%, p = 0.015, 55.1% vs. 41.0% vs. 36.9%, p = 0.010). Total MACE did not differ among groups of different vessel diameters and plaque phenotypes. Conclusions: Vessel size of culprit lesion is significantly associated with plaque phenotype in patients with STEMI. However, patients with different diameters and plaque phenotypes showed no significant difference of clinical outcomes. Clinical Trial Registration: NCT03593928.

Prognostic impacts of Lipoxin A4 in patients with acute myocardial infarction: A prospective cohort study.

Lipoxin A4 (LXA4) is one of the specialized pro-resolving lipid mediators proved to suppress the progression of atherosclerosis in vivo, but its clinical impacts in atherosclerotic patients is unclear. In this study, we assessed the prognostic impacts of LXA4 in patients with acute myocardial infarction (AMI). A total of 1569 consecutive AMI patients were prospectively recruited from March 2017 to January 2020. Plasma samples of AMI patients were collected, and LXA4 levels were determined using enzyme-linked immunosorbent assay. The primary outcome was major adverse cardiovascular event (MACE), a composite of all-cause death, recurrent MI, ischemic stroke, or ischemia-driven revascularization. Cox regression was used to assess associations between LXA4 and clinical outcomes. Overall, the median level of LXA4 was 5.637 (3.047-9.014) ng/mL for AMI patients. During a median follow-up of 786 (726-1108) days, high LXA4 (≥ 5.637 ng/mL) was associated with lower risk of MACE (hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.60-0.89, P = 0.002), which was sustained in propensity score matching (HR: 0.73, 95% CI: 0.60-0.90, P = 0.004) and inverse probability weighting analysis (HR: 0.74, 95% CI: 0.61-0.90, P = 0.002). Combined with pro-inflammatory biomarker, patients with high levels of LXA4 (≥ 5.637 ng/mL) but low levels of high-sensitivity C-reactive protein (< 5.7 mg/L) acquired the lowest risk of MACE (HR: 0.68, 95% CI: 0.51-0.92, P = 0.012). In sum, high levels of LXA4 were associated with lower risk of recurrent ischemic events for AMI patients, which could serve as new therapeutic target to tackle cardiovascular inflammation.