Improved PEG-Based Construction of Analog Fountain Codes.

This paper proposes an improved progressive edge-growth (PEG) construction of analog fountain codes (AFCs). During edge selection, it simultaneously allocates weight coefficients in descending order. Analysis shows that our proposed construction reduces the probability of large weight coefficients involved in harmful short cycles. Simulation results indicate that it has good block error rate (BLER) in short block length regime.

Association of SARS-CoV-2 infection during late pregnancy with maternal and neonatal outcomes.

BACKGROUND: Limited data on the impact of the coronavirus disease 2019 (COVID-19) during pregnancy on newborn outcomes are available. This study aimed to characterize and compare the clinical outcomes of newborns from women with and without the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during late pregnancy. METHOD: This was a retrospective cohort study of women who were either infected or not infected with the SARS-CoV-2 virus during late pregnancy. The neonatal complications associated with COVID-19-positive pregnant women were investigated and analyzed. RESULTS: Among 2063 pregnant women over 28 weeks of gestation, 1.2%, 3.3%, and 18.7% of patients with multiple pregnancies, abnormal fetal positions, and lack of maternal or neonatal follow-up data, respectively, were excluded. Patients who were COVID-19-negative (60.6%) and -positive (16.2%) remained for further analysis. SARS-CoV-2 infection was significantly associated with higher SARS-CoV-2 infection rates in newborns (0% vs. 1.49%, P < 0.01) and longer duration of hospital stay (6.39 ± 2.2 vs. 4.92 ± 1.6, P < 0.01). However, comparing neonatal complications, including Apgar score, preterm birth, low birth weight, cesarean section rate, newborn hearing, neonatal congenital heart defects, and height and weight compliance rate of 6-month-old children, between non-infected and infected participants did not reach statistical significance. CONCLUSION: SARS-CoV-2 infection in late pregnancy has no significant impact on neonatal outcomes. After six months of follow-up of the neonates, we observed that SARS-CoV-2 infection in the third trimester of pregnancy did not affect their growth and development. Hopefully, these findings will guide management strategies and clinical practice.

Association of diabetic retinopathy with plasma atherosclerotic index, visceral obesity index, and lipid accumulation products: NHANES 2005-2008.

BACKGROUND: Abdominal obesity, a significant risk factor for the progression of diabetic retinopathy (DR), may lead to improved visual outcomes through early assessment. This study aims to evaluate any potential associations between DR and novel lipid metabolism markers, including the Atherogenic Index of Plasma (AIP), Visceral Adiposity Index (VAI), and Lipid Accumulation Product (LAP). METHODS: This study aimed to elucidate the association between various lipid markers and DR by screening the National Health and Nutrition Examination Survey (NHANES) database in the United States from 2005 to 2008. To examine the correlation, multifactor logistic regression analysis, subgroup analysis, threshold effect analysis, interaction test, and smooth curve fitting were used. RESULTS: Among the 2591 participants included, the incidence of DR was 13.6% and the mean age was 59.55 ± 12.26 years. After adjusting for important confounding covariates, logistic regression studies suggested a possible positive association between LAP, VAI, AIP, and DR occurrence (odds ratio [OR] = 1.004; 95% confidence interval [CI]: 1.002, 1.006; P < 0.0001; [OR] = 1.090; 95% [CI]: 1.037, 1.146; P = 0.0007; [OR] = 1.802; 95% [CI]: 1.240, 2.618; P = 0.0020). The nonlinear association between LAP and DR was further illustrated using an S-shaped curve by smoothing curve fitting, with the inflection point of the curve located at 63.4. Subgroup analyses and interaction tests were performed with full variable adjustment (P > 0.05 for all interactions). CONCLUSION: Studies have shown that elevated levels of LAP, VAI, and AIP increase the likelihood of DR, suggesting that they have the potential to be predictive markers of DR, emphasizing their potential utility in risk assessment and prevention strategies, and advocating for early intervention to mitigate the likelihood of DR.

Dissecting the Clinical Characteristics and Treatment Outcomes Correlates of KRAS G12C-Mutated Non-Small Cell Lung Cancer.

Background: KRAS mutation is one of the most common driver oncogenes in non-small cell lung cancer (NSCLC), and the most common mutation subtype is G12C. However, there is still a lack of efficacy and prognosis data related to immunotherapy, which hinders the promotion of new strategies. Methods: Clinical characteristics and treatment outcomes were collected and analyzed for patients with NSCLC harboring KRAS mutations at West China Hospital of Sichuan University from June 2013 to March 2023. Results: Among the 231 patients with KRAS-mutated NSCLC, 29.4% had KRAS G12C mutations. Compared to the KRAS non-G12C NSCLC group, the KRAS G12C NSCLC group had a greater number of pack-years. The programmed death ligand 1 expression and the proportion of patients with a high tumor mutational burden were not significantly different between the two groups. Similar patterns of TP53, STK11, and CDKN2A mutations were observed between KRAS G12C and KRAS non-G12C NSCLC groups. The median progression-free survival (PFS) (8.4 vs 7.0 months, p=0.100) and overall survival (OS) (12.1 vs 18.1 months, p=0.590) were not statistically different between KRAS G12C and KRAS non-G12C. Compared to patients with KRAS G12C NSCLC who did not receive immunotherapy, patients who received immunotherapy had a better objective response rate (46.2% vs 0%, p=0.002), PFS (12.2 vs 7.5 months, p=0.087) and OS (49.9 vs 11.1 months, p=0.12). Conclusion: Patients with KRAS G12C were more likely to be smokers. Advanced KRAS G12C NSCLC patients who received immunotherapy had a better ORR than those who did not, suggesting that patients with G12C mutations are more likely to benefit from immunotherapy.

Successful treatment of large hemoptysis and pseudoaneurysm of the pulmonary artery associated to oesophagomediastinal fistula with amphotericin B cholesterol sulfate complex: A case report.

Oesophagomediastinal fistula is uncommon. Oesophageal fistulas, may manifest as recurrent pneumonias. While pulmonary infections can lead to pulmonary artery pseudoaneurysms (PAPs), particularly in fungal infections. PAPs pose a rupture risk, potentially causing life-threatening hemoptysis. We report a unique case of a 45-year-old male who presented with sudden cough, dyspnea, and hemoptysis. Bronchoscopy triggered massive hemoptysis, necessitating emergency embolization. Persistent hemoptysis prompted further imaging, revealing an aneurysmal dilation located next to the spine and infectious lesions, suggesting an oesophagomediastinal fistula. After initiating therapy with Amphotericin B Cholesterol Sulfate Complex and fistula closure, the patient's hemoptysis resolved, with imaging resolution of the PAP. Long-term Voriconazole therapy ensured continued improvement. This case highlights the rarity and severity of such fistulas may be associated with fungal infections and PAPs, emphasizing the importance of prompt recognition, aggressive treatment for favourable outcomes.

Aberrant dynamic functional and effective connectivity changes of the primary visual cortex in patients with retinal detachment via machine learning.

OBJECTIVE: Previous neuroimaging studies have identified significant alterations in brain functional activity in retinal detachment (RD) patients, these investigations predominantly concentrated on local functional activity changes. The potential directional alterations in functional connectivity within the primary visual cortex (V1) in RD patients remain to be elucidated. METHODS: In this study, we employed seed-based functional connectivity analysis along with Granger causality analysis to examine the directional alterations in dynamic functional connectivity (dFC) within the V1 region of patients diagnosed with RD. Finally, a support vector machine algorithm was utilized to classify patients with RD and healthy controls (HCs). RESULTS: RD patients exhibited heightened dynamic functional connectivity (dFC) and dynamic effective connectivity (dEC) between the Visual Network (VN) and default mode network (DMN), as well as within the VN, compared to HCs. Conversely, dFC between VN and auditory network (AN) decreased, and dEC between VN and sensorimotor network (SMN) significantly reduced. In state 4, RD patients had higher frequency. Notably, variations in dFC originating from the left V1 region proved diagnostically effective, achieving an AUC of 0.786. CONCLUSION: This study reveals significant alterations in the connectivity between the VN and the default mode network in patients with RD. These changes may disrupt visual information processing and higher cognitive integration in RD patients. Additionally, alterations in the left V1 region and whole-brain dFC show promising potential in aiding the diagnosis of RD. These findings offer valuable insights into the neural mechanisms underlying visual and cognitive impairments associated with RD.

Case report: A case of effective treatment of primary myelofibrosis with nodular panniculitis using ruxolitinib combined with corticosteroids.

We report the case of a 54-year-old healthy Han Chinese male presenting with fever, pallor, erythematous subcutaneous nodules on the limbs, and significant anemia as indicated by routine blood tests, with no response to antimicrobial therapy. Initial skin biopsy was inconclusive. The erythematous subcutaneous nodules on the limbs rapidly progressed to widespread subcutaneous nodules across the body, with worsening anemia. Bone marrow biopsy revealed multifocal fibroblastic proliferation with focal fibrosis, classified as MF-2, and positive for the JAK2V617F mutation alongside SRSF2 positivity. Whole-body PET-CT scans did not reveal any lymph nodes or suspect lesions with high SUV uptake. A subsequent skin biopsy identified the condition as nodular panniculitis (NP), leading to a final diagnosis of primary myelofibrosis(PMF)with NP. The patient initially received treatment with oral ruxolitinib and prednisone acetate, resulting in normalization of body temperature, resolution of erythematous nodules, and normalization of blood parameters.

Analysis of characteristics of peripheral blood lymphocytes in endometrial carcinoma: a single-center study based on five-year clinical data.

INTRODUCTION: This study analyzed and discussed the characteristics of peripheral blood lymphocytes (PBLs) in patients with endometrial carcinoma (EC) to explore the PBLs' clinical application value. METHODS: This single-center case‒control study analyzed the clinical data of patients with EC and uterine fibroids who underwent surgery at the First Affiliated Hospital of Chongqing Medical University between October 2018 and October 2023 retrospectively. The Center for Clinical Molecular Medical Detection of our hospital performed PBLs detection using flow cytometry, and recorded the detection results in the electronic medical records system. Between-group and subgroup comparisons of PBLs in patients with EC were analyzed using t-test or Mann-Whitney U test. The effect of surgery on PBLs in patients with EC was assessed using a paired t-test or the Wilcoxon signed rank test. RESULTS: The immune function of patients with EC was significantly lower than that of healthy people (P < 0.05) and those with benign uterine diseases (P < 0.05) and was related to body mass index (BMI), hypertension, diabetes, and blood lipids (P < 0.05). In patients with EC, the PBLs counts decreased significantly after surgery (P < 0.05) and more kinds of lymphocytes were affected in the laparoscopic surgery group than in the open surgery group. CONCLUSIONS: With the decrease of PBLs counts, the immune status of patients with EC is impaired. Metabolic syndrome (Mets), including obesity, hypertension, diabetes, and high blood lipids, also affects the immune function of patients with EC. And for EC patients, the effect of laparoscopic surgery is greater than that of open surgery. PBLs has the potential to be one of indicator during the diagnosis and treatment of EC. TRIAL REGISTRATION: This study was retrospectively registered by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (approval number K2023-578).

Qingqianliutianosides A-E: five new sweet dammarane triterpenoid glycosides derived from the leaves of Cyclocarya paliurus - identification, characterization and interactions with T1R2/T1R3 sweet taste receptors.

BACKGROUND: Cyclocarya paliurus, as a new food resource, is utilized extensively in human and animal diets due to its bioactive compounds, health benefits, and its highly prized sweet flavor. This study aimed to investigate the sweet-taste ingredient of C. paliurus leaves. RESULTS: Five new dammarane triterpenoid glycosides were isolated and identified as qingqianliutianosides A-E (1-5) by comprehensive spectroscopic data analysis and a single crystal X-ray diffraction experiment. Qingqianliutianoside A (1) and qingqianliutianoside C (3), present in relatively high quantities in the plant, were shown to exhibit sweetness by sensory evaluation and electronic tongue analysis. Further monitoring was conducted on the content changes in 3 in leaves at different growth stages, indicating that 3 reached its peak content in April and then showed a decreasing trend. Molecular docking studies revealed that T1R2/T1R3 receptors Ser212, Ser105, Thr239, Asn380, Thr305, and Val381 may play critical roles, demonstrating that hydrogen bonding and hydrophobic interactions were the dominant interaction forces between all of the identified compounds and the active sites in the Venus flytrap module of the T1R2/T1R3 receptors. CONCLUSION: Qingqianliutianosides A-E are promising natural source sugar substitutes for use in functional foods and beverages. © 2024 Society of Chemical Industry.

Genetic links between ovarian ageing, cancer risk and de novo mutation rates.

Human genetic studies of common variants have provided substantial insight into the biological mechanisms that govern ovarian ageing1. Here we report analyses of rare protein-coding variants in 106,973 women from the UK Biobank study, implicating genes with effects around five times larger than previously found for common variants (ETAA1, ZNF518A, PNPLA8, PALB2 and SAMHD1). The SAMHD1 association reinforces the link between ovarian ageing and cancer susceptibility1, with damaging germline variants being associated with extended reproductive lifespan and increased all-cause cancer risk in both men and women. Protein-truncating variants in ZNF518A are associated with shorter reproductive lifespan-that is, earlier age at menopause (by 5.61 years) and later age at menarche (by 0.56 years). Finally, using 8,089 sequenced trios from the 100,000 Genomes Project (100kGP), we observe that common genetic variants associated with earlier ovarian ageing associate with an increased rate of maternally derived de novo mutations. Although we were unable to replicate the finding in independent samples from the deCODE study, it is consistent with the expected role of DNA damage response genes in maintaining the genetic integrity of germ cells. This study provides evidence of genetic links between age of menopause and cancer risk.

Knowledge, attitude, and practice toward nutrition support and management among hemodialysis patients.

Nutrition support is an important care component for patients on hemodialysis. Also, patient self-management is important to maintaining proper nutritional intake during hemodialysis. This cross-sectional study investigated the knowledge, attitude, and practice (KAP) towards nutrition support and management among hemodialysis patients treated at the West China Hospital of Sichuan University between January and March 2023. Among 445 (95.91%) valid questionnaires, 58.43% were filled out by male patients. The knowledge, attitude, and practice scores were 11.44 ± 1.80 (possible range: 0-13), 30.29 ± 3.22 (possible range: 8-40), and 31.27 ± 5.67 (possible range: 8-40), respectively. Age > 60 years (OR = 0.487, 95%CI: 0.260-0.913, P = 0.025) and junior college or undergraduate or above (OR = 2.606, 95%CI: 1.621-4.189, P < 0.001) were independently associated with adequate knowledge. The knowledge (OR = 1.151, 95%CI: 1.024-1.294, P = 0.018) and female gender (OR = 0.632, 95%CI: 0.419-0.953, P = 0.029) were independently associated with positive attitude. The knowledge (OR = 1.404, 95%CI: 1.221-1.614, P < 0.001), attitude (OR = 1.146, 95%CI: 1.069-1.227, P < 0.001), age 51-60 years (OR = 1.879, 95%CI: 1.093-3.229, P = 0.022), and BMI of 24.0-27.9 kg/m2 (OR = 0.434, 95%CI: 0.269-0.700, P = 0.001) were independently associated with proactive practice. Hemodialysis patients showed adequate knowledge, positive attitudes, and proactive practice; however, there were also several gaps in knowledge and misconceptions regarding proper nutritional self-management. Accordingly, addressing these gaps and misconceptions through carefully designed and effectively implemented education is crucial for providing comprehensive guidance on optimal nutrition and self-management strategies.

[Effect of Trichosanthis Pericarpium extract on bile acid metabolism in coronary heart disease model rats].

This study aims to explore the potential mechanism of action of Trichosanthis Pericarpium(TP) in improving coronary heart disease(CHD) based on a CHD rat model and metabolomics. The rat model of CHD was built by subcutaneous injection of high-fat diet combined with isoprenaline hydrochloride(ISO). To compare the expression level of lactate dehydrogenase, cardiac troponin Ⅰ(cTnⅠ), creatine kinase-MB(CK-MB), creatine kinase(CK), tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß),interleukin-6(IL-16), hypersensitive C-reactive protein(hs-CRP) in serum and cardiac pathological changes of model animals after administration of TP, LTQ-Orbitrap-MS analysis was combined with principal component analysis. The effect of TP on endogenous metabolites in the feces of CHD rats was studied. In addition, biomarkers were identified using the HMDB database and metabolic pathway enrichment analysis was performed using the MetaboAnalyst online pathway enrichment tool. The content of bile acid was further determined in the feces and serum of different groups of rats. Compared with blank group, the myocardial injury markers(CK,LDH, cTnⅠ, CK-MB) and inflammatory factors(TNF-α, IL-1ß, IL-6, hs-CRP) in serum of CHD rats were significantly increased.Myocardial injury and inflammatory infiltration in CHD rats were significantly improved by TP extract. The primary bile acid biosynthetic metabolism pathway was enriched by non-targeted metabolome analysis. The levels of total bile acid, primary bile acid,secondary bile acid, and unconjugated bile acids in the feces of CHD rats were significantly lower than those of control rats. Fecal excretion of total bile acid, primary bile acid, and unconjugated bile acid was significantly improved by TP extract. The levels of total bile acid, primary bile acid, secondary bile acid, and unconjugated bile acids in the serum of CHD rats were significantly higher than those of control rats. Circulating blood levels of total bile acids, primary bile acids, secondary bile acids, and unconjugated bile acids were significantly reduced by TP extract. Increasing fecal excretion of bile acid and decreasing the level of bile acid in blood circulation can improve CHD, and maintaining proper bile acid metabolism is one of the mechanisms of TP to improve CHD.

Steroid-Refractory Myocarditis Induced by Immune Checkpoint Inhibitor Responded to Infliximab: Report of Two Cases and Literature Review.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death protein 1 and its ligand (PD-1/PD-L1) as well as anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4), have been widely used for treating solid tumors. Myocarditis is a potentially lethal immune-related adverse events (irAEs) caused by ICIs therapy. The treatment of steroid-refractory myocarditis is challenging. We reported two non-small-cell lung cancer patients with steroid-refractory myocarditis induced by ICI. The symptoms were not resolved after pulse corticosteroid therapy and subsequent treatment including intravenous immunoglobulin and mycophenolate mofetil. Considering the level of serum interleukin (IL)-6 decreased by > 50% and level of serum tumor necrosis factor-α (TNF-α) increased during the course of the disease, infliximab was used. Myocarditis gradually alleviated after infliximab treatment. The cases revealed that specific cytokine inhibitors have promising roles in the treatment of steroid-refractory myocarditis. Infliximab could be considered for patients with low level of IL-6 and elevated level of TNF-α.

Systematic multi-trait AAV capsid engineering for efficient gene delivery.

Broadening gene therapy applications requires manufacturable vectors that efficiently transduce target cells in humans and preclinical models. Conventional selections of adeno-associated virus (AAV) capsid libraries are inefficient at searching the vast sequence space for the small fraction of vectors possessing multiple traits essential for clinical translation. Here, we present Fit4Function, a generalizable machine learning (ML) approach for systematically engineering multi-trait AAV capsids. By leveraging a capsid library that uniformly samples the manufacturable sequence space, reproducible screening data are generated to train accurate sequence-to-function models. Combining six models, we designed a multi-trait (liver-targeted, manufacturable) capsid library and validated 88% of library variants on all six predetermined criteria. Furthermore, the models, trained only on mouse in vivo and human in vitro Fit4Function data, accurately predicted AAV capsid variant biodistribution in macaque. Top candidates exhibited production yields comparable to AAV9, efficient murine liver transduction, up to 1000-fold greater human hepatocyte transduction, and increased enrichment relative to AAV9 in a screen for liver transduction in macaques. The Fit4Function strategy ultimately makes it possible to predict cross-species traits of peptide-modified AAV capsids and is a critical step toward assembling an ML atlas that predicts AAV capsid performance across dozens of traits.

ITGB3-enriched extracellular vesicles mediate the formation of osteoclastic pre-metastatic niche to promote lung adenocarcinoma bone metastasis.

The regulatory mechanisms underlying bone metastasis in lung adenocarcinoma (LUAD) are not yet fully understood despite the frequent occurrence of bone involvement. This study aimed to examine the involvement and mechanism of integrin subunit beta 3 (ITGB3) in the process of LUAD bone metastasis. Our findings indicate that ITGB3 facilitates the migration and invasion of LUAD cells in vitro and metastasis to the bone in vivo. Furthermore, ITGB3 stimulates osteoclast production and activation, thereby expediting osteolytic lesion progression. Extracellular vesicles (EVs) isolated from the conditioned medium (CM) of LUAD cells overexpressing ITGB3 determined that ITGB3 facilitates osteoclastogenesis and enhances osteoclast activity by utilizing EVs-mediated transport to RAW264.7 cells. Our in vivo findings demonstrated that ITGB3-EVs augmented the population of osteoclasts, thereby establishing an osteoclastic pre-metastatic niche (PMN) conducive to the colonization and subsequent growth of LUAD cells in the bone. ITGB3 is enriched in serum EVs of patients diagnosed with LUAD bone metastasis, potentially facilitating osteoclast differentiation and activation in vitro. Our research illustrates that ITGB3-EVs derived from LUAD cells facilitate osteoclast differentiation and activation by modulating the phosphorylation level of p38 MAPK. This process ultimately leads to the generation of osteolytic PMN and accelerates the progression of bone metastasis.

Association between low incidence of TP53 mutations and reduced early relapse rates in Uygur DLBCL.

Diffuse large B-cell lymphoma (DLBCL) demonstrates significant heterogeneity, investigations into the distinctions in clinical and molecular characteristics between Chinese Uygur and Han DLBCL patients remain unexplored. We retrospectively reviewed 279 DLBCL patients (105 Uygur and 174 Han patients), of which 155 patients underwent genetic profiling by NGS. Compared with Han patient, Uygur patients have better clinical prognostic indicators, including a higher proportion of patients with 0-1 extranodal involvement and I/II Ann Arbor staging. Consistently, Uygur patients were significantly associated with lower risk of relapse (P = 0.06), with a one-year relapse rate of 5% vs 17% and two-year relapse rate of 19% vs 36% compared to Han patients. At the molecular level, TP53 (21.3%) was among the top frequently altered gene in the cohort. Notably, the Uygur patients exhibited a significantly lower frequency of TP53 alterations and higher frequency of ASXL3 alterations. Logistic regression analysis showed that the lowered frequency of TP53 and enrichment of ASXL3 in the Uygur patients were independent of other factors. However, only patients with TP53 mutations had higher relapse rate than those with wild type TP53 (one-year, 20% vs 10%; two-year, 51% vs 21%). Our findings highlight the notable contribution of a low TP53 mutation frequency in Uygur patients as a pivotal factor associated with the favorable prognosis of this population.

Safety and efficacy of allogenic human amniotic epithelial cells transplantation via ovarian artery in patients with premature ovarian failure: a single-arm, phase 1 clinical trial.

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).

Intermittent fasting attenuates cognitive dysfunction and systemic disease activity in mice with neuropsychiatric systemic lupus erythematosus.

AIMS: Cognitive dysfunction and systemic disease activity are common manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE), a condition that affects a patient's health and quality of life. Clinical and preclinical studies have demonstrated that intermittent fasting (IF) improves health conditions and quality of life. Therefore, we aimed to test whether IF improves cognitive dysfunction and systemic disease activities in mice with NPSLE and to examine the underlying mechanisms. MAIN METHODS: NPSLE-prone MRL/lpr mice underwent 8 weeks of alternate-day fasting or ad libitum feeding, followed by behavioral tests to assess cognitive manifestations and biochemical tests to evaluate systemic disease activities. KEY FINDINGS: IF significantly improved cognitive functionality, decreased blood-brain barrier permeability, and reduced the activation of astrocytes and microglia in the hippocampi of MRL/lpr mice. IF also improved systemic disease activities, including reduced kidney glomerular injury and interstitial inflammation, peripheral blood autoantibody titer, and splenic T lymphocyte contents. Mechanistic studies demonstrated that IF attenuates cognitive dysfunction by facilitating the microglial transition to the M2-like phenotype via the AMPK/PPARγ/NF-κB pathway. SIGNIFICANCE: Together, observations from this study suggest a potential therapeutic benefit of IF in the treatment of cognitive dysfunction in patients with NPSLE.