A deep learning model for personalized intra-arterial therapy planning in unresectable hepatocellular carcinoma: a multicenter retrospective study.

Background: Unresectable Hepatocellular Carcinoma (uHCC) poses a substantial global health challenge, demanding innovative prognostic and therapeutic planning tools for improved patient management. The predominant treatment strategies include Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC). Methods: Between January 2014 and November 2021, a total of 1725 uHCC patients [mean age, 52.8 ± 11.5 years; 1529 males] received preoperative CECT scans and were eligible for TACE or HAIC. Patients were assigned to one of the four cohorts according to their treatment, four transformer models (SELECTION) were trained and validated on each cohort; AUC was used to determine the prognostic performance of the trained models. Patients were stratified into high and low-risk groups based on the survival scores computed by SELECTION. The proposed AI-based treatment decision model (ATOM) utilizes survival scores to further inform final therapeutic recommendation. Findings: In this study, the training and validation sets included 1448 patients, with an additional 277 patients allocated to the external validation sets. The SELECTION model outperformed both clinical models and the ResNet approach in terms of AUC. Specifically, SELECTION-TACE and SELECTION-HAIC achieved AUCs of 0.761 (95% CI, 0.693-0.820) and 0.805 (95% CI, 0.707-0.881) respectively, in predicting ORR in their external validation cohorts. In predicting OS, SELECTION-TC and SELECTION-HC demonstrated AUCs of 0.736 (95% CI, 0.608-0.841) and 0.748 (95% CI, 0.599-0.865) respectively, in their external validation sets. SELECTION-derived survival scores effectively stratified patients into high and low-risk groups, showing significant differences in survival probabilities (P < 0.05 across all four cohorts). Additionally, the concordance between ATOM and clinician recommendations was associated with significantly higher response/survival rates in cases of agreement, particularly within the TACE, HAIC, and TC cohorts in the external validation sets (P < 0.05). Interpretation: ATOM was proposed based on SELECTION-derived survival scores, emerges as a promising tool to inform the selection among different intra-arterial interventional therapy techniques. Funding: This study received funding from the Beijing Municipal Natural Science Foundation, China (Z190024); the Key Program of the National Natural Science Foundation of China, China (81930119); The Science and Technology Planning Program of Beijing Municipal Science & Technology Commission and Administrative Commission of Zhongguancun Science Park, China (Z231100004823012); Tsinghua University Initiative Scientific Research Program of Precision Medicine, China (10001020108); and Institute for Intelligent Healthcare, Tsinghua University, China (041531001).

Fourier Convolution Block with global receptive field for MRI reconstruction.

Reconstructing images from under-sampled Magnetic Resonance Imaging (MRI) signals significantly reduces scan time and improves clinical practice. However, Convolutional Neural Network (CNN)-based methods, while demonstrating great performance in MRI reconstruction, may face limitations due to their restricted receptive field (RF), hindering the capture of global features. This is particularly crucial for reconstruction, as aliasing artifacts are distributed globally. Recent advancements in Vision Transformers have further emphasized the significance of a large RF. In this study, we proposed a novel global Fourier Convolution Block (FCB) with whole image RF and low computational complexity by transforming the regular spatial domain convolutions into frequency domain. Visualizations of the effective RF and trained kernels demonstrated that FCB improves the RF of reconstruction models in practice. The proposed FCB was evaluated on four popular CNN architectures using brain and knee MRI datasets. Models with FCB achieved superior PSNR and SSIM than baseline models and exhibited more details and texture recovery. The code is publicly available at https://github.com/Haozhoong/FCB.

Blood-brain barrier breakdown in dementia with Lewy bodies.

BACKGROUND: Blood-brain barrier (BBB) dysfunction has been viewed as a potential underlying mechanism of neurodegenerative disorders, possibly involved in the pathogenesis and progression of Alzheimer's disease (AD). However, a relation between BBB dysfunction and dementia with Lewy bodies (DLB) has yet to be systematically investigated. Given the overlapping clinical features and neuropathology of AD and DLB, we sought to evaluate BBB permeability in the context of DLB and determine its association with plasma amyloid-ß (Aß) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: For this prospective study, we examined healthy controls (n = 24, HC group) and patients diagnosed with AD (n = 29) or DLB (n = 20) between December 2020 and April 2022. Based on DCE-MRI studies, mean rates of contrast agent transfer from intra- to extravascular spaces (Ktrans) were calculated within regions of interest. Spearman's correlation and multivariate linear regression were applied to analyze associations between Ktrans and specific clinical characteristics. RESULTS: In members of the DLB (vs HC) group, Ktrans values of cerebral cortex (p = 0.024), parietal lobe (p = 0.007), and occipital lobe (p = 0.014) were significantly higher; and Ktrans values of cerebral cortex (p = 0.041) and occipital lobe (p = 0.018) in the DLB group were significantly increased, relative to those of the AD group. All participants also showed increased Ktrans values of parietal ( ß  = 0.391; p = 0.001) and occipital ( ß  = 0.357; p = 0.002) lobes that were significantly associated with higher scores of the Clinical Dementia Rating, once adjusted for age and sex. Similarly, increased Ktrans values of cerebral cortex ( ß  = 0.285; p = 0.015), frontal lobe ( ß  = 0.237; p = 0.043), and parietal lobe ( ß = 0.265; p = 0.024) were significantly linked to higher plasma Aß1-42/Aß1-40 ratios, after above adjustments. CONCLUSION: BBB leakage is a common feature of DLB and possibly is even more severe than in the setting of AD for certain regions of the brain. BBB leakage appears to correlate with plasma Aß1-42/Aß1-40 ratio and dementia severity.

Multifaceted paternal exposures before conception and their epigenetic impact on offspring.

As scientific research progresses, there is an increasing understanding of the importance of paternal epigenetics in influencing the health and developmental path of offspring. Prior to conception, the environmental exposures and lifestyle choices of fathers can significantly influence the epigenetic state of sperm, including DNA methylation and histone changes, among other factors. These alterations in epigenetic patterns have the potential for transgenerational transmission potential and may exert profound effects on the biological characteristics of descendants. Paternal epigenetic changes not only affect the regulation of gene expression patterns in offspring but also increase the risk to certain diseases. It is crucial to comprehend the conditions that fathers are exposed to before conception and the potential outcomes of these conditions. This understanding is essential for assessing personal reproductive decisions and anticipating health risks for future generations. This review article systematically summarizes and analyzes current research findings regarding how paternal pre-pregnancy exposures influence offspring as well as elucidates underlying mechanisms, aiming to provide a comprehensive perspective for an enhanced understanding of the impact that paternal factors have on offspring health.

Association between cardiometabolic index and asthma in adults: evidence from NHANES 2005-2018.

OBJECTIVES: Cardiometabolic Index (CMI) is a surrogate marker for metabolic disorders. It is associated with various chronic diseases. This study aims to investigate the relationship between CMI and asthma. METHODS: Data from seven consecutive National Health and Nutrition Examination Survey cycles between 2005 and 2018 were used. The study included adults with self-reported asthma diagnoses and complete information for CMI calculation. The formula for CMI is CMI = [WC (cm)/height (cm)] × [TG (mg/dL)/HDL-C (mg/dL)]. A multivariate logistic regression model was employed to examine the linear relationship between CMI and asthma. Subgroup analyses were conducted to explore potential influencing factors. Additionally, smooth curve fitting and threshold effect analysis were used to describe the non-linear relationship. RESULTS: A higher CMI was possibly associated with an increased prevalence of asthma. After adjusting for various covariates including marital status, Poverty Income Ratio, Body Mass Index, hypertension, diabetes, smoking, alcohol consumption, heart attack, and stroke, the results remained significant (OR = 1.03; 95%CI, 1.00-1.05, p = 0.0178, R2 = 0.52). Participants with the highest CMI had a 38% increased risk of asthma prevalence compared to those with the lowest CMI (OR = 1.38; 95%CI, 1.19-1.60, p < 0.0001). CONCLUSION: The findings reveal that elevated CMI levels correlate with an increased risk of asthma, highlighting CMI's potential as a predictive marker for asthma, particularly in populations with a CMI below 1.97. These results suggest that interventions aimed at improving metabolic health may prove effective in managing or preventing asthma.

Pre-operative spinal cord perfusion quantified by DSC MRI as a predictor of post-operative prognosis in patients with cervical spondylotic myelopathy.

OBJECTIVE: This study aims to investigate the potential of preoperative blood supply condition measured by dynamic susceptibility contract (DSC) MRI in prediction of postoperative outcomes for patients with cervical spondylotic myelopathy (CSM). MATERIALS AND METHOD: Thirty-nine patients (Age: 61 ± 7, male: 23, female: 16) with CSM who underwent laminoplasty were enrolled. All patients received DSC MRI before the operation. Five parameters include Enhance, rEnhance, full width at half maxima (FWHM), Slope1 and Slope2 in DSC MRI, were calculated at all the compressed spinal cord segments. Clinical outcomes were evaluated by modified Japanese Orthopaedic Association (mJOA) scores. Patients were divided into two groups based on mJOA recovery rate of 5 years: good recovery (> 50%) or poor recovery (≤ 50%). The difference between two groups were compared. The value of DSC MRI to CSM was evaluated by logistic and receiver operating characteristic (ROC) curve analysis. RESULTS: There were 26 patients in good recovery group and 13 patients in poor recovery group. The baseline characteristics, including age, gender, preoperative mJOA score, and smoking status showed no significant difference between the two groups (all p > 0.05). The FWHM was significantly higher in the poor recovery group (9.77 ± 2.78) compared to the good recovery group (6.64 ± 1.65) (p = 0.002). Logistic regression analysis indicated that an increased FWHM was a significant risk factor for poor prognosis recovery (p = 0.013, OR = 0.392, 95%CI: 0.187-0.822). The AUC of FWHM for ROC was 0.843 (95% CI: 0.710-0.975) with a p value of 0.001. In addition, an FWHM greater than 5.87, with a sensitivity of 92.3% and specificity of 69.2%, was found to be an independent risk factor for poor postoperative recovery in patients with CSM. CONCLUSION: In this study, we successfully quantified the spinal cord blood supply condition by DSC MRI technique. We found that an increase in FWHM was an independent risk factor for poor postoperative recovery in CSM patients. Specifically, patients with FWHM > 5.87 have a poor postoperative recovery.

Comparison of anesthesia methods for intra-arterial therapy of patients with acute ischemic stroke: an updated meta-analysis and systematic review.

OBJECTIVES: Currently, there remains debate regarding the optimal anesthesia approach for patients undergoing intra-arterial therapy for acute ischemic stroke. Therefore, we conducted a comparative analysis to assess the effects of general anesthesia versus non general anesthesia on patient outcomes. METHODS: The research methodology entailed comprehensive searches of prominent databases such as the Cochrane Library, PubMed, Scopus, and Web of Science, covering the period from January 1, 2010, to March 1, 2024. Data synthesis employed techniques like risk ratio or standardized mean difference, along with 95% confidence intervals. The study protocol was prospectively registered with PROSPERO (CRD42024523079). RESULTS: A total of 27 trials and 12,875 patients were included in this study. The findings indicated that opting for non-general anesthesia significantly decreased the risk of in-hospital mortality (RR, 1.98; 95% CI: 1.50 to 2.61; p<0.00001; I2 = 20%), as well as mortality within three months post-procedure (RR, 1.24; 95% CI: 1.15 to 1.34; p<0.00001; I2 = 26%), while also leading to a shorter hospitalization duration (SMD, 0.24; 95% CI: 0.15 to 0.33; p<0.00001; I2 = 44%). CONCLUSION: Ischemic stroke patients who undergo intra-arterial treatment without general anesthesia have a lower risk of postoperative adverse events and less short-term neurological damage. In routine and non-emergency situations, non-general anesthetic options may be more suitable for intra-arterial treatment, offering greater benefits to patients. In addition to this, the neuroprotective effects of anesthetic drugs should be considered more preoperatively and postoperatively.

Mediterranean diet improves blastocyst formation in women previously infected COVID-19: a prospective cohort study.

Objectives: Our study tries to investigate the effect of the Mediterranean diet (MeDiet) on assisted reproductive treatment outcomes in women after COVID-19 infection. Design: A prospective observational cohort study in the Reproductive and Genetic Hospital of CITIC-Xiangya from February 2023 to August 2023.Subjects: A total of 605 participants previously infected with COVID-19 were enrolled. Exposure: None. Main outcome measurement: The primary outcomes are oocyte and embryo quality. The secondary outcomes are pregnancy outcomes. Results: A majority of participants (n = 517) followed low to moderate MeDiet, and only a small group of them (n = 88) followed high MeDiet. The blastocyst formation rate is significantly higher in MeDiet scored 8-14 points women (46.08%), compared to the other two groups (which is 41.75% in the low adherence population and 40.07% in the moderate adherence population respectively) (p = 0.044). However, the follicle number on hCG day, yield oocytes, normal fertilized zygotes, fertilization rate, day three embryos (cleavage embryos), and embryo quality are comparable among the three groups. For those who received embryo transfer, we noticed an obvious trend that with the higher MeDiet score, the higher clinical pregnancy rate (62.37% vs. 76.09% vs. 81.25%, p = 0.197), implantation rate (55.84% vs. 66.44% vs. 69.23%, p = 0.240) and ongoing pregnancy rate (61.22% vs. 75.00% vs. 81.25%, p = 0.152) even though the p values are not significant. An enlarging sample size study, especially in a high adherence population should be designed to further verify the effects of MeDiet's role in improving IVF performance. Conclusion: High adherence to MeDiet is associated with improved blastocyst formation in women after COVID-19 infection. There is also a trend that high adherence to MeDiet might be beneficial to clinical pregnancy, embryo implantation as well as ongoing pregnancy in these women.

Pharmacokinetics, pharmacodynamics, and safety of asundexian in healthy Chinese and Japanese volunteers, and comparison with Caucasian data.

There is an unmet clinical need for effective anticoagulant therapies for the management of thromboembolic diseases that are not associated with a relevant risk of bleeding. Asundexian (BAY 2433334) is an oral, direct, small-molecule inhibitor of activated factor XI (FXIa). Phase I data from healthy Caucasian male participants indicated predictable pharmacokinetic (PK) and pharmacodynamic (PD) profiles and no clinically relevant bleeding-related adverse events (AEs). Reported here are data from two phase I, randomized, placebo-controlled, single- and multiple-dose escalation studies of asundexian conducted in 60 healthy men: 24 Japanese and 36 Chinese. Baseline characteristics were comparable between the treatment groups. All treatment-emergent AEs were mild, with no serious AEs or AEs of special interest reported. Systemic exposure to asundexian increased dose proportionally after single or multiple dosing, with relatively low accumulation following multiple once-daily dosing in both Chinese and Japanese volunteers. Asundexian induced dose-dependent prolongation of activated partial thromboplastin time and inhibition of FXIa activity, with no effects on prothrombin time or FXI concentration in Japanese participants. There were no clinically relevant interethnic differences in PK profile across the Japanese, Chinese, and Caucasian (data from the previous phase I study) participants and no clinically relevant difference in PD response between Japanese and Caucasian participants.

Pregnancy outcomes and risk factors analysis in patients with systemic lupus erythematous.

BACKGROUND: The management of systemic lupus erythematosus (SLE) during pregnancy remains a challenge currently. Identifying early predictors of adverse pregnancy outcomes in SLE patients can help to develop treatment plan and improve prognosis. The aim of this study is to explore the clinical and laboratory variables in the early pregnancy that can predict adverse neonatal and maternal outcomes, thereby facilitating the grading management of SLE. METHODS: A retrospective analysis was conducted on 126 pregnant women with SLE who were admitted to Zhongnan Hospital of Wuhan University between January 2017 and December 2022. All enrolled patients were diagnosed (including newly diagnosed and previously diagnosed) during first trimester of pregnancy and their clinical records, laboratory results and pregnancy outcomes were reviewed. The association between the clinical and laboratory characteristics of patients at 12 gestational age and the adverse neonatal (ANOs) as well as maternal outcomes (AMOs) were analyzed. RESULTS: A total of 117 live births (92.8%) were recorded in the study. ANOs occurred in 59 (46.8%) cases, including fetal loss in 9 cases (7.1%), preterm birth in 40 cases (31.7%), small for gestational (SGA) in 15 cases (11.9%), and complete heart block in 2 cases (1.5%). Univariate analysis showed that disease activity index (P < 0.0001), lupus nephritis (P = 0.0195), anti-SSB positivity (P = 0.0074) and hypocomplementemia (P = 0.0466) were related to ANOs. However, multivariate analysis showed that only disease activity during early pregnancy was an independent predictor for ANOs (OR = 7.053, 95% CI: 1.882 to 26.291, P = 0.004). In addition, 48 patients experienced AMOs during subsequent trimester, including 24 (19.0%) patients with disease flare and 23 (18.3%) patients with pre-eclampsia. Unplanned pregnancy (P = 0.010), active disease (P = 0.0004), new onset SLE (P = 0.0044) and lupus nephritis (P = 0.0009) were associated with AMOs in univariate analysis, while disease activity was identified as an independent risk factor for AMOs (OR = 2.553, 95% CI: 1.012-6.440, P = 0.047). CONCLUSION: Active disease in early pregnancy is associated with adverse pregnancy outcomes. For patients with high risk factor for ANOs and AMOs, more intensive treatment and follow-up should be a wise measure. Especially for those who suffer from active disease, they should be fully informed and given the option to terminate or continue their pregnancy.

Management and outcomes of aortic dissection type B in late pregnancy: A retrospective case series.

OBJECTIVE: Pregnancy complicated with type B aortic dissection is a rare but devastating condition. Guidelines for managing this condition are lacking. We present our observation and experiences in managing five pregnant women with complicated type B aortic dissection in the second or third trimesters, aiming to gain insights that can aid in proposing an appropriate management strategy. DESIGN: A retrospective study. SETTING: Zhongnan Hospital of Wuhan University. POPULATION: Pregnant women with complicated type B aortic dissection. METHODS: Clinical data of five pregnant women with complicated type B aortic dissection admitted to Zhongnan Hospital of Wuhan University from January 2022 to June 2023 were collected. The clinical characteristics, treatment strategies, and corresponding maternal and infant outcomes were retrospectively analysed. MAIN OUTCOME MEASURES: Survival of mothers and foetuses. RESULTS: All five study participants were diagnosed with complicated type B aortic dissection by computed tomography angiography (CTA). The range of gestational weeks at admission was 27 weeks + 3 days to 36 weeks + 6 days. The first patient, planning a caesarean section (C-section) followed by thoracic endovascular aortic repair (TEVAR), died of aortic dissection rupture during C-section. Her neonate was successfully rescued. In contrast, the remaining four patients who underwent TEVAR first survived. Among them, three patients underwent single-stage aortic repair and delivery, while one patient received C-section 31 days after TEVAR. Three preterm live births were recorded among these surviving mothers. Neonatal death occurred in one case with a gestational age of 29 weeks + 5 days, who had foetal distress before surgery. During the follow-up period of up to 3 months, no maternal or infant death occurred. No device-related or systemic complications were observed in the surviving mothers after discharge. Routine physical examinations of the four live births showed no abnormalities. CONCLUSIONS: For pregnant women with thoracic back pain and high suspicion of aortic dissection, CTA should be conducted promptly to prevent missed or delayed diagnosis. Maternal survival should be prioritised over foetal outcome once diagnosed. TEVAR was demonstrated to be safe and feasible for such patients. For women with complicated type B aortic dissection in late pregnancy, TEVAR followed by C-section may be a promising treatment strategy.

Role of arachidonic acid in ischemic heart disease under different comorbidities: risk or protection?

In a translational study involving animal models and human subjects, Lv et al. demonstrate that arachidonic acid (AA) exhibits cardioprotective effects in diabetic myocardial ischemia, suggesting a departure from its known role in promoting ferroptosis-a form of cell death characterized by iron-dependent lipid peroxidation. However, the study does not address how underlying diabetic conditions might influence the metabolic pathways of AA, which are critical for fully understanding its impact on heart disease. Diabetes can significantly alter lipid metabolism, which in turn might affect the enzymatic processes involved in AA's metabolism, leading to different outcomes in the disease process. Further examination of the role of diabetes in modulating AA's effects could enhance the understanding of its protective mechanism in ischemic conditions. This could also lead to more targeted and effective therapeutic strategies for managing myocardial ischemia in diabetic patients, such as optimizing AA levels to prevent heart damage while avoiding exacerbating factors like ferroptosis.

Curcumin Nanoparticles-related Non-invasive Tumor Therapy, and Cardiotoxicity Relieve.

Non-invasive antitumor therapy can treat tumor patients who cannot tolerate surgery or are unsuitable. However, tumor resistance to non-invasive antitumor therapy and cardiotoxicity caused by treatment seriously affect the quality of life and prognosis of patients. As a kind of polyphenol extracted from herbs, curcumin has many pharmacological effects, such as anti-inflammation, antioxidation, antitumor, etc. Curcumin plays the antitumor effect by directly promoting tumor cell death and reducing tumor cells' invasive ability. Curcumin exerts the therapeutic effect mainly by inhibiting the nuclear factor-κB (NF-κB) signal pathway, inhibiting the production of cyclooxygenase-2 (COX-2), promoting the expression of caspase-9, and directly inducing reactive oxygen species (ROS) production in tumor cells. Curcumin nanoparticles can solve curcumin's shortcomings, such as poor water solubility and high metabolic rate, and can be effectively used in antitumor therapy. Curcumin nanoparticles can improve the prognosis and quality of life of tumor patients by using as adjuvants to enhance the sensitivity of tumors to non-invasive therapy and reduce the side effects, especially cardiotoxicity. In this paper, we collect and analyze the literature of relevant databases. It is pointed out that future research on curcumin tends to alleviate the adverse reactions caused by treatment, which is of more significance to tumor patients.

P2X3 Receptor Antagonist Eliapixant in Phase I Clinical Trials: Safety and Inter-ethnic Comparison of Pharmacokinetics in Healthy Chinese and Japanese Participants.

BACKGROUND: Afferent neuronal hypersensitization via P2X3 receptor signaling has been implicated as a driver of several disorders, including refractory chronic cough, endometriosis, diabetic neuropathic pain, and overactive bladder. Eliapixant, a selective P2X3 receptor antagonist, has been in clinical development for all four disorders. OBJECTIVE: This paper describes pharmacokinetic (PK) and safety data from two phase I studies of eliapixant in healthy Japanese and Chinese participants and compares those data within the two populations and with previous multiple dose data from Caucasian participants. METHODS: Two separate phase I, single-center, randomized, placebo-controlled studies were conducted with healthy male participants. The Japanese study was single-blind and the Chinese study was double-blind. Eliapixant was administered as an oral amorphous solid dispersion immediate-release tablet in strengths of 25 mg, 75 mg, and 150 mg. PK characteristics after a single dose (SD) and at steady state (multiple dose [MD], twice daily), adverse events (AEs), and tolerability were evaluated. A post hoc comparison of PK characteristics after SD of eliapixant in Japanese and Chinese participants, and after MD of eliapixant in Japanese, Chinese, and Caucasian participants, was performed. RESULTS: Overall, 36/39 participants enrolled in the Japanese/Chinese studies, respectively (mean [standard deviation] age 25.4 [6.5] and 26.7 [5.0] years, respectively). After SD administration, maximum plasma concentration (Cmax) was higher among Japanese than Chinese participants in the 25 mg and 75 mg dose groups, but comparable in the 150 mg dose group. The area under the concentration-time curve (AUC) was comparable between Japanese and Chinese participants in the 25 mg and 75 mg dose groups, but lower among Japanese participants in the 150 mg group. Half-lives after SD and MD administration were also comparable in Japanese and Chinese participants. The post hoc analysis included 26 Japanese, 30 Chinese, and 50 Caucasian participants. Comparable exposure (Cmax,md and AUC[0-12]md) was observed after MD administration of eliapixant in Chinese and/or Japanese compared with Caucasian participants (geometric mean inter-ethnic ratios close to 1). The trough plasma concentration after eliapixant 150 mg MD, which was assumed to be relevant to eliapixant efficacy, was comparable across all ethnicity groups. Most AEs reported in the Japanese (eliapixant 75 mg SD, n = 2; eliapixant 150 mg MD, n = 2) and Chinese participants (eliapixant 25 mg SD, n = 7; eliapixant 75 mg SD, n = 6; eliapixant 150 mg SD, n = 7; eliapixant 150 mg MD, n = 9; placebo SD, n = 5; placebo MD, n = 1) were of mild intensity. Higher incidences of AEs in the Chinese population were likely due to differing standards of AE reporting between investigators. CONCLUSION: Eliapixant was well tolerated by Japanese and Chinese participants. The inter-ethnic evaluation demonstrated similar PK characteristics across Japanese, Chinese, and Caucasian participants. REGISTRATION: ClinicalTrials.gov identifier numbers: NCT04265781 and NCT04802343.

Vitamin D binding protein correlate with estrogen increase after administration of human chorionic gonadotropin but do not affect ovulation, embryo, or pregnancy outcomes.

Background: Vitamin D binding protein (DBP) might increase substantially after ovarian stimulation and hence could be associated with IVF/ICSI outcomes because it determines the fraction of free bioavailable 25(OH) vitamin D. In this study, we aim to determine whether DBP is associated with E2 level after ovarian stimulation and IVF/ICSI outcomes. Design: Post-hoc analysis of a prospective observational cohort. Setting: Single-center study. Participants: 2569 women receiving embryo transfer. Intervention: None. Main outcome measures: The main outcomes were oocyte and embryo quality as well as pregnancy outcomes. Results: DBP concentration correlates with E2 on hCG day (=day of inducing ovulation with hCG; correlation coefficient r = 0.118, P<0.001) and E2 x-fold change to baseline level (r = 0.108, P<0.001). DBP is also positively correlated with total 25(OH)D (r = 0.689, R2 = 0.475, P<0.001) and inversely with free 25(OH)D (r=-0.424, R2=0.179, P<0.001), meaning that E2-stimulated DBP synthesis results in a decrease of free 25(OH)D during ovarian stimulation. However, such alteration does not affect IVF/ICSI outcomes when considering confounding factors, such as the number and quality of oocytes nor embryo quality as well as pregnancy outcomes. Conclusion: DBP concentration correlates with the degree of E2 increase after ovarian stimulation. DBP is also positively correlated with total 25(OH)D and inversely with free 25(OH)D, suggesting that the proportion of free 25(OH)D decreases during ovarian stimulation caused by E2-stimulated DBP synthesis. However, such alteration does not affect clinical IVF/ICSI outcomes.

Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis.

OBJECTIVE: To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis. METHODS: PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software. RESULTS: A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59-5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (ß2-MG). Importantly, the sensitivity analysis confirmed the study's stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or ß2-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias. CONCLUSIONS: The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.

Renin-angiotensin-aldosterone system (RAAS) inhibitors are commonly used to treat diabetic neuropathy (DN) and Astragalus membranaceus components are known to improve DN symptoms.We aimed to establish the efficacy and safety of using Astragalus combined with RAAS inhibitors.Astragalus combined with RAAS inhibitors enhances the total effective rate of diabetic neuropathy response to treatment and reduces urinary protein excretion rate, serum creatinine, blood urea nitrogen and HbAlc.Sensitivity analysis affirms study stability, while publication bias was detected for total effective rate, serum creatinine, and 24 h urinary protein levels.

Inverse association of prepregnancy systolic blood pressure and live birth rate in normotensive women undergoing in vitro fertilization/intracytoplasmic sperm injection.

OBJECTIVE: To explore whether maternal baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) affect pregnancy outcomes particularly in normotensive women (SBP, 90-139 mm Hg; DBP, 60-89 mm Hg) and hypertensive women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective cohort study. SETTING: Maximum care hospital for reproductive medicine. PATIENT(S): This study included 73,462 patients who underwent IVF/ICSI at the Reproductive and Genetic Hospital of CITIC-Xiangya between January 1, 2016, and November 30, 2020, selected on the basis of pre-established criteria. Analysis was limited to the first transfer cycle of the first stimulation cycle. INTERVENTION: Baseline SBP and DBP. MAIN OUTCOME MEASURE(S): The primary outcome focused on the live birth rate (LBR), with the secondary outcomes including clinical pregnancy rate, ectopic pregnancy rate, first-trimester miscarriage rate, second- or third-trimester fetal loss, and delivery/neonatal/maternal outcomes. Analytic methods included Poisson regression, linear regression, linear mixed-effect model, and restricted cubic spline analysis as appropriate. RESULT(S): For normotensive women, a 10-mm Hg increase in SBP was associated with an adjusted relative risk of 0.988 (95% confidence interval, 0.981-0.995) for live birth likelihood. However, DBP was not significantly associated with LBR after adjustments. The secondary outcomes indicated that increases in SBP and DBP were associated with higher risks of first-trimester miscarriage, gestational diabetes mellitus, and gestational hypertension in the normotensive subset. Sensitivity analyses confirmed these associations between SBP/DBP and LBR, consistent with the main findings even under stricter guidelines and after adjusting for multiple confounders. Subgroup analyses showed variation in the impact of blood pressure on LBR across different demographics and conditions. Consistent with earlier studies on blood pressure and birth outcomes, we found a 10-mm Hg increase in SBP was associated with a 5.4% (adjusted relative risk per 10 mm Hg, 0.946; 95% confidence interval, 0.907-0.986) reduction in LBR in the hypertensive subgroup. CONCLUSION(S): Systolic blood pressure impacted LBR outcomes in normotensive women who underwent IVF/ICSI, which suggests the need for reconsidering blood pressure management guidelines for reproductive-age women, focusing on reproductive health in addition to cardiovascular risk.

Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticancer and antiinflammatory agents.

Introduction: Cancer, a significant global health concern, necessitates innovative treatments. The pivotal role of chronic inflammation in cancer development underscores the urgency for novel therapeutic strategies. Benzothiazole derivatives exhibit promise due to their distinctive structures and broad spectrum of biological effects. This study aims to explore new anti-tumor small molecule drugs that simultaneously anti-inflammatory and anticancer based on the advantages of benzothiazole frameworks. Methods: The compounds were characterized by nuclear magnetic resonance (NMR), liquid chromatograph-mass spectrometer (LC-MS) and high performance liquid chromatography (HPLC) for structure as well as purity and other related physicochemical properties. The effects of the compounds on the proliferation of human epidermoid carcinoma cell line (A431) and human non-small cell lung cancer cell lines (A549, H1299) were evaluated by MTT method. The effect of compounds on the expression levels of inflammatory factors IL-6 and TNF-α in mouse monocyte macrophages (RAW264.7) was assessed using enzyme-linked immunosorbent assay (ELISA). The effect of compounds on apoptosis and cell cycle of A431 and A549 cells was evaluated by flow cytometry. The effect of compounds on A431 and A549 cell migration was evaluated by scratch wound healing assay. The effect of compounds on protein expression levels in A431 and A549 cells was assessed by Western Blot assay. The physicochemical parameters, pharmacokinetic properties, toxicity and drug similarity of the active compound were predicted using Swiss ADME and admetSAR web servers. Results: Twenty-five novel benzothiazole compounds were designed and synthesized, with their structures confirmed through spectrogram verification. The active compound 6-chloro-N-(4-nitrobenzyl) benzo[d] thiazol-2-amine (compound B7) was screened through a series of bioactivity assessments, which significantly inhibited the proliferation of A431, A549 and H1299 cancer cells, decreased the activity of IL-6 and TNF-α, and hindered cell migration. In addition, at concentrations of 1, 2, and 4 µM, B7 exhibited apoptosis-promoting and cell cycle-arresting effects similar to those of the lead compound 7-chloro-N-(2, 6-dichlorophenyl) benzo[d] thiazole-2-amine (compound 4i). Western blot analysis confirmed that B7 inhibited both AKT and ERK signaling pathways in A431 and A549 cells. The prediction results of ADMET indicated that B7 had good drug properties. Discussion: This study has innovatively developed a series of benzothiazole derivatives, with a focus on compound B7 due to its notable dual anticancer and anti-inflammatory activities. B7 stands out for its ability to significantly reduce cancer cell proliferation in A431, A549, and H1299 cell lines and lower the levels of inflammatory cytokines IL-6 and TNF-α. These results position B7B7 as a promising candidate for dual-action cancer therapy. The study's mechanistic exploration, highlighting B7's simultaneous inhibition of the AKT and ERK pathways, offers a novel strategy for addressing both the survival mechanisms of tumor cells and the inflammatory milieu facilitating cancer progression.

Pharmacokinetics, pharmacodynamics, and safety of fesomersen, a novel antisense inhibitor of factor XI, in healthy Chinese, Japanese, and Caucasian volunteers.

The inhibition of coagulation factor XI (FXI) presents an attractive approach for anticoagulation as it is not expected to increase the risk of clinically relevant bleeding and is anticipated to be at least as effective as currently available anticoagulants. Fesomersen is a conjugated antisense oligonucleotide that selectively inhibits the expression of FXI. The article describes three clinical studies that investigated the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of fesomersen after subcutaneous (s.c.) injection to healthy participants. The studies included participants from diverse ethnic backgrounds (Caucasian, Japanese, and Chinese). Fesomersen demonstrated good safety and tolerability in all three studies. No major bleeding events were observed. After single-dose s.c. injection, fesomersen was rapidly absorbed into the systemic circulation, with maximum fesomersen-equivalent (fesomersen-eq) concentrations (Cmax) in plasma observed within a few hours. After reaching Cmax, plasma fesomersen-eq concentrations declined in a biphasic fashion. The PD analyses showed that the injection of fesomersen led to dose-dependent reductions in FXI activity and increases in activated partial thromboplastin time (aPTT). The maximum observed PD effects were reached between Day 15 and 30, and FXI activity and aPTT returned to near-baseline levels by Day 90 after a single dose. The PK/PD profiles after a single injection were similar among the various ethnic groups. Collectively, the study results suggest that fesomersen has a favorable safety profile and predictable and similar PK and PD profiles across Chinese, Japanese, and Caucasian participants.

Estimating the prevalence of depression in people with acute coronary syndromes: A systematic review and meta-analysis.

BACKGROUND: The epidemic of acute coronary syndromes (ACS) poses a great challenge to depression. However, the prevalence of depression among ACS patients has not been fully determined. This meta-analysis aimed to provide an estimation of the global prevalence of depression among ACS patients (ACS depression). METHODS: Online databases including PubMed, Cochrane Library, Web of Science, and Scopus were searched for all relevant studies that reported the prevalence of ACS depression through March 2023. Pooled prevalence of ACS depression with 95% confidence interval (CI) was estimated by the random-effect model. All statistical analyses were performed using comprehensive meta-analysis software. This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (identifier CRD42023409338). RESULTS: A total of 28 studies (17 cohort studies, 9 cross-sectional studies, and 2 case-control studies) were included. The overall pooled prevalence of depression in ACS, derived from 28 studies, was 28.5% (95% CI: 0.28-0.29, P = .000, I2 = 99%). 21 included studies showed a prevalence of 20.3% (95% CI: 0.20-0.21, P = .000, I2 = 96%) in men, and the prevalence in women was 13.6% (95% CI: 0.13-0.14, P = .000, I2 = 95%). Subgroup analysis showed the lowest prevalence in Europe (20.7%, 95% CI: 0.20-0.22, P = .000, I2 = 98%); On different diagnostic criteria, the diagnostic and statistical manual of mental disorders (DSM-IV) (36.8%, 95% CI: 0.35-0.38, P = .000, I2 = 96%) has the highest prevalence. In terms of end year of data collection, the prevalence of ACS depression was lower for studies that ended data collection after 2012 (25.7%, 95% CI: 0.25-0.27, P = .000, I2 = 99%) than in studies before 2012 (30%, 95% CI: 0.29-0.31, P = .000, I2 = 98%). CONCLUSION SUBSECTIONS: This systematic review and meta-analysis suggest high global prevalence of depression among ACS patients, underlining the necessity of more preventive interventions among ACS patients especially in Asian and North American regions.