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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

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 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 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.

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 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

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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.

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.

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.

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.

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 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.

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.

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

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

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 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 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.

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.

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.

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.

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.

Background. Altered maternal serum lipid metabolism is associated with hypertensive disorders in pregnancy (HDP). However, its range in pregnancy and characteristic among different subgroups of HDPs are unclear. Methods. Pregnant women with HDP who underwent antenatal care and delivered in Obstetrics and Gynecology Hospital of Fudan University during January 2018 to August 2022 were enrolled. The levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), apolipoprotein (Apo)-A, B, and E, free fatty acids (FFA), and small and dense low-density lipoprotein cholesterol (sdLDL) were measured during 4–16 weeks and 28–42 weeks of pregnancy. Results. A total of 2648 pregnant women were diagnosed with HDP, 1,880 of whom were enrolled for final analysis, including 983 (52.3%) preeclampsia (PE), 676 (36.0%) gestational hypertension (GH), and 221 (11.7%) chronic hypertension (CH). For all HDPs, serum TC, TG, LDLC, HDLC, Apo-A, Apo-B, Apo-E, and sdLDL increased significantly during pregnancy, while FFA decreased significantly. Notably, the levels of TC, LDLC, Apo-B, and sdLDL in PE group were equal to or lower than those in CH group at 4–16 weeks of pregnancy, but increased greatly during pregnancy (P

ObjectiveTo investigate the positivity rates and drug resistance characteristics of Mycobacterium tuberculosis (MTB) among suspected tuberculosis (TB) patients in Shandong Province, the second-largest population province in China.MethodsA prospective, multi-center study was conducted from April 2022 to June 2023. Pathogen and drug resistance were identified using nucleotide matrix-assisted laser desorption ionization time-of-flight mass spectrometry (nucleotide MALDI-TOF MS).ResultsOf 940 suspected TB patients included in this study, 552 cases were found to be infected with MTB giving an overall positivity rate of 58.72%. Total of 346 cases were resistant to arbitrary anti-TB drug (62.68%), with Zibo (76.47%), Liaocheng and Weihai (both 69.23%) ranking top three and TB treatment history might be a related factor. Monoresistance was the most common pattern (33.53%), with isoniazid the highest at 12.43%, followed by rifampicin at 9.54%. Further analysis of gene mutations conferring resistance revealed diverse types with high heteroresistance rate found in multiple anti-TB drugs.ConclusionA relatively high rate of MTB positivity and drug resistance was found in Shandong Province during and after the COVID-19 pandemic, indicating the need for strengthening rapid identification of species and drug resistance among suspected TB patients to guide better medication and minimize the occurrence of drug resistance.

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.

Patients with type 2 diabetes mellitus (T2DM) are at higher risk for urinary tract infections (UTIs), which greatly impacts their quality of life. Developing a risk prediction model to identify high-risk patients for UTIs in those with T2DM and assisting clinical decision-making can help reduce the incidence of UTIs in T2DM patients. To construct the predictive model, potential relevant variables were first selected from the reference literature, and then data was extracted from the Hospital Information System (HIS) of the Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital for analysis. The data set was split into a training set and a test set in an 8:2 ratio. To handle the data and establish risk warning models, four imputation methods, four balancing methods, three feature screening methods, and eighteen machine learning algorithms were employed. A 10-fold cross-validation technique was applied to internally validate the training set, while the bootstrap method was used for external validation in the test set. The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to evaluate the performance of the models. The contributions of features were interpreted using the SHapley Additive ExPlanation (SHAP) approach. And a web-based prediction platform for UTIs in T2DM was constructed by Flask framework. Finally, 106 variables were identified for analysis from a total of 119 literature sources, and 1340 patients were included in the study. After comprehensive data preprocessing, a total of 48 datasets were generated, and 864 risk warning models were constructed based on various balancing methods, feature selection techniques, and a range of machine learning algorithms. The receiver operating characteristic (ROC) curves were used to assess the performances of these models, and the best model achieved an impressive AUC of 0.9789 upon external validation. Notably, the most critical factors contributing to UTIs in T2DM patients were found to be UTIs-related inflammatory markers, medication use, mainly SGLT2 inhibitors, severity of comorbidities, blood routine indicators, as well as other factors such as length of hospital stay and estimated glomerular filtration rate (eGFR). Furthermore, the SHAP method was utilized to interpret the contribution of each feature to the model. And based on the optimal predictive model a user-friendly prediction platform for UTIs in T2DM was built to assist clinicians in making clinical decisions. The machine learning model-based prediction system developed in this study exhibited favorable predictive ability and promising clinical utility. The web-based prediction platform, combined with the professional judgment of clinicians, can assist to make better clinical decisions.

Lightweight composite tubes have been widely used in vehicle safety systems as energy absorbers. To improve the crashworthiness of tubes, composite skeletons with a variety of cross-sectional profiles were ingeniously designed as internal reinforcements. Herein, a novel composite skeleton comprising cross-ribs and an inner circle (OS-skeleton) was proposed and integrally fabricated through the special assembling molds. The novel OS-skeleton presented a steady progressive failure mode under dynamic impact loads, leading to remarkable material utilization and energy absorption characteristics. Subsequently, finite element analysis (FEA) models were developed. The predicted response curves and deformation modes were consistent with the experimental results. Finally, a multi-objective optimization utilizing the back propagation neural network (BPNN) was then conducted to further enhance the mean crushing force (MCF) and specific energy absorption (SEA) by adjusting several structural parameters. The results showed that MCF and SEA increased with the increasing thickness of the skeletons and the number of circumferential ribs. By comparison, the diameter of inner tube and the number of circumferential ribs showed a non-linear relationship with the energy absorption characteristics due to their combined effects. In sum, the proposed composite tubes filled with OS-skeletons could maximize certain aspects of crashworthiness performance through proper structural design, demonstrating great potential for lightweight energy absorbers.

AbstractObjectives To evaluate the timing and safety of hysteroscopic myomectomy for large submucosal fibroids pretreated with high intensity focused ultrasound (HIFU).Materials and methods From June 2011 to December 2020, 74 patients with solitary submucousal fibroid with size larger than 4 cm who received HIFU treatment followed by hysteroscopic myomectomy were enrolled.Results The average age of patients was 40.2 ± 6.7 years. Among them, 1 had type 0, 18 had type I and 55 patients had type II submucosal fibroids. The mean diameter of fibroids was 5.7 ± 1.2 cm. All patients completed HIFU in one session, and the median non-perfused volume (NPV) ratio achieved in fibroids was 90.5%. Hysteroscopic myomectomy was performed in 0–1, 1–3, 3–6, and 6–12 months after HIFU. The mean shrinkage rate of fibroids post-HIFU was 68.19 ± 19.86%, 61.10 ± 16.89%, and 63.76 ± 26.68% in 1–3 months, 3–6 months and 6–12 months, respectively. All patients completed hysteroscopic myomectomy successfully, and no intrauterine adhesion after HIFU was observed. The complete resection of fibroids achieved in 69 patients in one session of the procedure. The mean operation time was 66.66 ± 31.61 min, the median blood loss was 20 ml, and the median distention medium deficit was 275 ml. No significant difference was observed in the operation time, blood loss and distention medium deficit among patients who received hysteroscopic myomectomy at different time points (p > 0.05).Conclusions HIFU can be used as a pretreatment for large submucosal fibroids before hysteroscopic myomectomy. Based on our results, hysteroscopic myomectomy could be performed at any time point, even within 1 month after HIFU.

ABSTRACTBackground: Posterior oropharyngeal saliva (POS) is increasingly recognized as an alternative specimen for detecting respiratory pathogens. The accuracy of Xpert® MTB/RIF Ultra (X-Ultra), when performed on POS obtained from patients with paucibacillary pulmonary tuberculosis (TB) is unclear. Methods: We consecutively recruited adults with symptoms suggestive of pulmonary TB who were negative by both smear microscopy and Xpert MTB/RIF (X-Classic). Each participant was required to provide one bronchoalveolar lavage fluid (BALF) and one POS specimen, respectively. Diagnostic performances of X-Ultra and X-Classic on POS were compared against clinical and mycobacterial reference standards. Findings: 686 participants meeting inclusion criteria were consecutively enrolled into the study. The overall diagnostic sensitivities of X-Ultra and X-Classic on POS samples were 78.9% [95% confidence interval (CI): 72.8–83.8] and 56.4% (95% CI: 49.7–62.9), respectively; the specificities were 96.6% (95% CI: 94.3–98.1) for X-Ultra and 97.6 (95CI: 95.5–98.8) for X-Classic in POS specimens. Notably, the sensitivity of X-Ultra on POS was as sensitive as X-Classic on BALF against microbiological reference standard (78.9% VS 73.1%). Against clinical diagnosis as a reference standard, the sensitivities of X-Ultra and X-Classic on POS were 55.9% (95% CI: 50.5–61.2; 193/345) and 40.0% (95% CI: 34.8–45.4; 138/345), respectively. The risk of negative results with POS was dramatically increased with decreasing bacterial loads. Conclusions: The testing of POS using X-Ultra shows promise as a tool to identify patients with paucibacillary TB. Considering that bronchoscopy is a semi-invasive procedure, POS testing ahead of bronchoscopy, may decrease the need for bronchoscopic procedures, and the cost of care.

Abstract Objective This study aims to build a prognostic model of hepatocellular carcinoma (HCC) with ferroptosis-associated genes and explore their molecular function. Methods Gene expression data and clinical information were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and the International Cancer Genome Consortium (ICGC). A ferroptosis-associated gene set was obtained from the FerrDb database to identify differentially expressed genes. Then, we performed pathway enrichment analysis and immune infiltration analysis. A combined model based on ferroptosis-associated genes for predicting the overall survival of HCC was built by univariate and multivariate Cox regression analyses. Quantitative real-time polymerase chain reaction, Western blotting, colony formation, CCK-8, and EdU incorporation assays were performed to clarify the function of CAPG in the regulation of cell proliferation in human HCC. Ferroptosis was evaluated by glutathione (GSH), malondialdehyde (MDA), and total iron detection. Results Forty-nine ferroptosis-related genes were significantly correlated with HCC, 19 of which had prognostic significance. CAPG, SLC7A11 and SQSTM1 were used to construct a novel risk model. The areas under the curves (AUCs) were 0.746 and 0.720 (1 year) in the training and validation groups, respectively. The survival analysis indicated that patients with high risk scores exhibited worse survival in the training and validation groups. The risk score was also identified as an independent prognostic factor of overall survival (OS), which established and validated the predictive abilities of the nomogram. The risk score was also significantly correlated with the expression of immune checkpoint genes. In vitro data showed that CAPG knockdown dramatically suppressed HCC cell proliferation, and the underlying molecular mechanisms might be that the silencing of CAPG reduced the expression of SLC7A11 and promoted ferroptosis. Conclusion The established risk model can be used to predict the prognosis of HCC. At the mechanistic level, CAPG may drive HCC progression by regulating SLC7A11, and ferroptosis activation in HCC patients with high CAPG expression may serve as a potential therapeutic strategy.

Objective: This study aimed to explore the differences in the aroma of watermelon seeds under different thermal processes. Methods: The analysis technics such as Headspace-Solid Phase Micro Extraction-Gas Chromatography-Olfactory-Mass Spectrometry (HS-SPME-GC-O-MS) and Electronic Nose (E-nose) were applied. Results: Thermal processing changed the flavor of watermelon seeds from light fragrance to strong roasted flavor; A total of 18 categories including 115 volatile compounds were detected with the help of HS-SPME-GC-O-MS, among which pyrazines, alcohols and aldehydes accounted for 34.25%, 21.07% and 10.99% of the total volatile compounds, respectively; In addition, 63 volatile compounds were discovered in watermelon seeds after microwave treatment, and pyrazines accounted for 53.31% among all these volatile compounds. Conclusion: Thermal processing treatment showed significant influence on the aroma of watermelon seeds, and the aroma of watermelon seeds after microwave treatment was more intense than air-frying and baking treatment.

Abstract This study aimed to investigate the prognostic impact of lymphovascular and perineural invasions in patients with squamous cell carcinoma of the tongue who received surgery-based treatment at our institution between January 2013 and December 2020. Patients were divided into four groups based on the presence of perineural (P−/P +) and lymphovascular invasions (V−/V +): P–V−, P–V + , P + V−, and P + V + . Log-rank and Cox proportional hazard models were used to evaluate the association between perineural /lymphovascular invasion and overall survival (OS). Altogether, 127 patients were included, and 95 (74.8%), 8 (6.3%), 18 (14.2%), and 6 (4.7%) cases were classified as P–V−, P–V + , P + V−, and P + V + , respectively. Pathologic N stage (pN stage), tumor stage, histological grade, lymphovascular invasion, perineural invasion, and postoperative radiotherapy were significantly associated with OS (p

As SARS-CoV-2 continues to evolve and COVID-19 cases rapidly increase among children and adults, there is an urgent need for a safe and effective vaccine that can elicit systemic and mucosal humoral immunity to limit the emergence of new variants. Using the Chinese Hu191 measles virus (MeV-hu191) vaccine strain as a backbone, we developed MeV chimeras stably expressing the prefusion forms of either membrane-anchored, full-length spike (rMeV-preFS), or its soluble secreted spike trimers with the help of the SP-D trimerization tag (rMeV-S+SPD) of SARS-CoV-2 Omicron BA.2. The two vaccine candidates were administrated in golden Syrian hamsters through the intranasal or subcutaneous routes to determine the optimal immunization route for challenge. The intranasal delivery of rMeV-S+SPD induced a more robust mucosal IgA antibody response than the subcutaneous route. The mucosal IgA antibody induced by rMeV-preFS through the intranasal routine was slightly higher than the subcutaneous route, but there was no significant difference. The rMeV-preFS vaccine stimulated higher mucosal IgA than the rMeV-S+SPD vaccine through intranasal or subcutaneous administration. In hamsters, intranasal administration of the rMeV-preFS vaccine elicited high levels of NAbs, protecting against the SARS-CoV-2 Omicron BA.2 variant challenge by reducing virus loads and diminishing pathological changes in vaccinated animals. Encouragingly, sera collected from the rMeV-preFS group consistently showed robust and significantly high neutralizing titers against the latest variant XBB.1.16. These data suggest that rMeV-preFS is a highly promising COVID-19 candidate vaccine that has great potential to be developed into bivalent vaccines (MeV/SARS-CoV-2).

Polygala crotalarioides, a perennial herbaceous plant found in southwest China, has the potential to be used in the treatment of Alzheimer’s disease. Endophytic fungi that reside within medicinal herbs play an important ecological role in their host plants and can serve as a valuable source for identifying active components. However, little is known about the diversity, and structure of endophytic fungi in P. crotalarioides. In this study, we investigated the community structure and diversity of endophytic fungi in the leaves, stems, and roots of P. crotalarioides at both 1- and 2-year-growth stages using a modern culture-independent method using both culture-independent (high-throughput sequencing, HTS) and culture-based methods. Using HTS, our results revealed that the richness and diversity of endophytic fungi in P. crotalarioides varied depending on the organs and growth stages. Specifically, stems and leaves exhibited significantly higher diversity compared to roots. Additionally, the highest diversity of endophytic fungi was observed in the stems of the 2-year-old plants. At the genus level, Fusarium, Colletotrichum, and Phoma were the most abundant endophytic fungi in 1-year-old samples, while Cercospora, Apiotrichum, and Fusarium were prevalent in 2-year-old samples. A total of 55 endophytic fungal strains belonging to two phyla and 24 genera were isolated from 150 plant tissue segments using culture-based methods. The anti-acetylcholinesterase activity of these isolates was evaluated in vitro and five of them, Phialophora mustea PCAM010, Diaporthe nobilis PCBM027, Fusarium oxysporum LP41, F. oxysporum SR60, and Phoma herbarum SM81, showed strong activity (>50% inhibition rate). These findings will serve as a theoretical basis and practical guide for comprehending the structural composition, biological diversity and bioactivity of endophytic fungi in P. crotalarioides.

Paxlovid (nirmatrelvir/ritonavir) is an antiviral drug used to treat COVID-19, nirmatrelvir, a SARS-CoV-2 main protease inhibitor, works by inhibiting viral replication in the early stages, and ritonavir is a strong cytochrome P450 (CYP) 3A inhibitor that helps the nirmatrelvir reach and maintain the therapeutic concentrations. Paxlovid has a potential risk of drug interaction by elevating the plasma concentration of other drugs metabolized by CYP3A, like tacrolimus. This report examines the case of a 57-year-old female lung transplant patient self-administered Paxlovid for 5 days without discontinuing tacrolimus. She presented to the hospital with symptoms of headache, dizziness, palpitations, abdominal distension, nausea, vomiting, and diarrhea. The patient presented with tacrolimus toxicity and the blood concentration of tacrolimus was measured at 106 ng/mL. Urgent medical intervention was initiated, and Rifampin was administered to induce enzyme activity and rapidly decrease the concentration of tacrolimus. By adjusting the tacrolimus dosage, the final concentration was brought within the appropriate range. Clinical pharmacists should prioritize medication education for transplant patients to prevent severe drug interactions and minimize the impact on the patient’s overall well-being.

IntroductionThe use of magnesium sulfate for treating aneurysmal subarachnoid hemorrhage (aSAH) has shown inconsistent results across studies. To assess the impact of magnesium sulfate on outcomes after aSAH, we conducted a systematic review and meta-analysis of relevant randomized controlled trials.MethodsPubMed, Embase, and the Cochrane Library were searched for relevant literature on magnesium sulfate for aSAH from database inception to March 20, 2023. The primary outcome was cerebral vasospasm (CV), and secondary outcomes included delayed cerebral ischemia (DCI), secondary cerebral infarction, rebleeding, neurological dysfunction, and mortality.ResultsOf the 558 identified studies, 16 comprising 3,503 patients were eligible and included in the analysis. Compared with control groups (saline or standard treatment), significant differences were reported in outcomes of CV [odds ratio (OR) = 0.61, p = 0.04, 95% confidence interval (CI) (0.37–0.99)], DCI [OR = 0.57, p = 0.01, 95% CI (0.37–0.88)], secondary cerebral infarction [OR = 0.49, p = 0.01, 95% CI (0.27–0.87)] and neurological dysfunction [OR = 0.55, p = 0.04, 95% CI (0.32–0.96)] after magnesium sulfate administration, with no significant differences detected in mortality [OR = 0.92, p = 0.47, 95% CI (0.73–1.15)] and rebleeding [OR = 0.68, p = 0.55, 95% CI (0.19–2.40)] between the two groups.ConclusionThe superiority of magnesium sulfate over standard treatments for CV, DCI, secondary cerebral infarction, and neurological dysfunction in patients with aSAH was demonstrated. Further randomized trials are warranted to validate these findings with increased sample sizes.