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Abstract Background Fetal growth restriction (FGR) is a major determinant of perinatal morbidity and mortality. Our study aimed to develop a prediction model for the risk of FGR developing adverse perinatal outcome (APO) and evaluate its performance. Methods This was a prospective observational cohort study of consecutive singleton gestations meeting the ACOG-endorsed criteria for FGR from January 2022 to June 2023 at Obstetrics and Gynecology Hospital of Fudan University. Clinical information, ultrasound indicators and serum biomarkers were collected. The primary composite APO comprised one or more of: perinatal death, intrauterine demise, intraventricular hemorrhage, periventricular leukomalacia, seizures, necrotizing enterocolitis, neonatal respiratory distress syndrome, sepsis and the length of stay in the neonatal intensive care unit > 7 days. Least absolute shrinkage and selection operator regression was used to screen variables for nomogram model construction. The discrimination, calibration and clinical effectiveness of the nomogram were evaluated using receiver operating characteristic curve, calibration plots and decision curve analysis in training and validation cohorts. Results A total of 122 pregnancies were enrolled in the final statistical analysis. Five variables were identified to establish a nomogram, including gestational weeks at diagnosis, abnormal umbilical artery Doppler, abnormal uterine artery Doppler, and multiples of the median values of placental growth factor and soluble fms-like tyrosine kinase-1. The area under the receiver-operating-characteristics curve of 0.87 (95% CI, 0.75–0.99) and 0.86 (95% CI, 0.74–0.98) in the training and validation cohort respectively, indicated satisfactory discriminative ability of the nomogram. The calibration plots showed favorable consistency between the nomogram’s predictions and actual observations. Decision curve analysis supported its practical value in a clinical setting. Conclusions A nomogram was developed and validated to possess the promising capacity of predicting APO in FGR-afflicted neonates, and may prove useful in counseling and management of pregnancies complicated by FGR.

Abstract Chronic kidney disease (CKD) is a major health concern, with renal interstitial fibrosis (RIF) as a key feature. Effective management of RIF is crucial for treating CKD. Yiqi Juanshen decoction (YQJSD), as traditional Chinese medicine, has shown promising results in CKD treatment. This study evaluates YQJSD’s effectiveness in ameliorating RIF and explores the underlying molecular mechanisms using the unilateral ureteral obstruction (UUO) model. YQJSD has been shown to effectively reduce serum creatinine and blood urea nitrogen levels, decrease extracellular matrix deposition, and down-regulate the expression of α-SMA, COL4α1, Fibronectin (FN). Mechanistically, YQJSD exerts its effects by modulating multiple pathways: it inhibits the NF-κB signaling pathway, inhibiting the expression of pro-inflammatory cytokines like NF-κB1, IL-1β, TNF-α, and CCR1. Simultaneously, YQJSD suppresses the epithelial-mesenchymal transition (EMT) by downregulating the expression of Snail1, Vimentin, Twist1, and FSP1, while increasing E-cadherin expression. Moreover, YQJSD can regulate the PI3K/AKT signaling pathway by decreasing the expression of LOXL2 and PIK3R1, along with p-AKT1/2/3. This modulation of the LOXL2/PI3K/AKT pathway contributes to the inhibition of both EMT and inflammation, highlighting a critical role in the therapeutic intervention against RIF. These findings suggest that YQJSD may serve as a promising therapeutic management of RIF in CKD patients.

Abstract Anion exchange membrane fuel cells (AEMFCs) are one of the ideal energy conversion devices. However, platinum (Pt), as the benchmark catalyst for the hydrogen oxidation reaction (HOR) of AEMFCs anodes, still faces issues of insufficient performance and susceptibility to CO poisoning. Here, we report the Joule heating-assisted synthesis of a small sized Ru1Pt single-atom alloy catalyst loaded on nitrogen-doped carbon modified with single W atoms (s-Ru1Pt@W1/NC), in which the near-range single Ru atoms on the Ru1Pt nanoparticles and the long-range single W atoms on the support simultaneously modulate the electronic structure of the active Pt-site, enhancing alkaline HOR performance of s-Ru1Pt@W1/NC. The mass activity of s-Ru1Pt@W1/NC is 7.54 A mgPt+Ru -1 and exhibits notable stability in 1000 ppm CO/H2-saturated electrolyte. Surprisingly, it can operate stably in H2-saturated electrolyte for 1000 h with only 24.60 % decay. Theoretical calculations demonstrate that the proximal single Ru atoms and the remote single W atoms synergistically optimize the electronic structure of the active Pt-site, improving the HOR activity and CO tolerance of the catalyst.

Abstract Combination antiretroviral therapy (ART) has improved outcomes for human immunodeficiency virus (HIV) associated non-Hodgkin lymphoma. This is an analysis of 127 patients with HIV with Burkitt lymphoma (HIV-BL) and diffuse large B-cell lymphoma (HIV-DLBCL) treated at the Zhongnan Hospital of Wuhan University over a 17-year period during the ART and rituximab era. The median CD4 count for the cohorts was 0.141 × 109/L (range, 0.001-0.861 × 109/L). DA-EPOCH ± R (54%) were most commonly used in HIV-BL. CHOP± R (42%) was most commonly used to treat HIV-DLBCL. The complete response rate after first-line curative therapy was 10/28 (36%) in HIV-BL and 25/57 (44%) in HIV-DLBCL. The 2-year progression-free survival (PFS) and overall survival (OS) for the HIV-BL cohort was 50% and 41% respectively. The 2-year PFS and OS for the HIV-DLBCL cohort was 55% and 47% respectively. Current China practice favours the treatment of HIV-BL and HIV-DLBCL similarly to the HIV-negative population with the use of concurrent ART. However, due to the extremely low percentage of patients receiving ART prior to the lymphoma diagnosis, the high percentage of patients with poor performance status, and the advanced stage at diagnosis, the treatment of HIV-related lymphoma remains the major challenge in China.

The emergence of electric vehicles has contributed to mitigating air pollution and greenhouse effects caused by traditional fuel vehicles. The power battery industry chain, which is a primary component of electric vehicles, requires more attention to monitor its development status. This study proposes a novel method for forecasting the development status of the power battery industry chain by monitoring the market value index of all listed companies in the power battery industry. It proposes a new forecasting model, RRMIDAS-SVR, which outlines reverse-restricted mixed data sampling (RRMIDAS) into support vector regression (SVR) to end the data-driven challenges of mixed-frequency data and nonlinear relationships. We estimate the RRMIDAS-SVR model using a quadratic programming problem and mixed-frequency West Texas Intermediate crude oil futures prices, electric vehicle sales, and the consumer price index as predictors of the market value of all listed companies in the power battery industry chain. The experimental findings reveal that the RRMIDAS-SVR model outperforms the other models, as evidenced by its lower mean absolute error and root-mean-square error. This study contributes to understanding the development status of the power battery industry value chain by proposing and developing a new approach, RRMIDAS-SVR, to monitor the industry's development status that considers a multi-source information set. Moreover, this study provides strategic insights for stakeholders in the power battery industry.

Abstract The management of overactive bladder (OAB) in women encompasses a range of strategies, from behavioral modifications to pharmacotherapy and nerve stimulation techniques. This prospective, randomized, controlled trial evaluates the efficacy of the combination of TTNS and mirabegron in symptom improvement over three months in women diagnosed with OAB. The study was designed as a randomized controlled trial. A total of 40 patients were prospectively randomized into two groups. Twenty patients in the combination group accepted TTNS and mirabegron therapy, and the other 20 patients as control only accepted mirabegron therapy. Primary outcomes were changes from baseline in the lower urinary tract symptoms. The severity of symptoms and quality of life (QoL) were assessed using the validated OAB questionnaire (OAB-q). TTNS reduced the clinical symptoms of OAB, and the difference was statistically significant at all study sites (p

Asparagus officinalis L. has long been used as a medicinal food since ancient times. Despite identifying the active compounds, the anti-inflammatory properties of these compounds remain underexplored. This study explored the anti-inflammatory activity of white asparagus polysaccharide (WAPS) against skin inflammation. WAPS, a pectin polysaccharide, was identified to coexist with α-glycosidic and β-glycosidic linkages glucan and probably has triple-helix confirmation suggested by Fourier-transform infrared and nuclear magnetic resonance spectroscopy. Cellular experiments indicated that WAPS attenuated the expression of inflammatory cytokines and enhanced macrophage viability. Skin inflammation was ameliorated with WAPS liposomal-loaded gel; the mechanism regulating NF-κB/MAPK signal pathways was further explored. Notably, the formulation augmented the bioavailability of WAPS, downregulated the expression of NF-κB p50 and MMP9, and amplified the inhibitory potential of WAPS against inflammation. This study suggests WAPS as a medicinal substance with anti-inflammatory efficacy.

Ehlers-Danlos Syndrome (EDS) refers to a group of connective tissue disorders characterized by significant clinical and genetic variability, affecting multiple systems in the body. Classified as a rare disease, EDS includes 14 subtypes, all marked by joint hypermobility, skin extensibility, and tissue fragility. These subtypes present with a wide range of clinical manifestations and severities, including frequent joint dislocations, scoliosis, arterial dissections, and organ ruptures. Hypermobile EDS (hEDS) is the most common subtype, with newly established clinical diagnostic guidelines. In this case, a patient presented with minor hemoptysis over 8 h, and a chest CT scan revealed a massive hematoma in the left lower lung. Due to the complexity and varied presentations of EDS, misdiagnosis is common. This report shares our experience with diagnosis and treatment in this case, highlighting the importance of increasing awareness for improved survival outcomes.

Orchidaceae serves as a “flagship” group in global biodiversity conservation efforts, drawing substantial interest from researchers in China, but research on the variation of orchid species diversity along elevational gradients in mid-subtropical mountain forests in China remains limited. In this study, we conducted an investigation of orchids across more than 1900 5 m × 5 m plots in six mountains located in central China, spanning an elevational range from 166 m to 1930 m, and then converted these survey data into the distribution data in 100 m elevational bands to study the trend of species richness (S), Shannon-Wiener index (H'), Simpson index (D), and Pielou evenness (e) of orchids variation along the elevational gradients. We discovered that although the diversity patterns vary among each mountain, overall, S, H', and D exhibit hump-shaped patterns, while e shows a slight monotonic increase pattern along the elevation. There are no significant difference between elevational patterns of diversity of terrestrial and epiphytic orchids. In addition, slope, canopy closure, and disturbance have no significant impact on all the four diversity indices, mean annual temperature positively correlates with species richness, while annual precipitation shows negative correlations with S, H', and D. Meanwhile, we also found that significant differences in the composition and abundance of orchid communities between high and low elevations. These results significantly enhance our understanding of elevation-dependent diversity patterns among rare and endangered plants in the mid-subtropical regions of China.

Abstract Background The reconstruction of complex wounds of the hand still has challenges in achieving aesthetic, functional and sensory recovery. We presented our experience of using the polyfoliate and chimeric radial collateral artery perforator flaps (RCAPF) to repair complex hand defects, aiming to explore the feasibility of special-form RCAPFs in hand coverage and enhance the comprehension of their respective indications. Methods From June 2014 to March 2021, 26 cases (19 males and 7 females, mean 44.4 years) underwent defect and sensation reconstruction of their hands with special-form RCAPFs, which manifested as multiple adjacent or irregular single wounds and composite tissue defects complicated with a degree of nerve injury. The clinical effects of the free RCAPFs were evaluated by integrating the postoperative and long-term follow-up outcomes of all cases. Results Altogether 8 polyfoliate flaps, 17 chimeric flaps and 1 polyfoliate-chimeric flap were harvested. Of them, 23 flaps survived uneventfully in one stage. Venous congestion occurred in 3 cases, two of which survived through vascular exploration and another one was finally repaired by the contralateral RCAPF. The follow-up results showed that the appearance of both the recipient and donor sites mostly recovered satisfactory. All the bone flaps properly healed. The BMRC sensory evaluation results of all skin flaps were S4 in 8 flaps, S3 in 18 flaps, and S2 in 9 flaps. Conclusions The free RCAPFs can be designed in various forms with a reliable blood supply, contributing to reconstructing simple and multiple wounds of the hand with or without bone defects and dead space.

Abstract Glioblastoma (GBM), a primary brain tumor, exhibits remarkable invasiveness and is characterized by its intricate location, infiltrative behavior, the presence of both the blood–brain barrier (BBB) and the blood–brain tumor barrier (BBTB), phenotypic diversity, an immunosuppressive microenvironment with limited development yet rich vascularity, as well as the resistant nature of glioblastoma stem cells (GSCs) towards traditional chemotherapy and radiotherapy. These formidable factors present substantial obstacles in the quest for effective GBM treatments. Following extensive research spanning three decades, the hepatocellular receptor A2 (EphA2) receptor tyrosine kinase has emerged as a promising molecular target with translational potential in the realm of cancer therapy. Numerous compounds aimed at targeting EphA2 have undergone rigorous evaluation and clinical investigation. This article provides a comprehensive account of the distinctive roles played by canonical and non-canonical EphA2 signaling in various contexts, while also exploring the involvement of the EphA2-ephrin A1 signaling axis in GBM pathogenesis. Additionally, the review offers an overview of completed clinical trials targeting EphA2 for GBM treatment, shedding light on both the prospects and challenges associated with EphA2-directed interventions in the domain of cancer therapeutics.

Abstract Background This study aimed to investigate the epidemiological changes in scarlet fever before, during and after the COVID-19 pandemic (2005–2023) and predict the incidence of the disease in 2024 and 2025 in Chongqing Municipality, Southwest China. Methods Descriptive analysis was used to summarize the characteristics of the scarlet fever epidemic. Spatial autocorrelation analysis was utilized to explore the distribution pattern of the disease, and the seasonal autoregressive integrated moving average (SARIMA) model was constructed to predict its incidence in 2024 and 2025. Results Between 2005 and 2023, 9,593 scarlet fever cases were reported in Chongqing, which resulted in an annual average incidence of 1.6694 per 100,000 people. Children aged 3–7 were the primary victims of this disease, with the highest average incidence found among children aged 6 (5.0002 per 100,000 people). Kindergarten children were the dominant infected population, accounting for as much as 54.32% of cases, followed by students (34.09%). The incidence for the male was 1.51 times greater than that for the female. The monthly distribution of the incidence showed a bimodal pattern, with one peak occurring between April and June and another in November or December. The spatial autocorrelation analysis revealed that scarlet fever cases were markedly clustered; the areas with higher incidence were mainly concentrated in Chongqing’s urban areas and its adjacent districts, and gradually spreading to remote areas after 2020. The incidence of scarlet fever increased by 106.54% and 39.33% in the post-upsurge period (2015–2019) and the dynamic zero-COVID period (2020–2022), respectively, compared to the pre-upsurge period (2005–2014) (P

Abstract Background The predictive value of systemic inflammatory response index (SIRI) for stroke-associated pneumonia (SAP) risk in patients with acute ischemic stroke (AIS) treated by thrombectomy remains unclear. This study aimed to investigate the predictive value of SIRI for SAP in patients with AIS treated by thrombectomy. Methods We included AIS patients treated by thrombectomy between August 2018 and August 2022 at our institute. We used multivariate logistic regression to construct the prediction model and performed a receiver operating characteristic curve analysis to evaluate the ability of SIRI to predict SAP and constructed a calibration curve to evaluate the prediction accuracy of the model. We evaluated the clinical application value of the nomogram using decision curve analysis. Results We included 84 eligible patients with AIS in the analysis, among which 56 (66.7%) had SAP. In the univariate analysis, there were significant differences in sex (p = 0.035), National Institute of Health Stroke Scale score at admission ≥ 20 (p = 0.019) and SIRI (p

To optimize seasonal influenza control and prevention programs in regions with potentially complicated seasonal patterns. Descriptive epidemiology was used to analyze the etiology of influenza, and chi-square tests were used to compare the epidemic patterns among different influenza virus types and subtypes/lineages. From January 2010 to December 2019, a total of 63,626 ILI cases were reported in Chongqing and 14,136 (22.22%) were laboratory-confirmed influenza cases. The proportions of specimens positive for influenza A and influenza B were 13.32% (8,478/63,626) and 8.86% (5,639/63,626), respectively. The proportion of positive specimens for influenza A reached the highest in winter (23.33%), while the proportion of positive specimens for influenza B reached the highest in spring (11.88%). Children aged 5–14 years old had the highest proportion of positive specimens for influenza. The influenza virus types/subtypes positive was significantly different by seasons and age groups (P

Influenza vaccination is the most cost-effective strategy for influenza prevention. Influenza vaccines have been found to be effective against symptomatic and medically attended outpatient influenza illnesses. However, there is currently a lack of data regarding the effectiveness of inactivated influenza vaccines in Chongqing, China. We conducted a prospective observational test-negative design study. Outpatient and emergency cases presenting with influenza-like illnesses (ILI) and available influenza reverse transcription polymerase chain reaction (RT-PCR) were selected and classified as cases (positive influenza RT-PCR) or controls (negative influenza RT-PCR). A total of 7,307 cases of influenza and 7,905 control subjects were included in this study. The overall adjusted influenza vaccine effectiveness (IVE) was 44.4% (95% confidence interval (CI): 32.5–54.2%). In the age groups of less than 6 years old, 6–18 years old, and 19–59 years old, the adjusted IVE were 32.2% (95% CI: 10.0–48.9%), 48.2% (95% CI: 30.6–61.4%), and 72.0% (95% CI: 43.6–86.1%). The adjusted IVE for H1N1, H3N2 and B (Victoria) were 71.1% (95% CI: 55.4–81.3%), 36.1% (95% CI: 14.6–52.2%) and 33.7% (95% CI: 14.6–48.5%). Influenza vaccination was effective in Chongqing from 2018 to 2022. Evaluating IVE in this area is feasible and should be conducted annually in the future.

Objectives To investigate all pregnancies and analyze the factors influencing pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound (HIFU).Materials and methods A total of 231 patients with adenomyosis who completed HIFU and wished to conceive were enrolled. The symptom improvement and information of pregnancy were recorded during the follow-up period. Factors influencing pregnancy outcomes were analyzed using multivariate regression analysis and survival analysis.Results After HIFU, 100 of 231 (43.3%) patients became pregnant within 96 months, including 77 (77/194, 39.7%) in natural and 23 (23/37, 62.2%) in vitro fertilization and embryo transfer (IVF-ET) pregnancies following gonadotropin-releasing hormone agonist (GnRHa). Among the 108 (46.8%, 108/231) infertile patients (defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse, 40 primary infertility and 68 secondary infertility), 31 (28.7%) became pregnant. At the end of the follow-up, 70 successfully delivered 71 healthy babies. No uterine rupture occurred during pregnancy and delivery. Patients with pelvic adhesion and infertility history had a lower pregnancy chance than that of patients without pelvic adhesion and infertility history (OR < 1, p

B-cell maturation antigen(BCMA)-directed chimeric antigen receptor (CAR)-T-cell therapy has significantly improved the treatment of relapsed or refractory multiple myeloma (MM). Nevertheless, the uncommon phenomenon of biphasic CAR-T cell expansion in vivo and its related severe toxicities have not been methodically described and studied. Herein, we report a case of patients with MM who experienced two CAR-T cell expansion peaks and subsequently developed multiple severe toxicities following BCMA CAR-T cell infusion. The first expansion peak occurred on Day 7, accompanied by grade 3 cytokine release syndrome. The second peak occurred on Day 28, associated with severe immune effector cell-associated hematotoxicity (ICAHT), immune effector-cell associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), and polymicrobial infections. Both ICAHT and IEC-HS were refractory to our standard treatments; however, human umbilical cord mesenchymal stem cell infusion exhibited some efficacy in improving cytopenia. Despite the administration of a broad-spectrum anti-infective regimen, cytomegalovirus viremia remained uncontrollable, resulting in the development of central nervous system infection, neurological symptoms, and ultimately death. Additionally, we also employed high-dimensional 33-color spectral flow cytometry to describe the dynamic changes in immune cell components and functions between the two expansion peaks. Collectively, this case provides novel insights into the biphasic CAR-T expansion and related immune effector cell-associated toxicities.

Obsessional slowness (OS) is characterized by a syndrome of extreme slowness in doing ordinary, day-to-day activities. Several scholars regarded OS as secondary to obsessive compulsive disorder (OCD). Therefore, it is commonly thought to be the consequence of extensive rituals and has been paid minimal attention in its own right. A combination of behavior therapy and aromatherapy are recommended for treatment of this condition. However, the outcome is often frustrating. Reports of surgical management for OS are limited. Patient concerns:She had symptoms characterized by repeated checking and progressive slowness in self-care behavior. Diagnosis:At the age of 19, the patient had the first presentation. The patient was diagnosed with a case of OCD with obsessional slowness according to the International Classification of Diseases and Related Health Problems (ICD-10).Interventions:Considering the lack of a response to pharmacotherapy and cognitive behavioral therapy (CBT), we treated this case with anterior capsulotomy and accumbensotomy. Outcomes: Moderate somnolence, urticaria, juvenile behavior, mild short-term memory impairment and slight nonsense were noted during the first postoperative days. At 10 months, the patient’s OCD symptoms recovered nearly to her preoperative level. The OS symptom also had an obvious rebound at 10 months. Through comprehensive judgment, we decided to choose accumbensotomy. At 9 months after the accumbensotomy, the OCD symptoms started to rebound. Soon after, the OS symptoms also recurred. At the last timepoint of 30 months, the patient’s OCD and OS symptoms had completely rebounded. This time, the patient and parents refused any treatment. Conclusion: This case suggests that OCD with OS, as a special category, might not be suitable for stereotactic neurosurgery. Furthermore, multiple surgeries in this kind of OCD patient should be considered with as much caution as much as possible.

The stability of the surrounding rock is an important engineering challenge for soft rock tunnels. Based on the FLAC3D finite difference numerical simulation software, this paper analyzes the typical area of the Fenghuang Mountain tunnel in the Chuxiong section of the Central Yunnan Water Diversion Project. Three construction methods are implemented: three-bench method, reserved core soil method, and CD method, with two excavation parameters being different lengths of the upper step and heights of the lower step. The whole excavation process of the red layer soft rock tunnel is simulated under four supporting conditions: different bolt lengths, different bolt spacings, different initial support thicknesses, and varying advanced grouting strengths. The results indicate that the CD method has a strong constraint on the vertical displacement of the surrounding rock at the arch, while the reserved core soil method has a better effect on controlling the uplift value, and the three-step method has a better constraint on the horizontal convergence of the surrounding rock at the arch waist. The increase in the distance between the upper and lower steps has a great influence on the horizontal convergence value of the tunnel, and the lower steps have a better inhibition effect on the horizontal convergence value of the surrounding rock at the tunnel arch. The increase in the lining thickness has a significant effect on restraining the deformation of the surrounding rock, and advanced grouting is efficient in enhancing the mechanical parameters of the surrounding rock and reducing the displacement of the surrounding rock. The support optimization engineering application is carried out in the 6# construction branch tunnel of the Fenghuang Mountain tunnel, yielding good results.

IntroductionSensorimotor synchronization (SMS) is the human ability to align body movement rhythms with external rhythmic stimuli. While the effects of rhythmic stimuli containing only temporal information on SMS have been extensively studied, less is known about how spatial information affects SMS performance. This study investigates the neural mechanisms underlying SMS with rhythmic stimuli that include both temporal and spatial information, providing insights into the influence of these factors across different sensory modalities.MethodsThis study compared the effects temporal information and spatial information on SMS performance across different stimuli conditions. We simultaneously recorded the electroencephalogram (EEG), the electromyogram (EMG), and behavioral data as subjects performed synchronized tapping to rhythmic stimuli. The study analyzed SMS performance under conditions including auditory, visual, and auditory-visual motion stimuli (containing both temporal and spatial information), as well as auditory, visual, and auditory-visual non-motion stimuli (containing only temporal information). Specifically, the research examined behavioral data (i.e., mean asynchrony, absolute asynchrony, and variability), neural oscillations, cortico-muscular coherence (CMC), and brain connectivity.ResultsThe results demonstrated that SMS performance was superior with rhythmic stimuli containing both temporal and spatial information compared to stimuli with only temporal information. Moreover, sensory-motor neural entrainment was stronger during SMS with rhythmic stimuli containing spatial information within the same sensory modality. SMS with both types of rhythmic stimuli was found to be dynamically modulated by neural oscillations and cortical-muscular coupling in the beta band (13-30 Hz).DiscussionThese findings provide deeper insights into the combined effects of temporal and spatial information, as well as sensory modality, on SMS performance. The study highlights the dynamic modulation of SMS by neural oscillations and CMC, particularly in the beta band, offering valuable contributions to understanding the neural basis of sensorimotor synchronization.

BackgroundDespite the widespread use in ischemic stroke, cancer, and malnutrition, the predictive ability of serum albumin to globulin ratio (A/G) among patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) remains unknown. This study aimed to determine if serum A/G ratio is associated with the occurrence of delayed cerebral ischemia (DCI) after aSAH.MethodsWe retrospectively viewed the medical records of aSAH patients from 08/2017 to 08/2022. Serum albumin and globulin laboratory test results were collected within 24 hours after admission. Serum A/G were dichotomized based on whether the DCI occurred. Logistic regression was used to determine the predictors of DCI. The relationship between serum A/G and the occurrence of DCI was analyzed with receiver operating characteristic(ROC) curve.ResultsA total of 363 eligible patients with aSAH were included in the study, among which DCI occurred in 87 patients(23.97%). Serum A/G[OR=2.720, 95%CI (1.190-6.270), P=0.018], non-surgical[OR=0.228, 95%CI (0.065-0.621), P=0.008], lactate dehydrogenase[OR=1.004, 95%CI (1.000-1.008), P=0.029], P[OR=0.354, 95%CI (0.130-0.926), P=0.038], plasma fibrinogen[OR=1.266, 95%CI (1.019-1.583), P=0.035] were associated with the occurrence of DCI. ROC showed that serum A/G, non-surgical, LDH, P, plasma fibrinogen could predict the occurrence of DCI in aSAH patients with values 0.575, 0.560, 0.602, 0.571 and 0.539 for serum A/G, non-surgical, LDH, P, plasma fibrinogen, respectively.ConclusionsIn conclusion, serum A/G levels are correlated with DCI in individuals with aSAH, and high serum A/G levels on admission may be associated with the occurrence of DCI.

Abstract The diagnostic value of contrast-enhanced ultrasound combined with ultrasound elastography for benign and malignant thyroid nodules is still controversial, so we used meta-analysis to seek controversial answers. The PubMed, OVID, and CNKI databases were searched according to the inclusion and exclusion criteria. The literature was selected from the establishment of each database to February 2024. The QUADAS-2 tool assessed diagnostic test accuracy. SROC curves and Spearman's correlation coefficient were made by Review Manager 5.4 software to assess the presence of threshold effects in the literature. Meta-Disc1.4 software was used for Cochrane-Q and χ 2 tests, which be used to evaluate heterogeneity, with P-values and I 2 indicating heterogeneity levels. The appropriate effect model was selected based on the results of the heterogeneity test. Stata18.0 software was used to evaluate publication bias. The diagnostic accuracy of contrast-enhanced ultrasound combined with ultrasound elastography for benign and malignant thyroid nodules was evaluated by calculating the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, DOR, and area under the SROC curve. A total of 31 studies included 3811 patients with 4718 nodules were analyzed. There is no heterogeneity caused by the threshold effect, but there is significant non-threshold heterogeneity. Combined diagnostic metrics were: sensitivity = 0.93, specificity = 0.91, DOR = 168.41, positive likelihood ratio = 10.60, and negative likelihood ratio = 0.07. The SROC curve area was 0.97. Contrast-enhanced ultrasound and elastography show high diagnostic accuracy for thyroid nodules, offering a solid foundation for early diagnosis and treatment. Trial registration. CRD42024509462.

Retinal organoids are three-dimensional (3D) microscopic tissues that are induced and differentiated from stem cells or progenitor cells in vitro and have a highly similar structure to the retina. With the optimization and development of 3D retinal culture system and the improvement of induced differentiation technology, retinal organoids have broad application prospects in retinal development, regenerative medicine, biomaterial evaluation, disease mechanism investigation, and drug screening. In this review we summarize recent development of retinal organoids and their applications in ophthalmic regenerative medicine. In particular, we highlight the promise and challenges in the use of retinal organoids in disease modeling and drug discovery.

Silver nanowire (AgNW)-based electrodes are susceptible to unstable behavior under external light illumination, humidity, or heat treatment due to their material and structural limitations. To clarify the correlations between the stability of AgNW-based electrodes and their intrinsic factors, AgNW electrodes with PET (polyethylene terephthalate) substrates and AgNW electrodes with PVA (polyvinyl alcohol) substrates were prepared using vacuum filtration and substrate transfer methods. The effects of the intrinsic parameters of AgNW electrodes, including the bonding strength between AgNWs and flexible substrates, AgNW surface densities, and AgNW network connections on the stability of AgNW-based electrodes were investigated. It was found that the stability of AgNW-based electrodes is strongly dependent on the encapsulation of flexible substrates, the surface density of AgNWs, and the curing strength of AgNW network junctions. PVA-AgNW electrodes have much higher stability than PET-AgNWs because PVA substrates can encapsulate AgNWs and protect AgNWs from external damage. Modifying the surface of AgNW electrodes with graphene oxide (GO) can also significantly improve the thermal and light stability of AgNW electrodes because the covering of GO can strengthen the underlying AgNW connecting junctions.

The use of nanoparticles is becoming increasingly apparent in a growing number of medical fields. To exploit the full potential of these particles, it is essential to examine their behavior in the blood and their possible interactions with blood cells. Dendritic core multi-shell DendroSol™ nanoparticles (DS-NPs) are able to penetrate into viable layers of human skin, but nothing is known about their interaction with blood cells. In the present study, we analyze the effect of DS-NPs on red blood cells (RBCs) using confocal laser scanning microscopy (CLSM), flow cytometry, sedimentation rate analysis, spectrophotometry, and hemolysis assays. DS-NPs labeled with Nile red (NR) were added to RBC suspensions and their accumulation in the area of the RBC membranes was demonstrated by CLSM as well as by flow cytometry. In the presence of DS-NPs, the RBCs show an increased sedimentation rate, which also confirms the binding of the NPs to the cells. Interestingly, in the presence of DS-NPs, the RBCs are stabilized against hypotonic hemolysis as well as against the hemolytic action of Triton X-100. This proven anti-hemolytic effect could be utilized to enhance the circulation time of RBCs loaded with drugs for prolonged sustained release and drug delivery with enhanced bioavailability.

Abstract Stimuli‐responsive materials exhibiting exceptional room temperature phosphorescence (RTP) hold promise for emerging technologies. However, constructing such systems in a sustainable, scalable, and processable manner remains challenging. This work reports a bio‐inspired strategy to develop RTP nanofiber materials using bacterial cellulose (BC) via bio‐fermentation. The green fabrication process, high biocompatibility, non‐toxicity, and abundant hydroxyl groups make BC an ideal biopolymer for constructing durable and stimuli‐responsive RTP materials. Remarkable RTP performance is observed with long lifetimes of up to 1636.79 ms at room temperature. Moreover, moisture can repeatedly quench and activate phosphorescence in a dynamic and tunable fashion by disrupting cellulose rigidity and permeability. With capabilities for repeatable moisture‐sensitive phosphorescence, these materials are highly suitable for applications such as anti‐counterfeiting and information encryption. This pioneering bio‐derived approach provides a reliable and sustainable blueprint for constructing dynamic, scalable, and processable RTP materials beyond synthetic polymers.

Background: Mesangial cell (MC)-mediated immune inflammatory injury is a basic pathological process in glomerulonephritis. However, due to the limited drug accumulation and serious adverse effects, it remains challenging to explore a rational delivery system integrating high efficiency and low toxicity to deliver anti-inflammatory drugs to the glomerular MC region. Results: Salvianolic acid B (SAB)-loaded hybrid membrane biomimetic nanovesicles (SAB@HMVs) were developed by fusing erythrocyte membrane nanovesicles with mesenchymal stem cells biomimetic membrane nanovesicles. SAB@HMVs had a spheroidal structure, low cytotoxicity, particle size of 143.83 ± 1.33 nm and exhibited a high drug loading capacity (7.02 %±0.30 %) along with a good sustained release function. The in vitro anti-inflammatory results revealed that HMVs were effectively taken up by MCs and showed significant anti-inflammatory activity. Furthermore, in vivo pharmacodynamic studies revealed that SAB@HMVs could deliver SAB to kidney tissue and elicit an effective anti-inflammatory response to improve the pathological changes in the glomerular mesangial region, significantly reducing the levels of cytokines and alleviating kidney inflammation. Especially, noteworthy was the observation that SAB@HMVs augmented the renal delivery of SAB, downregulated the gene expression of p38 MAPK and NF-κB, inhibited the levels of MMP9 and TNF-α proteins as well as elevated the level of iκB protein, indicating that the anti-inflammatory mechanism of SAB@HMVs should be based on regulating MAPK and NF-κB signaling pathways. Conclusion: We provided a novel strategy to increase nanovesicles accumulation in MCs with the potential to exert anti-inflammatory regulatory effects in glomerulonephritis. Furthermore, this biomimetic hybrid membrane loaded with pure drugs may offer a functional platform to address multiple clinical needs.

For patients with repeated stenosis of autologous arteriovenous fistula, percutaneous transluminal angioplasty (PTA) or bare metal stent placement had limited efficacy. Rapamycin was reported to inhibit neointimal hyperplasia and keep blood vessels patent. In this study, we reported a case with refractory stenosis, i.e., a short duration of patency maintenance after each repeated PTA, which was treated with a rapamycin-eluting stent (RES). The RES extended the patency duration from 4 to 5 months on average to 14 months. The stent was used to maintain dialysis for over 30 months. RES may be an effective way to treat refractory stenosis and salvage limited vascular resources.

ObjectiveSubcutaneous Immunotherapy (SCIT) is the long-lasting causal treatment of allergic rhinitis (AR). How to enhance the adherence of patients to maximize the benefit of allergen immunotherapy (AIT) plays a crucial role in the management of AIT. This study aims to leverage novel machine learning models to precisely predict the risk of non-adherence of AR patients and related local symptom scores in 3 years SCIT.MethodsThe research develops and analyzes two models, sequential latent-variable model (SLVM) of Stochastic Latent Actor-Critic (SLAC) and Long Short-Term Memory (LSTM). SLVM is a probabilistic model that captures the dynamics of patient adherence, while LSTM is a type of recurrent neural network designed to handle time-series data by maintaining long-term dependencies. These models were evaluated based on scoring and adherence prediction capabilities.ResultsExcluding the biased samples at the first time step, the predictive adherence accuracy of the SLAC models is from 60% to 72%, and for LSTM models, it is 66%–84%, varying according to the time steps. The range of Root Mean Square Error (RMSE) for SLAC models is between 0.93 and 2.22, while for LSTM models it is between 1.09 and 1.77. Notably, these RMSEs are significantly lower than the random prediction error of 4.55.ConclusionWe creatively apply sequential models in the long-term management of SCIT with promising accuracy in the prediction of SCIT nonadherence in AR patients. While LSTM outperforms SLAC in adherence prediction, SLAC excels in score prediction for patients undergoing SCIT for AR. The state-action-based SLAC adds flexibility, presenting a novel and effective approach for managing long-term AIT.

Abstract Background CircRNA‐encoded proteins (CEPs) are emerging as new players in health and disease, and function as baits for the common partners of their cognate linear‐spliced RNA encoded proteins (LEPs). However, their prevalence across human tissues and biological roles remain largely unexplored. The placenta is an ideal model for identifying CEPs due to its considerable protein diversity that is required to sustain fetal development during pregnancy. The aim of this study was to evaluate circRNA translation in the human placenta, and the potential roles of the CEPs in placental development and dysfunction. Methods Multiomics approaches, including RNA sequencing, ribosome profiling, and LC‐MS/MS analysis, were utilised to identify novel translational events of circRNAs in human placentas. Bioinformatics methods and the protein bait hypothesis were employed to evaluate the roles of these newly discovered CEPs in placentation and associated disorders. The pathogenic role of a recently identified CEP circPRKCB119aa in preeclampsia was investigated through qRT‐PCR, Western blotting, immunofluorescence imaging and phenotypic analyses. Results We found that 528 placental circRNAs bound to ribosomes with active translational elongation, and 139 were translated to proteins. The CEPs showed considerable structural homology with their cognate LEPs, but are more stable, hydrophobic and have a lower molecular‐weight than the latter, all of which are conducive to their function as baits. On this basis, CEPs are deduced to be closely involved in placental function. Furthermore, we focused on a novel CEP circPRKCB119aa, and illuminated its pathogenic role in preeclampsia; it enhanced trophoblast autophagy by acting as a bait to inhibit phosphorylation of the cognate linear isoform PKCβ. Conclusions We discovered a hidden circRNA‐encoded proteome in the human placenta, which offers new insights into the mechanisms underlying placental development, as well as placental disorders such as preeclampsia. Key points A hidden circRNA‐encoded proteome in the human placenta was extensively identified and systematically characterised. The circRNA‐encoded proteins (CEPs) are potentially related to placental development and associated disorders. A novel conserved CEP circPRKCB119aa enhanced trophoblast autophagy by inhibiting phosphorylation of its cognate linear‐spliced isoform protein kinase C (PKC) β in preeclampsia.

ObjectiveThe appropriate use of statins plays a vital role in reducing the risk of atherosclerotic cardiovascular disease (ASCVD). However, due to changes in diet and lifestyle, there has been a significant increase in the number of individuals with high cholesterol levels. Therefore, it is crucial to ensure the rational use of statins. Adverse reactions associated with statins, including liver enzyme abnormalities and statin-associated muscle symptoms (SAMS), have impacted their widespread utilization. In this study, we aimed to develop a predictive model for statin efficacy and safety based on real-world clinical data using machine learning techniques.MethodsWe employed various data preprocessing techniques, such as improved random forest imputation and Borderline SMOTE oversampling, to handle the dataset. Boruta method was utilized for feature selection, and the dataset was divided into training and testing sets in a 7:3 ratio. Five algorithms, including logistic regression, naive Bayes, decision tree, random forest, and gradient boosting decision tree, were used to construct the predictive models. Ten-fold cross-validation and bootstrapping sampling were performed for internal and external validation. Additionally, SHAP (SHapley Additive exPlanations) was employed for feature interpretability. Ultimately, an accessible web-based platform for predicting statin efficacy and safety was established based on the optimal predictive model.ResultsThe random forest algorithm exhibited the best performance among the five algorithms. The predictive models for LDL-C target attainment (AUC = 0.883, Accuracy = 0.868, Precision = 0.858, Recall = 0.863, F1 = 0.860, AUPRC = 0.906, MCC = 0.761), liver enzyme abnormalities (AUC = 0.964, Accuracy = 0.964, Precision = 0.967, Recall = 0.963, F1 = 0.965, AUPRC = 0.978, MCC = 0.938), and muscle pain/Creatine kinase (CK) abnormalities (AUC = 0.981, Accuracy = 0.980, Precision = 0.987, Recall = 0.975, F1 = 0.981, AUPRC = 0.987, MCC = 0.965) demonstrated favorable performance. The most important features of LDL-C target attainment prediction model was cerebral infarction, TG, PLT and HDL. The most important features of liver enzyme abnormalities model was CRP, CK and number of oral medications. Similarly, AST, ALT, PLT and number of oral medications were found to be important features for muscle pain/CK abnormalities. Based on the best-performing predictive model, a user-friendly web application was designed and implemented.ConclusionThis study presented a machine learning-based predictive model for statin efficacy and safety. The platform developed can assist in guiding statin therapy decisions and optimizing treatment strategies. Further research and application of the model are warranted to improve the utilization of statin therapy.

Addressing the devastating and often irreversible effects of stroke necessitates innovative therapeutic strategies that go beyond the limitations of current treatments. This study heralds a promising interdisciplinary approach by employing LAP/PDA composite nanomaterials integrated into silk fibroin-based hydrogels. These engineered materials not only demonstrated significantly enhanced mechanical properties, but also showed excellent biocompatibility when co-cultured with human mesenchymal stem cells (hMSCs). Importantly, the application of these composite hydrogels in stroke models yielded remarkable therapeutic outcomes. The results indicated a substantial reduction in cerebral infarction volumes, improved survival rates of transplanted hMSCs, and increased neurogenesis, underlining their transformative potential in stroke management. Molecular markers such as AQP4, α-DG, and β-DG were also explored, revealing modulated astrocyte activation and cellular signaling pathways. In summary, the composite LAP/PDA nanomaterials, in conjunction with hMSCs and Brain-Derived Neurotrophic Factor (BDNF), unveil a compelling and multifaceted approach for addressing the unmet needs in stroke treatment, thereby opening new avenues in regenerative medicine and tissue engineering.

Abstract Human cerebellum encompasses numerous neurons, exhibiting a distinct developmental paradigm from cerebrum. Here we conducted scRNA-seq, scATAC-seq and spatial transcriptomic analyses of fetal samples from gestational week (GW) 13 to 18 to explore the emergence of cellular diversity and developmental programs in the developing human cerebellum. We identified transitory granule cell progenitors that are conserved across species. Special patterns in both granule cells and Purkinje cells were dissected multidimensionally. Species-specific gene expression patterns of cerebellar lobes were characterized and we found that PARM1 exhibited inconsistent distribution in human and mouse granule cells. A novel cluster of potential neuroepithelium at the rhombic lip was identified. We also resolved various subtypes of Purkinje cells and unipolar brush cells and revealed gene regulatory networks controlling their diversification. Therefore, our study offers a valuable multi-omics landscape of human fetal cerebellum and advances our understanding of development and spatial organization of human cerebellum.

Superoxide dismutase (SOD) and Catalase (CAT) play a crucial role as the first line of defense antioxidant enzymes in a living cell. These enzymes neutralize the superoxide anion from the autooxidation of oxyhemoglobin (Oxy-Hb) and convert hydrogen peroxides into water and molecular oxygen. In this study, we fabricated hemoglobin submicron particles (HbMPs) using the Coprecipitation Crosslinking Dissolution (CCD) technique and incorporating first-line antioxidant enzymes (CAT, SOD) and second-line antioxidant (ascorbic acid, Vit. C) to investigate a protective effect of modified HbMPs via cyclically oxygenation and deoxygenation. Thereafter, the total hemoglobin (Hb) content and Oxy-Hb content to HbMPs were determined. The results revealed that the HbMPs have a protective effect against oxidation from hydrogen peroxide and potentially neutralizing hydrogen peroxide to water over 16 times exposure cycles. No significant differences in total Hb content were found between normal HbMPs and enzyme-modified HbMPs in the absence of Vit. C. The Oxy-Hb of CAT-HbMPs showed significantly higher values than normal HbMPs. The functional Hb of normal HbMPs and enzyme-modified HbMPs was increased by 60–77% after a short time Vit. C (1:25) exposure. The co-immobilization of CAT and SOD in hemoglobin particles (CAT-SOD-HbMPs) in the presence of Vit. C provides protective effects against oxidation in cyclic Oxygenation and Deoxygenation and shows the lowest reduction of functional Hb. Our studies show that the CCD technique-modified HbMPs containing antioxidant enzymes and a reducing agent (ascorbic acid) demonstrate enhanced Hb functionality, providing protective effects and stability under oxidative conditions.

Silicon carbide-coated carbon fiber-reinforced carbon aerogel (SiC-C/CA) composites are ideal for high-temperature applications due to their ability to endure rapid temperature changes without losing structural integrity. However, assessing and optimizing the Thermal Shock Resistance (TSR) of these composites is challenging due to the complexities in measuring thermal and mechanical responses accurately under rapid fluctuations. Herein, we introduce a novel approach combining the cohesive finite element method (CFEM) with machine learning (ML) to address these challenges. The CFEM simulates crack initiation and propagation and captures mechanical behavior under thermal stress, while ML predicts TSR using simulation datasets, reducing the need for empirical trial-and-error processes. Our method achieves a prediction error for coating residual stress within 15.70% to 24.11% before and after thermal shock tests. Additionally, the ML model, developed to predict the average stiffness degradation factor of the SiC coating after three thermal shock cycles, achieves a coefficient of determination (R2) of 0.9171. This combined approach significantly improves the accuracy and efficiency of TSR assessment and can be extended to other coating materials, accelerating the development of high-temperature-resistant materials with optimized TSR for industrial applications.

Abstract Background A novel CT-linac (kilovolt fan-beam CT-linac) has been introduced into total marrow and lymphoid irradiation (TMLI) treatment. Its integrated kilovolt fan-beam CT (kV FBCT) can be used not only for image guidance (IGRT) but also to re-calculate the dose. Purpose This study reported our clinical routine on performing TMIL treatment on the CT-linac, as well as dose distribution comparison between planned and re-calculated based on IGRT FBCT image sets. Methods 11 sets of data from 5 male and 6 female patients who had underwent the TMLI treatment with uRT-linac 506c were selected for this study. The planning target volumes consist of all skeletal bones exclusion of the mandible and lymphatic sanctuary sites. A planned dose of 10 Gy was prescribed to all skeletal bones exclusion of the mandible in two fractions and 12 Gy in two fractions was prescribed to lymphatic sanctuary sites. Each TMLI plan contained two sub-plans, one dynamic IMRT for the upper body and the other VMAT for the lower extremity. Two attempts were made to obtain homogeneous dose in the overlapping region, i.e., applying two plans with different isocenters for the treatment of two fractions, and using a dose gradient matching scheme. The CT scans, including planning CT and IGRT FBCT, were stitched to a whole body CT scan for dose distribution evaluation. Results The average beam-on time of Planupper is 30.6 min, ranging from 24.9 to 37.5 min, and the average beam-on time of Planlower is 6.3 min, ranging from 5.7 to 8.2 min. For the planned dose distribution, the 94.79% of the PTVbone is covered by the prescription dose of 10 Gy (V10), and the 94.68% of the PTVlymph is covered by the prescription dose of 12 Gy (V12). For the re-calculated dose distribution, the 92.17% of the PTVbone is covered by the prescription dose of 10 Gy (V10), and the 90.07% of the PTVlymph is covered by the prescription dose of 12 Gy (V12). The results showed that there is a significant difference (p 0.05) between planned dose and re-calculated dose on selected organs, except for right lens (p

Hemoglobin-based oxygen carriers (HBOCs) as blood substitutes are one of the great hopes of modern transfusion and emergency medicine. After the major safety-relevant challenges of the last decades seem to be largely overcome, current developments have in common that they are affected by degradation and excretion at an early stage in test organisms. Several possible mechanisms that may be responsible for this are discussed in the literature. One of them is CD163, the receptor of the complex of haptoglobin (Hp) and hemoglobin (Hb). The receptor has been shown in various studies to have a direct affinity for Hb in the absence of Hp. Thus, it seems reasonable that CD163 could possibly also bind Hb within HBOCs and cause phagocytosis of the particles. In this work we investigated the role of CD163 in the uptake of our hemoglobin sub-micron particles (HbMPs) in monocytes and additionally screened for alternative ways of particle recognition by monocytes. In our experiments, blockade of CD163 by specific monoclonal antibodies proved to partly inhibit HbMP uptake by monocytes. It appears, however, that several other phagocytosis pathways for HbMPs might exist, independent of CD163 and also Hb.

Abstract Background The Przewalski's horse (Equus ferus przewalskii) is the only surviving wild horse species in the world. A significant population of Przewalski's horses resides in Xinjiang, China. Parasitosis poses a considerable threat to the conservation of this endangered species. Yet, there is limited information on the nematode parasites that infect these species. To deepen our understanding of parasitic fauna affecting wild horses, we identified the intestinal nematodes of Przewalski’s horses in Xinjiang and added new barcode sequences to a public database. Methods Between 2018 and 2021, nematodes were collected from 104 dewormed Przewalski's horses in Xinjiang. Each nematode was morphologically identified to the species level, and selected species underwent DNA extraction. The extracted DNA was used for molecular identification through the internal transcribed spacer 2 (ITS2) genetic marker. Results A total of 3758 strongylids were identified. To the best of our knowledge, this is the first study to identify four specific parasitic nematodes (Oesophagodontus robustus, Bidentostomum ivashkini, Skrjabinodentus caragandicus, Petrovinema skrjabini) and to obtain the ITS2 genetic marker for P. skrjabini. Conclusions The ITS2 genetic marker for P. skrjabini enriches our understanding of the genetic characteristics of this species and expands the body of knowledge on parasitic nematodes. Our findings extend the known host range of four strongylid species, thereby improving our understanding of the relationship between Przewalski’s horses and strongylids. This, in turn, aids in the enhanced conservation of this endangered species. This study introduces new instances of parasitic infections in wild animals and offers the DNA sequence of P. skrjabini as a valuable resource for molecular techniques in nematode diagnosis among wildlife. Graphical Abstract

ObjectivesAbnormal hippocampal neurodevelopment, particularly in the dentate gyrus region, may be a key mechanism of attention-deficit/hyperactivity disorder (ADHD). In this study, we investigate the effect of the most commonly used Chinese herb for the treatment of ADHD, Rehmanniae Radix Preparata (RRP), on behavior and hippocampal neurodevelopment in spontaneously hypertensive rats (SHR).MethodsBehavior tests, including Morris water maze (MWM) test, open field test (OFT) and elevated plus maze (EPM) test were performed to assess the effect of RRP on hyperactive and impulsive behavior. Hippocampal neurodevelopment was characterized by transmission electron microscopy, immunofluorescence, Golgi staining and Nissl staining approaches. Regulatory proteins such as Trkb, CDK5, FGF2/FGFR1 were examined by Western blot analysis.ResultsThe results showed that RRP could effectively control the impulsive and spontaneous behavior and improve the spatial learning and memory ability. RRP significantly reduced neuronal loss and increased the number of hippocampal stem cells, and promoted synaptic plasticity. In addition, FGF/FGFR signaling was upregulated after RRP treatment.ConclusionRRP can effectively reduce impulsive and spontaneous behavior and ameliorate hippocampal neurodevelopmental abnormalities in ADHD rat model.

Abstract Background The application of coagulation-related markers in laryngeal squamous cell carcinoma(LSCC) remains unclear. This study explored the prognostic role of coagulation markers in the progression and metastasis of LSCC. Methods Coagulation markers of patients with LSCC receiving surgery in the Second Affiliated Hospital of Fujian Medical University in China, from January 2013 to May 2022 were retrospectively analyzed and compared with those of contemporary patients with benign laryngeal diseases. The relationship between clinicopathological features of LSCC and coagulation markers was analyzed with the chi-square and rank sum tests. The ROC curve analysis was utilized to evaluate the diagnostic efficacy of seven coagulation markers for LSCC and its different clinicopathological features, and to find the optimal cutoff value of each coagulation marker. Results 303 patients with LSCC and 533 patients with benign laryngeal diseases were included in the present analysis. Compared to the control group, prothrombin time (PT) (p

Abstract Fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) are key indicators reflecting blood glucose control in type 2 diabetes mellitus (T2DM) patients. The purpose of this study is to establish a predictive model for blood glucose changes in T2DM patients after 3 months of treatment, achieving personalized treatment.A retrospective study was conducted on type 2 diabetes mellitus real-world medical data from 4 cities in Sichuan Province, China from January 2015 to December 2020. After data preprocessing, data inputting, data sampling, and feature screening, 16 kinds of machine learning methods were used to construct prediction models, and 5 prediction models with the best prediction performance were screened respectively. A total of 100,000 cases were included to establish the FBG model, and 2,169 cases were established to establish the HbA1c model. The best prediction model both of FBG and HbA1c finally obtained are realized by ensemble learning and modified random forest inputting, the AUC values are 0.819 and 0.970, respectively. The most important indicators of the FBG and HbA1c prediction model were FBG and HbA1c. Medication compliance, follow-up outcome, dietary habits, BMI, and waist circumference also had a greater impact on FBG levels. The prediction accuracy of the models of the two blood glucose control indicators is high and has certain clinical applicability.HbA1c and FBG are mutually important predictors, and there is a close relationship between them.

Abstract Objective Giant cervical disc herniation (GCDH) was defined as a herniated intervertebral disc that accounted for more than 50% of the spinal canal. The purpose of this study was to analyse the feasibility of anterior cervical discectomy and fusion (ACDF) for the treatment of GCDH. Methods Patient demographic and imaging data, clinical results, and perioperative complications were analysed retrospectively. Results A total of 23 patients were included in the study. Spinal cord recovery pulsation was observed under a microscope in all cases. Postoperative magnetic resonance imaging showed complete decompression of the spinal cord and no residual intervertebral disc. The patients were followed up for 12 to 18 months. The average visual analogue scale score and Neck Disability Index decreased from 8.6 ± 0.5 and 86.0 ± 2.7% to 2.2 ± 0.2 and 26.7 ± 2.0%, respectively, three days after surgery. The average Japanese Orthopedic Association score increased from 6.9 ± 2.1 to 13.9 ± 1.1. The cervical spinal cord function improvement rate was 69.3%. No neurological complications after surgery were observed. Conclusion This study shows that ACDF is feasible for the treatment of GCDH disease. The results indicate that this approach can be used to safely remove herniated disc fragments, effectively relieve compression of the spinal cord, and improve neurological function.

Abstract A drug-loaded diaphragm is an easy-to-use and effective drug delivery system that is often used to treat mouth ulcers. In this study, an ultrafine fiber film loaded with capsaicin was successfully prepared using the electrospinning technology. poly-l-lactic acid and gelatin were selected as the matrix materials to form the composite fiber, and trifluoroethanol was used as a co-solvent for poly-l-lactic acid, gelatin and capsaicin to prepare the spinning solution, which was simple to fabricate. The prepared fiber films were characterized based on their microscopic morphology and tested to derive their mechanical properties. Thereafter, the capsaicin release behavior of the film was investigated. In vitro experiments revealed certain anti-inflammatory and antibacterial abilities while animal experiments revealed that the capsaicin-loaded ultrafine fiber film could promote the healing of oral ulcers in rats. Healing of the tongue tissue in rats administered 10% capsaicin-loaded fiber film was found to be better than that in rats administered the commercial dexamethasone patch. Overall, this development strategy may prove to be promising for the development of oral ulcer patch formulations.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide because of rapid progression and high incidence of metastasis or recurrence. Accumulating evidence shows that CD58-expressing tumor cell is implicated in development of various cancers. The present study aimed to reveal the functional significance of CD58 in HCC progression and the underlying mechanisms. Methods Immunohistochemical staining (IHC), and western blotting were used to detect the expression of CD58 in HCC tissues and cells. The levels of sCD58 (a soluble form of CD58) in the cell supernatants and serum were assessed by ELISA. CCK-8, colony formation, and xenograft assays were used to detect the function of CD58 on proliferation in vitro and in vivo. Transwell assay and sphere formation assay were performed to evaluate the effect of CD58 and sCD58 on metastasis and self-renewal ability of HCC cells. Western blotting, immunofluorescence (IF), TOP/FOP Flash reporter assay, and subcellular fractionation assay were conducted to investigate the molecular regulation between CD58/sCD58 and AKT/GSK-3β/β-catenin axis in HCC cells. Results CD58 was significantly upregulated in HCC tissues. Elevation of CD58 expression correlated with more satellite foci and vascular invasion, and poorer tumor-free and overall survival in HCC patients. Higher sCD58 levels were in HCC patients' serum compared to healthy individuals. Functionally, CD58 promotes the proliferation of HCC cells in vitro and in vivo. Meanwhile, CD58 and sCD58 induce metastasis, self-renewal and pluripotency in HCC cells in vitro. Mechanistically, CD58 activates the AKT/GSK-3β/β-catenin signaling pathway by increasing phosphorylation of AKT or GSK3β signaling, promoting expression of Wnt/β-catenin target proteins and TCF/LEF-mediated transcriptional activity. Furthermore, AKT activator SC-79 or inhibitor LY294002 abolished the inhibitory effect of CD58 silencing on the proliferation, metastasis, and stemness of HCC cells. Conclusions Taken together, CD58 promotes HCC progression and metastasis via activating the AKT/GSK-3β/β-catenin pathway, suggesting that CD58 is a novel prognostic biomarker and therapeutic target for HCC. Graphical Abstract

Abstract Background Preeclampsia is a common pregnancy complication characterized by high blood pressure and damage to organs. Abnormal placenta and vascular function can lead to preeclampsia. Accumulating evidence has suggested a potential link between circular RNAs (circRNAs) and preeclampsia. As a placenta and endothelial-expressed circRNA, hsa_circ_0002348, may be promising to be the novel molecular target for preeclampsia. However, the function and mechanism of hsa_circ_0002348 in preeclampsia has not been elucidated. Materials and methods An overlap analysis of two circRNA profiles from placenta and endothelial cells was used to identify a functionally unknown circRNA, hsa_circ_0002348. Quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH) were used to detect its expression in the trophoblast cells and placental tissues. The mouse model of lipopolysaccharide (LPS)-induced preeclampsia was established to determine the in vivo role of hsa_circ_0002348. RNA immunoprecipitation (RIP), Luciferase reporter assay, qRT-PCR, western blot, gain- and loss-of-function and rescue experiments were conducted to uncover the role of hsa_circ_0002348 and its interaction with miR-126-3p and BAK1 in regulating trophoblast proliferation and apoptosis. Fluorescence in situ hybridization (FISH) and Immunohistochemistry (IHC) were performed to examine the expression of miR-126-3p and BAK1 in mice and human placentas, respectively. Results Hsa_circ_0002348 was significantly increased in the preeclampsia placentas, and positively correlated with the severity of preeclampsia patients’ clinical manifestations. Its overexpression exacerbated preeclampsia-like features in the mouse model of LPS-induced preeclampsia. Functionally, hsa_circ_0002348 was found to inhibit trophoblast proliferation and promote trophoblast apoptosis. Mechanistically, hsa_circ_0002348, as an endogenous miR-126-3p sponge, upregulated the expression of BAK1. Additionally, both hsa_circ_0002348 knockdown and miR-126-3p overexpression enhanced the mammalian target of rapamycin (mTOR) and ERK1/2 signaling pathway. Conclusions Hsa_circ_0002348 might be a novel regulator of trophoblast proliferation and apoptosis through miR-126-3p/BAK1 axis in preeclampsia, which may serve as a potential target for detecting and treating preeclampsia.

Background: Influenza vaccination is essential for type 2 diabetes mellitus (T2DM) patients due to their higher risks of severe complications and mortality from influenza. This study investigated the willingness of T2DM patients in Chongqing, China, to receive the influenza vaccination during the 2023/2024 season, using behavioral and social drivers (BeSD) tools to improve vaccination uptake in this high-risk group. Methods: A multi-stage sampling method was used to select participants, and face-to-face surveys were conducted in community health centers between March 1 and May 1, 2023. Binary logistic regression was used to analyze the factors influencing vaccination willingness, and standardized scores identified barriers and drivers. Results: Among 1672 T2DM patients, 11.7% had been vaccinated during the 2022/2023 season, and 59.6% were willing to receive the vaccination in the 2023/2024 season. Higher willingness was associated with ethnic minorities (odds ratio [OR], 3.18, 95% confidence interval [CI]: 1.58–6.39), being unemployed individuals (OR 2.69, 95% CI: 1.60–4.52), higher monthly household income per capita (OR 2.72, 95% CI: 1.65–4.50), having diabetes complications (OR 1.76, 95% CI: 1.23–2.51), sufficient vaccine knowledge (OR 1.87, 95% CI: 1.48–2.37), and previous vaccination (OR 7.75, 95% CI: 4.83–12.44). Concerning BeSDs, fear of infecting friends or family members and trust in vaccine efficacy were the predominant drivers, while high vaccine costs were the greatest barrier. Conclusions: Future strategies should focus on improving vaccine knowledge, supporting healthcare workers and peer recommendations, and enhancing vaccination policies. Key interventions such as health education among high-risk groups, such as unemployed individuals, advocacy campaigns, pay-it-forward strategies, and policies for free vaccination could improve coverage in Chongqing.

In tight reservoir development, traditional enhanced oil recovery (EOR) methods are incapable of effectively improving oil recovery in tight reservoirs. Given this, inter-fracture flooding is proposed as a new EOR method, and physical model simulation and numerical simulation are performed for inter-fracture water flooding. Compared with inter-fracture water flooding, inter-fracture gas flooding has a higher application prospect. However, few studies on inter-fracture gas flooding have been reported, and its EOR mechanisms and performance are unclear. This paper used the geological model of the actual tight reservoir to carry out numerical simulations for two horizontal wells in the Changqing Yuan 284 block. The results showed that (1) inter-fracture gas flooding can effectively supplement formation energy and increase formation pressure; (2) inter-fracture gas flooding delivers simultaneous displacement, which can effectively increase the swept area in tight reservoirs; (3) injected CO2 dissolves into the reservoir fluid, reduces fluid viscosity, and improves fluid flow through the reservoir; and (4) the recovery factor increment of the CO2 injection is higher than those of natural gas injection and N2 injection. The findings of this research provide references for the production and development of tight reservoirs.

IntroductionMonoclonal antibodies (mAbs) against cytokines and chemokines or their receptors promise to be a potential therapeutic option to address chronic obstructive pulmonary disease (COPD). We aim to provide a comprehensive literature review of the improvement in FEV1 and safety when comparing mAbs with conventional dichotomous agents.MethodsWe systematically searched 3 electronic databases (PubMed, EMBASE, and CENTRAL) up to August 1, 2023 to collect eligible randomized controlled trials (RCTs). A frequentist network meta-analysis using a random-effects model was deployed to calculate mean differences (MD) for FEV1, relative risk (RR) of treatment-emergent adverse events (TEAEs), and estimate the surface under cumulative rankings (SUCRA). A higher SUCRA indicates a better outcome.ResultsThis study included 23 RCTs involving a total of 20,853 patients. Overall, except for Dupilumab, mAbs did not significantly improve FEV1 compared to traditional conventional dichotomous agents. Among all the interventions included, Aclidinium bromide/Formoterol (AB/FF) (SUCRA 97.7%) ranked highest, followed by Umeclidinium/vilanterol (UMEC/VI) (SUCRA 93.5%), and Glycopyrrolate Formoterol Fumarate (GFF) (SUCRA 84.7%). Dupilumab (SUCRA 66.9%) ranked the fourth among all interventions but ranked the first among all the mAbs. Importantly, all mAbs demonstrated a good safety profile compared with placebo.ConclusionConsidering the improvement in FEV1 and its safety, the development of mAbs for COPD still holds significant clinical potential.Systematic review registrationPROSPERO, CRD42023452714.

Extramedullary hematopoiesis (EMH) is a rare condition characterized by proliferation of hematopoietic stem cells outside the bone marrow, usually as a compensatory response to hematological disease. Although EMH primarily occurs in the liver and spleen, it can manifest in atypical locations, such as the mediastinum. We herein describe an asymptomatic 66-year-old man with incidentally discovered posterior mediastinal EMH. A 28- × 32-mm mass was detected during a routine examination. Laboratory findings were within normal limits. Computed tomography revealed a well-defined enhancing mass with a density of 60 Hounsfield units, suggestive of a neurogenic tumor. Surgical resection confirmed EMH, characterized by megakaryocytes and hematopoietic precursors. The patient recovered smoothly and was discharged 5 days postoperatively. Accurate preoperative diagnosis of EMH is challenging, as illustrated by this case. Although typically associated with anemia or hematological abnormalities, EMH can present without such signs. Surgical resection and histopathological examination are essential for diagnosis. This case emphasizes the diagnostic complexity of posterior mediastinal EMH, even in patients without overt hematological disorders. Posterior mediastinal EMH is exceedingly rare and diagnostically demanding. A high index of suspicion and histological tissue analysis are crucial for optimal management. Video-assisted thoracoscopic surgery enables both diagnosis and treatment through mass excision.