Small Extracellular Vesicles Derived from Altered Peptide Ligand-Loaded Dendritic Cell Act as A Therapeutic Vaccine for Spinal Cord Injury Through Eliciting CD4+ T cell-Mediated Neuroprotective Immunity.

The balance among different CD4+ T cell subsets is crucial for repairing the injured spinal cord. Dendritic cell (DC)-derived small extracellular vesicles (DsEVs) effectively activate T-cell immunity. Altered peptide ligands (APLs), derived from myelin basic protein (MBP), have been shown to affect CD4+ T cell subsets and reduce neuroinflammation levels. However, the application of APLs is challenging because of their poor stability and associated side effects. Herein, it is demonstrate that DsEVs can act as carriers for APL MBP87-99 A91 (A91-DsEVs) to induce the activation of 2 helper T (Th2) and regulatory T (Treg) cells for spinal cord injury (SCI) in mice. These stimulated CD4+ T cells can efficiently "home" to the lesion area and establish a beneficial microenvironment through inducing the activation of M2 macrophages/microglia, inhibiting the expression of inflammatory cytokines, and increasing the release of neurotrophic factors. The microenvironment mediated by A91-DsEVs may enhance axon regrowth, protect neurons, and promote remyelination, which may support the recovery of motor function in the SCI model mice. In conclusion, using A91-DsEVs as a therapeutic vaccine may help induce neuroprotective immunity in the treatment of SCI.

Higher Cumulative Blood Pressure in Midlife Predicts an Increased Risk of Atrial Fibrillation: Evidence From the Atherosclerosis Risk in Communities Study.

BACKGROUND: Elevated blood pressure (BP) is reportedly associated with an increased risk of atrial fibrillation (AF). However, the association between cumulative BP exposure in midlife and incident AF in mid-to-late life remains unclear. METHODS AND RESULTS: Participants enrolled in the ARIC (Atherosclerosis Risk in Communities) study with 4 consecutive BP measurements and no prevalent AF at baseline were included. Cumulative BP was calculated as the area under the curve from visit 1 to visit 4. Incident AF was identified by study visit ECGs, hospital discharge codes, or death certificates. A total of 9892 participants were included (44.6% men and mean age 62.9±5.7 years at visit 4) with 1550 (15.7%) individuals who developed new-onset AF during an average follow-up of 15.4 years. The incidence rates of AF per 1000 person-years across the 4 quartiles of cumulative systolic BP were 7.9, 9.2, 12.5, and 16.9, respectively. After multivariable adjustment, the hazard ratios for incident AF among participants in the highest quartile of cumulative systolic BP, pulse pressure, and mean arterial pressure were 1.48 (95% CI, 1.27-1.72), 1.81 (95% CI, 1.53-2.13), and 1.22 (95% CI, 1.05-1.41), respectively, compared with those in the lowest quartile. The addition of cumulative systolic BP or pulse pressure slightly improved the ability to predict new-onset AF. CONCLUSIONS: Higher exposure to cumulative systolic BP, pulse pressure, and mean arterial pressure was significantly associated with increased risk of incident AF.

Prevalence and Multilocus Genotyping of Giardia duodenalis in Donkeys in Shanxi Province, North China.

Giardia duodenalis is a ubiquitous flagellated protozoan, causing significant economic losses to animal husbandry and posing threats to public health. China ranks the world's sixth largest major producer of donkeys, rearing approximately 2.6 million donkeys in 2019, but limited investigation of G. duodenalis prevalence has been conducted in the past, and it is yet to be known whether donkeys in Shanxi Province are infected with G. duodenalis. In the present study, a total of 815 fecal samples collected from donkeys in representative regions of Shanxi Province, North China, were examined for G. duodenalis using nested PCR. Then, the assemblages and multilocus genotypes (MLGs) were examined based on three established loci: namely, ß-giardin (bg), triosephosphate isomerase (tpi), and glutamate dehydrogenase (gdh). The overall prevalence of G. duodenalis in donkeys in Shanxi Province was 16.81% (137/815). The region was identified as the main risk factor for the observed difference in G. duodenalis prevalence in donkeys among the three study areas (χ2 = 21.611, p < 0.001). Assemblages A, E, and B were identified, with the latter as the predominant assemblage. Three MLGs (MLG-novel-1 to 3) were formed based on sequence variation among the three loci. The present study reveals the presence of G. duodenalis in donkeys in Shanxi Province, North China, for the first time, which not only enriches the data on the distribution of G. duodenalis in donkeys in China but also provides useful baseline data for planning control strategies against G. duodenalis infection in the sampled areas.

Single-cell analysis of spinal cord injury reveals functional heterogeneity of oligodendrocyte lineage cells.

Spinal cord injury (SCI) is a traumatic condition that causes myelin destruction and neuronal death, making it challenging to reverse. In spinal cord tissue, oligodendrocyte progenitor cells and oligodendrocytes are essential for maintaining myelin morphology and axon regeneration. The decrease in oligodendrocyte lineage cells after SCI is a major factor contributing to the difficulty in restoring spinal cord function. However, there is still a lack of research on the status and intercellular communication between oligodendrocyte lineage cells after injury. The development of single-cell sequencing technology has enabled researchers to obtain highly accurate cellular transcriptional information, facilitating detailed studies of cellular subpopulations. This study delved into the cellular heterogeneity of oligodendrocyte lineage cells using a single-cell transcriptomic approach to uncover functional changes and cellular interactions during different time points after SCI. Our findings highlighted the critical roles of Psap (Prosaposin)/Gpr37l1 and Psap/Gpr37 ligand-receptor pairs among oligodendrocyte lineage cells. Furthermore, we predicted the transcription factors that may play a key regulatory role. We demonstrated for the first time that Junb acts almost exclusively in mature oligodendrocytes, which provides a potential target for the study of oligodendrocyte transcriptional mechanisms.

A simple ATTR-CM score to identify transthyretin amyloid cardiomyopathy burden in HFpEF patients.

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is often found in patients with heart failure with preserved ejection fraction (HFpEF). However, the evidence regarding ATTR-CM and prognosis in HFpEF remains scarce. This study sought to determine whether the ATTR-CM burden was associated with clinical outcomes in HFpEF patients. METHODS: We evaluated the associations of baseline ATTR-CM score with adverse outcomes in HFpEF patients from the TOPCAT trial using the Cox proportional hazards model or the competing risk regression model. The discriminatory ability of the ATTR-CM score was assessed using the area under the time-dependent receiver operating characteristic curve (AUC). RESULTS: We included 870 HFpEF patients, 18.9% of which had an ATTR-CM score ≥6. Per 1 increment in the ATTR-CM score was significantly associated with an increased risk of the primary outcome (adjusted hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.12-1.27) with an AUC of 0.652 (0.594-0.711), whereas patients with ATTR-CM score ≥6 presented higher risks of the primary outcome (adjusted HR 2.20, 95% CI 1.65-2.95). Similar results were observed toward the secondary outcomes. CONCLUSIONS: The simple ATTR-CM score identified an 18.9% ATTR-CM burden in HFpEF patients, and a higher ATTR-CM burden might predict adverse outcomes with moderate discriminatory abilities in HFpEF.

Periprocedural, short-term, and long-term outcomes following transcatheter tricuspid valve repair: a systemic review and meta-analysis.

Background: There has been an increasing use of transcatheter tricuspid valve repair (TTVR) recently. However, the periprocedural, short-term, and long-term outcomes of TTVR remain unclear. Objectives: To determine the clinical outcomes in patients with significant tricuspid regurgitation undergoing TTVR. Design: Systematic review and meta-analysis. Data Source and Methods: The systematic review and meta-analysis is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and EMBASE were searched for clinical trials and observational studies until March 2022. Studies reporting the incidence of clinical outcomes after TTVR were included. The clinical outcomes included periprocedural, short-term (in-hospital or within 30 days), and long-term (>6-month follow-up) outcomes. The primary outcome was all-cause mortality whereas the secondary outcomes included technical success, procedural success, cardiovascular mortality, rehospitalization for heart failure (HHF), major bleeding, and single leaflet device attachment. The incidence of these outcomes across studies was pooled by a random-effects model. Results: A total of 21 studies with 896 patients were included. A total of 729 (81.4%) patients underwent isolated TTVR while only 167 (18.6%) patients underwent combined mitral and tricuspid valve repair. Over 80% of the patients used coaptation devices while approximately 20% used annuloplasty devices. The median follow-up duration was 365 days. Technical and procedural success was high at 93.9% and 82.1%, respectively. The pooled perioperative, short-term, and long-term all-cause mortality for patients undergoing TTVR was 1.0%, 3.3%, and 14.1%, respectively. The long-term cardiovascular mortality rate was 5.3% while the HHF rate was 21.5%. Major bleeding and single leaflet device attachment were two major complications, accounting for 14.3% and 6.4%, respectively, during long-term follow-up. Conclusion: TTVR is associated with high procedural success and low procedural and short-term mortality. However, all-cause mortality, cardiovascular mortality, and HHF rates remain high during long-term follow-up. Registration: PROSPERO (CRD42022310020).

Effectiveness of non-invasive chromosomal screening for normal karyotype and chromosomal rearrangements.

Purpose: To study the accuracy of non-invasive chromosomal screening (NICS) results, in normal chromosomes and chromosomal rearrangement groups and to investigate whether using trophoblast cell biopsy along with NICS, to choose embryos for transfer can improve the clinical outcomes of assisted pregnancy. Methods: We retrospectively analyzed 101 couples who underwent preimplantation genetic testing at our center from January 2019 to June 2021 and collected 492 blastocysts for trophocyte (TE) biopsy. D3-5 blastocyst culture fluid and blastocyst cavity fluid were collected for the NICS. Amongst them, 278 blastocysts (58 couples) and 214 blastocysts (43 couples) were included in the normal chromosomes and chromosomal rearrangement groups, respectively. Couples undergoing embryo transfer were divided into group A, in which both the NICS and TE biopsy results were euploid (52 embryos), and group B, in which the TE biopsy results were euploid and the NICS results were aneuploid (33 embryos). Results: In the normal karyotype group, concordance for embryo ploidy was 78.1%, sensitivity was 94.9%, specificity was 51.4%, the positive predictive value (PPV) was 75.7%, and the negative predictive value (NPV) was 86.4%. In the chromosomal rearrangement group, concordance for embryo ploidy was 73.1%, sensitivity was 93.3%, specificity was 53.3%, the PPV was 66.3%, and the NPV was 89%. In euploid TE/euploid NICS group, 52 embryos were transferred; the clinical pregnancy rate was 71.2%, miscarriage rate was 5.4%, and ongoing pregnancy rate was 67.3%. In euploid TE/aneuploid NICS group, 33 embryos were transferred; the clinic pregnancy rate was 54.5%, miscarriage rate was 5.6%, and ongoingpregnancy rate was 51.5%. The clinical pregnancy and ongoing pregnancy rates were higher in the TE and NICS euploid group. Conclusion: NICS was similarly effective in assessing both normal and abnormal populations. Identification of euploidy and aneuploidy alone may lead to the wastage of embryos due to high false positives. More suitable reporting methods for NICS and countermeasures for a high number of false positives in NICS are needed. In summary, our results suggest that combining biopsy and NICS results could improve the outcomes of assisted pregnancy.

Dynamics of bacterial community in the foregut and hindgut of earthworms with the nutrition supplied by kitchen waste during vermicomposting.

Earthworm gut microbiota is vital in degrading bio-waste during vermicomposting. However, microbial dynamics in earthworm gut during this process are unclear. Thus, the aim is to firstly report the bacterial dynamics in both foregut and hindgut of earthworms over a 28 days' timeframe of vermicomposting by Eisenia foetida with the nutrition supplied by kitchen waste. Results showed that except the changing of the bacterial diversity, composition and structure, dynamics of the foregut and hindgut bacteria also differed during vermicomposting which related to the changes of nutrient provision. Day 3 was a turning point. The abundant bacteria of the top 20 % genera nearly did not overlap between the foregut and hindgut. In the end of vermicomposting, a remarkable stable bacterial structure appeared in the hindgut compared to somewhat muddled one in the foregut. Understanding the dynamics of earthworm gut microbiota enables the improvements to regulate the efficiency of organic waste vermicomposting.

Effectiveness of early rhythm control in improving clinical outcomes in patients with atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Current guidelines recommend rhythm control for improving symptoms and quality of life in symptomatic patients with atrial fibrillation (AF). However, the long-term prognostic outcomes of rhythm control compared with rate control are still inconclusive. In this meta-analysis, we aimed to assess the effects of early rhythm control compared with rate control on clinical outcomes in newly diagnosed AF patients. METHODS: We systematically searched the PubMed and Embase databases up to August 2022 for randomized and observational studies reporting the associations of early rhythm control (defined as within 12 months of AF diagnosis) with effectiveness outcomes. The primary outcome was a composite of death, stroke, admission to hospital for heart failure (HF), or acute coronary syndrome (ACS). Hazard ratios (HRs) and 95% confidence intervals (CIs) from each study were pooled using a random-effects model, complemented with an inverse variance heterogeneity or quality effects model. RESULTS: A total of 8 studies involving 447,202 AF patients were included, and 23.5% of participants underwent an early rhythm-control therapy. In the pooled analysis using the random-effects model, compared with rate control, the early rhythm-control strategy was significantly associated with reductions in the primary composite outcome (HR = 0.88, 95% CI: 0.86-0.89) and secondary outcomes, including stroke or systemic embolism (HR = 0.78, 95% CI: 0.71-0.85), ischemic stroke (HR = 0.81, 95% CI: 0.69-0.94), cardiovascular death (HR = 0.83, 95% CI: 0.70-0.99), HF hospitalization (HR = 0.90, 95% CI: 0.88-0.92), and ACS (HR = 0.86, 95% CI: 0.76-0.98). Reanalyses using the inverse variance heterogeneity or quality effects model yielded similar results. CONCLUSIONS: Our current meta-analysis suggested that early initiation of rhythm control treatment was associated with improved adverse effectiveness outcomes in patients who had been diagnosed with AF within 1 year. REGISTRATION: The study protocol was registered to PROSPERO (CRD42021295405).

[Comparative study of two elastic fixation systems in single-segment lumbar disc herniation surgery for nucleus pulposus extraction].

OBJECTIVE: To investigate the clinical application of two elastic pedicle internal fixation systems in single-segment lumbar disc herniation fenestration. METHODS: A retrospective analysis of 64 patients with lumbar intervertebral disc herniation treated by surgery from June 2019 to March 2021. According to the different elastic fixation systems placed during the operation, the patients were divided into ordinary pedicle screw elastic rod link group (elastic rod group) and a special elastic pedicle screw rigid rod fixed connection group (elastic screw group). There were 33 cases in the elastic rod group, including 18 males and 15 females, aged from 30 to 69 years old with an average of(49.18±10.23) years old;and 31 cases in the elastic screw group, including 16 males and 15 females, aged from 32 to 68 with an average of (49.81±9.24) years old. The operation time, intraoperative blood loss, postoperative wound drainage, and postoperative landing time of the two groups were recorded separately. The visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) score, and Oswestry Disability Index (ODI) were compared before and 3, 12 months after operation. The height of the adjacent vertebral space on the lateral DR film before and 12 months after the operation was measured. The clinical efficacy was evaluated by Macnab standard. RESULTS: All the patients successfully completed the operation, and were followed up. The operation time, intraoperative blood loss, postoperative wound drainage and postoperative landing time in the elastic rod group were(63.73±12.01) min, (89.55±16.07) ml, (81.67±16.00) ml, (3.45±0.75) d , while in the elastic nail group was (62.96±11.54) min, (88.35±17.14) ml, (82.29±15.40) ml, (3.29±0.78) d, the difference was not statistically significant. The symptoms of low back pain and lower extremity numbness were significantly improved in all patients after operation. There was no significant difference in VAS, JOA score and ODI between the two groups before and after surgery (P>0.05). At 12 months after operation, there was no significant difference in the height of the adjacent vertebral space between the upper adjacent vertebral body and the same segment before operation(P>0.05), and there was no significant difference between the groups before and after the operation. According to Macnab criteria, the elastic rod group was excellent in 30 cases, good in 2 cases, fair in 1 case, while the elastic nail group was excellent in 29 cases, good in 2 cases, fair in 0 cases, and there was no significant difference(Z=-0.42, P=0.68). CONCLUSION: In fenestrated nucleus pulposus extraction for lumbar disc herniation, the two elastic pedicle internal fixation systems are equally effective and can be used. The elastic screw internal fixation system has certain advantages when the distance between the two vertebral bodies is short, and the elastic rod cannot be placed or is difficult to be placed, and it is more widely used.

Worsening of Renal Function Among Hospitalized Patients With Acute Heart Failure: Phenotyping, Outcomes, and Predictors.

OBJECTIVE: To define clinical phenotyping and its associated outcome of worsening of renal function (WRF) in hospitalized acute heart failure (AHF) patients. PATIENTS AND METHODS: Latent class analysis was performed in 113 AHF patients who developed WRF within 72 hours in the DOSE (Diuretic Optimization Strategies Evaluation) trial (from March 2008 to November 2009) and ROSE-AHF (Renal Optimization Strategies Evaluation in Acute Heart Failure) trial (from September 2010 to March 2013) to identify potential WRF phenotypes. Clinical characteristics and outcome (in-hospital and post-discharge) were compared between different phenotypes. RESULTS: Two WRF phenotypes were identified by latent class analysis, which we named WRF minimally responsive to diuretics (WRF-MRD) and WRF responsive to diuretics (WRF-RD). Among the population, 58 (9.5%) developed WRF-MRD and 55 (9.0%) developed WRF-RD. Patients with WRF-MRD had more comorbidities than WRF-RD. In WRF-MRD, there were an early increase in serum creatinine, a smaller amount of net fluid loss and weight loss, and a higher rate of worsening or persistent heart failure over 72 hours. In contrast, for those with WRF-RD, they had faster in-hospital net fluid loss and weight loss and a better 60-day survival after discharge even compared with patients without WRF (P=.004). Furthermore, baseline chronic obstructive pulmonary disease, diabetes, and cystatin C were independent predictors of WRF-MRD, whereas serum hemoglobin and sodium predicted WRF-RD. CONCLUSIONS: Among hospitalized AHF patients, we identified two phenotypes of WRF with distinct response to heart failure treatment, predictors, and short-term prognosis after discharge. The results could help early differentiation of WRF phenotypes in clinical practice.

Non-vitamin K antagonist oral anticoagulants versus warfarin in atrial fibrillation patients with heart failure and preserved, mildly reduced, and reduced ejection fraction: A systemic review and meta-analysis.

Background: Patient prevalence of atrial fibrillation (AF) and heart failure (HF) is increasing, and anticoagulation for patients from heterogeneous backgrounds with both conditions remains controversial. In this meta-analysis, we are aiming to compare the effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in AF patients with HF and preserved (HFpEF), mildly reduced (HFmrEF), and reduced (HFrEF) ejection fraction. Methods and results: We systematically searched the PubMed, Cochrane, and Embase databases until January 2022. The primary effectiveness and safety outcomes were stroke or systemic embolism (SSE) and major bleeding, respectively. We abstracted risk ratios (RR) and 95% confidence intervals (CIs) and compiled them using a random-effects model. We analyzed data of 266,291 patients from 10 studies. By comparing NOACs with warfarin, patients with AF and HF have reduced the risk of SSE (RR: 0.83, 95% CI 0.76-0.91), all-cause mortality (RR: 0.85, 95% CI 0.80-0.91), major bleeding (RR: 0.79, 95% CI 0.69-0.90), and intracranial hemorrhage (RR: 0.54, 95% CI 0.46-0.63). Further analyses based on the HF subtypes showed that NOACs reduced the chances of SSE (RR: 0.71, 95% CI 0.53-0.94) in the HFrEF group and major bleeding (RR: 0.74, 95% CI 0.57-0.95) in HFmrEF and HFpEF groups. There were no differences regarding SSE (RR: 0.91, 95% CI 0.76-1.09) in HFmrEF and HFpEF groups and major bleeding (RR: 0.99, 95% CI 0.79-1.23) in the HFrEF group. Conclusion: For patients with AF and HF, NOACs have better or similar effectiveness and safety than warfarin, but the stroke prevention superiority of NOACs over warfarin varies in different HF subtypes.

MYB Transcription Factors Becoming Mainstream in Plant Roots.

The function of the root system is crucial for plant survival, such as anchoring plants, absorbing nutrients and water from the soil, and adapting to stress. MYB transcription factors constitute one of the largest transcription factor families in plant genomes with structural and functional diversifications. Members of this superfamily in plant development and cell differentiation, specialized metabolism, and biotic and abiotic stress processes are widely recognized, but their roles in plant roots are still not well characterized. Recent advances in functional studies remind us that MYB genes may have potentially key roles in roots. In this review, the current knowledge about the functions of MYB genes in roots was summarized, including promoting cell differentiation, regulating cell division through cell cycle, response to biotic and abiotic stresses (e.g., drought, salt stress, nutrient stress, light, gravity, and fungi), and mediate phytohormone signals. MYB genes from the same subfamily tend to regulate similar biological processes in roots in redundant but precise ways. Given their increasing known functions and wide expression profiles in roots, MYB genes are proposed as key components of the gene regulatory networks associated with distinct biological processes in roots. Further functional studies of MYB genes will provide an important basis for root regulatory mechanisms, enabling a more inclusive green revolution and sustainable agriculture to face the constant changes in climate and environmental conditions.

Genome-Wide Characterization of High-Affinity Nitrate Transporter 2 (NRT2) Gene Family in Brassica napus.

Nitrate transporter 2 (NRT2) plays an essential role in Nitrogen (N) uptake, transport, utilization, and stress resistance. In this study, the NRT2 gene family in two sequenced Brassica napus ecotypes were identified, including 31 genes in 'Zhongshuang11' (BnaZSNRT2s) and 19 in 'Darmor-bzh' (BnaDarNRT2s). The candidate genes were divided into three groups (Group I-III) based on phylogenetic analyses, supported by a conserved intron-exon structure in each group. Collinearity analysis revealed that the large expansion of BnaZSNRT2s attributed to allopolyploidization of ancestors Brassica rapa and Brassica oleracea, and small-scale duplication events in B. napus. Transcription factor (TF) binding site prediction, cis-element analysis, and microRNA prediction suggested that the expressions of BnaZSNRT2s are regulated by multiple factors, and the regulatory pattern is relatively conserved in each group and is tightly connected between groups. Expression assay showed the diverse and differentiated spatial-temporal expression profiles of BnaZSNRT2s in Group I, but conserved patterns were observed in Group II/III; and the low nitrogen (LN) stress up-regulated expression profiles were presented in Group I-III, based on RNA-seq data. RT-qPCR analyses confirmed that BnaZSNRT2.5A-1 and BnaZSNRT2.5C-1 in Group II were highly up-regulated under LN stress in B. napus roots. Our results offer valid information and candidates for further functional BnaZSNRT2s studies.

Efficacy of INtensive Treatment vs. Standard Treatment of COmpound DanshEn Dripping Pills in Refractory Angina Patients With Incomplete Revascularization (INCODER Study): Study Protocol for a Multicenter, Double-Blind, Randomized Controlled, Superiority Trial.

Introduction: Patients with incomplete revascularization (ICR) tend to develop refractory angina despite optimal medical therapy. The Compound Danshen Dripping Pills (CDDP) is a widely used antianginal drug in China and is shown to significantly alleviate myocardial ischemia. Previous studies showed dose-efficacy tendency when increasing doses of CDDP. This study aims to investigate the efficacy and safety of intensive doses of CDDP in patients with refractory angina with ICR. Methods and Analysis: The INCODER study is a multicenter, double-blind, randomized controlled, superiority trial. We plan to recruit 250 patients aged 18-85 years with a diagnosis of refractory angina with ICR. Patients will be randomized (1:1) to intensive treatment group (CDDP 20 pills three times per day) or standard treatment group (10 pills CDDP and 10 pills placebo three times per day). Patients will have a 6-week medication period and be followed up every 2 weeks. The primary endpoint is the change of total exercise time from baseline to week 6 as assessed by cardiopulmonary exercise testing (CPET). Secondary endpoints include changes in the frequency of angina, Canadian Cardiovascular Society angina class, nitroglycerin use, Seattle Angina Questionnaire scores, peak oxygen uptake (VO2 peak) and other parameters as measured by CPET, and the levels of plasma C-reactive protein, homocysteine, and N-terminal pro-B-type natriuretic peptide. Safety events related to CDDP use will be monitored. Ethics and Dissemination: The research had been approved by the Clinical research and laboratory animal ethics committee of the First Affiliated Hospital, Sun Yat-sen University ([2019]65). The results will be reported through peer-reviewed journals, seminars, and conference presentations. Trial Registration Number: www.chictr.org.cn (ChiCTR2000032384). Registered on 27 April 2020.

Case Report: Area of Focus of Myocardial Infarction With Non-obstructive Coronary Arteries in Eosinophilic Granulomatosis With Polyangiitis.

Background: Eosinophilic granulomatosis with polyangitis manifested as myocardial infarction with non-obstructed coronary arteries (MINOCA) is rarely reported. Case: We report a 43-year-old male patient without any cardiovascular risk factors presenting with acute chest pain. Electrocardiogram was suggestive of acute anterior and inferior myocardial infarction. MINOCA was confirmed based on significant elevated cardiac troponin and normal coronary arteries. Cardiac magnetic resonance (CMR) imaging revealed extended late gadolinium enhancement (LGE). Further diagnosis of eosinophilic granulomatosis with polyangitis (EGPA) was based on clinical manifestations and auxiliary examination. Subsequent immunosuppressive therapy led to regression of symptoms and significant resolution of LGE on CMR. Conclusion: Our case highlights that EGPA can be a rare cause of MINOCA. CMR is useful for differentiation diagnosis and evaluation of cardiac involvement.

Association Between Ambient Air Pollutants Exposure and Preterm Birth in Women Who Underwent in vitro Fertilization: A Retrospective Cohort Study From Hangzhou, China.

Objectives: Exposure to air pollutants has been linked to preterm birth (PTB) after natural conception. However, few studies have explored the effects of air pollution on PTB in patients who underwent in vitro fertilization (IVF). We aimed to investigate the association between ambient air pollutants exposure and PTB risk in IVF patients. Methods: This retrospective cohort study included 2,195 infertile women who underwent IVF treatment from January 2017 and September 2020 in Hangzhou Women's Hospital. Totally 1,005 subjects who underwent a first fresh embryo(s) transfer cycle were analyzed in this study. Residential exposure to ambient six air pollutants (PM2.5, PM10, SO2, NO2, CO, O3) during various periods of the IVF timeline were estimated by satellite remote-sensing and ground measurement. Cox proportional hazards models for discrete time were used to explore the association between pollutants exposure and incident PTB, with adjustment for confounders. Stratified analyses were employed to explore the effect modifiers. Results: The clinical pregnancy and PTB rates were 61.2 and 9.3%, respectively. We found that PM2.5 exposure was significantly associated with an increased risk of PTB during 85 days before oocyte retrieval [period A, adjusted hazard ratio, HR=1.09, 95%CI: 1.02-1.21], gonadotropin start to oocyte retrieval [period B, 1.07 (1.01-1.19)], first trimester of pregnancy [period F, 1.06 (1.01-1.14)], and the entire IVF pregnancy [period I, 1.07 (1.01-1.14)], respectively. An interquartile range increment in PM10 during periods A and B was significantly associated with PTB at 1.15 (1.04-1.36), 1.12 (1.03-1.28), and 1.14 (1.01-1.32) for NO2 during period A. The stratified analysis showed that the associations were stronger for women aged <35 years and those who underwent two embryos transferred. Conclusions: Our study suggests ambient PM2.5, PM10, and NO2 exposure were significantly associated with elevated PTB risk in IVF patients, especially at early stages of IVF cycle and during pregnancy.

Early Follicular Phase Human Chorionic Gonadotropin Addition May Improve the Outcomes of In Vitro Fertilization/Intracytoplasmic Sperm Injection in Patients With "Unpredictable" Poor Response to Gonadotropin-Releasing Hormone Antagonist Protocol.

Purpose: To compare the effects of early and mid-late follicular phase administration of 150 IU of human chorionic gonadotropin (hCG) on gonadotropin-releasing hormone (GnRH) antagonist protocol in "unpredictable" poor ovarian response (POR) women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. Methods: A retrospective single-center cohort study was conducted on 67 patients with "unpredictable" POR in their first IVF/ICSI cycle receiving GnRH antagonist protocol. Patients were treated with a second IVF/ICSI cycle using the same GnRH antagonist protocol with the same starting dose of recombinant follicle-stimulating hormone (rFSH) as the first cycle; a daily dose of 150 IU of hCG was administrated on either stimulation day 1 (Group A, n = 35) or day 6 (Group B, n = 32). The number of oocytes retrieved, number of usable embryos, serum level of estradiol (E2) on day of hCG trigger, and clinical pregnant outcomes were studied. Results: The addition of 150 IU of hCG on either the first day or sixth day of stimulation increases the serum level of E2, luteinizing hormone (LH), and hCG on the day of hCG trigger. Only the use of 150 IU of hCG on the first stimulation day improved the number of oocytes retrieved, mature of oocytes, and usable embryos, but not the addition of hCG on stimulation day 6. Implantation rate, clinical pregnancy rate, and ongoing pregnancy rate showed an increasing trend in patients receiving 150 IU of hCG in the early phase compared with mid-late phase, even thought there was no statistically significant difference. Conclusions: Our study demonstrated that adding 150 IU of hCG in subsequent GnRH antagonist cycle in "unpredictable" poor responders is associated with the improvement of response to stimulation. Furthermore, early follicular phase addition of 150 IU of hCG significantly increased the number of oocytes retrieved and usable embryos than did the mid-late addition of the same dose.

Ultra-Long GnRH Agonist Protocol During IVF/ICSI Improves Pregnancy Outcomes in Women With Adenomyosis: A Retrospective Cohort Study.

Objective: This study aimed to compare the ultra-long gonadotropin-releasing hormone agonist (GnRH-a) protocol and the long GnRH-a protocol during in vitro fertilization (IVF) or intracytoplasmic sperm (ICSI) treatment on fertility outcomes in women with adenomyosis. Materials and Methods: This study was a retrospective cohort study. From January 2011 to May 2018, a total of 371 fresh IVF/ICSI cycles were included. Among the cycles included, 237 cycles of 212 women underwent the ultra-long GnRH-a protocol, while 134 cycles of 116 women underwent the long GnRH-a protocol. The rates of implantation, clinical pregnancy per embryo transfer, live birth, and early miscarriage were estimated between the compared protocols. Results: In the study, the early miscarriage rate in women undergoing the ultra-long GnRH-a protocol was significantly lower than those undergoing the long GnRH-a protocol (12.0% versus 26.5%, p = 0.045), whereas the differences in the rates of biochemical pregnancy, implantation, clinical pregnancy, and live birth in women between the two groups showed no statistical significance. The pregnancy outcomes were also sub-analyzed according to the adenomyotic region (diffuse and focal). As for diffuse adenomyosis, the rates of clinical pregnancy and live birth in women undergoing the ultra-long GnRH-a protocol were significantly higher than those undergoing the long GnRH-a protocol (55.3% versus 37.9%, p = 0.025; 43.4% versus 25.9%, p = 0.019, respectively). However, pregnancy outcomes showed no difference between the two protocols in women with focal adenomyosis. Conclusions: The ultra-long GnRH-a protocol during IVF/ICSI improves pregnancy outcomes in women with adenomyosis, especially in women with diffuse adenomyosis when compared with the long GnRH-a protocol.

Effect of aggressive diuresis in acute heart failure with reduced and preserved ejection fraction.

AIMS: Heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) had distinct haemodynamic characteristics in the setting of acute heart failure. The aim of our study is to evaluate the differential response to aggressive diuresis in HFrEF and HFpEF. METHODS AND RESULTS: Patients in the Diuretic Optimization Strategies Evaluation trial with left ventricular ejection fraction measurement were included (n = 300) and classified into HFrEF [left ventricular ejection fraction (LVEF) < 40%] (n = 193) and HFpEF (LVEF ≥ 40%) (n = 107). Effect of high-dose vs. low-dose furosemide strategy was compared separately in HFrEF and HFpEF. In HFrEF, high-dose strategy did not increase change in creatinine or cystatin C at 72 h [treatment difference: -0.05, 95% confidence interval (CI): -0.14 to 0.03 mg/dL; P = 0.23 for creatinine, and treatment difference: -0.06, 95% CI: -0.15 to 0.02 mg/dL; P = 0.15 for cystatin C] compared with low-dose strategy, but there were significantly more net fluid loss, weight loss, and congestion-free patients at 72 h in high-dose group. It was also associated with a significantly lower risk of composite clinical outcome of death, total hospitalizations, and unscheduled visits due to heart failure. In HFpEF, high-dose strategy significantly increased change in creatinine and cystatin C at 72 h (treatment difference: 0.16; 95% CI: 0.02-0.30 mg/dL; P = 0.03 for creatinine, and treatment difference: 0.26; 95% CI: 0.09-0.43 mg/dL; P = 0.003 for cystatin C), but did not significantly affect net fluid loss, weight loss, proportion of congestion-free patients at 72 h, and risk of the composite clinical outcome. CONCLUSIONS: Acute heart failure on the basis of HFrEF and HFpEF responded differently to aggressive diuresis. Future trials should be designed separately for HFrEF and HFpEF.