BACKGROUND:For patients undergoing surgical valve procedures with concomitant coronary artery disease, current guidelines recommend that coronary artery bypass grafting (CABG) should be anatomically guided on the basis of stenosis severity, as assessed by coronary angiography. We aimed to test whether a physiologically guided strategy using angiography-derived fractional flow reserve (FFR) could improve clinical outcomes in this population. METHODS:FAVOR IV-QVAS is an investigator-initiated, multicentre, randomised, triple-blind trial done at 12 tertiary hospitals in China. Eligible patients were aged 18 years or older and were scheduled for valve surgery, with at least one clinically significant stenosis in a major coronary artery. Patients were randomly assigned (1:1) to undergo physiologically guided CABG (for lesions with an angiography-derived FFR value ≤0·80) or anatomically guided CABG (for lesions with a stenosis diameter ≥50% on coronary angiography). Randomisation was done using a web-based program and stratified by site with fixed blocks of four. Patients, surgeons, follow-up physicians, and outcome assessors were masked to treatment allocation. The primary outcome was a composite of death, myocardial infarction, stroke, unplanned coronary revascularisation, and new renal failure requiring dialysis within 30 days after surgery. The key secondary outcome was a composite of death, myocardial infarction, stroke, unplanned coronary revascularisation, and hospitalisation for unstable angina or heart failure at a minimum follow-up of 1 year. The primary analysis of the primary and key secondary outcomes was done in a modified intention-to-treat population that included all randomly assigned patients who underwent surgery and had available data for the primary outcome. Missing data for the primary outcome were planned to be analysed using complete-case analysis or multiple imputation, with a proportion of missing data of 2% as the threshold. This trial is registered at ClinicalTrials.gov (NCT03977129); extended follow-up is ongoing. FINDINGS:Between Aug 4, 2019, and Aug 13, 2024, 793 patients were enrolled. 396 were randomly assigned to the angiography-derived FFR group and 397 to the coronary angiography group; one patient in the coronary angiography group declined surgery and was excluded from the modified intention-to-treat population. The median age was 65 years (IQR 59-70), 221 (28%) patients were female, and 571 (72%) were male. Concomitant CABG was done in 223 (56%) patients in the angiography-derived FFR group and in 388 (98%) patients in the coronary angiography group. The primary outcome occurred in 31 (7·8%) patients in the angiography-derived FFR group and 53 (13·4%) in the coronary angiography group (absolute difference -5·6 percentage points [95% CI -9·9 to -1·3]; risk ratio 0·58 [95% CI 0·38 to 0·89]; p=0·011). Death within 30 days occurred in 11 (2·8%) patients in the angiography-derived FFR group and 17 (4·3%) patients in the coronary angiography group. At a median follow-up of 27 months (28 months [IQR 18-44] in the angiography-derived FFR group and 27 months [18-42] in the coronary angiography group), the key secondary outcome occurred in 82 (20·7%) patients in the angiography-derived FFR group and in 106 (26·8%) patients in the coronary angiography group (hazard ratio 0·74 [95% CI 0·55-0·98]; p=0·036). INTERPRETATION:Among patients undergoing valve surgery with concomitant coronary artery disease, physiologically guided CABG using angiography-derived FFR reduced the incidence of the composite perioperative outcome compared with anatomically guided CABG. These findings support a selective approach to surgical coronary revascularisation guided by physiological assessment in patients undergoing valve procedures. FUNDING:Shanghai Hospital Development Center, Shanghai Municipal Science and Technology Commission, and Ministry of Science and Technology of the People's Republic of China.

Objectives:Reverse Potts shunt is a promising yet high-risk therapy for pediatric pulmonary arterial hypertension. Postoperative hemodynamics is critically influenced by shunt configuration but is difficult to predict. This study aimed to quantify the effects of shunt size and location on hemodynamics to guide surgical planning. Methods:Based on a patient-specific model, four postoperative models with two different shunt locations [left pulmonary artery (LPA)-descending aorta (DAO) and pulmonary artery bifurcation-aortic arch] and three conduit sizes (4, 5, and 6 mm) were created. The direct Potts shunt model was created by a direct side-to-side anastomosis between the LPA and DAO with a 6-mm circular opening. Quantitative parameters including the shunt ratio (SR), which was defined as the percentage of the shunt flow rates to the total pulmonary inflow rate, lower limb oxygen saturation, and pressure were analyzed. Results:Increasing the shunt size from 4 mm to 6 mm elevated the SR from 6.01% to 9.80%, concurrently reducing lower limb oxygen saturation from 89.57% to 86.52%. When taking 11,000 Pa as the threshold, this increased SR resulted in a reduction of the high-pressure area from 17.32% of the total pulmonary artery area to almost zero. Meanwhile, the high-pressure area on the aorta expanded from 8.72% of the total aortic area to 14.94%. These results indicated a reduction in the right ventricular afterload and an increase in the left ventricular afterload. Notably, a 6-mm shunt at the pulmonary artery bifurcation yielded a significantly larger SR than at the LPA (9.80% vs. 2.68%), which is attributed to a higher pressure gradient at the pulmonary artery bifurcation (1,201 Pa vs. 162 Pa). Conclusion:The shunt location had a greater impact on the SR than shunt size within the 4 mm-6 mm range in this specific case. A 6-mm shunt at the pulmonary artery bifurcation yielded a significantly larger SR than at the LPA, which is attributed to the higher preoperative pressure gradient at the bifurcation site. Left heart function is as critical as right heart function in maintaining pressure balance and determining outcomes, as the shunt flow increases the left ventricular afterload.

The adverse impacts of homeostasis disturbance of plasma trace elements on female reproduction, including premature ovarian insufficiency (POI), have received increasing attention recently, yet limited evidence has been reported so far. POI significantly affects women’s quality of life and poses risks such as infertility and cardiovascular disease, necessitating the exploration of alternative risk factors. The metals studied included Iron (Fe), Zinc (Zn), Selenium (Se), Cobalt (Co), Magnesium (Mg), Strontium (Sr), Lithium (Li), Copper (Cu), Aluminum (Al), Chromium (Cr), Manganese (Mn), Arsenium (As), Titanium (Ti), Vanadium (V), and Iodine (I) in POI patients (n = 30) and controls (n = 31). Using a case-control design, we employed logistic regression and Bayesian Kernel Machine Regression (BKMR) analyses to evaluate the relationship between individual and combined plasma metal exposures and the risk of developing POI. Mn levels were higher in the POI group (median [IQR]: 2.20 [1.58–2.81] µg/L) compared to controls (1.44 [1.04–2.57] µg/L; p = 0.050). Similarly, V levels were significantly elevated in the POI group (mean ± SD: 1.19 ± 0.32 µg/L) versus controls (1.00 ± 0.38 µg/L; p = 0.049). Logistic regression indicated that higher Co levels were associated with a 98

Pulmonary arterial hypertension (PAH), a life-threatening disorder in children, necessitates palliative interventions like Potts shunt (surgical/transcatheter) for medically refractory cases. Perioperative anesthesia management remains challenging due to hemodynamic instability. This study describes our institutional anesthetic approach and summarizes the perioperative outcomes of 28 pediatric patients who underwent Potts shunt creation. A retrospective analysis was conducted on 28 consecutive children who underwent either surgical or transcatheter Potts shunt at Shanghai Children’s Medical Center between 2021 and 2024. Perioperative data were extracted from structured electronic medical records. Among the 28 patients, 18 underwent surgical Potts shunt creation (100

Background Premature ovarian insufficiency (POI) is defined by ovarian dysfunction and consequent decreased fertility. While follicular depletion is an acknowledged factor, dynamic changes in follicular subpopulations and single-cell-level niche remodeling remains largely unexplored. Human amniotic epithelial cells (hAECs) represent a promising regenerative approach for restoring ovarian function; however, the underlying mechanism in promoting follicular development remains unclear.Methods We established a chemotherapy-induced POI mouse model and conducted single-nucleus RNA sequencing (snRNA-seq) to systematically characterize ovarian cellular heterogeneity, residual follicular development, and ovarian microenvironmental alteration. A human-derived cell projection model was established to track the distribution of transplanted hAECs. Furthermore, the functional role of IGF1R signaling in granulosa cells was validated using both in vitro culture assays and in vivo interventions.Results We identified eight distinct ovarian cell types and uncovered stage-specific injury patterns: acute chemotherapy exposure induced massive loss of granulosa cells and oocytes, while the chronic phase was characterized by fibrotic accumulation and immune infiltration. Furthermore, residual follicles exhibited aberrant development trajectories and compromised progression, primarily due to disrupted granulosa cells -oocytes communication. Notably, hAEC transplantation significantly enhanced follicle survival, partially attenuated fibrosis and promoted ovarian structural restoration. Mechanistically, hAECs-derived IGFBP2 regulated IGF1R expression in granulosa cells, thereby reactivating the Akt/FoxO3A signaling pathway and downregulating the senescence marker P21.Conclusions This study presents a time-resolved snRNA-seq atlas capturing both acute and chronic injury phases in a chemotherapy-induced POI model, combined with a human-mouse projection approach to track transplanted hAECs in damaged ovaries. Our study establishes a novel cell-based therapeutic strategy for partial ovarian functional recovery, in which hAEC-derived IGFBP2 restores granulosa cell function and intercellular communication by regulating the IGF1R/Akt/mTOR signaling axis.

Niche, also known as cesarean scar defect, is a long-term complication of cesarean sections (CS), and its pathogenesis remains incompletely understood. Here, we profile 135,793 individual cells from adjacent myometrium tissue of niche (Adjacent, n = 48,587), well-healed cesarean scar tissue (Control, n = 47,653), and niche tissue (Niche, n = 39,553) using single-cell RNA sequencing. We identify a deficiency in LRP1 within a specific subgroup of fibroblasts in niche tissue, which correlate with a reduced ability to synthesize extracellular matrix (ECM). Through in vitro experiments, we demonstrate that LRP1 deficiency inhibited CTGF from effectively activating both the ERK and WNT signaling pathways in fibroblasts, thereby impairing their function. Tissue staining (30 non-healing vs 30 healing groups) validates our findings, showing decreased expression of LRP1 in non-healing groups. In a rat uterine scar model, treatment with recombinant human CTGF (rhCTGF) promoted myometrial regeneration and enhanced collagen production in uterine fibroblasts. Our analysis provides deep insights into the defective healing microenvironment of CS incisions and identifies critical cell types and signaling pathways involved in the formation of the niche. These results may inform novel prognostic approaches for predicting and treating niches.

Reduced fertility has become a global health problem. Female fertility is closely related to the normal physiological function of the ovary. Stress has been implicated in ovarian dysfunction, but the mechanisms driving this association are poorly understood. Norepinephrine (NE), a classic stress hormone, has not been extensively studied in the context of ovarian function. This study aimed to investigate the molecular mechanism of NE-induced ferroptosis in ovarian granulosa cells. Our results demonstrate that NE activates the adrenergic α1 receptor, resulting in elevated intracellular calcium levels and subsequent downregulation of FDXR gene expression. This disruption in FDXR expression dysregulates iron metabolism in the ovary, leading to iron accumulation, increased reactive oxygen species (ROS), and lipid peroxidation. These changes are accompanied by elevated levels of lipid peroxidation products, including malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Ultimately, these processes induce mitochondrial damage, trigger ferroptosis in granulosa cells, and lead to ovarian dysfunction. These findings reveal a stress-induced pathway driving ovarian decline, suggesting α1 antagonists or FDXR modulation as therapeutic strategies.

BACKGROUND:Infantile idiopathic pulmonary arterial hypertension complicated by recurrent episodes of pulmonary hypertensive crisis is an extremely rare and critical condition with high mortality. CASE SUMMARY:We present the case of a 5-month-old infant with a pulmonary hypertension crisis refractory to medical therapy, who underwent successful treatment with an emergency reversed Potts shunt (RPS), along with postoperative venopulmonary extracorporeal membrane oxygenation (V-P ECMO) support. DISCUSSION:From an imaging perspective, the mechanism by which RPS improves symptoms in patient with sustained pulmonary hypertension crises is explained. Additionally, this is the first reported case of successful postoperative use of V-P ECMO support after RPS. TAKE-HOME MESSAGES:It is important to recognize the importance of RPS and V-P ECMO in the treatment of pulmonary hypertension crises. By comparing pre- and postoperative imaging data, the mechanism by which RPS improves cardiac function is better understood.

Aorta-right atrial tunnel (ARAT) is an extremely rare congenital heart malformation with an average age of diagnosis of approximately 20 years. Its clinical symptoms are varied and often atypical. ARAT usually originates from the left or right sinus of Valsalva. In this case report, we aim to share a rare case of ARAT originating from the noncoronary sinus in an infant. The patient presented with a cardiac murmur, a dilated right heart, and a tortuous tunnel originating from the dilated noncoronary sinus and terminating at the right atrium in echocardiogram and computed tomography angiography. The patient underwent surgical closure of the tunnel to prevent possible heart failure. Postoperative echocardiography revealed complete closure of the tunnel with no residual flow. No evidence of aortic valve regurgitation or aortic root dilation was detected during 6-month follow-up.

Objectives:This study aims to analyze the disease burden of ischemic heart disease (IHD) in China from 1990 to 2021 utilizing data from Global Burden of Disease (GBD) 2021 database. Methods:Data from the GBD 2021 database were used to evaluate the prevalence, incidence, mortality, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) attributable to IHD in China from 1990 to 2021. Age-standardized rates and Joinpoint analysis were employed to assess temporal trends, with comparisons across gender and age groups. Results:In 2021, the incidence rate was 365.67 per 100,000 population (95 % CI: 293.32-440.07), and the mortality rate was 110.91 per 100,000 population (95 % CI: 92.42-128.56). Males exhibited a significantly higher disease burden compared to females. Among the population, incidence rates increased markedly after age 60, peaking at ages 70-74, while mortality rates rose sharply after age 75. From 1990 to 2021, the incidence, prevalence, mortality, and DALY rates showed an upward trend. However, after age standardization, the trends for incidence and prevalence flattened, while mortality and DALY rates showed a downward trend. Joinpoint analysis indicated a downward trend in age-standardized incidence, prevalence, mortality, and DALY rates. Conclusion:The overall burden of IHD in China remains high, but age-standardized data reflects the effectiveness of disease prevention and control. In the future, greater emphasis should be placed on high-risk populations, particularly aging population and postmenopausal women, to further alleviate the social burden of IHD.

STUDY QUESTION Is elevated plasma molybdenum level associated with increased risk for idiopathic premature ovarian insufficiency (POI)? SUMMARY ANSWER Elevated plasma molybdenum level is associated with an increased risk of idiopathic POI through vascular endothelial injury and inhibition of granulosa cell proliferation. WHAT IS KNOWN ALREADY Excessive molybdenum exposure has been associated with ovarian oxidative stress in animals but its role in the development of POI remains unknown. STUDY DESIGN, SIZE, DURATION Case-control study of 30 women with idiopathic POI and 31 controls enrolled from August 2018 to May 2019. In vitro experimentation. Animal studies using distilled water containing sodium molybdate. PARTICIPANTS/MATERIALS, SETTING, METHODS Logistic regression analysis of the association between plasma concentrations of molybdenum and calcium and POI odds ratio. Plasma samples were from 30 patients with idiopathic POI and 31 controls. Both groups were comparable in terms of age and body mass index. Proliferation assay, flow cytometry analyses for cell cycle, nitric oxide and calcium, gene expression, and protein analysis using human umbilical vein endothelial cells and KGN (human ovarian granulosa-like tumor cell line) cells. Sexual hormones, ovarian function, vascular injury, and platelet activation were evaluated in mice exposed to excessive molybdenum. MAIN RESULTS AND THE ROLE OF CHANCE Case-control study showed that the elevation of plasma concentrations of molybdenum and calcium was positively associated with the POI odds ratio. In vitro study showed that molybdenum treatment increased the permeability of human umbilical vein endothelial cells through enhancing nitric oxide generation and cytosolic calcium influx. In vivo study showed that increased vascular permeability induced by molybdenum resulted in platelet activation and serotonin release within mouse ovaries. Serotonin decreased granulosa cell proliferation by inducing cellular quiescence. Molybdenum also directly inhibited granulosa cell proliferation by downregulating isocitrate dehydrogenase (IDH1). Inhibition of granulosa cell proliferation ultimately led to ovarian dysfunction in mice, including altered estrus cycles, serum sex hormone concentrations, ovarian morphology, and ovarian reserve. LIMITATIONS, REASONS FOR CAUTION There are two limitations in the current study. First, it remains unclear whether the elevation of plasma molybdenum content is due to environmental exposure or altered metabolism. Second, rigorous and multicenter studies, with a larger sample size, should be carried out to confirm the elevation of plasma molybdenum and calcium concentrations in patients with idiopathic POI. WIDER IMPLICATIONS OF THE FINDINGS Our findings highlight an association between elevated plasma concentrations of molybdenum and calcium and increased risk of idiopathic POI. This discovery offers crucial insights into the pathogenesis of idiopathic POI and the search for effective preventive measures. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Natural Science Foundation of China (82271664), the interdisciplinary program of Shanghai Jiao Tong University (YG2022ZD028), the Research Projects of Shanghai Municipal Health Committee (202240343), and Shanghai Clinical Research Center for Cell Therapy (23J41900100). None of the authors has any conflict of interest to disclose. TRIAL REGISTRATION NUMBER N/A.

BACKGROUND:The optimal antispastic treatment after coronary artery bypass grafting using radial artery (RA) grafts is controversial. This clinical trial aimed to generate pilot comparative data on the effects of nicorandil, isosorbide mononitrate, or diltiazem on RA grafts. METHODS:This was a single-center, randomized, open-label, parallel-group pilot trial. Eligible patients who underwent coronary artery bypass grafting using RA grafts were randomized in a 1:1:1 ratio to receive oral nicorandil (15 mg daily), isosorbide mononitrate (50 mg daily), or diltiazem (180 mg daily) for 24 weeks post-coronary artery bypass grafting. The primary outcome was RA graft failure (modified Fitzgibbon grade B, S, or O) at 1 and 24 weeks, assessed by coronary computed tomography angiography. RESULTS:Among 150 randomized participants, 149 (mean age, 56.8 years; 13.4% women) with 177 RA grafts were assessed at least once by coronary computed tomography angiography, including 50 participants with 64 RA grafts in the nicorandil group, 50 participants with 57 RA grafts in the isosorbide mononitrate group, and 49 participants with 56 RA grafts in the diltiazem group, respectively. At 1 week post-coronary artery bypass grafting, the RA graft failure rates were lower with nicorandil versus diltiazem (19.4% versus 25.0%; difference, -5.6% [95% CI, -20.6% to 9.3%]) and isosorbide mononitrate versus diltiazem (18.2% versus 25.0%; difference, -6.8% [95% CI, -21.8% to 8.6%]). The RA graft failure rates were slightly higher with nicorandil versus isosorbide mononitrate (19.4% versus 18.2%; difference, 1.2% [95% CI, -13.3% to 15.2%]). At 24 weeks, RA graft failure rates were lower with nicorandil versus diltiazem (16.1% versus 27.8%; difference, -11.7% [95% CI, -26.6% to 3.4%]), and isosorbide mononitrate versus diltiazem (12.5% versus 27.8%; difference, -15.3% [95% CI, -29.8% to -0.2%]), and slightly higher with nicorandil versus isosorbide mononitrate (16.1% versus 12.5%; difference, 3.6% [95% CI, -9.6% to 16.4%]). CONCLUSIONS:In this pilot trial, treatment with nicorandil or isosorbide mononitrate was associated with a lower RA graft failure rate compared with diltiazem. Larger hypothesis-testing trials are warranted. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04310995.

INTRODUCTION:Premature ovarian insufficiency (POI), marked by ovarian function loss before age 40, is linked to a higher risk of dementia, including Alzheimer's disease (AD). However, the associated brain structural changes remain poorly understood. METHODS:We analyzed T1-weighted and diffusion tensor imaging in 33 idiopathic POI women and 51 healthy controls, using voxel-based, surface-based morphometry, and network analyses to assess gray matter volume (GMV), cortical thickness, and brain connectivity. RESULTS:Women with POI showed significant GMV and cortical thickness reductions in the frontal, parietal, and temporal regions (p < 0.05), alongside impaired connectivity with key regions such as the hippocampus, thalamus, and amygdala (p < 0.05). Younger POI subgroups exhibited changes in more widespread brain regions. In additionally, notable atrophy was observed in specific hippocampal and thalamic subregions in POI (p < 0.05). DISCUSSION:This preliminary study suggests early neurodegenerative patterns in POI, potentially contributing to dementia risk. Further research is needed to explore the underlying mechanisms and potential interventions. HIGHLIGHTS:We evaluated brain structural changes in participants with idiopathic premature ovarian insufficiency (POI). The observed brain alterations in POI participants closely resemble those seen in early dementia, including regions specifically associated with Alzheimer's disease (AD). These findings highlight the critical need for early interventions to reduce the long-term risks of cognitive impairment and dementia in women with POI.

Objectives: The guidelines recommend fractional fl ow reserve-guided coronary artery bypass grafting (CABG) during primary valve surgery without evidence. Quantitative fl ow ratio (QFR) is a novel coronary angiography (CAG)-based fractional fl ow reserve measurement. We aimed to compare the early clinical outcomes between QFR-guided and CAG-guided CABG in these patients. Methods: This observational study screened all 2081 patients admitted to our institution for elective primary mitral and/or aortic valve surgery from January 2017 to September 2020. Of them, all 188 patients with comorbid coronary artery lesions (visual estimated stenosis >= 50 % ) were included. Sixty-nine patients with QFR analysis received bypasses only for lesions with QFR <= 0.80 (QFR-guided group). The remaining 119 patients without QFR analysis received bypasses for all stenosis >= 50 % (CAG-guided group). Propensity overlap weighting was used to neutralize the intergroup imbalance. The primary end point was major adverse cardiovascular events. Results: After propensity score weighting, the baseline characteristics were comparable. Concomitant coronary artery bypass grafting was performed 58.1% versus 100% in the QFR-guided and CAG-guided groups, respectively. The mean number of grafts was significantly lower in QFR-guided group than in the CAG-guided group (0.9 +/- 0.7 vs 1.6 +/- 0.5 [P < .001]). The weighted 30-day incidence of major adverse cardiovascular events was numerically lower in the QFR-guided group than in the CAG-guided group, but not statistically significant (6.3% vs 11.8% [P = .429]). After a median follow-up of 31.6 months, the weighted risk of major adverse cardiovascular events and mortality were significantly lower in the QFR-guided group than in the CAG-guided group (major adverse cardiovascular events: hazard ratio, 0.45; 95% CI, 0.24-0.84; P = .012; mortality: hazard ratio, 0.38; 95% CI, 0.16-0.93; P = .029). Conclusions: Compared with CAG-guided coronary artery bypass grafting, QFRguided CABG is associated with less grafting and better clinical outcome in primary valve surgery with comorbid coronary artery disease. To confirm this fi nding, the Quantitative Flow Ratio Guided Revascularization Strategy for Patients Undergoing Primary Valve Surgery With Comorbid Coronary Artery Disease trial (NCT03977129) is ongoing. (JTCVS Open 2024;21:90-108)

Background Premature ovarian failure (POF) is a prevalent and severe condition that impairs female health but there is currently no effective treatment available to restore ovarian function. Human amniotic epithelial cells (hAECs) exhibit ovarian protection in pre-clinical models. Thus, we conducted a single-arm, phase 1 clinical trial to assess the safety and efficacy of allogenic hAECs in treating POF. Methods A total of 35 patients received 6 × 107 hAECs via ovarian artery and completed a five-month follow-up from December 30, 2020 to January 31, 2022. The follow-up assessments were conducted at various intervals after hAECs treatment, including one month (Visit-1, V-1), three months (Visit-2, V-2), and five months (Visit-3, V-3) post-treatment. The primary endpoints were incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of transvaginal ultrasound results, sex hormone levels, Menopausal Quality of Life (MENQOL) questionnaire, as well as reproductive indicators. This trial was registered at www.clinicaltrials.gov as NCT02912104. Findings No serious AEs were observed throughout the five-month follow-up period. The most common AE was hematoma (7/35, 20.00%), and other AEs include pelvic pain (4/35, 11.43%), fever (2/35, 5.71%), anaphylaxis (2/35, 5.71%), and hepatotoxicity (1/35, 2.86%). After hAECs transplantation (hAECT), significant improvements were observed in the levels of endometrial thickness, left ovarian volume, sex hormones (follicle-stimulating hormone (FSH) and estradiol (E2)), and MENQOL scores in all patients during the five-month follow-up period. Among them, 13 participants (37.14%) experienced spontaneous menstrual bleeding, and 20.00% (7/35) reported more than one regular menstrual bleeding post-hAECT. In this response group, significant improvements were observed in endometrial thickness, left ovarian volume, levels of FSH, E2, anti-Müllerian hormone (AMH), and MENQOL scores one month after hAECT in comparison to pre-hAECT. Interpretation hAECT via ovarian artery is safe, well-tolerated and temporarily ameliorates endometrial thickness, ovarian size, hormone levels, and menopausal symptoms in POF patients. Further randomized controlled trial of hAECs with longer follow-up period and a larger sample size is warranted. Funding National Natural Science Foundation of China (No. 82271664), the Interdisciplinary Program of Shanghai Jiao Tong University (YG2022ZD028), the Shanghai Municipal Health Committee (202240345), Shanghai Key Laboratory of Embryo Original Diseases (No. Shelab2022ZD01), Shanghai Municipal Education Commission (No. 20152236), and National Key Research and Development Program of China (No. 2018YFC1004802), Shanghai Clinical Research Center for Cell Therapy, China (No. 23J41900100).

Abstract Background The pancreatic index (PI) is a useful preoperative imaging predictor for pancreatic ductal adenocarcinoma (PDAC). In this retrospective study, we determined the predictive effect of PI to distinguish patients of pancreatic body/tail cancer (PBTC) with vascular involvement who can benefit from upfront surgery. Method All patients who received distal pancreatectomy for PDAC from 2016 to 2020 at the Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine were considered for the study. A total of 429 patients with PBTC were assessed in relation to the value of PI. Fifty‐five patients were eventually included and divided into low PI group and 29 patients in the normal PI group. Results The median overall survival (mOS) was significantly shorter in the low PI group (13.1 vs. 30.0 months, p = 0.002) in this study, and PI ≥ 0.78 (OR = 0.552, 95% CI: 0.301–0.904, p = 0.020) was an independent influencing factor confirmed by multivariate analysis. Subgroup analysis showed that PI was an independent prognostic factor for LA‐PBTC (OR = 0.272, 95% CI: 0.077–0.969, p = 0.045). As for BR PBTC, PI (OR = 0.519, 95% CI: 0.285–0.947, p = 0.033) combined with carbohydrate antigen 125 (CA125) (OR = 2.806, 95% CI: 1.206–6.526, p = 0.017) and chemotherapy (OR = 0.327, 95% CI: 0.140–0.763, p = 0.010) were independent factors. Conclusion This study suggests that the PI can be used as a predictive factor to optimize the surgical indication for PBTC with vascular involvement. Preoperative patients with normal PI and CA125 can achieve a long‐term prognosis comparable to that of resectable PBTC patients.

Background and PurposePrimary ovarian insufficiency (POI) has serious physical and psychological consequences due to estradiol deprivation, leading to increased morbidity and mortality. However, the causes of most POI cases remain unknown. Psychological stress, usually caused by stressful life events, is known to be negatively associated with ovarian function. It is important to explore high-frequency adverse life events among women with POI for future interventions.MethodsForty-three women (mean age=33·8 years) were recruited who were newly- diagnosed with idiopathic POI (FSH levels >40 IU/L) to participate in semi-structured interviews through convenience sampling. The main questions covered by the topic guide were designed to explore adverse life events prior to POI diagnosis. Interviews were audio recorded, transcribed and analyzed thematically. Data were analyzed from June 2019 to August 2020.ResultsAmong the women with POI, mean age at diagnosis of POI was 33·8 years (range from 19 to 39 years), and the average time between the onset of irregular menstruation and POI diagnosis was 2.3 years. These women with POI had a relatively normal menstrual cycle before the diagnosis. A number of stressful life events prior to POI diagnosis were discussed by them as important factors influencing their health. Four core themes emerged: 1) persistent exposure to workplace stress, 2) persistent exposure to family-related adverse life events, 3) sleep problem/disturbance existed in women with POI before diagnosis, and 4) participants’ general cognition and concerns about POI.ConclusionsPersistent exposures to adverse life events related to work stress, family stress and sleep problem existed in women with POI. Our findings are consistent with the hypothesis that adverse life events play a role in the development of POI. Future research should investigate how social environmental factors influence POI disease risks, and whether provision of tailored interventions (i.e. preventing or mitigating impact of adverse life events) aimed at high-risk populations may help prevent new POI cases and improve conditions of women with POI. We gained an in-depth understanding of the experiences of these women via 1:1 qualitative method, and find adverse life events are frequent in women with POI prior to the diagnosis.

An increasing number of studies demonstrate that changes in neurotransmitters metabolic levels in follicular fluid are directly related to oocyte maturation, fertilization, the quality of embryo and pregnancy rates. However, the relationship between the intra-follicular neurotransmitters and the function of granulosa cells (GCs), and the outcome of in vitro fertilization-embryo transfer (IVF-ET) is not clear. Human follicular fluid and cumulus GCs were harvested from large follicles obtained from patients undergoing IVF. Neurotransmitters and steroid hormones in follicular fluid were measured through liquid chromatography-tandem mass spectrometry (LC–MS/MS) and high-performance liquid chromatography-mass spectrometry (HPLC–MS/MS). Based on the content of glutamine (Gln) in follicular fluid, the samples were divided into two groups: high Gln level group and low Gln level group. The expression of proliferation-, steroidogenesis- and antioxidant-related genes in GCs was detected by qRT-PCR. In vitro, KGN cells were used to further verify the effects of Gln and NE on GCs function. Primary and secondary outcomes were the number of mature and retrieved oocytes, and the ratio of high-quality embryos, respectively. Gln (46.75 ± 7.74 μg/mL) and norepinephrine (NE, 0.20 ± 0.07 μg/mL) were abundant neurotransmitters in follicular fluid, and exhibited a significantly positive correlation (R = 0.5869, P < 0.005). In high Gln level group, the expression of proliferation, steroidogenesis and antioxidant-related genes in GCs were higher than those in low Gln level group, and the contents of estriol and E2 in follicular fluid were more abundant. Moreover, the concentrations of Gln and NE in follicular fluid showed significantly positive correlation with IDH1 expression in GCs (R = 0.3822, R = 0.4009, P < 0.05). Importantly, a significantly positive correlation was observed between IDH1 expression in GCs and the ratio of higher-quality/cleaved embryos (R = 0.4480, P < 0.05). In vitro studies further demonstrated that Gln and NE played synergistically function in improving GCs proliferation and E2 production by upregulating IDH1 expression. These data demonstrate that Gln and NE in follicular fluid might play significant positive roles in GCs function, and may be potential predictors for selecting optimal quality oocytes and evaluating the quality of embryonic development.

Background: In children with hypoplastic left heart syndrome (HLHS), volume overload (VO) is inevitable, and the right ventricle (RV) pumps blood into the systemic circulation. Understanding the molecular differences and their different responses to VO between the RV and left ventricle (LV) at the neonatal and highly plastic stages may improve the long-term management of children with HLHS. Methods and Results: A neonatal rat ventricular VO model was established by the creation of a fistula between the inferior vena cava and the abdominal aorta on postnatal day 1 (P1) and confirmed by echocardiographic and histopathological analyses. Transcriptomic analysis demonstrated that some of the major differences between a normal neonatal RV and LV were associated with the thyroid hormone and insulin signaling pathways. Under the influence of VO, the levels of insulin receptors and thyroid hormone receptors were significantly increased in the LV but decreased in the RV. The transcriptomic analysis also demonstrated that under the influence of VO, the top two common enriched pathways between the RV and LV were the insulin and thyroid hormone signaling pathways, whereas the RV-specific enriched pathways were primarily associated with lipid metabolism and arrhythmogenic right ventricular cardiomyopathy (ARVC); further, the LV-specific enriched pathways were primarily associated with nucleic acid metabolism and microRNAs in cancer. Conclusions: Insulin and thyroid hormones may play critical roles in the differences between a neonatal RV and LV as well as their common responses to VO. Regarding the isolated responses to VO, the RV favors an ARVC change and the LV favors a reduction in microRNAs in cancer. The current study suggests that insulin, thyroid hormone, and cancer-associated microRNAs are potential therapeutic targets that should be explored by basic science studies to improve the function of the RV to match that of the LV.