Vitamin C inactivates c-Jun N-terminal kinase to stabilize heart and neural crest derivatives expressed 1 (Hand1) in regulating placentation and maintenance of pregnancy.

Vitamin C (VC) serves as a pivotal nutrient for anti-oxidation process, metabolic responses, and stem cell differentiation. However, its precise contribution to placenta development and gestation remains obscure. Here, we demonstrated that physiological levels of VC act to stabilize Hand1, a key bHLH transcription factor vital for the development trajectory of trophoblast giant cell (TGC) lineages, thereby promoting the differentiation of trophoblast stem cells into TGC. Specifically, VC administration inactivated c-Jun N-terminal kinase (JNK) signaling, which directly phosphorylates Hand1 at Ser48, triggering the proteasomal degradation of Hand1. Conversely, a loss-of-function mutation at Ser48 on Hand1 not only significantly diminished both intrinsic and VC-induced stabilization of Hand1 but also underscored the indispensability of this residue. Noteworthy, the insufficiency of VC led to severe defects in the differentiation of diverse TGC subtypes and the formation of labyrinth's vascular network in rodent placentas, resulting in failure of maintenance of pregnancy. Importantly, VC deficiency, lentiviral knockdown of JNK or overexpression of Hand1 mutants in trophectoderm substantially affected the differentiation of primary and secondary TGC in E8.5 mouse placentas. Thus, these findings uncover the significance of JNK inactivation and consequential stabilization of Hand1 as a hitherto uncharacterized mechanism controlling VC-mediated placentation and perhaps maintenance of pregnancy.

A case of heat stroke with significantly elevated troponin and dynamic ECG changes: Myocardial infarction or Myocardial injury?

We described an 82-year-old man who was taken to our emergency department after being found unconscious. His electrocardiogram (ECG) showed ST-segment elevation in leads V4-V6 and cardiac troponin I (cTnI) was abnormally elevated. In addition to ECG and cTnI changes, this patient was combined with unconsciousness, high fever, abnormal liver function, acute renal failure, and rhabdomyolysis. The initial diagnosis was heat stroke, so cooling measures were initiated immediately, but a concurrent myocardial infarction was suspected. Meanwhile, emergency coronary angiography was performed, but no severe coronary stenosis or thrombosis was found. We first evaluated quantitative flow ratio (QFR) and coronary angiography-derived index of microvascular resistance (ca-IMR) in patients with heat stroke. Ca-IMR was 260 mmHg*s/m in the left circumflex artery, indicating the presence of coronary microvascular dysfunction (CMD). After several days of treatment, the patient recovered from multiple organ damage. Therefore, ECG and troponin results should be interpreted carefully in patients with high fever and coma during high temperature seasons.

A case-control study of the risk factors for fistula-in-ano in infants and toddlers.

BACKGROUND: Limited data are available regarding the risk factors for fistula-in-ano (FIA) in infants and toddlers, potentially affecting their daily lives. OBJECTIVES: The purpose of this study was to identify potential risk factors for FIA in infants and toddlers, in order to implement early preventive interventions, avoid disease progression, and develop therapeutic strategies. DESIGN AND SETTINGS: A retrospective case-control study was conducted, comparing 41 infants and toddlers diagnosed with FIA with 41 healthy controls, between August 2020 and December 2021. INDEPENDENT VARIABLES: (a) maternal characteristics during pregnancy and delivery, (b) perinatal characteristics, dietary behaviors, and defecation-related behaviors in infants and toddlers, (c) family dietary behaviors. RESULTS: Mothers of infants and toddlers with FIA had given birth more times in the past, while the infants and toddlers themselves had less mealtime, a higher rate of exclusive breastfeeding, frequent loose stools, and a larger proportion of used wipes, experiencing perianal skin anomalies. The logistic regression analysis revealed that there are four significant risk factors associated with the development of FIA in infants and toddlers, including the number of previous deliveries by the mother (OR 6.327), defecation frequency score (OR 5.351), stool consistency score (OR 5.017), and cleaning with wipes after defecation (OR 8.089). CONCLUSION: Based on our data, it appeared that FIA in infants and toddlers could be attributed to several factors. These included an increased number of previous deliveries by mothers, frequent loose stools, and repeated wipe use. To prevent the occurrence and worsening of the disease, it is important to improve the frequency and consistency of stooling and provide proper care. Further research is required to verify these findings in other clinical settings.

Transcriptomic analysis of the effect of shaking and tumbling degree on quality formation of Wuyi rock tea.

Shaking and tumbling are extremely important for the formation of the special flavor of Wuyi rock tea. In this study, we analyzed the effects of different shaking and tumbling degrees on the quality index content of tea leaves and determined changes in gene expression in tea leaves using RNA sequencing technology. On this basis, the correlation between gene expression intensities in tea leaves and tea quality index content was analyzed. The results showed that heavy shaking and tumbling (MW3) increased gene expression of metabolic pathways, biosynthesis of secondary metabolites, starch and sucrose metabolism, biosynthesis of amino acids, glycine, serine, and threonine metabolism, alpha-linolenic acid metabolism pathways and decreased gene expression of flavonoid biosynthesis, carbon fixation in photosynthetic organisms, phenylpropanoid biosynthesis, and plant hormone signal transduction pathways in tea leaves, which in turn increased the content of caffeine, soluble sugar, amino acid and decreased the content of flavone, tea polyphenol, catechin component in tea leaves; the opposite was true for light shaking and tumbling. Second, this study found that MW3 was more beneficial in improving the mellowness, sweetness, and fresh and brisk taste of tea leaves and reducing the bitterness of tea leaves. This study provides some references to guide the processing of Wuyi rock tea with different flavors. PRACTICAL APPLICATION: Heavy shaking and tumbling was more beneficial in improving the mellowness, sweetness, and fresh and brisk taste of tea leaves and reducing the bitterness of tea leaves. Therefore, the degree of shaking and tumbling in Wuyi production can be appropriately improved to produce high-quality tea and improve the economic benefits of tea.

Rationale and design of a comparison of angiography-derived fractional flow reserve-guided and intravascular ultrasound-guided intervention strategy for clinical outcomes in patients with coronary artery disease: a randomised controlled trial (FLAVOUR II).

INTRODUCTION: Percutaneous coronary intervention (PCI) guided by coronary angiography-derived fractional flow reserve (FFR) or intravascular ultrasound (IVUS) has shown improved clinical outcomes compared with angiography-only-guided PCI. In patients with intermediate stenoses, FFR resulted in fewer coronary interventions and was non-inferior to IVUS with respect to clinical outcomes. However, whether this finding can be applied to angiography-derived FFR in significant coronary artery disease (CAD) remains unclear. METHOD AND ANALYSIS: The comparison of angiography-derived FFR-guided and IVUS-guided intervention strategies for clinical outcomes in patients with coronary artery disease (FLAVOUR II) trial is a multicentre, prospective, randomised controlled trial. A total of 1872 patients with angiographically significant CAD (stenoses of at least 50% as estimated visually through angiography) in a major epicardial coronary artery will be randomised 1:1 to receive either angiography-derived FFR-guided or IVUS-guided PCI. Patients will be treated with second-generation drug-eluting stent according to the predefined criteria for revascularisation: angiography-derived FFR≤0.8 and minimal lumen area (MLA)≤3 mm2 or 3 mm270%. The primary endpoint is a composite of all-cause death, myocardial infarction and revascularisation at 12 months after randomisation. We will test the non-inferiority of the angiography-derived FFR-guided strategy compared with the IVUS-guided decision for PCI and the stent optimisation strategy.The FLAVOUR II trial will provide new insights into optimal evaluation and treatment strategies for patients with CAD. ETHICS AND DISSEMINATION: FLAVOUR II was approved by the institutional review board at each participating site (The Second Affiliated Hospital of Zhejiang University School of Medicine Approval No: 2020LSYD410) and will be conducted in line with the Declaration of Helsinki. Informed consent would be obtained from each patient before their participation. The study results will be submitted to a scientific journal. TRIAL REGISTRATION NUMBER: NCT04397211.

Rare rectal gastrointestinal stromal tumor case: A case report and review of the literature.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal tract accounting for less than 1% of all gut tumors. GISTs occurring in the rectum are extremely rare, and these usually present at an advanced stage compared with other sites. CASE SUMMARY: A 60-year-old male who presented with features of sensations of rectal tenesmus was referred to our department with a mass in the lower rectum that was detected during a routine checkup. Colonoscopy, transrectal ultrasound, perianal magnetic resonance imaging and ultrasonic contrast were used to diagnose the rectum GIST, and then the patient underwent complete transanal resection using the ultrasonic scalpel. The patient was discharged ten days after the operation and was defined as low risk. Therefore, he had no need to receive subsequent adjuvant therapies, and he had not suffered any anal dysfunction or had any evidence of recurrence at follow up. CONCLUSION: Surgical resection with histologically negative margins is the standard curative treatment for rectal GISTs. Appropriate surgical techniques based on the location, size, and resectability of the tumor should attract great attention from clinicians.

Analysis of the effect of different withering methods on tea quality based on transcriptomics and metabolomics.

Withering is very important to the quality of Wuyi rock tea. In this study, transcriptomics and metabolomics were used to analyze the effects of different withering methods on tea quality formation. The results showed that sunlight withering (SW) was most beneficial in increasing the gene expression of ubiquinone and other terpenoid-quinone biosynthesis (ko00130), pyruvate metabolism (ko00620), starch and sucrose metabolism (ko00500), and tryptophan metabolism (ko00380) pathways, and increasing the content of nucleotides and derivatives, terpenoids, organic acids and lipids, thus enhancing the mellowness, fresh and brisk taste and aroma of tea. Withering trough withering (WW) was most beneficial in increasing the gene expression of glutathione metabolism (ko00480), phenylpropanoid biosynthesis (ko00940) pathways, increasing the content of phenolic acids and flavonoids, thus enhancing tea bitterness. A comprehensive evaluation of the metabolite content and taste characteristics of tea leaves showed SW to be the best quality and charcoal fire withering (FW) to be the worst quality. This study provided an important basis for guiding the processing of Wuyi rock tea with different flavors.

Dysregulation of Histone Deacetylases Inhibits Trophoblast Growth during Early Placental Development Partially through TFEB-Dependent Autophagy-Lysosomal Pathway.

Dysregulated biological behaviors of trophoblast cells can result in recurrent spontaneous abortion (RSA)-whose underlying etiology still remains insufficient. Autophagy, a conserved intracellular physiological process, is precisely monitored throughout whole pregnancy. Although the exact mechanism or role remains elusive, epigenetic modification has emerged as an important process. Herein, we found that a proportion of RSA patients exhibited higher levels of autophagy in villus tissues compared to controls, accompanied with impaired histone deacetylase (HDAC) expression. The purpose of this study is to explore the connection between HDACs and autophagy in the pathological course of RSA. Mechanistically, using human trophoblast cell models, treatment with HDAC inhibitor (HDACI)-trichostatin A (TSA) can induce autophagy by promoting nuclear translocation and transcriptional activity of the central autophagic regulator transcription factor EB (TFEB). Specifically, overactivated autophagy is involved in the TSA-driven growth inhibition of trophoblast, which can be partially reversed by the autophagy inhibitor chloroquine (CQ) or RNA interference of TFEB. In summary, our results reveal that abnormal acetylation and autophagy levels during early gestation may be associated with RSA and suggest the potential novel molecular target TFEB for RSA treatment.

Diagnostic performance of computational fluid dynamics (CFD)-based fractional flow reserve (FFR) derived from coronary computed tomographic angiography (CCTA) for assessing functional severity of coronary lesions.

Background: Fractional flow reserve (FFR) is the gatekeeper for lesion-specific revascularization decision-making in patients with stable coronary artery disease (CAD). The potential of noninvasive calculation of FFR from coronary computed tomographic angiography (CCTA) to identify ischemia-causing lesions has not been sufficiently assessed. The objective of this study was to evaluate the feasibility and diagnostic accuracy of a novel computational fluid dynamics (CFD)-based technology, termed as AccuFFRct, for the diagnosis of functionally significant lesions from CCTA, using wire-based FFR as a reference standard. Methods: A total of 191 consecutive patients who underwent CCTA and FFR measurement for suspected or known CAD were retrospectively enrolled at 2 medical centers. Three-dimensional anatomic model of coronary tree was extracted from CCTA data, CFD was applied subsequently with a novel strategy for the computation of FFR in a blinded fashion by professionals. Results were compared to invasive FFR, a threshold of ≤0.80 was used to indicate the hemodynamically relevant stenosis. Results: On a per-patient basis, the overall accuracy, sensitivity, specificity of AccuFFRct for detecting ischemia were 91.78% (95% CI: 86.08% to 95.68%), 92.31% (95% CI: 81.46% to 97.86%) and 91.49% (95% CI: 83.92% to 96.25%), respectively; those for per-vessel basis were 91.05% (95% CI: 86.06% to 94.70%), 92.73% (95% CI: 82.41% to 97.98%) and 90.37% (95% CI: 84.10% to 94.77%), respectively. The AccuFFRct and FFR was well correlated on per-patient (r=0.709, P<0.001) and per-vessel basis (r=0.655, P<0.001). The AUC of AccuFFRct determination was 0.935 (95% CI: 0.881 to 0.969) and 0.927 (95% CI: 0.880 to 0.960) on per-patient and per-vessel basis. Conclusions: This novel CFD-based CCTA-derived FFR shows good diagnostic performance for detecting hemodynamic significance of coronary stenoses and may potentially become a new gatekeeper for invasive coronary angiography (ICA).

Functional Assessment of Coronary Artery Stenosis from Coronary Angiography and Computed Tomography: Angio-FFR vs. CT-FFR.

This study was designed to compare the diagnostic performance of angio-FFR and CT-FFR for detecting hemodynamically significant coronary stenosis. Angio-FFR and CT-FFR were measured in 110 patients (139 vessels) with stable coronary disease using invasive FFR as the reference standard. On per-patient basis, angio-FFR was highly correlated with FFR (r =0.78, p <0.001), while the correlation was moderate between CT-FFR and FFR (r =0.68, p <0.001). Diagnostic accuracy, sensitivity, and specificity for angio-FFR were 94.6%, 91.4%, and 96.0%, respectively; and those of CT-FFR were 91.8%, 91.4%, and 92%, respectively. Bland-Altman analysis showed that angio-FFR had a larger average difference and a smaller root mean squared deviation than CT-FFR compared with FFR (-0.014±0.056 vs. 0.0003±0.072). Angio-FFR had a slightly higher AUC than that of CT-FFR (0.946 vs. 0.935, p =0.750). Angio-FFR and CT-FFR computed from coronary images could be accurate and efficient computational tools for detecting lesion-specific ischemia of coronary artery stenosis. Angio-FFR and CT-FFR calculated based on the two types of images can both accurately diagnose functional ischemia of coronary stenosis. CT-FFR can act as a gatekeeper to the catheter room, assisting doctors in determining whether patients need to be screened by coronary angiography. Angio-FFR can be used in the catheter room to determine the functional significant stenosis for helping decision-making in revascularization.

Establishment of a mouse model of inflammatory bowel disease using dextran sulfate sodium.

BACKGROUND: Dextran sulfate sodium (DSS)-induced murine colitis is the most commonly used model for the analysis of the pathogenesis of inflammatory bowel disease (IBD) and for the assessment of the efficacy of putative therapeutics. It has been suggested that mice should be given 2.5-10% DSS for 3-7 days to establish the model. OBJECTIVES: To compare the IBD model in C57BL/6J mice given free access to water containing DSS at concentrations of 2.0%, 2.5% or 3.0% for 5, 7 or 10 days. MATERIAL AND METHODS: Female mice (9 weeks old) were given access to drinking water containing DSS (2.0%, 2.5% or 3.0%) for 5-10 days. Body weight and colon length were then measured. Signs of edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction, and severe colitis-related clinical signs were observed and analyzed. RESULTS: Weight of the mice decreased and disease activity index (DAI) score immediately increased in all 3 groups. The colon of mice in the 3.0% DSS group was shortened after 5 days, and the colon of mice in the 2.0% and 2.5% DSS groups was shortened after 7 days. A significantly increased intestinal injury score was observed on day 5 in the 3.0% DSS group, on day 7 in the 2.5% DSS group and on day 10 in the 2.0% DSS group. Cytokines were found to be elevated in all 3 groups after 5 days of DSS exposure, with higher DSS concentrations and longer administration times found to be associated with more serious inflammation of the intestinal tract. After 10 days of DSS administration, all mice in the 3.0% DSS group died. CONCLUSIONS: It took 10 days for the 2.0% DSS group, 5 days for the 3.0% DSS group and 7 days for the 2.5% DSS group to develop obvious observable changes related to the induction of the IBD model. The individual differences within groups (within 10 days) could be reduced by prolonging the administration time. Excessive DSS concentration and longer DSS administration time (exceeding 7 days) may increase mortality of the mice.

Atg9A-mediated mitophagy is required for decidual differentiation of endometrial stromal cells.

Endometrial decidualization is the foundation of a healthy pregnancy. Mitochondrial dysfunction is an independent cause of disease for energy-intensive organs. Mitochondrial homeostasis plays a key role in the differentiation processes of many cell types. We showed increased activation of mitophagy (mitochondrial autophagy) in the decidua compared with proliferative or secretory endometrium. To better comprehend the mechanisms underlying healthy conception, understanding the mechanism of endometrial stromal cell decidualization is of great importance. Here, we artificially induced decidualization of a human endometrial stromal cell line (T HESCs) and characterized subsequent activation of mitophagy using immunofluorescence assay, electron microscopy and Western blot assay. Knockdown of autophagy-related 9A (ATG9A) led to an obvious reduction of mitophagy and deficiencies in decidualization. Our findings demonstrate a key role for proper mitochondrial dynamics in decidual differentiation and identify ATG9A-mediated mitophagy as a novel therapeutic target for repeated implantation failure or recurrent abortion.

Concurrent acute myocardial infarction and acute ischemic stroke: Case reports and literature review.

Acute myocardial infarction (AMI) and acute ischemic stroke (AIS) are the main causes of disability and mortality worldwide. Although reperfusion therapy is the most effective treatment for the two diseases, it is still a great challenge for treating the two diseases at the same time. Here we share 2 cases: one patient was hospitalized for AMI, developed AIS after receiving percutaneous coronary intervention (PCI), and suffered from cardiac rupture after alteplase thrombolytic therapy. The other patient was admitted for AIS, who had sudden chest pain during the thrombolytic process of alteplase. Considering AMI, emergency PCI was performed, and he was finally discharged.

S100P promotes trophoblast syncytialization during early placenta development by regulating YAP1.

Recurrent pregnancy loss (RPL) is a severe complication of pregnancy that is caused by genetic abnormalities, immune dysfunction, aberrant cell biology, and tissue structure destruction. Among which, placental dysfunction is crucial in the pathogenetic progression of RPL. Although some regulatory factors associated with RPL have been reported, the placental changes correlated with RPL still need to be elucidated. Here, we found that a portion of RPL patients presented with low serum and placental S100P expression. Using a human trophoblast stem cell model, we demonstrated that S100P was exclusively expressed in syncytiotrophoblast (ST)-like syncytia (ST(2D)-TSCT) and that loss of S100P expression in ST(2D)-TSCT cells impaired ß-hCG secretion, leading to syncytialization failure during early placental development. Moreover, we found that S100P is involved in regulating trophoblast syncytialization by downregulating the protein level of Yes-associated protein 1 (YAP1), which plays a pivotal role in maintaining trophoblast stemness. Together, our findings suggest that S100P plays an essential role in regulating trophoblast syncytialization during early placental development in humans via YAP1. Additionally, lower serum S100P levels may predict poor pregnancy outcomes and represent a potentially useful marker for evaluating placental biological function during early pregnancy.

Recurrent bleeding after rubber band ligation diagnosed as mild hemophilia B: a case report and literature review.

BACKGROUND: Hemophilia is a recessive hemorrhagic disease relevant to X chromosome. In mild hemophilia cases, spontaneous bleeding is rare and the blood clotting function is normal, but severe bleeding may occur after trauma or surgery. Therefore, missed diagnosis of hemophilia before operation may contribute to bleeding after hemorrhoid operation. CASE PRESENTATION: A 21-year-old male was hospitalized in the anorectal department because of repeated bleeding after hemorrhoid surgery. Despite several suture hemostasis procedures, the patient still suffered from recurrent bleeding. He had no family history of hemophilia or bleeding tendency, and had not been diagnosed with hemophilia before this admission. The diagnosis of mild hemophilia B was made after further examination of coagulation indexes. By using frozen plasma and coagulation factor complex to supplement coagulation factors, the patient's bleeding was stopped and he was discharged after 23 days in hospital. During the follow-up, lower-than-normal coagulation factors were still found in him, but no bleeding occurred again. CONCLUSIONS: The undiagnosed patient with mild hemophilia B has an increased risk of bleeding after hemorrhoid surgery because of the consumption of coagulation factors. This case report aims to address the importance of hemophilia screening before operation and reduce the risk of postoperative bleeding. For patients with recurrent bleeding after hemorrhoid surgery, hemophilia should be further excluded. Wound bleeding may recur in hemophilia patients after suture hemostasis. Therefore, prompt supplementation of coagulation factors is needed to help stop bleeding once the diagnosis of hemophilia is made.

Toxicity from a single injection of human umbilical cord mesenchymal stem cells into rat ovaries.

Intraovarian injection of human umbilical cord mesenchymal stem cells (hUC-MSCs) has been applied and with promising therapeutic effects, but its toxicity and safety remain uncertain. This study evaluated the toxic effects and the affected target organs after a single injection of hUC-MSCs into bilateral rat ovaries. Sixty Sprague-Dawley rats were randomly divided into four groups and intraovarian injected with three different doses of hUC-MSC suspension. Toxicity-related manifestations occurred over the following 14 days postinjection. On day (D)5 and D15, we assessed the clinical pathology; immunotoxicity, including the cytokine IFN-γ, TNF-α, IL-4, and IL-6 levels; the immune organs, and the organ weights. On D5, inflammatory cells mainly infiltrated the ovaries of the low- and medium-dose groups, whereas inflammatory cells infiltrated the oviduct in the medium- and high-dose groups. On D15, inflammatory cells infiltrated the corpus luteal cysts, ovarian sacs and oviducts in each group. Body weights; organ weights; immunotoxicity; clinical pathology and histopathological examinations of the immune organs did not significantly differ among the groups. No obvious hUC-MSC-related clinical symptoms were observed except in the rats that died. The high-dose group exhibited significantly higher mortality than did the control and low-dose groups. Deaths in the high-dose group, who received approximately 50 times the standard clinical dose, were related to the intraovarian hUC-MSC injection. The maximum tolerated dose was approximately ten times the standard clinical dose. The ovary and oviduct may be the target organs for this toxicity. This report provides dosage references and guidance for clinical applications of intraovarian hUC-MSC injections.

Diagnostic Performance of Angiography-Based Fractional Flow Reserve for Functional Evaluation of Coronary Artery Stenosis.

Background: A new method for calculating fraction flow reserve (FFR) without pressure-wire (angiography-derived FFR) based on invasive coronary angiography (ICA) images can be used to evaluate the functional problems of coronary stenosis. Objective: The aim of this study was to assess the diagnostic performance of a novel method of calculating the FFR compared to wire-based FFR using retrospectively collected data from patients with stable angina. Methods: Three hundred patients with stable angina pectoris who underwent ICA and FFR measurement were included in this study. Two ICA images with projections >25° apart at the end-diastolic frame were selected for 3D reconstruction. Then, the contrast frame count was performed in an angiographic run to calculate the flow velocity. Based on the segmented vessel, calculated velocity, and aortic pressure, AccuFFRangio distribution was calculated through the pressure drop equation. Results: Using FFR ≤ 0.8 as a reference, we evaluated AccuFFRangio performance for 300 patients with its accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Comparison of AccuFFRangio with wire-measured FFR resulted in an area under the curve (AUC) of 0.954 (per-vessel, p < 0.0001). Accuracy for AccuFFRangio was 93.7% for Pa set from measurement and 87% for Pa = 100 mmHg in this clinical study. Overall sensitivity, specificity, PPV, and NPV for per-vessel were 90, 95, 86.7, 96.3, and 57.5, 97.7, 90.2, 86.3%, respectively. Overall accuracy, sensitivity, specificity, PPV, and NPV for 2-dimensional (2D) quantitative coronary angiography (QCA) were 63.3, 42.5, 70.9, 34.7, and 77.2%, respectively. The average processing time of AccuFFRangio was 4.30 ± 1.87 min. Conclusions: AccuFFRangio computed from coronary ICA images can be an accurate and time-efficient computational tool for detecting lesion-specific ischemia of coronary artery stenosis.

Diagnostic accuracy of coronary computed tomography angiography-derived fractional flow reserve.

BACKGROUND: Fractional flow reserve (FFR) is a widely used gold standard to evaluate ischemia-causing lesions. A new method of non-invasive approach, termed as AccuFFRct, for calculating FFR based on coronary computed tomography angiography (CCTA) and computational fluid dynamics (CFD) has been proposed. However, its diagnostic accuracy has not been validated. OBJECTIVES: This study sought to present a novel approach for non-invasive computation of FFR and evaluate its diagnostic performance in patients with coronary stenosis. METHODS: A total of 54 consecutive patients with 78 vessels from a single center who underwent CCTA and invasive FFR measurement were retrospectively analyzed. The CT-derived FFR values were computed using a novel CFD-based model (AccuFFRct, ArteryFlow Technology Co., Ltd., Hangzhou, China). Diagnostic performance of AccuFFRct and CCTA in detecting hemodynamically significant coronary artery disease (CAD) was evaluated using the invasive FFR as a reference standard. RESULTS: Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for AccuFFRct in detecting FFR ≤ 0.8 on per-patient basis were 90.7, 89.5, 91.4, 85.0 and 94.1%, respectively, while those of CCTA were 38.9, 100.0, 5.71, 36.5 and 100.0%, respectively. The correlation between AccuFFRct and FFR was good (r = 0.76 and r = 0.65 on per-patient and per-vessel basis, respectively, both p < 0.0001). Area under the curve (AUC) values of AccuFFRct for identifying ischemia per-patient and per-vessel basis were 0.945 and 0.925, respectively. There was much higher accuracy, specificity and AUC for AccuFFRct compared with CCTA. CONCLUSIONS: AccuFFRct computed from CCTA images alone demonstrated high diagnostic performance for detecting lesion-specific ischemia, it showed superior diagnostic power than CCTA and eliminated the risk of invasive tests, which could be an accurate and time-efficient computational tool for diagnosing ischemia and assisting clinical decision-making.

Dual Trigger for Final Follicular Maturation Improves Cumulative Live-Birth Rate in Ovarian Stimulation for Freeze-All In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles.

Study Question: Does dual trigger in freeze-all in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles improve the cumulative live-birth outcome compared with human chorionic gonadotropin (hCG) trigger? Summary Answer: Dual trigger for final follicular maturation improves the cumulative pregnancy and live-birth rates compared with hCG trigger in freeze-all IVF/ICSI cycles. What Is Known Already: Dual trigger could increase the numbers of oocytes and mature oocytes and improve pregnancy rates. Study Design Size Duration: This retrospective cohort analysis included data from 4438 freeze-all IVF/ICSI cycles between January 2012 and December 2017. Participants/Materials Setting Methods: Women aged 20-49 years who underwent ovarian stimulation and oocyte retrieval for autologous IVF/ICSI with a freeze-all policy in our centre were enrolled. Data on number of oocytes retrieved, number of mature oocytes, clinical pregnancy rate, live-birth rate, cumulative pregnancy rate, and cumulative live-birth rate (CLBR) were assessed and compared between patients who underwent a dual trigger and hCG trigger. Multivariate logistic regression was performed to identify and adjust for factors known to independently affect the CLBR. Main Results and the Role of Chance: A total of 4438 IVF/ICSI cycles were analyzed, including 1445 cycles with single hCG trigger and 2993 cycles with dual trigger. The cumulative biochemical pregnancy rate (60.8% vs. 68.1%, P<0.001; odds ratio (OR): 0.727; 95% confidence interval (CI): 0.638-0.828), cumulative clinical pregnancy rate (52.9% vs. 58.5%, P<0.001; OR: 0.796; 95%CI: 0.701-0.903), and CLBR (44.3% vs. 50.5%, P<0.001; OR: 0.781; 95%CI: 0.688-10.886) were all significantly lower in the hCG-trigger group compared with the dual-trigger group. The clinical pregnancy rate (48.2% vs. 58.2%, P=0.002; OR: 0.829; 95%CI: 0.737-0.934) and embryo implantation rate (34.4% vs. 38.9%, P<0.001; OR: 0.823; 95%CI: 0.750-0.903) in each transfer cycle were also significantly lower in the hCG-trigger group compared with the dual-trigger group. After controlling for all potential confounding variables, the trigger method was identified as an independent factor affecting the CLBR. The OR and 95%CI for hCG trigger were 0.780 and 0.641-0.949 (P=0.013). Limitations Reasons for Caution: The data used to analyse the effect of dual trigger on cumulative pregnancy and live-birth outcomes were retrospective, and the results may thus have been subject to inherent biases. Further prospective randomized controlled trials are required to verify the beneficial effects of dual trigger. Wider Implications of the Findings: Dual trigger had a positive effect on CLBRs, suggesting that it could be used as a routine trigger method in freeze-all cycles. Study Funding/Competing Interests: This study was supported by grants from National Key Research and Development Program of China (2018YFC1004800), the Natural Science Program of Zhejiang (LY19H040009), the National Natural Science Foundation of China (No. 81601236). No authors have competing interests to declare.

Unresponsive thin endometrium caused by Asherman syndrome treated with umbilical cord mesenchymal stem cells on collagen scaffolds: a pilot study.

BACKGROUND: Unresponsive thin endometrium caused by Asherman syndrome (AS) is the major cause of uterine infertility. However, current therapies are ineffective. This study is to evaluate the effect of transplantation with collagen scaffold/umbilical cord mesenchymal stem cells (CS/UC-MSCs) on this refractory disease. METHODS: Eighteen infertile women with unresponsive thin endometrium, whose frozen-thawed embryo transfers (FETs) were cancelled due to reduced endometrial thickness (ET ≤ 5.5 mm), were enrolled in this before and after self-control prospective study. Hysteroscopic examination was performed to confirm no intrauterine adhesions, then twenty million UC-MSCs loaded onto a CS were transplanted into the uterine cavity in two consecutive menstrual cycles. Then uterine cavity was assessed through hysteroscopy after two transplants. FETs were performed in the following cycle. Pregnancy outcomes were followed up. Endometrial thickness, uterine receptivity and endometrial angiogenesis, proliferation and hormone response were compared before and after treatment. RESULTS: Sixteen patients completed the study. No treatment-related serious adverse events occurred. Three months after transplantation, the average ET increased from 4.08 ± 0.26 mm to 5.87 ± 0.77 mm (P < 0.001). Three of 15 patients after FET got pregnant, of whom 2 gave birth successfully and 1 had a miscarriage at 25 weeks' gestation. One of 2 patients without FET had a natural pregnancy and gave birth normally after transplantation. Immunohistochemical analysis showed increased micro-vessel density, upregulated expression of Ki67, estrogen receptor alpha, and progesterone receptor, indicating an improvement in endometrial angiogenesis, proliferation, and response to hormones. CONCLUSION: CS/UC-MSCs is a promising and potential approach for treating women with unresponsive thin endometrium caused by AS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03724617 . Registered on 26 October 2018-prospectively registered, https://register.clinicaltrials.gov/.