Machine Learning for Detecting Atrial Fibrillation from ECGs: Systematic Review and Meta-Analysis.

Background: Atrial fibrillation (AF) is a common arrhythmia that can result in adverse cardiovascular outcomes but is often difficult to detect. The use of machine learning (ML) algorithms for detecting AF has become increasingly prevalent in recent years. This study aims to systematically evaluate and summarize the overall diagnostic accuracy of the ML algorithms in detecting AF in electrocardiogram (ECG) signals. Methods: The searched databases included PubMed, Web of Science, Embase, and Google Scholar. The selected studies were subjected to a meta-analysis of diagnostic accuracy to synthesize the sensitivity and specificity. Results: A total of 14 studies were included, and the forest plot of the meta-analysis showed that the pooled sensitivity and specificity were 97% (95% confidence interval [CI]: 0.94-0.99) and 97% (95% CI: 0.95-0.99), respectively. Compared to traditional machine learning (TML) algorithms (sensitivity: 91.5%), deep learning (DL) algorithms (sensitivity: 98.1%) showed superior performance. Using multiple datasets and public datasets alone or in combination demonstrated slightly better performance than using a single dataset and proprietary datasets. Conclusions: ML algorithms are effective for detecting AF from ECGs. DL algorithms, particularly those based on convolutional neural networks (CNN), demonstrate superior performance in AF detection compared to TML algorithms. The integration of ML algorithms can help wearable devices diagnose AF earlier.

Synergistic dual cell therapy for atherosclerosis regression: ROS-responsive Bio-liposomes co-loaded with Geniposide and Emodin.

The development of nanomaterials for delivering natural compounds has emerged as a promising approach for atherosclerosis therapy. However, premature drug release remains a challenge. Here, we present a ROS-responsive biomimetic nanocomplex co-loaded with Geniposide (GP) and Emodin (EM) in nanoliposome particles (LP NPs) for targeted atherosclerosis therapy. The nanocomplex, hybridized with the macrophage membrane (Møm), effectively evades immune system clearance and targets atherosclerotic plaques. A modified thioketal (TK) system responds to ROS-rich plaque regions, triggering controlled drug release. In vitro, the nanocomplex inhibits endothelial cell apoptosis and macrophage lipid accumulation, restores endothelial cell function, and promotes cholesterol effluxion. In vivo, it targets ROS-rich atherosclerotic plaques, reducing plaque area ROS levels and restoring endothelial cell function, consequently promoting cholesterol outflow. Our study demonstrates that ROS-responsive biomimetic nanocomplexes co-delivering GP and EM exert a synergistic effect against endothelial cell apoptosis and lipid deposition in macrophages, offering a promising dual-cell therapy modality for atherosclerosis regression.

[Chaihu Sanshen Capsules protect rats from myocardial ischemia reperfusion injury via PKCßâ ¡/NOX2/ROS signaling pathway].

This study aims to explore the pathogenesis of myocardial ischaemia reperfusion injury(MIRI) based on oxidative stress-mediated programmed cell death and the mechanism and targets of Chaihu Sanshen Capsules in treating MIRI via the protein kinase Cß(PKCßⅡ)/NADPH oxidase 2(NOX2)/reactive oxygen species(ROS) signaling pathway. The rat model of MIRI was established by the ligation of the left anterior descending branch. Rats were randomized into 6 groups: sham group, model group, clinically equivalent-, high-dose Chaihu Sanshen Capsules groups, N-acetylcysteine group, and CGP53353 group. After drug administration for 7 consecutive days, the area of myocardial infarction in each group was measured. The pathological morphology of the myocardial tissue was observed by hematoxylin-eosin(HE) staining. The apoptosis in the myocardial tissue was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL). Enzyme-linked immunosorbent assay(ELISA) was employed to measure the le-vels of indicators of myocardial injury and oxidative stress. The level of ROS was detected by flow cytometry. The protein and mRNA levels of the related proteins in the myocardial tissue were determined by Western blot and real-time quantitative PCR(RT-qPCR), respectively. Compared with the sham group, the model group showed obvious myocardial infarction, myocardial structural disorders, interstitial edema and hemorrhage, presence of a large number of vacuoles, elevated levels of myocardial injury markers, myocardial apoptosis, ROS, and malondialdehyde(MDA), lowered superoxide dismutase(SOD) level, and up-regulated protein and mRNA le-vels of PKCßⅡ, NOX2, cysteinyl aspartate specific proteinase-3(caspase-3), and acyl-CoA synthetase long-chain family member 4(ACSL4) in the myocardial tissue. Compared with the model group, Chaihu Sanshen Capsules reduced the area of myocardial infarction, alleviated the pathological changes in the myocardial tissue, lowered the levels of myocardial injury and oxidative stress indicators and apoptosis, and down-regulated the mRNA and protein levels of PKCßⅡ, NOX2, caspase-3, and ACSL4 in the myocardial tissue. Chaihu Sanshen Capsules can inhibit oxidative stress and programmed cell death(apoptosis, ferroptosis) by regulating the PKCßⅡ/NOX2/ROS signaling pathway, thus mitigating myocardial ischemia reperfusion injury.

Evolocumab loaded Bio-Liposomes for efficient atherosclerosis therapy.

PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating atherosclerosis. In this study, by utilizing the significant advantages of nano-materials, a biomimetic nanoliposome loading with Evolocumab (Evol), a PCSK9 inhibitor, was designed to alleviate atherosclerosis. In vitro results showed that (Lipo + M)@E NPs up-regulated the levels of α-SMA and Vimentin, while inhibiting the expression of OPN, which finally result in the inhibition of the phenotypic transition, excessive proliferation, and migration of VSMCs. In addition, the long circulation, excellent targeting, and accumulation performance of (Lipo + M)@E NPs significantly decreased the expression of PCSK9 in serum and VSMCs within the plaque of ApoE-/- mice.

The effect of perioperative pelvic floor muscle exercise on urinary incontinence after radical prostatectomy: a meta-analysis.

BACKGROUND: Pelvic floor muscle exercise (PFME) is the most common conservative management for urinary incontinence (UI) after radical prostatectomy (RP). We performed this meta-analysis to investigate whether PFME during the entire perioperative period, including before and after RP, can significantly improve the recovery of postoperative UI. METHODS: We systematically reviewed randomized controlled trials (RCT) from PubMed, Medline, web of science, Cochrane library, and clinicalitrials.com prior to October 2022. Efficacy data were pooled and analyzed using Review Manager Version 5.3. Pooled analyses of urinary incontinence rates 1, 3, 6, and 12 months postoperatively were conducted, using odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: We included a total of 15 RCT studies involving 2178 patients received RP. Postoperative UI could be improved after 1 month, 3 months and 6 months, and the OR were 0.26 (95%CI:0.15-0.46) 0.30 (95%CI: 0.11-0.80) 0.20 (95%CI: 0.07- 0.56) in postoperative PFME group compared to no PFME group. However, there was no significant difference between the two groups in 12 months after surgery, and the OR was 0.85(95%CI: 0.48,1.51). There were similar results in perioperative PFME group compared to no PFME group with the OR of 0.35 (95%CI: 0.12, 0.98) and 0.40 (95%CI: 0.21, 0.75) in 1 and 3 months after surgery. Our results indicated no significant difference between perioperative PFME group and postoperative PFME group. The OR was 0.58 (95%CI: 0.20-1.71) 0.58 (95%CI:0.20-0.71) and 0.66 (95%CI: 0.32-1.38) in 1, 3 and 6 months after surgery. CONCLUSION: Application of PFME after RP significantly reduced the incidence of early postoperative UI, and additional preoperative PFME had no significant improvement on the recovery of UI.

Impact of body mass index on size and composition of urinary stones: a systematic review and meta-analysis.

BACKGROUND: Several studies have explored the impact of BMI on size and composition of urinary stones. Because there were controversies, a meta-analysis was necessary to be carried out to provide some evidence of the relationship of BMI and urolithiasis. MATERIALS AND METHODS: PubMed, Medline, Embase, Web of Science databases, and the Cochrane Library were searched up to August 12th 2022 for eligible studies. The urolithiasis patients were summarized into two groups: BMI < 25 and ≥ 25 kg/m2. Summary weighted mean difference (WMD), relative risk (RR) and 95% confidence intervals (CI) were calculated through random effects models in RevMan 5.4 software. RESULTS: A total of fifteen studies involving 13,233 patients were enrolled in this meta-analysis. There was no significant correlation of BMI and size of urinary stone (WMD -0.13mm, 95% CI [-0.98, 0.73], p = 0.77). Overweight and obesity increased the risk of uric acid stones in both genders and in different regions (RR=0.87, [95% CI] = 0.83, 0.91, p<0.00001). There was a higher risk of calcium oxalate stones formation in overweight and obesity group in total patients (RR=0.95, [95% CI] = 0.91, 0.98, p = 0.006). The relationship of BMI and calcium phosphate was not observed in this meta-analysis (RR=1.12, [95% CI] = 0.98, 1.26, p = 0.09). Sensitivity analysis was performed and indicated similar results. CONCLUSIONS: The current evidence suggests a positive association between BMI and uric acid and calcium oxalate stones. It would be of great guiding significance to consider losing weight when treating and preventing urinary stones.

[Regulation of myocardial ischemia reperfusion injury signal pathway by flavonoid monomer].

Acute myocardial infarction seriously endangers the health of people due to its high morbidity and high mortality. Reperfusion strategy is the preferred treatment strategy for acute myocardial infarction. However, reperfusion may lead to additional heart damage, namely myocardial ischemia reperfusion injury(MIRI). Therefore, how to reduce myocardial ischemia reperfusion injury has become one of the urgent problems to be solved in cardiovascular disease. Traditional Chinese medicine(TCM) has the multi-component, multi-channel, and multi-target advantages in the treatment of MIRI, which offers new ideas in this aspect. TCM containing flavonoids has a variety of biological activities and plays a significant role in the treatment of MIRI, which has great research and development application value. TCM containing flavonoids can regulate multiple signaling pathways of MIRI, such as phosphatidylinositol 3 kinase/kinase B(PI3K/Akt) signaling pathway, Janus kinase/signal transducer and activator of transcriptions(JAK/STAT) signaling pathway, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway, mitogen-activated protein kinase(MAPK) signaling pathway, nuclear factor-erythroid 2-related factor 2/antioxidant response element(Nrf2/ARE) signaling pathway, nuclear factor kappa-B(NF-κB) signaling pathway, silent information regulator 1(Sirt1) signaling pathway, and Notch signaling pathway. It reduces MIRI by inhibiting calcium overload, improving energy metabolism, regulating autophagy, and inhibiting ferroptosis and apoptosis. Therefore, a review has been made based on the regulation of relative signaling pathways against MIRI by TCM containing flavonoids, thus providing theoretical support and potential therapeutic strategies for TCM to alleviate MIRI.

[Efficacy and mechanism of Xuefu Zhuyu Decoction on model rats of coronary heart disease with heart blood stasis syndrome based on metabolomics].

This study investigated the effects of Xuefu Zhuyu Decoction on myocardial metabolites in a rat model of coronary heart disease with heart blood stasis syndrome and explored the therapeutic mechanism of blood circulation-promoting and blood stasis-removing therapy. SD rats were randomly divided into a sham operation group, a model group, a Xuefu Zhuyu Decoction group(14.04 g·kg~(-1)), and a trimetazidine group(5.4 mg·kg~(-1)). The sham operation group underwent thread insertion without ligation, while the other groups underwent coronary artery left anterior descending branch ligation to induce a model of coronary heart disease with heart blood stasis syndrome. Three days after modeling, drug intervention was performed, and samples were taken after 14 days of intervention. General conditions were observed, and electrocardiogram and cardiac ultrasound indices were measured. Hematoxylin-eosin(HE) staining and Masson staining were used to observe tissue pathological morphology. The enzyme linked immunosorbent assay(ELISA) was used to measure the levels of triglyceride(TG) and total cholesterol(TC) in the serum. Ultra high performance liquid chromatography-quantitative exactive-mass spectrometry(UHPLC-QE-MS) technology was used to screen differential metabolites in myocardial tissue and conduct metabolic pathway enrichment analysis. The results showed that Xuefu Zhuyu Decoction significantly improved the general condition of the model rats, reduced heart rate and ST segment elevation in the electrocardiogram, increased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), and decreased left ventricular internal diameter in diastole(LVIDd) and left ventricular internal diameter in systole(LVIDs). HE staining and Masson staining showed that Xuefu Zhuyu Decoction effectively alleviated myocardial tissue structural disorders, inflammatory cell infiltration, and collagen fiber deposition in the model rats. ELISA results showed that Xuefu Zhuyu Decoction effectively regulated serum TG and TC levels in the model rats. There were significant differences in the metabolic phenotypes of myocardial samples in each group. Fourteen differential metabolites were identified in the Xuefu Zhuyu Decoction group, involving five metabolic pathways, including arginine and proline metabolism, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, ether lipid metabolism, and alanine, aspartate, and glutamate metabolism. Xuefu Zhuyu Decoction improved cardiac function and myocardial structural damage in the rat model of coronary heart disease with heart blood stasis syndrome, and its biological mechanism involved the regulation of lipid metabolism, choline metabolism, amino acid metabolism, energy metabolism, and protein synthesis pathways.

Activation and function of receptor tyrosine kinases in human clear cell renal cell carcinomas.

BACKGROUND: The receptor tyrosine kinases (RTKs) play critical roles in the development of cancers. Clear cell renal cell carcinoma (ccRCC) accounts for 75% of the RCC. The previous studies on the RTKs in ccRCCs mainly focused on their gene expressions. The activation and function of the RTKs in ccRCC have not been fully investigated. METHODS: In the present study, we analyzed the phosphorylation patterns of RTKs in human ccRCC patient samples, human ccRCC and papillary RCC cell lines, and other kidney tumor samples using human phospho-RTK arrays. We further established ccRCC patient-derived xenograft models in nude mice and assessed the effects of RTKIs (RTK Inhibitors) on the growth of these cancer cells. Immunofluorescence staining was used to detect the localization of keratin, vimentin and PDGFRß in ccRCCs. RESULTS: We found that the RTK phosphorylation patterns of the ccRCC samples were all very similar, but different from that of the cell lines, other kidney tumor samples, as well as the adjacent normal tissues. 9 RTKs, EGFR1-3, Insulin R, PDGFRß, VEGFR1, VEGFR2, HGFR and M-CSFR were found to be phosphorylated in the ccRCC samples. The adjacent normal tissues, on the other hand, had predominantly only two of the 4 EGFR family members, EGFR and ErbB4, phosphorylated. What's more, the RTK phosphorylation pattern of the xenograft, however, was different from that of the primary tissue samples. Treatment of the xenograft nude mice with corresponding RTK inhibitors effectively inhibited the Erk1/2 signaling pathway as well as the growth of the tumors. In addition, histological staining of the cancer samples revealed that most of the PDGFRß expressing cells were localized in the vimentin-positive periepithelial stroma. CONCLUSIONS: Overall, we have identified a set of RTKs that are characteristically phosphorylated in ccRCCs. The phosphorylation of RTKs in ccRCCs were determined by the growing environments. These phosphorylated/activated RTKs will guide targeting drugs development of more effective therapies in ccRCCs. The synergistical inhibition of RTKIs combination on the ccRCC suggest a novel strategy to use a combination of RTKIs to treat ccRCCs.

Second-line treatment strategy for urothelial cancer patients who progress or are unfit for cisplatin therapy: a network meta-analysis.

BACKGROUND: Second-line treatment for urothelial carcinoma (UC) patients is used if progression or failure after platinum-based chemotherapy occurs or if patients are cisplatin-unfit. However, there is still no widely accepted treatment strategy. We aimed to analyze the effectiveness and safety of second-line treatment strategies for UC patients. METHODS: The PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) that included UC patients who were cisplatin-ineligible or unfit up to April 19, 2019. The primary outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). RESULTS: Thirteen trials that assessed 3502 UC patients were included. This study divided the network comparisons into three parts. The first part contained studies comparing taxanes and other interventions; the second part assessed investigator's choice chemotherapy (ICC)-related comparisons; and the third part assessed best support care (BSC). In the OS results of the first part, pembrolizumab (87.5%), ramucirumab plus docetaxel (74.6%), and atezolizumab (71.1%) had a relative advantage. Pembrolizumab also had advantages in ORR and severe adverse effect (SAE) results. Vinflunine and ramucirumab plus docetaxel had a relatively high surface under the cumulative ranking curve (SUCRA) rank by exploratory cluster analysis. CONCLUSIONS: This study concluded that atezolizumab and pembrolizumab are superior to other treatments, mainly in OS results, but no treatment confers a significant advantage in PFS. Pembrolizumab still has relative advantages in ORR and SAE results compared to ICC. Due to limitations, more studies are necessary to confirm the conclusions.

Hematopoietic stem/progenitor cell differentiation towards myeloid lineage is modulated by LIGHT/LIGHT receptor signaling.

The cytokine LT-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells (LIGHT) is a member of the tumor necrosis factor (TNF) superfamily. It is expressed primarily on activated T lymphocytes, and detectable on monocytes, granulocytes, and immune dendritic cells. It mainly plays a role in immune regulation including T cell activation and dendritic cell maturation. We recently reported its role as an inducer in embryonic stem cell differentiation, but its role in regulation of adult stem cell has not been defined. In the present study, we examined the expression of LIGHT receptor in Lin- c-kit+ Sca-1+ hematopoietic stem/progenitor cells (HSC/HPCs). We found that HSC express HVEM, a LIGHT receptor, on its surface. We further identified the role of LIGHT in promoting myeloid differentiation of HSCs driven by granulocyte-monocyte colony stimulating factor (GM-CSF). Further studies showed that LIGHT enhances both GM-CSF and GM-CSF receptor (GM-CSFR) expression in HSCs. LIGHT stimulation increases PU.1 expression in HSC/HPCs. In vivo administration of LIGHT increases the colony-forming unit-granulocyte/monocyte (CFU-GM) colony formation and plasma GM-CSF level. Altogether, the data suggest LIGHT promote myeloid differentiation of HSC/HPCs.

MicroRNA-27a Suppresses Detrusor Fibrosis in Streptozotocin-Induced Diabetic Rats by Targeting PRKAA2 Through the TGF-ß1/Smad3 Signaling Pathway.

BACKGROUND/AIMS: We examined the effects of microRNA-27a (miR-27a) on detrusor fibrosis in streptozotocin (STZ)-induced diabetic rats. METHODS: Eighty healthy Sprague-Dawley (SD) rats were randomly allocated into control, diabetic, miR-27a mimics, mimics control, miR-27a inhibitors, inhibitors control, siRNA-PRKAA2 (siPRKAA2) and inhibitors + siPRKAA2 groups (the latter 7 groups were established as STZ-induced diabetic rat models and treated in different manners). Detrusor cell apoptosis in bladder tissues was determined through terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining. Detrusor cells were assigned to the blank, miR-27a mimics, mimics control, miR-27a inhibitors, inhibitors control, siPRKAA2 and inhibitors + siPRKAA2 groups. Flow cytometry determined the cell cycle stage and apoptosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting (WB) were used to assess the expression of miR-27a, PRKAA2, TGF-ß1, Smad3, p-Smad3, fibronectin (FN), connective tissue growth (CTGF), and collagen-I (COL-I) in tissues and cells. RESULTS: Compared with the control group, the diabetic, miR-27a mimics, and siPRKAA2 groups showed reduced weight and PRKAA2 expression, but elevated blood glucose, serum creatinine (sCr), blood urea nitrogen (BUN), cell apoptosis, and expression of TGF-ß1, Smad3, FN, COL-I, CTGF, and p-Smad3. The opposite trend was observed in the miR-27a inhibitors group. PRKAA2 is a target gene of miR-27a. Compared to the blank group, the miR-27a mimics and siPRKAA2 groups indicated markedly increased TGF-ß1, Smad3, FN, COL-I, CTGF and p-Smad3 expression; decreased PRKAA2 expression; and increased cell apoptosis. The miR-27a inhibitors group showed the opposite trend. CONCLUSION: These results indicate that miR-27a may contribute to detrusor fibrosis in STZ-induced diabetic rats by targeting PRKAA2 via the TGF-ß1/Smad3 signaling pathway.

MicroRNA-214 Affects Fibroblast Differentiation of Adipose-Derived Mesenchymal Stem Cells by Targeting Mitofusin-2 during Pelvic Floor Dysfunction in SD Rats with Birth Trauma.

BACKGROUND/AIMS: This study investigated whether microRNA-214 (miR-214) targets mitofusin-2 (Mfn2) in the process of fibroblast differentiation of adipose-derived mesenchymal stem cells (ADMSCs) during pelvic floor dysfunction (PFD) in Sprague Dawley (SD) rats with birth trauma. METHODS: The ADMSCs were isolated from 4-6 week male SD rats (n = 20) and were cultured and divided into the blank, miR-214 mimic negative control (NC), miR-214 mimic, miR-214 inhibitor NC, miR-214 inhibitor, empty vector, Mfn2 over-expression and miR-214 + Mfn2 over-expression groups. Fibroblast differentiation of ADMSCs was measured with immunocytochemistry and immunofluorescence methods. The expression of miR-214 and the mRNA and protein expression of Mfn2, FSP1, Collagen I, Collagen III, Elastin, LOX, Fibulin-5, PPAR-γ and Runx2 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. A dual-luciferase reporter assay was performed to confirm whether Mfn2 was the target gene of miR-214. RESULTS: During ADMSC differentiation into fibroblasts, miR-214 expression was up-regulated, but the expression of Mfn2 was down-regulated. Fibroblast differentiation of ADMSCs was promoted in the miR-214 mimic group but was inhibited in the miR-214 inhibitor and Mfn2 over-expression groups. The expression of Mfn2 was decreased, but the expression of FSP1, Collagen I, Collagen III, Elastin, LOX, Fibulin-5, PPAR-γ or Runx2 was increased in the miR-214 mimic group; the miR-214 inhibitor group and Mfn2 over-expression group exhibited the opposite results. Mfn2 was the target gene of miR-214. CONCLUSIONS: The study provided strong evidence that miR-214 could promote fibroblast differentiation of ADMSCs by down-regulating Mfn2 to improve PFD in SD rats with birth trauma.

Preoperative 3D and 4D-CT imaging using 640-Multislice CT (640-MSCT) in diagnosis of female urethral diverticulum.

OBJECTIVE: To determine the sensitivity and specificity of 640-Multislice CT (640-MSCT) in diagnosing the female UD. MATERIALS AND METHODS: We investigated 16 patients with symptomatic UDs preoperatively in our hospital from August 2010 to March 2016. The patients' average age was 38.8 years. All patients were performed 640-MSCT of pelvis; then, 3D and 4D images were reconstructed preoperatively. RESULTS: In 3D and 4D-CT images, out of 16 patients, thirteen patients had one ostium, two had 2 ostia and one had 3 ostia. Out of those thirteen patients, eight patients' ostia were located at 5 o'clock and five patients' at 7 o'clock. Patients with 2 ostia location were at 5 and 6 o'clock and 5 and 7 o'clock, respectively. Patients with 3 ostia location were at 5, 6 and 7 o'clock. The mean distance from the bladder neck to the ostia was 22.5 mm. The shape of UD was out-pouching in 11 patients (68.8%), U-shaped in four patients (25.0%) and circumferential in 1 patient (6.2%). The CT findings were confirmed by surgical findings. CONCLUSIONS: 640-MSCT is a useful tool in identifying UD's shape and ostium (including number, location) before operation. Preoperative 640-MSCT should be an adaptable modality for clinically suspected UD patients. ADVANCES IN KNOWLEDGE: Several imaging methods have been used to diagnose female UD. 640-MSCT may be more suitable to diagnose it for its higher sensitivity and specificity in diagnosis of female UD, especially in identifying UD's shape and number and location of ostium.

Discovery of IDO1 and DNA dual targeting antitumor agents.

The development of small molecules for cancer immunotherapy is highly challenging and indoleamine 2,3-dioxygenase 1 (IDO1) represents a promising target. Inspired by the synergistic effects between IDO1 inhibitors and traditional antitumor chemotherapeutics, the first orally active dual IDO1 and DNA targeting agents were designed by the pharmacophore fusion strategy. The bifunctional hybrids exhibited enhanced IDO1 enzyme inhibitory activity and in vitro cytotoxicity as compared to IDO1 inhibitor 1-methyl-tryptophan and DNA alkylating agent melphalan. In a murine LLC tumor model, the dual targeting agents demonstrated excellent antitumor efficacy, highlighting the advantages of this novel design strategy to improve the efficacy of small molecule cancer immunotherapy.

Digital financial inclusion and household financial vulnerability: An empirical analysis of rural and urban disparities in China.

In recent times, a notable increase in the leverage ratios among numerous households across China has been witnessed, culminating in heightened household financial vulnerability. Concurrently, the sphere of digital inclusive finance has witnessed rapid advancement, establishing itself as a crucial mechanism for Chinese households to counteract financial risk shocks. This research article meticulously constructs an ordered regression model, anchored in micro-level data from household surveys, to delve into the influence and operative mechanisms of digital inclusive finance on the vulnerability of household finances. Empirical findings from this study robustly indicate that the evolution of digital inclusive finance significantly mitigates the household financial vulnerability. A thorough mechanism analysis reveals that digital inclusive finance primarily curtails household financial vulnerability through several avenues: it notably enhances financial literacy, augments the income derived from household financial assets, and elevates contributions to commercial insurance. Intriguingly, a heterogeneity analysis underscores that the impact of digital inclusive finance is more pronounced in reducing financial vulnerability amongst households registered in rural areas and those with lower income levels. This article contributes to the expansion of the theoretical framework concerning household financial vulnerability, offering insightful guidance and policy implications for addressing financial vulnerability concerns and forestalling macro-financial risks.

Role of macrophage polarization in heart failure and traditional Chinese medicine treatment.

Heart failure (HF) has a severe impact on public health development due to high morbidity and mortality and is associated with imbalances in cardiac immunoregulation. Macrophages, a major cell population involved in cardiac immune response and inflammation, are highly heterogeneous and polarized into M1 and M2 types depending on the microenvironment. M1 macrophage releases inflammatory factors and chemokines to activate the immune response and remove harmful substances, while M2 macrophage releases anti-inflammatory factors to inhibit the overactive immune response and promote tissue repair. M1 and M2 restrict each other to maintain cardiac homeostasis. The dynamic balance of M1 and M2 is closely related to the Traditional Chinese Medicine (TCM) yin-yang theory, and the imbalance of yin and yang will result in a pathological state of the organism. Studies have confirmed that TCM produces positive effects on HF by regulating macrophage polarization. This review describes the critical role of macrophage polarization in inflammation, fibrosis, angiogenesis and electrophysiology in the course of HF, as well as the potential mechanism of TCM regulation of macrophage polarization in preventing and treating HF, thereby providing new ideas for clinical treatment and scientific research design of HF.

Machine learning constructs a diagnostic prediction model for calculous pyonephrosis.

In order to provide decision-making support for the auxiliary diagnosis and individualized treatment of calculous pyonephrosis, the study aims to analyze the clinical features of the condition, investigate its risk factors, and develop a prediction model of the condition using machine learning techniques. A retrospective analysis was conducted on the clinical data of 268 patients with calculous renal pelvic effusion who underwent ultrasonography-guided percutaneous renal puncture and drainage in our hospital during January 2018 to December 2022. The patients were included into two groups, one for pyonephrosis and the other for hydronephrosis. At a random ratio of 7:3, the research cohort was split into training and testing data sets. Single factor analysis was utilized to examine the 43 characteristics of the hydronephrosis group and the pyonephrosis group using the T test, Spearman rank correlation test and chi-square test. Disparities in the characteristic distributions between the two groups in the training and test sets were noted. The features were filtered using the minimal absolute value shrinkage and selection operator on the training set of data. Auxiliary diagnostic prediction models were established using the following five machine learning (ML) algorithms: random forest (RF), xtreme gradient boosting (XGBoost), support vector machines (SVM), gradient boosting decision trees (GBDT) and logistic regression (LR). The area under the curve (AUC) was used to compare the performance, and the best model was chosen. The decision curve was used to evaluate the clinical practicability of the models. The models with the greatest AUC in the training dataset were RF (1.000), followed by XGBoost (0.999), GBDT (0.977), and SVM (0.971). The lowest AUC was obtained by LR (0.938). With the greatest AUC in the test dataset going to GBDT (0.967), followed by LR (0.957), XGBoost (0.950), SVM (0.939) and RF (0.924). LR, GBDT and RF models had the highest accuracy were 0.873, followed by SVM, and the lowest was XGBoost. Out of the five models, the LR model had the best sensitivity and specificity is 0.923 and 0.887. The GBDT model had the highest AUC among the five models of calculous pyonephrosis developed using the ML, followed by the LR model. The LR model was considered be the best prediction model when combined with clinical operability. As it comes to diagnosing pyonephrosis, the LR model was more credible and had better prediction accuracy than common analysis approaches. Its nomogram can be used as an additional non-invasive diagnostic technique.

Simulation and Experimental Study on Stress Relaxation Response of Polycrystalline γ-TiAl Alloy under Nanoindentation Based on Molecular Dynamics.

This study employed nano-indentation technology, molecular dynamics simulation, and experimental investigation to examine the stress relaxation behaviour of a polycrystalline γ-TiAl alloy. The simulation enabled the generation of a load-time curve, the visualisation of internal defect evolution, and the mapping of stress distribution across each grain during the stress relaxation stage. The findings indicate that the load remains stable following an initial decline, thereby elucidating the underlying mechanism of load change during stress relaxation. Furthermore, a nano-indentation test was conducted on the alloy, providing insight into the load variation and stress relaxation behaviour under different loading conditions. By comparing the simulation and experimental results, this study aims to guide the theoretical research and practical application of γ-TiAl alloys.

Efficacy and safety of Yangxinshi tablet for chronic heart failure: A systematic review and meta-analysis.

BACKGROUND: The specific benefits of Yangxinshi tablet (YXST) in the treating chronic heart failure (CHF) remain uncertain. AIM: To systematically evaluate the efficacy and safety of YXST in the treatment of CHF. METHODS: Randomized controlled trials (RCTs) investigating YXST for CHF treatment were retrieved from eight public databases up to November 2023. Meta-analyses of the included clinical studies were conducted using Review Manager 5.3. RESULTS: Twenty RCTs and 1845 patients were included. The meta-analysis results showed that the YXST combination group, compared to the conventional drug group, significantly increased the clinical efficacy rate by 23% [relative risk (RR) = 1.23, 95%CI: 1.17-1.29], P < 0.00001), left ventricular ejection fraction by 6.69% [mean difference (MD) = 6.69, 95%CI: 4.42-8.95, P < 0.00001] and 6-min walk test by 49.82 m (MD = 49.82, 95%C: 38.84-60.80, P < 0.00001), and reduced N-terminal pro-B-type natriuretic peptide by 1.03 ng/L [standardized MD (SMD) = -1.03, 95%CI: -1.32 to -0.74, P < 0.00001], brain natriuretic peptide by 80.95 ng/L (MD = -80.95, 95%CI: -143.31 to -18.59, P = 0.01), left ventricular end-diastolic diameter by 3.92 mm (MD = -3.92, 95%CI: -5.06 to -2.78, P < 0.00001), and left ventricular end-systolic diameter by 4.34 mm (MD = -4.34, 95%CI: -6.22 to -2.47, P < 0.00001). Regarding safety, neither group reported any serious adverse events during treatment (RR = 0.54, 95%CI: 0.15-1.90, P = 0.33). In addition, Egger's test results indicated no significant publication bias (P = 0.557). CONCLUSION: YXST effectively improves clinical symptoms and cardiac function in patients with CHF while maintaining a favorable safety profile, suggesting its potential as a therapeutic strategy for CHF.