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Shi-Hua Yan,1,2 Yong Chen,3 Zhi-Qian Huang,1 Wen-Xi Zhong,1 Xiao-Tian Wang,1 Yang-Can Tang,1 Xu-Yi Zhao,1 Yu-Shan Wu,1 Chun Zhou,4 Wei Zhu,5 Wei Xiao,1,6 Xuan Li,2 Dong-Shu Zhang1,2 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 2Department of Traditional Chinese Medicine, The Tenth affiliated Hospital, Southern Medical University (Dongguan People’s Hospital), Dongguan, Guangdong, 523058, People’s Republic of China; 3Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 4School of Pharmaceutical Sciences; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 5Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, People’s Republic of China; 6Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of ChinaCorrespondence: Dong-Shu Zhang, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China, Email nyzds@sina.com Wei Xiao, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of China, Email xw7688@smu.edu.cnPurpose: Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in terms of therapeutic efficacy and mechanism of action is still largely unknown.Methods: This study aimed to evaluate the therapeutic efficacies and action mechanisms of intramuscular injections of autologous whole blood (AWB) and mouse immunoglobulin G (IgG) (autologous or heterologous) at acupoints on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse models. Serum levels of total immunoglobulin E (IgE), IgG, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) were measured, as well as mRNA expression levels of Forkhead box P3 (FoxP3), IL-10 and IFN-γ in dorsal skin lesions, and IL-10+, IFN-γ+ and FoxP3+CD4+T cells in murine spleen.Results: It showed that repeated acupoint injection of AWB, autologous total IgG (purified from autologous blood in AD mice) or heterologous total IgG (purified from healthy blood in normal mice) effectively reduced the severity of AD symptoms and decreased epidermal and dermal thickness as well as mast cells in skin lesions. Additionally, AWB acupoint injection was found to upregulate FoxP3+, IL-10+ and IFN-γ+ CD4+T cells in murine spleen, suppressing the production of IgE antibodies and increasing that of IgG antibodies in the serum. Furthermore, both AWB and autologous total IgG administrations significantly elevated FoxP3 expression, mRNA levels of IL-10 and IFN-γ in dorsal skin lesions. However, acupoint injection of heterologous total IgG had no effect on regulatory T (Treg) and Th1 cells modulation.Conclusion: These findings suggest that the therapeutic effects of A-AHT on AD are mediated by IgG-induced activation of Treg cells.Keywords: autologous whole blood, acupoint injection, atopic dermatitis, anti-idiotypic immunomodulation, Tregs

Objective To systematically evaluate the impact of chronic kidney disease (CKD) on pregnancy outcomes in pregnant patients. Methods Computer searching was conducted within the databases of MEDLINE, EMBASE, WANFANG DATA, China National Knowledge Infrastructure (CNKI) and China Biomedical Literature Database (CBM) from the establishment to July 2023 to identify the relevant literature items on the impact of CKD on pregnancy outcomes in pregnant patients. Two researchers independently screened the literature, extracted data and evaluated the quality of the included studies. Meta-analysis was performed with Review Manager 5.3 and STATA 17.0 software. ResultsA total of 15 case-control and cohort studies, including 2,785,115 subjects, were included for final analysis. The results of Meta-analysis demonstrated the following adverse pregnancy outcomes: CKD elevated the risk of adverse pregnancy outcomes, including preeclampsia (OR=2.68, 95%CI:1.47-4.89), gestational hypertension (OR=6.29, 95%CI:2.58-15.32), preterm birth (OR=4.62, 95%CI:2.78-7.67), small for gestational age (OR=1.54, 95%CI:1.24-1.91) and low birth weight (OR=2.44, 95%CI:1.78-3.35). CKD stage 3-5 patients were more prone to severe preeclampsia (OR=2.31, 95%CI:1.35-3.94), preterm birth (OR=5.06, 95%CI:3.28-7.79), small for gestational age (OR=3.85, 95%CI:1.91-7.76), low birth weight (OR=2.90, 95%CI:1.37-6.13) and fetal mortality (OR=3.41, 95%CI:1.33-8.73) as compared with CKD stage 1-2 counterparts. Pregnant patients with massive proteinuria were more prone to severe preeclampsia (OR=2.76, 95%CI:1.89-4.04), gestational hypertension (OR=2.38, 95%CI:1.62-3.50), preterm birth (OR=3.84, 95%CI:2.69-5.47), low birth weight (OR=2.38, 95%CI:1.62-3.50) and fetal mortality (OR=2.45, 95%CI:1.44-4.17) as compared with those with mild proteinuria. Conclusion CKD elevates the risk of adverse pregnancy outcomes, including preeclampsia, gestational hypertension, preterm birth, small for gestational age and low birth weight. Pregnant patients with CKD stage 3-5 or massive proteinuria (≥1 g) are more prone to adverse pregnancy outcomes as compared with those with CKD stage 1-2 or mild proteinuria (

Abstract Aiming at problems such as slow cutting speed, poor cutting quality and inability to cut thick plates effectively with traditional single-layer nozzle structure, it is proposed to add an outer ring core to form a double-layer nozzle structure on the basis of the single-layer nozzle structure to improve its cutting performance. The three-dimensional entity of single- and double-layer nozzle is established, and the simulation model of auxiliary gas flow field is established by using N-S equation and SST k-ω turbulence model assisted by laser cutting in this paper. The simulation results show that under the same cutting parameters, the auxiliary gas flow rate, oxygen concentration, mass flow rate, shear force and dynamic pressure of the double-layer nozzle structure are higher than those of the single-layer nozzle structure. In addition, compared with the single-layer nozzle structure, the double-layer nozzle structure can effectively improve the attenuation of oxygen concentration in the direction of sheet thickness. Two nozzle structures were used to laser cutting carbon steel plates with a thickness of 20 mm in the experiment, and the experimental parameters of cutting speed were 1.2–1.6 m/min. The comparison results show that the cutting speed and cutting section quality of the double-layer nozzle are better than those of the single-layer nozzle, and the results of simulation analysis are consistent with the cutting test results.

Abstract Notch signaling activation drives an endothelial-to-mesenchymal transition (EndMT) critical for heart development, although evidence suggests that the reprogramming of endothelial cell metabolism can regulate endothelial function independent of canonical cell signaling. Herein, we investigated the crosstalk between Notch signaling and metabolic reprogramming in the EndMT process. Biochemically, we find that the NOTCH1 intracellular domain (NICD1) localizes to endothelial cell mitochondria, where it interacts with and activates the complex to enhance mitochondrial metabolism. Targeting NICD1 to mitochondria induces more EndMT compared with wild-type NICD1, and small molecule activation of PDH during pregnancy improves the phenotype in a mouse model of congenital heart defect. A NOTCH1 mutation observed in non-syndromic tetralogy of Fallot patients decreases NICD1 mitochondrial localization and subsequent PDH activity in heart tissues. Altogether, our findings demonstrate NICD1 enrichment in mitochondria of the developing mouse heart, which induces EndMT by activating PDH and subsequently improving mitochondrial metabolism.

Abstract MEMS gyroscopes are well known for their outstanding advantages in Cost Size Weight and Power (CSWaP), which have inspired great research attention in recent years. A higher signal-to-noise ratio (SNR) for MEMS gyroscopes operating at larger vibrating amplitudes provides improved measuring resolution and ARW performance. However, the increment of amplitude causes strong nonlinear effects of MEMS gyroscopes due to their micron size, which has negative influences on the performance. This paper carries out detailed research on a general nonlinear mechanism on the sensors using parallel-plate capacitive transducers, which is called the gain nonlinearity in electrostatic actuation. The theoretical model established in this paper demonstrates the actuation gain nonlinearity causes the control-force coupling and brings extra angle-dependent bias with the 4th component for the whole-angle gyroscopes, which are verified by the experiments carried out on a micro-shell resonator gyroscope (MSRG). Furthermore, a real-time correction method is proposed to restore a linear response of the electrostatic actuation, which is realized by the gain modification with an online parameter estimation based on the harmonic-component relationship of capacitive detection. This real-time correction method could reduce the 4th component of the angle-dependent bias by over 95% from 0.003°/s to less than 0.0001°/s even under different temperatures. After the correction of actuation gain nonlinearity, the bias instability (BI) of whole-angle MSRG is improved by about 3.5 times from 0.101°/h to 0.029°/h and the scale factor nonlinearity (SFN) is reduced by almost one order of magnitude from 2.02 ppm to 0.21 ppm.

Abstract Background Cardiac arrest presents a variety of causes and complexities, making it challenging to develop targeted treatment plans. Often, the original data are either inadequate or lack essential patient information. In this study, we introduce an intelligent system for diagnosing and treating in-hospital cardiac arrest (IHCA), aimed at improving the success rate of cardiopulmonary resuscitation and restoring spontaneous circulation. Methods To compensate for insufficient or incomplete data, a hybrid mega trend diffusion method was used to generate virtual samples, enhancing system performance. The core of the system is a modified episodic deep reinforcement learning module, which facilitates the diagnosis and treatment process while improving sample efficiency. Uncertainty analysis was performed using Monte Carlo simulations, and dependencies between different parameters were assessed using regular vine copula. The system's effectiveness was evaluated using ten years of data from Utstein-style IHCA registries across seven hospitals in China's Hebei Province. Results The system demonstrated improved performance compared to other models, particularly in scenarios with inadequate data or missing patient information. The average reward scores in two key stages increased by 2.3–9 and 9.9–23, respectively. Conclusions The intelligent diagnosis and treatment effectively addresses IHCA, providing reliable diagnosis and treatment plans in IHCA scenarios. Moreover, it can effectively induce cardiopulmonary resuscitation and restoration of spontaneous circulation processes even when original data are insufficient or basic patient information is missing.

Objective: Discuss the value of Artificial Intelligence (AI) in post-processing head and carotid artery CTA images and diagnosing head and carotid artery stenosis. Methods: The imaging data of 42 patients who all underwent head and neck CTA and digital subtraction angiography (DSA) of head and carotid arteries from November 2022 to October 2023 at our hospital were retrospectively collected. Image post-processing and diagnosis were divided into AI and manual groups to compare the differences in image post-processing time and subjective scores of image quality and identification of head and carotid artery plaque properties (calcified plaque, non-calcified plaque and mixed plaque) between the two groups. To compare the differences in sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the two groups in diagnosing head and neck artery stenosis, using DSA results as the gold standard, and to perform the Kappa test for consistency between the two groups’ diagnostic results and DSA results. The diagnostic efficacy of the AI and manual groups on the head and carotid artery stenosis was analyzed by subject operator characteristic curve (ROC) and compared by Z-test. Results: The post-processing and diagnostic time in the AI group was (366.48±18.54) s, which was approximately 71.65% shorter than that in the manual group (1291.63±52.27) s. The difference was statistically significant. The difference between the subjective scores of image quality obtained by the two methods was not statistically significant. A total of 145 head and neck artery plaques were identified in the manual group and 145 in the AI group, of which 141 plaques of different nature were accurately identified in the AI group, with an overall accuracy rate of 97.24% (141/145). There was no statistically significant difference between the AI group and the manual group for identifying calcified plaque, non-calcified plaque and mixed plaque in the head and carotid arteries, and the agreement between the two groups for identifying the nature of plaque was good (Kappa=0.845). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the AI group in diagnosing head and neck artery stenosis were 87.09% (27/31), 81.82% (9/11), 93.10% (27/29), 69.23% (9/13) and 85.71% (36/42), respectively, which were in good agreement with DSA in diagnosing head and neck artery stenosis (Kappa= 0.792). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the manual group in diagnosing head and neck artery stenosis were 90.32% (28/31), 81.82% (9/11), 93.33% (28/30), 75.00% (9/12) and 88.10% (37/42), respectively, which were in good agreement with DSA in diagnosing head and neck artery stenosis (Kappa=0.801), and the difference in diagnostic efficacy was not statistically significant in either group. The results of the ROC curve analysis showed that the area under the curve (AUC) for the diagnosis of head and neck artery stenosis was 0.845 and 0.861 in the AI and manual groups, respectively, with no significant difference. Conclusion: AI technology has high clinical value in time spent on post-processing head and neck CTA images, assessing head and neck artery stenosis and identifying the nature of carotid plaque, and can be used as a useful aid for physicians in analyzing and diagnosing head and neck CTA.

Objective To analyze three-dimensional(3D) radiographic characterizations of bone island(BI) in jaw using cone-beam computed tomography(CBCT). Methods CBCT data from four thousand patients were selected, reconstructed and analyzed using NNT 10.0 software. The sagittal, coronal and axial planes were used to analyze the 3D radiographic characteristics of BIs, including the localization, shape, density, boundary, the relationship between BIs and tooth and bone cortex, diameter and anatomical structures and complications involved. Their relationship with gender were analyzed. Results A total of 803 people had BIs, with the prevalence rate of 20.08%, including 338 males with 389 BIs and 465 females with 526 BIs. Both males and females had a dominant BI, and the ratio between male and female was 1∶1.38, but the difference was not statistically significant(P>0.05). The BIs of both male and female mostly occurred in the mandibular premolars and molars area, and appeared irregular in shape, dense and contact with lingual bone cortex. Mostly BIs were apical type and with unclear boundary. The mean maximum diameter of mesial/distal direction was greater than buccal/lingual direction(P

Abstract Asthma is a complex chronic respiratory inflammatory disease affected by both genetic and environmental factors. Therefore, our study explored the influence of TRIM11 on asthma and its underlying mechanisms. Our research involved patients diagnosed with asthma and healthy volunteers recruited from our hospital. We observed a reduction in serum TRIM11 expression in asthma patients, which positively correlated with the levels of anti-IgE or IgE. Additionally, both TRIM11 mRNA and protein expression in lung tissue were diminished. The introduction of the TRIM11 gene resulted in a reduction in inflammation in an in vitro asthma model and prevented the development of asthma in a mouse model. Moreover, the TRIM11 gene exhibited a suppressive effect on Ferroptosis and mitigated ROS-induced mitochondrial damage in the asthma model. TRIM11 was found to stimulate UBE2N-TAX1BP1 signaling in the asthma model, with UBE2N being identified as the specific target for TRIM11’s effects on Ferroptosis. Furthermore, TRIM11 protein interacted with UBE2N protein and facilitated the dissociation of UBE2N-UBE2N in the asthma model. In conclusion, TRIM11 plays a vital role in preventing Ferroptosis in the asthma model through UBE2N-TAX1BP1 signaling. This indicates that targeting the TRIM11 mechanism could serve as a promising strategy for anti-Ferroptosis immunotherapy in asthma treatment.

Abstract To analyze the clinical features, epidemiological characteristics, risk factors, and complication characteristics of pulmonary tuberculosis (PTB) combined with extrapulmonary tuberculosis (EPTB) in elderly patients (aged > 60 years). Clinical data were collected from pathogen positive elderly patients with PTB hospitalized in a teaching hospital in Zhejiang from 2017 to 2023. We retrospectively analyzed the risk factors for complications of EPTB in elderly patients with PTB by univariate and multivariate logistic regression models. We also described the characteristics of complications in PTB with EPTB. A total of 781 PTB elderly patients were enrolled, of whom 86 (11.01%) had complicated EPTB. The most commonly invasive sites for EPTB were thoracic spine (17.53%), cervical lymph nodes (13.40%), and meninges (12.37%). 60

Abstract Background To evaluate the feasibility and safety of the superficial circumflex iliac perforator flap (SCIP) for maxillary reconstruction with intraoral anastomosis, pedicle elongation, and super-microsurgery techniques to overcome its anatomical shortcomings due to the attractive merits of the flap. Methods Patients who underwent reconstruction of maxillary defects with SCIPs from July 2020 to December 2022 were included. Intraoral anastomosis, pedicle elongation, and super-microsurgery were performed during surgery with or without a neck incision. The sizes, pedicle lengths, inner calibres of vessels, complications and flap survival statuses were recorded. Results A total of 12 patients were included, with 3 males and 9 females, and the median age was 45 years, ranging from 14 to 74 years. There were 5 class IIa and 7 class IIb defects, 6 cases underwent maxillary defect reconstruction via SCIPs with intraoral anastomosis, and the other 6 cases with distally design and/or de-epidermis pedicle elongation. Super-microsurgery interventions were needed in 5 patients. The size ranged from 3 cm×4 cm to 6 cm×8 cm. The pedicle length ranged from 4 cm to 12 cm, with a median of 6 cm. The inner caliber of the arteries ranged from 0.7 mm to 2 mm, with a median of 1 mm, and the veins ranged from 1.5 mm to 4 mm, with a median of 2.5 mm. All the flaps survived, and no donor site complications occurred. Conclusion Superficial circumflex iliac perforator flaps can be regarded as feasible and safe choices for maxillary defects with the support of intraoral anastomosis, pedicle elongation and super-microsurgery.

Polydiacetylene (PDA) liposomes have been widely applied for detection due to their distinctive optical properties. However, the liquid phase in which PDA liposomes are dispersed generates several drawbacks, for instance, instability, compromise of detection sensitivity induced by dilution, and separation of target sampling and detection, making it inconvenient for application. In this paper, various functionalized PDA liposomes for detecting target were prepared, which were also immobilized into swelling microneedles to construct a solid-phase detection system. The PDA liposomes-complexed microneedles (PDA/MNs) enable the integration of target sampling and detection in one platform. The effects of the dispersing matrix phase on the detection sensitivity of PDA liposomes were systematically investigated from both environmental and chemical perspectives. PDA/MNs exhibited higher sensitivity than their counterparts in liquid phase. PDA/MNs were optimized and validated for lead ion (Pb2+) and sialic acid (SA) detections. For Pb2+ detection, the limit of detection (LOD) of the PDA/MNs was 13.7 μM and 2.5 times lower than the liquid phase. For SA detection, the LOD of the PDA/MNs was 0.83 μM and 1.7 times lower than the liquid phase. The results suggested that such PDA/MNs were validated to provide a label-free, stable, sensitive, and convenient tool in an all-in-one manner for physiologic target detection.

The effects of Cr on the microstructure of as-cast Al-Cu-Mg-Ag alloys and the distribution， size and number density of dispersoids after double-stage homogenization were investigated by OM， XRD， SEM-EDS and TEM methods. The effects of Cr on the dynamic recrystallization behavior of Al-Cu-Mg-Ag alloys under different equivalent strain were studied by high-throughput isothermal compression experiments. The results show that spherical Al7（Cr， Mn） dispersoids with average diameter and number density of 67.4 nm and 4.7 μm－2 are precipitated during the homogenization process， in addition to the rod-like T-Al20Cu2Mn3 dispersoids. The opposite equilibrium distribution coefficient of Cr and Mn （KMn1） reduces the area fraction of dispersoid-free zones from 29.5% to 13.8%， the average length of rod-like T-Al20Cu2Mn3 decreases from 275.4 nm to 147.3 nm， and its number density increases from 3.5 μm－2 to 10.4 μm－2. EBSD and tensile test results indicate that the Al7（Cr， Mn） dispersoids hinder the dislocation movement， reducing the transition from low-angle grain boundaries to high-angle grain boundaries during thermal compression， and inhibiting the dynamic recrystallization. The addition of Cr increases the mechanical properties of Al-Cu-Mg-Ag alloys at different temperatures， and the yield strength contributions of Al7（Cr， Mn） dispersoids to the alloys at 25，250 ℃ and 300 ℃ are 21.9，16.2 MPa and 15.3 MPa， respectively.

Abstract Evidences regarding the feasibility of transcatheter arterial chemoembolization (TACE)-based therapy for unresectable hepatocellular carcinoma (uHCC) remains limited. This study aimed to investigate the efficacy and safety of TACE combined with envafolimab and lenvatinib for uHCC. Eligible patients with uHCC received envafolimab and lenvatinib after TACE until disease progression, conversion to surgery, intolerable toxicities, or death. The primary endpoint was the objective response rate (ORR) assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Between March 2022 and July 2022, 38 patients were included for safety analysis, and 36 patients were included for efficacy analysis. As of the data cutoff (13 December 2023), the median follow-up was 16.9 months. The ORR was 50%, and disease control rate (DCR) was 83.3% per RECIST 1.1 (ORR and DCR of both 83.3% per modified RECIST (mRECIST)). The median progression-free survival (PFS) was 7.58 months. Of 36 patients, 17 patients were converted to resectable HCC with a surgical conversion rate of 47.2%, and 16 patients underwent surgery with R0 resection rate of 100%, pathologic complete response (pCR) rate of 31.3%. Overall incidences of treatment-related adverse events (TRAEs) of any grade was 97.4%. Grade ≥ 3 TRAEs were observed in 52.6% patients. No treatment-related deaths occurred. Image mass cytometry (IMC) analysis revealed that combined treatment improved the immune status of the tumor microenvironment, and resident macrophages had the potential to predict efficacy of this treatment. Envafolimab plus lenvatinib and TACE yielded promising survival outcomes and conversion efficiency with a tolerable safety profile. Trial registration Clinical trials: NCT05213221.

Abstract [Objective] The study aims to clone the fructokinase (FRK ) gene of red pitaya (Hylocereus polyrhizus), detect its expression and enzyme activity, and analyze its physiological function in soluble sugar accumulation during fruit development. [Methods] HpFRK1 gene was cloned from ‘Zihonglong’ fruits, and bioinformatics and subcellular localization analysis were carried out. Gene expression was detected by qRT-PCR. Recombinant protein was obtained by E.coli induction and enzyme activity was detected. [Results] The open reading frame (ORF) of HpFRK1 was 993 bp in length, encoding 330 amino acids with a phosphofructokinase type B (pfkB) domain. HpFRK1 had the closest genetic relationship with sugar beet BvFRK, both of which belonged to cytoplasm localized FRKs. HpFRK1 was expressed in different developmental stages of mature stems and fruits. The expression level of HpFRK1 was the highest at 20 days after flowering and the lowest at 30 days after flowering (fruit ripening), and was gradually decreased with fruit development. Subcellular localization assay showed that HpFRK1 was mainly localized in the nucleus and cytoplasm. HpFRK1 recombinant protein specifically catalyzed fructose phosphorylation (K m=11.01 mmol/L). [Conclusion] HpFRK1 specifically catalyzes fructose phosphorylation in the cytoplasm and negatively regulates fruit soluble sugar accumulation during the development of red-fleshed pitaya fruits

Abstract Background Dysphagia, a common complication of acute stroke, is associated with increased mortality and morbidity. Acupuncture, a widely used swallowing therapy in China, has been suggested as an effective therapy for treating Post-Stroke Dysphagia (PSD) by recent meta-analyses and guidelines. The use of resting-state functional Magnetic Resonance Imaging (rs-fMRI) and Diffusion Tensor Imaging (DTI) could explore the change of regional spontaneous neural activity, functional relationships between brain regions, and white matter connectivity patterns after acupuncture intervention for PSD. This trial aims to evaluate the efficacy of acupuncture treatment for PSD and explore its central mechanism by neuroimaging. Methods/design This randomized controlled trial will recruit 40 PSD patients. All patients will be randomized to either the Real Acupuncture (RA) or Sham Acupuncture (SA) group by a ratio of 1:1. All patients will receive immediate acupuncture treatment in the MRI scanning room, followed by four weeks of long-term acupuncture treatment. The primary outcomes are the rs-fMRI and DTI indicators, which will be evaluated after the immediate and long-term acupuncture treatment. The secondary outcomes are the scales that assess the efficacy, including the Functional Oral Intake Scale (FOIS), Water Swallowing Test (WST), Swallowing Quality Of Life Questionnaire (SWAL-QOL), and National Institute of Health Stroke Scale (NIHSS). The modified version of the Massachusetts General Hospital Acupuncture Sensation Scale (M-MASS) and fMRI sensation record table will also be evaluated. Discussion This protocol presents the design of a randomized, single-blind trial that will evaluate the efficacy and explore the neural plasticity of acupuncture treatment for PSD. This trial will deepen our insight into the clinical value of acupuncture for PSD and initially probe into the time-dosage-effect mechanism of acupuncture. Trial registration numbers Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2300067480. This study was registered on 9th January 2023.

Abstract The reduction of adverse environmental effects and the socioeconomic advantages of renewable energy systems promote greater integration of distributed energy systems into the traditional electrical networks. A new type of sharing economy is emerging with the sharing of energy resources to reduce transaction costs by using platform services in the cloud. Given the obstacles posed by the legacy system and various forms of renewable energy integration, Distributed Energy and Micro Grids (DE‐MG) are an efficient means of raising the quality of energy services. Rules for microgrid scalability, maintaining a budget, and security can make this difficult. Consumers are better at receiving the best renewable energy allotment price using a cloud‐based Peer‐to‐Peer (P2P) network. The main objective is to lower the daily energy cost of microgrid power in commercial buildings. In the proposed work, cloud‐based P2P for peer‐Multi Agent System (p‐MAS) optimization techniques are used to reduce system peak and integrated Demand Response (DR) with Energy Management System (EMS) in a commercial MG. To fill knowledge gaps about how various power market architectures and individual decision‐making processes impact local interactions and market outcomes, cloud‐based P2P for Modelling Leveraging Agents (MLA) is used for bill calculation. A performance measure is finally created for cost evaluation and reliability to measure the social benefits of cloud‐based P2P models for exchanging energy. For various price environments and resource types, a comparison between the proposed cloud‐based P2P model with an existing P2P model for exchanging energy is provided. The primary use of a distributed P2P model for exchanging power in a microgrid is to reduce electricity costs and increase grid environment reliability.

To support the "people-centered" chronic disease health management work, Shanghai has developed a community chronic disease health management information system. This system provides an efficient tool for achieving integrated medical care and disease prevention, as well as collaborative management between doctors and patients, through functions such as information registration and management, risk assessment, chronic disease screening, patient evaluation, and categorized follow-up. It delivers comprehensive, precise, and high-quality health management services for various chronic diseases, effectively promoting the implementation of comprehensive chronic disease prevention and control strategies and the transformative development of chronic disease health management services. However, the system currently requires the inclusion of a broader range of chronic diseases and the enhancement of interactive integration between clinic-based doctor follow-ups and home-based self-management. Future improvements may include the integration of additional disease types and the fusion of complex interaction scenarios to continuously adapt to the new situations and challenges in chronic disease prevention and control.

The energy structure, characterized by abundant coal, limited oil, and gas shortages, contributes to China’s prevalent coal consumption. In the context of carbon peaking and carbon neutrality, coal combustion exacerbates environmental pollution, highlighting the urgent need to promote clean and efficient coal use. As coal gasification technology rapidly advances as a pivotal method for achieving cleaner and more efficient coal use, the challenge of effectively managing coal gasification solid waste becomes increasingly important. The substantial carbon content and complex distribution of carbon and inorganic minerals in coal gasification residue hinder its comprehensive use in building materials and mixed combustion processes. Consequently, the primary disposal methods for coal gasification slag remain stacking and landfilling, which waste land resources and pollute the environment. To realize sustainable and eco-friendly development within the coal chemical industry, addressing the efficient disposal of coal gasification slag is of paramount importance. An abundance of aluminum, silicon, and carbon residue resources endows coal gasification slag with immense potential for the production of high-value-added materials, garnering considerable attention from researchers. The inorganic mineral composition of coal gasification slag is rich in silicon oxide, alumina, and iron oxide components, which can be harnessed for synthesizing zeolite, mesoporous silica, and various micro/nano materials. The carbon residue within coal gasification slag exists in a flocculent porous form, exhibiting a certain degree of graphitization and possessing a large specific surface area, thereby facilitating the production of porous carbon materials. Moreover, a strategy of simultaneous use of carbon and ash can be leveraged to prepare carbon–silicon mesoporous and zeolite–carbon composite materials from coal gasification slag. Looking ahead, based on large-scale coal gasification slag consumption through bulk resource use, the high-value utilization path of coal gasification slag must be further explored to increase the added value of the industry. Building upon the understanding of the production process of coal gasification slag, this paper introduces the composition and micromorphology of coal gasification slag while systematically detailing the preparation methods for synthesizing mesoporous silica, porous carbon, carbon–silicon mesoporous composite materials, zeolite, and zeolite–carbon composite materials. Additionally, the paper delves into the applications of functional micro/nano materials derived from coal gasification slag across various domains, such as adsorbents, catalysts, filling materials, supercapacitors, and microwave-absorbing materials. Finally, the existing problems and future development trends of coal gasification slag resource usage are addressed, aiming to provide guidance for the comprehensive use of coal gasification slag.

X-chromosomal genetic markers are frequently employed in forensic parentage determination owing to their distinctive inheritance patterns. The kinship analysis revealed that two sisters who were not identical twins had identical genotypes on the X chromosome, encompassing 36 X-chromosomal short tandem repeats (X-STRs) and 29 X-chromosomal single-nucleotide polymorphisms (X-SNPs) that spanned the whole X chromosome from the p-telomere to the q-telomere. The identical X-STRs and X-SNPs in the daughters could be the result of linkage or a rare chance of occurrence. This highlights the need for careful analysis and interpretation when dealing with X chromosome markers and that in individual cases, even if two women share an allele at each locus, this does not necessarily mean that they are paternal sisters. The likelihood of random concordance due to maternal alleles must be taken into account.

Abstract Aim To investigate the associations between insulin use and diabetic retinopathy (DR), and retinal vascular parameters in type 2 diabetes (T2DM). Methods A total of 6,374 T2DM patients, consisting of 2,231 patients receiving insulin alone and 4143 patients without any hypoglycemic medication, were included in cross-sectional analyses. Among those without DR at baseline, 791 patients were followed for three years in longitudinal analyses. Fundus photography was taken to diagnose DR and calculate central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriolar-to-venular ratio (AVR), and vascular tortuosity. Inverse probability treatment-weighted analyses were performed. Results After adjusting for gender, age, body mass index, blood pressure, blood glucose, T2DM duration, smoking, and alcohol use, insulin users showed a higher risk of DR (odds ratio (OR) = 2.27, 95% confidence interval (95%CI) = 2.08–2.48, P

Abstract Background Multiple system atrophy (MSA) is recognized as an atypical Parkinsonian syndrome, distinguished by a more rapid progression than that observed in Parkinson’s disease. Unfortunately, the prognosis for MSA remains poor, with a notable absence of globally recognized effective treatments. Although preliminary studies suggest that transcranial magnetic stimulation (TMS) could potentially alleviate clinical symptoms in MSA patients, there is a significant gap in the literature regarding the optimal stimulation parameters. Furthermore, the field lacks consensus due to the paucity of robust, large-scale, multicenter trials. Methods This investigation is a multi-center, randomized, double-blind, sham-controlled trial. We aim to enroll 96 individuals diagnosed with MSA, categorized into Parkinsonian type (MSA-P) and cerebellar type (MSA-C) according to their predominant clinical features. Participants will be randomly allocated in a 1:1 ratio to either the TMS or sham stimulation group. Utilizing advanced navigation techniques, we will ensure precise targeting for the intervention, applying theta burst stimulation (TBS). To assess the efficacy of TBS on both motor and non-motor functions, a comprehensive evaluation will be conducted using internationally recognized clinical scales and gait analysis. To objectively assess changes in brain connectivity, functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) will be employed as sensitive indicators before and after the intervention. Discussion The primary aim of this study is to ascertain whether TBS can alleviate both motor and non-motor symptoms in patients with MSA. Additionally, a critical component of our research involves elucidating the underlying mechanisms through which TBS exerts its potential therapeutic effects. Ethics and dissemination All study protocols have been reviewed and approved by the First Affiliated Medical Ethics Committee of the Air Force Military Medical University (KY20232118-F-1). Trial registration Chinese Clinical Trial Registry ChiCTR2300072658. Registered on 20 June 2023.

Abstract Background Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM) and a significant cause of acquired blindness in the working-age population worldwide. Aging is considered as an important risk factor for DR development. Macrophages in aged mice bear typical M2 marker proteins but simultaneously express a pro-inflammatory factor profile. This may explain why the level of intraocular inflammation does not decrease during proliferative diabetic retinopathy (PDR) despite the occurrence of neovascularization and fibrosis (M2 activation). α-Klotho (KL) was originally discovered as a soluble anti-aging factor, which is mainly expressed in kidney tubular epithelium, choroid plexus in the brain and secreted in the blood. However, the role of KL in DR pathophysiology has not been previously reported. Methods Type 1 (streptozotocin [STZ]-induced) and type 2 (a high-fat diet along with a low dose of STZ) diabetic mouse models were established and injected with or without KL adenovirus via the tail vein for 12 weeks. Vldlr−/− mice were injected intravitreally with or without soluble KL protein from P8 to P15. The retinal structure and function were analyzed by electroretinogram and optical coherence tomography. The neovascular lesions were analyzed by retinal flat mount and RPE flat mount. The senescence markers, macrophage morphology, and KL expression levels were detected by immunofluorescence staining. A cell model was constructed using RAW264.7 cells stimulated by 4-hydroxynonenal (4HNE) and transfected with or without KL adenovirus. The senescence-associated secretory phenotypes were detected by qRT-PCR. Senescence was detected by SA-β-Gal staining. Serum, aqueous humor, and vitreous humor KL levels of proliferative diabetic retinopathy (PDR) patients were measured by enzyme‐linked immunosorbent assay. Quantitative proteomics and bioinformatics were applied to predict the change of proteins and biological function after overexpression of KL in macrophages. The effects of KL on the HECTD1 binding to IRS1 were analyzed by bioinformatics, molecular docking, and Western Blot. Results Serum, aqueous humor, and vitreous humor KL levels were lower in patients with PDR than in those with cataracts. KL relieved the retinal structure damage, improved retina function, and inhibited retinal senescence in diabetic mice. KL administration attenuated the neovascular lesions in VLDLR−/− mice by decreasing the secretion of VEGFA and FGF2 from macrophages. KL also protected RAW264.7 cells from 4HNE-induced senescence. Additionally, it inhibited E3 ubiquitin ligase HECTD1 expression in both diabetic mouse peripheral blood mononuclear cells and 4HNE-treated RAW264.7 cells. KL inhibited HECTD1 binding to IRS1 and reduced the ubiquitination of IRS1. Conclusions Macrophage aging is involved in DM-induced retinopathy. KL alleviates DM-induced retinal macrophage senescence by downregulating HECTD1 and decreasing IRS1 ubiquitination and degradation. Meanwhile, KL administration attenuated the neovascular lesions by altering the activation state of macrophages and decreasing the expression of VEGFA and FGF2.

Abstract Background Understanding the role of cytokines in tooth development is critical for advancing dental tissue engineering. Fibroblast growth factor 9 (FGF9) is the only FGF consistently expressed throughout dental epithelial tissue, from the initiation of tooth bud formation to tooth maturation. However, mice lacking Fgf9 (Fgf9 −/− ) surprisingly show no obvious abnormalities in tooth development, suggesting potential compensation by other FGFs. Here we report findings from an Fgf9 S99N mutation mouse model, a loss-of-function mutation with a dominant negative effect. Our study reveals that Fgf9 is crucial for dental epithelial stem cell (DESC) survival and enamel formation. Methods To dissect the role of Fgf9 in tooth development, we performed the micro-CT, histomorphological analysis and gene expression assay in mice and embryos with S99N mutation. In addition, we assessed the effect of FGF9 on the DESC survival and dental epithelial differentiation by DESC sphere formation assay and tooth explant culture. Cell/tissue culture methods, gene expression analysis, specific inhibitors, and antibody blockage analysis were employed to explore how Fgf9 regulates enamel differentiation and DESC survival through both direct and indirect mechanisms. Results The Fgf9 S99N mutation in mice led to reduced ameloblasts, impaired enamel formation, and increased apoptosis in the cervical loop (CL). DESC sphere culture experiments revealed that FGF9 facilitated DESC survival via activating ERK/CREB signaling, without affecting cell proliferation. Furthermore, in vitro tissue culture experiments demonstrated that FGF9 promoted enamel formation in a manner dependent on the presence of mesenchyme. Interestingly, FGF9 stimulation inhibited enamel formation in isolated enamel epithelia and DESC spheres. Further investigation revealed that FGF9 supports DESC survival and promotes amelogenesis by stimulating the secretion of FGF3 and FGF10 in dental mesenchymal cells via the MAPK/ERK signaling pathway. Conclusions Our study demonstrates that Fgf9 is essential for DESC survival and enamel formation. Fgf9 performs as a dual-directional regulator of the dental enamel epithelium, not only inhibiting DESC differentiation into ameloblasts to preserve the stemness of DESC, but also promoting ameloblast differentiation through epithelial-mesenchymal interactions.

Abstract Background “The hidden costs of informal caregiving” is an interdisciplinary concept. While caregivers make a significant contribution to the process of caregiving, they sacrifice their leisure time, and incur risks of dropping out of the job, impaired mental and physical health, and decreased well-being within the context of caregiving. Those invisible sacrifices are often overlooked and described as hidden costs of informal caregiving. However, the conceptualisation of hidden costs of informal caregiving has not yet been clarified and scientifically assessed. The research aimed to clarify the concept of hidden costs of informal caregiving and develop an operational definition. Methods Walker and Avant’s concept analysis was conducted. Databases of CBM, CNKI, WanFang, VIP, PubMed, Embase, CINAHL, Web of Science, MEDLINE, Cochrane Library, Econlit, CINAHL and ProQuest were searched with the term “hidden costs of informal caregiving”. Information about the uses of the concept, defining attributes, model cases, antecedents, consequences and empirical referents of hidden costs of informal caregiving was extracted and synthesized. Results A total of 25 articles were included. The six defining attributes of hidden costs of informal caregiving were identified as including “undertaken by informal caregivers”, “the time costs of caregiving”, “costs of career development” “physical well-being costs”, “mental well-being costs” and “social relationship costs”. Personal characteristics of the caregivers and care recipients, along with caregiving attributes, were among the antecedents. The consequences of hidden costs of informal caregiving resulted in negative influences which included poor quality of life, life-altering decisions, options for the type of care, some degree of economic hardship, decreased compliance with treatment plans and monetary value informal caregivers are willing to pay to be replaced. Conclusion This concept analysis decisively illuminated the hitherto nebulous concept and expanded the contents of hidden costs of informal caregiving, which will foster a deeper appreciation of the invisible cost of caregivers. Moreover, it will provide a reference for the study of the hidden costs of informal caregiving in future, contribute to the development of assessment tools and theoretical models of hidden costs of informal caregiving, and create a basis for designing an evidence-based care program.

AIM: To observe the clinical outcomes of 30-gauge (G) needle-guided 10-0 prolene suture purse-string pupilloplasty for atonic pupil management. METHODS: Eight patients with atonic pupils who underwent suture purse-string pupilloplasty were retrospectively analyzed. Preoperative data and at least 6mo of postoperative data were collected from all the patients. RESULTS: The corrected distance visual acuity (CDVA) before and after surgery was 0.58±0.22 and 0.20±0.10 logMAR, respectively (P=0.002). The pre- and postoperative pupil size was 7.38±0.88 and 3.09±0.71 mm (P=0.000), respectively. The corneal endothelial cell count was 2841±176/mm2 before and 2692±143/mm2 after surgery (P=0.000). No intraoperative or postoperative complications were reported. During the follow-up period of at least 6mo, all treated pupils were centered and generally or nearly round. Furthermore, the patients did not exhibit photophobia, glare, or diplopia. CONCLUSION: This technique is a simple and effective method for pupil reduction.

Background Pseudomonas aeruginosa (P. aeruginosa) is widely distributed in air, soil, and water, human respiratory tract, intestinal tract, and skin. It can induce bloodstream infection, urinary tract infection, gastrointestinal tract infection, respiratory tract infection, etc. Conventional bacterial isolation, culture, and identification are time-consuming, and many false negative results, which cannot meet the needs of precise clinical diagnosis，and proper treatment. This study aims to develop a rapid isothermal amplification assay of Pseudomonas aeruginosa.Methods Specific primers were designed according to the National Center for Biotechnology Information (NCBI) database based on the highly conserved sequence of Pseudomonas aeruginosa virulence factor gene lecA, and a recombinase polymerase amplification (RPA) detection method was established. The sensitivity and specificity were calculated, as well as the collection and processing of clinical samples.Results The thermostatic amplification technique for Pseudomonas aeruginosa established in this paper allows nucleic acid detection within 10 minutes without cross-amplification with other bacterial strains. 27 P. aeruginosa infections were accurately detected in 300 clinical samples.Conclusion The rapid detection system based on thermostatic amplification had shown high sensitivity and specificity in this study, indicated that this method can effectively assist clinical bacterial detection.

ObjectiveTo explore the effect of Xingbi gel nasal drops on rats with allergic rhinitis (AR) based on the nasal mucosa-hippocampus neuroimmune mechanism.MethodsA total of 40 SPF SD rats at postnatal day 21 (PND21) were randomly divided into normal group, model group, traditional Chinese medicine group and western medicine group, with 10 cases in each group. Except for the normal group, the other three groups were sensitized by ovalbumin (OVA) to establish AR animal models. After the model was successfully established, the normal group and model group were both given normal saline nasal drops (50 μL once), the traditional Chinese medicine group was given Xingbi gel nasal drops (50 μL once), and the western medicine group was given budesonide nasal spray (20 μL once), twice a day, and the interventions were continued for 12 days. The AR rat behavioral scoring criteria was used to evaluate rhinitis behavior of rats; Morris water maze test was used to evaluate learning and memory function of rats; enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of immunoglobulin E (IgE) and transforming growth factor-β1 (TGF-β1); hematoxylin-eosin (HE) staining was used to observe pathological changes of nasal mucosa and eosinophil (EOS) count; immunohistochemistry method was used to detect expression levels of non-receptor tyrosine kinases Fyn, substance P (SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) in the hippocampus; and real-time polymerase chain reaction (RT-PCR) was used to detect mRNA transcription levels of Fyn, SP, VIP and NPY in the hippocampus.Results(1) Behavioral scores of rhinitis: compared with the normal group, behavioral scores of rhinitis were significantly higher in the model group, the traditional Chinese medicine group and the western medicine group before treatment (PPPPPPPPPPPPP

This paper summarized the Huolong pot comprehensive moxibustion combined with Chinese herbal medicine wound dressing and TDP electromagnetic wave irradiation in the treatment of stage 4 pressure injuries in a patient with multiple injuries and complete paraplegia. The ward round team consisted of doctor, nurse and rehabilitation therapist was established to comprehensively evaluate the wound condition of the patient. In addition to effective decompression, nutritional support and emotion regulation, Huolong pot comprehensive moxibustion combined with Chinese herbal medicine wound dressing and TDP electromagnetic wave irradiation were carried out to regulate Qi and blood, activate the channels and collaterals, improve the infection control and wound healing of the pressure injuries. (本文总结1例多发伤并完全性截瘫伴4期压力性损伤患者采用火龙罐综合灸联合生肌玉红膏换药、特定电磁波谱(TDP)照射治疗的护理经验。患者入科后由医护康查房小组和压疮小组对伤口进行动态评估, 中医护理小组会诊, 在有效减压、营养支持、情志调护等基础上, 实施火龙罐综合灸联合生肌玉红膏换药、TDP照射中医特色护理, 以温经通络、行气活血、去腐生肌, 控制感染, 促进患者创面愈合。)

Abstract Background Coarctation of the aorta (CoA) is the most common undiagnosed congenital heart defect during prenatal screening. High false positive and false negative rates seriously affect prenatal consultation and postnatal management. The objective of the study was to assess the utility of various measurements to predict prenatal CoA and to derive a diagnostic algorithm. Methods One hundred and fifty-four fetuses with suspected CoA who presented at Fuwai Hospital between December 2017 and August 2021 were enrolled and divided into confirmed CoA cases (n = 47) and false positive cases (n = 107), according to their postnatal outcomes. The transverse aortic arch, isthmus, and descending aorta were measured in the long-axis view of the aortic arch. The angle between the transverse aortic arch (TAO) and the descending aortic arch (DAO) was defined as the TAO-DAO angle and measured in the long axis or sagittal view. Based on the database in GE Voluson E10 and the formula (Z = $$\frac{\text{x}-{\mu }}{\alpha }$$ ), the standard score (Z-score) of the dimensions of the aorta were calculated in relation to the gestational age. The main echocardiographic indices were combined to design a 3-step diagnostic protocol. The TAO-DAO angle was used as the first step in the diagnostic model. The diameter of the transverse arch and the Z-score of the isthmus were the second step. The third-step indices included a Z-score of the transverse arch, diameter of the isthmus, distance from the left subclavian artery (LSA) to left common carotid artery (LCCA), the ratio of isthmus diameter and LSA diameter and ratio of the distances (the distance between the LSA and LCCA to the distance between the right innominate artery and LCCA). The receiver operating characteristic (ROC) curve determined the predictive capability of each diagnostic parameter, and the kappa test determined the diagnostic accuracy of the proposed model. Results The cases with confirmed CoA had thinner transverse arches (1.92 ± 0.32 mm vs. 3.06 ± 0.67 mm, P = 0.0001), lower Z-scores of the isthmus (-8.97 ± 1.45 vs. -5.65 ± 1.60, P = 0.0001), smaller TAO-DAO angles (105.54 ± 11.51° vs. 125.29 ± 8.97°, P = 0.0001) and larger distance between the LSA and LCCA (4.45 ± 1.75 mm vs. 2.74 ± 1.07 mm, P = 0.0001) than the false positive cases. The area under the curve (AUC) was 0.947 (95% CI 0.91–0.98) for the TAO-DAO angle ≤ 115.75°, 0.942 (95% CI 0.91–0.98) for the transverse arch diameter ≤ 2.31 mm, 0.937 (95% CI 0.90–0.98) for the Z-score of the isthmus ≤ -7.5, and 0.975 (95% CI 0.95–1.00) for the 3-step diagnostic protocol with 97.8% sensitivity and 97.2% specificity. The kappa test showed that the model’s diagnostic accuracy was consistent with postnatal outcomes (kappa value 0.936, P = 0.0001). Conclusions The 3-step diagnostic protocol included the three most useful measurements and the additional indices with appropriate cut-off values. The algorithm is useful for the detection of aortic coarctation in fetuses with a high degree of accuracy. Trial registration Retrospectively registered.

This paper proposes an efficient method for acquiring the global solution of the sum of affine ratios problem (SARP) in the reduced outer space. Using equivalence conversions, the original problem was transformed into an equivalent problem. Then, an affine relaxation problem of the equivalent problem was constructed by exploiting linearization techniques. Subsequently, an outcome space branch-and-bound algorithm was proposed, the convergence of the algorithm was proved and the computational complexity was estimated. Finally, numerical examples were presented to demonstrate the effectiveness and feasibility of the presented algorithm.

Abstract Background Melanoma, one of the most lethal forms of skin cancer, has the potential to develop in any area where melanocytes are present. Currently, postoperative recurrence due to the emergence of systemic drug resistance represents a significant challenge in the treatment of melanoma. In this study, terphenyllin (TER), a distinctive inhibitory impact on melanoma cells was identified from the natural p-terphenyl metabolite. This study aimed to elucidate the intrinsic mechanism of this inhibitory effect, which may facilitate the discovery of novel chemotherapeutic agents. Methods A transcriptome sequencing and metabolomic analysis of TER-treated A375 cells was conducted to identify potential pathways of action. The key proteins were knocked out and backfilled using CRISPR-Cas9 technology and molecular cloning. Subsequently, the results of cytosolic viability, LDH release, immunofluorescence and flow cytometry were employed to demonstrate the cell death status of the drug-treated cells. Results The p53 signalling pathway was markedly upregulated following TER treatment, leading to the activation of CASP3 via the intrinsic apoptotic pathway. The activated CASP3 initiated apoptosis, while simultaneously continuing to cleave the GSDME, thereby triggering pyroptosis. The knockout of p53, a key protein situated upstream of this pathway, resulted in a significant rescue of TER-induced cell death, as well as an alleviation of the decrease in cell viability. However, the knockout of key proteins situated downstream of the pathway (CASP3 and GSDME) did not result in a rescue of TER-induced cell death, but rather a transformation of the cells from apoptosis and pyroptosis. Conclusions The induction of apoptosis and pyroptosis in A375 cells by TER is mediated via the p53-BAX/FAS-CASP3-GSDME signalling pathway. This lays the foundation for TER as a potential anti-melanoma drug in the future. It should be noted that CASP3 and GSDME in this pathway solely regulate the mode of cell death, rather than determine whether cell death occurs. This distinction may prove valuable in future studies of apoptosis and pyroptosis.

Abstract Background Effective bone formation relies on osteoblast differentiation, a process subject to intricate post-translational regulation. Ubiquitin-specific proteases (USPs) repress protein degradation mediated by the ubiquitin-proteasome pathway. Several USPs have been documented to regulate osteoblast differentiation, but whether other USPs are involved in this process remains elusive. Methods In this study, we conducted a comparative analysis of 48 USPs in differentiated and undifferentiated hFOB1.19 osteoblasts, identifying significantly upregulated USPs. Subsequently, we generated USP knockdown hFOB1.19 cells and evaluated their osteogenic differentiation using Alizarin red staining. We also assessed cell viability, cell cycle progression, and apoptosis through MTT, 7-aminoactinomycin D staining, and Annexin V/PI staining assays, respectively. Quantitative PCR and Western blotting were employed to measure the expression levels of osteogenic differentiation markers. Additionally, we investigated the interaction between the USP and its target protein using co-immunoprecipitation (co-IP). Furthermore, we depleted the USP in hFOB1.19 cells to examine its effect on the ubiquitination and stability of the target protein using immunoprecipitation (IP) and Western blotting. Finally, we overexpressed the target protein in USP-deficient hFOB1.19 cells and evaluated its impact on their osteogenic differentiation using Alizarin red staining. Results USP36 is the most markedly upregulated USP in differentiated hFOB1.19 osteoblasts. Knockdown of USP36 leads to reduced viability, cell cycle arrest, heightened apoptosis, and impaired osteogenic differentiation in hFOB1.19 cells. USP36 interacts with WD repeat-containing protein 5 (WDR5), and the knockdown of USP36 causes an increased level of WDR5 ubiquitination and accelerated degradation of WDR5. Excessive WDR5 improved the impaired osteogenic differentiation of USP36-deficient hFOB1.19 cells. Conclusions These observations suggested that USP36 may function as a key regulator of osteoblast differentiation, and its regulatory mechanism may be related to the stabilization of WDR5.

Abstract Plasma homocysteine (Hcy) has been globally recognized as an independent risk factor for various neurovascular diseases. In this study, the authors investigated the relationship between critical Hcy concentration and the risk of rupture in intracranial aneurysms (IAs). This study collected data from 423 patients with both ruptured and unruptured IAs. We compared demographic data, vascular rupture risk factors, and laboratory test results between the two groups. Multivariable logistic regression analysis was employed to determine the correlation between critical plasma Hcy levels and the risk of rupture in small to medium-sized IAs. A total of 330 cases of ruptured intracranial aneurysms (RIA) and 93 cases of unruptured intracranial aneurysms (UIA) were included. Univariate analysis revealed statistically significant differences between the ruptured and unruptured groups in terms of hypertension, hyperlipidemia, plasma Hcy levels, and IA morphology (all P

Abstract The origin of elemental chromium for the archaeological weapons from the pits of Qin terracotta warriors in China has been highly controversial. Although previous studies have highlighted that the chromium on the surface of weapon originated from the contamination of surrounding lacquer, the exact origin of chromium in the lacquer remains unclear. In this work, the measurement by inductively coupled plasma-mass spectrometer (ICP-MS) firstly confirmed that the elemental chromium was indeed contained in the archaeological Qin original lacquer. Nevertheless, the amount of elemental chromium in the Qin lacquer was as low as 0.0759 μg/mg, disclosing that it was impossible to artificially add extra refined chromium-containing substance to the lacquer in the preparation of the terracotta warriors. The soil from the archaeological site of Qin lacquer was found to have a chromium amount of 0.0660 μg/mg by ICP-MS. After the hygrothermal and soil-buried aging cycles for the lab-prepared lacquer, the surface and depth elemental analyses by time of flight-secondary ion mass spectrometer (TOF–SIMS) showed a gradient distribution of elemental chromium from the surface to interior of aged lacquer, indicating the migration and enrichment behavior of elemental chromium from the burial soil towards the lacquer. To explore the migration mechanism of elemental chromium, fluorescence imaging technique was employed in combination with Fourier transform infrared spectrometry (FT-IR) and X-ray photoelectron spectroscopy (XPS) characterizations. The results revealed that catechol-containing fragments were formed during hygrothermal and soil-buried aging of lacquer and consequently coordinated with chromium ions, inducing the migration of elemental chromium towards the lacquer.

A new type of ternesite-ye'elimite (TCSA) cement was prepared with different amounts of ternesite. The effect of the ternesite content on the mechanical properties and hydration products of cement pastes was studied. The influence of the added gypsum content on the performance of TCSA cement was also discussed. The results showed that increasing the contents of ternesite prolonged the setting times of the TCSA clinkers. Increasing the ternesite content promoted the strength development. The increase in the ternesite content caused the lower expansion of the TCSA clinkers. The formation of ettringite, stratlingite and monosulfate was observed in the hydrated clinker pastes. The amount of stratlingite and monosulfate decreased at 28 days, while the formation of ettringite continued to increase due to the hydration of ternesite. The higher added gypsum content increased the compressive strength between 1 and 28 d. However, 15% gypsum was not conducive to the strength development at later ages. In the presence of gypsum, the formation of stratlingite was not observed. A higher gypsum content favoured ettringite precipitation at 1 d, but excess gypsum hindered the ternesite hydration.

In response to the strong multi-solution problem of conventional seismic exploration methods in geological sweet spot prediction of shale， this paper fully explored one-dimensional whole rock analysis data and well logging data， two-dimensional geological data， three-dimensional post-stack seismic data， and five-dimensional offset vector tile （OVT） orientation information. In addition， the paper researched geological sweet spot identification technology of shale based on fuzzy fusion prediction to improve the accuracy of geological sweet spot prediction of shale. Firstly， the approximate distribution direction of faults in the study area and the distribution area of favorable shale lithofacies were statistically analyzed， and the sensitive azimuthal section was selected to stack the OVT data based on azimuth. Then， the fractures on the plane were analyzed based on pre-stack preferred azimuth， and the two-dimensional prediction of favorable shale lithofacies was carried out using a feedforward neural network. Finally， a fuzzy fusion technology based on an improved Sigmoid and Takagi-Sugeno （TS） function was developed， which could weigh the significance of controlling factors in geological sweet spot identification of shale according to their degree of influence and effectively integrate the predicted results of azimuthal anisotropy fractures on the plane with those of neural network-based shale lithofacies， so as to realize decision-making integration for identifying geological sweet spots of shale. This technology has been applied in the classification and grading evaluation of geological sweet spots of shale in the Lower Submember of the 3rd Member of Shahejie formation （Es3U） in Bonan Depression. Areas with poorly developed fractures and unfavorable lithofacies that could interfere with the analysis of geological sweet spots of shale were filtered out. Based on the predictions of fractures and lithofacies， The geological sweet spots of shale in the study area were categorized into three classes. The areas characterized by the superposition of developed fractures and favorable lithofacies were classified as sweet spots of Class I， which showed a high degree of consistency with actual drilling results and achieved notable application effects. The research results indicate that the classification and grading evaluation can be achieved using the geological sweet spot identification technology of shale based on fuzzy fusion prediction， which improves prediction reliability and provides reliable technical support for shale oil exploration.

Polymer solid electrolytes have advantages such as high safety， large flexibility， rich variety and low price， laying the foundation for the industrialization of high energy density lithium metal batteries. However， due to the limitations of interface and other problems， the electrochemical performance of polymer solid electrolytes is still poor. In recent years， the in-situ technology has received more and more attention in the field of electrolyte research and development. In-situ technology represented by in-situ polymerization and in-situ characterization has greatly promoted the research of polymer solid electrolytes. In-situ polymerization improves the electrochemical performance of batteries by optimizing electrode and electrolyte interface， and in-situ characterization can explore the electrochemical mechanism inside battery without damage. The historical development of polymer solid electrolytes and in-situ technology was reviewed in this paper. The development and application of in-situ polymerization in various types of polymer solid electrolytes in recent years were discussed， as well as the use of in-situ characterization in in-situ polymer electrolyte preparation. The in-situ technology has great application prospects in the preparation and the characterization of polymer solid electrolytes was pointed out. Simultaneously， several recommendations about focusing on mechanism research，developing new initiation conditions and reaction are proposed to address the problem of the difficulty in controlling the degree of polymerization and the lack of design of matrix structure in in-situ polymerization.

Abstract Mechanical overloading and aging are two essential factors for osteoarthritis (OA) development. Mitochondria have been identified as a mechano-transducer situated between extracellular mechanical signals and chondrocyte biology, but their roles and the associated mechanisms in mechanical stress-associated chondrocyte senescence and OA have not been elucidated. Herein, we found that PDZ domain containing 1 (PDZK1), one of the PDZ proteins, which belongs to the Na+/H+ Exchanger (NHE) regulatory factor family, is a key factor in biomechanically induced mitochondrial dysfunction and chondrocyte senescence during OA progression. PDZK1 is reduced by mechanical overload, and is diminished in the articular cartilage of OA patients, aged mice and OA mice. Pdzk1 knockout in chondrocytes exacerbates mechanical overload-induced cartilage degeneration, whereas intraarticular injection of adeno-associated virus-expressing PDZK1 had a therapeutic effect. Moreover, PDZK1 loss impaired chondrocyte mitochondrial function with accumulated damaged mitochondria, decreased mitochondrion DNA (mtDNA) content and increased reactive oxygen species (ROS) production. PDZK1 supplementation or mitoubiquinone (MitoQ) application alleviated chondrocyte senescence and cartilage degeneration and significantly protected chondrocyte mitochondrial functions. MRNA sequencing in articular cartilage from Pdzk1 knockout mice and controls showed that PDZK1 deficiency in chondrocytes interfered with mitochondrial function through inhibiting Hmgcs2 by increasing its ubiquitination. Our results suggested that PDZK1 deficiency plays a crucial role in mediating excessive mechanical load-induced chondrocyte senescence and is associated with mitochondrial dysfunction. PDZK1 overexpression or preservation of mitochondrial functions by MitoQ might present a new therapeutic approach for mechanical overload-induced OA.

Abstract Stretchable electronics commonly assemble multiple material modules with varied bulk moduli and surface chemistry on one packaging substrate. Preventing the strain-induced delamination between the module and the substrate has been a critical challenge. Here we develop a packaging substrate that delivers mechanically stable module/substrate interfaces for a broad range of stiff and stretchable modules with varied surface chemistries. The key design of the substrate was to introduce module-specific stretchability and universal adhesiveness by regionally tuning the bulk molecular mobility and surface molecular polarity of a near-hermetic elastic polymer matrix. The packaging substrate can customize the deformation of different modules while avoiding delamination upon stretching up to 600%. Based on this substrate, we fabricated a fully stretchable bioelectronic device that can serve as a respiration sensor or an electric generator with an in vivo lifetime of 10 weeks. This substrate could be a versatile platform for device assembly.

Abstract Objectives The purpose of this study was to investigate the preferred modes of transportation to the hospital among patients with acute stroke and acute myocardial infarction (AMI), as well as to identify the factors that influence the utilization of ambulances. Methods We conducted a cross-sectional study, including patients who were diagnosed with acute stroke and AMI, at the people’s hospital of Zhongjiang, from September 30th, 2022 to August 30th, 2023. All patients were divided into emergency medical service (EMS)-activation group and self-transportation group. Chi-square and t-tests were utilized to discern differences between groups at baseline. To screen relevant variables, we employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis using R package glmnet. Subsequently, we performed a logistic regression analysis to identify predictors of EMS activation according the results of LASSO regression. Results we collected 929 valid questionnaires. 26.16% of the patients required the services of EMS. 90.9% of individuals have not received any formal first aid education. 42.1% of them reported that they had no understanding of cardiovascular and cerebrovascular diseases. Diagnosed as AMI (OR 0.22, 95%CI 0.06 to 0.88) or acute cerebral infarction (OR 0.26, 0.10 to 0.68), the distance between the patient and the nearest 120 network hospital when the patient had these symptoms (OR 0.97, 0.94 to 0.99), the patient’s son or daughter was there when the patient was symptomatic (OR 0.58, 0.37 to 0.94), the patient (OR 0.19, 0.05 to 0.72) and the patient’s partner (wife or husband) (OR 0.36, 0.16 to 0.85) had decided that the patient needed further medical help, Among patients who did not seek immediate help after symptom onset, thinking that the symptoms will disappear spontaneously (OR 0.34, 0.13 to 0.92) or not wanting to disturb others (OR 0.06, 0.01 to 0.66) or believing that they are not important symptoms (OR 0.15, 0.05 to 0.42) were factors independently associated with less ambulance use. Age (OR 1.02, 1.00 to 1.04), Stroke patients have experienced symptoms of disturbance of consciousness or convulsions (OR 2.99, 1.72 to 5.2) were independent factors associated with increased ambulance use. Conclusion There is still ambulance underutilization among patients with acute stroke and AMI in county territory of China. Moreover, it is needed to raise the level of first aid education and awareness about EMS. Additionally, private clinic doctors and the public should gain adequate understanding of the severity of acute stroke and AMI, as well as their common symptoms, the crucial importance of prompt medical intervention. Finally, we propose that all township hospitals should be integrated into the 120 emergency networks and equipped with emergency first aid capabilities, pre-hospital care, and transportation abilities.

Abstract Background Oncology nurses are considered the group with the highest risk for moral distress, compassion fatigue and burnout. Mindful self-care may help oncology nurses improve their well-being and solve psychological problems. However, the investigation and in-depth analysis of mindful self-care among oncology nurses in China is lacking. Objectives To identify heterogeneity groups of oncology nurses on mindful self-care ability and examine the sociodemographic correlation to these profiles. Design Cross-sectional descriptive study. Participants The study was carried out among oncology nurses in two affiliated comprehensive hospitals and one affiliated oncology hospital. A total of 839 oncology nurses were enrolled in this survey. Methods From January to May 2023, a cross-sectional study was carried out among oncology nurses using convenient sampling. The subjects were given the brief Mindful Self-Care Scale (B-MSCS) and the General Demographic Information Questionnaire. Latent profile analysis using the Mplus 7.4 program was used to separate oncology nurses’ mindful self-care into a variety of subgroups. The SPSS 25.0 statistical program was used to analyze the data. One-way ANOVA and the chi-square test were performed to compare the score of B-MSCS in each class and the difference in sociodemographic characteristics among the subgroups. Multinomial logistic regression was used to examine the influence of the sociodemographic variables on each class. Results The total score of the B-MSCS was 76.40 ± 13.19. The support structure dimension had the highest score, with an average mean value of 3.60, and physical care had the lowest score at 2.57. The findings of the latent profile analysis showed that respondents were divided into three classes, moderate mindful self-care(51.2%), low-low mindful relaxation(14.8%), and high-high mindfulness self-awareness(34.0%). Across scale scores and dimensions, three groups demonstrated statistically significant differences (p

Abstract Since 2017, immune checkpoint inhibitors (ICIs) have been available for the treatment of advanced hepatocellular carcinoma (HCC) or unresectable HCC, but their adoption into national medical insurance programs is still limited. Cost-effectiveness evidence can help to inform treatment decisions. This systematic review aimed to provide a critical summary of economic evaluations of ICIs as a treatment for advanced HCC and identify key drivers (PROSPERO 2023: CRD42023417391). The databases used included Scopus, Web of Science, PubMed, Embase, and Cochrane Central. Economic evaluations of ICIs for the treatment of advanced HCC were included. Studies were screened by two people. Of the 898 records identified, 17 articles were included. The current evidence showed that ICIs, including atezolizumab plus bevacizumab, sintilimab plus bevacizumab/bevacizumab biosimilar, nivolumab, camrelizumab plus rivoceranib, pembrolizumab plus lenvatinib, tislelizumab, durvalumab, and cabozantinib plus atezolizumab, are probably not cost-effective in comparison with tyrosine kinase inhibitors or other ICIs. The most influential parameters were price of anticancer drugs, hazard ratios for progression-free survival and overall survival, and utility for health statest. Our review demonstrated that ICIs were not a cost-effective intervention in advanced HCC. Although ICIs can significantly enhance the survival of patients with advanced HCC, decision-makers should consider the findings of economic evaluations and affordability before adoption of new therapies.

Abstract Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), remains a highly lethal malignancy with limited therapeutic options and a dismal prognosis. By targeting the underlying molecular abnormalities responsible for PDAC development and progression, gene therapy offers a promising strategy to overcome the challenges posed by conventional radiotherapy and chemotherapy. This study sought to explore the therapeutic potential of small activating RNAs (saRNAs) specifically targeting the CCAAT/enhancer-binding protein alpha (CEBPA) gene in PDAC. To overcome the challenges associated with saRNA delivery, tetrahedral framework nucleic acids (tFNAs) were rationally engineered as nanocarriers. These tFNAs were further functionalized with a truncated transferrin receptor aptamer (tTR14) to enhance targeting specificity for PDAC cells. The constructed tFNA-based saRNA formulation demonstrated exceptional stability, efficient saRNA release ability, substantial cellular uptake, biocompatibility, and nontoxicity. In vitro experiments revealed successful intracellular delivery of CEBPA-saRNA utilizing tTR14-decorated tFNA nanocarriers, resulting in significant activation of tumor suppressor genes, namely, CEBPA and its downstream effector P21, leading to notable inhibition of PDAC cell proliferation. Moreover, in a mouse model of PDAC, the tTR14-decorated tFNA-mediated delivery of CEBPA-saRNA effectively upregulated the expression of the CEBPA and P21 genes, consequently suppressing tumor growth. These compelling findings highlight the potential utility of saRNA delivered via a designed tFNA nanocarrier to induce the activation of tumor suppressor genes as an innovative therapeutic approach for PDAC.

Background:. Pancreatic fistula after distal pancreatectomy is a common and potentially lethal complication. The optimal closure method for the pancreatic remnant during minimally invasive distal pancreatectomy (MDP) remains unclear. Methods:. Data of consecutive patients who underwent MDP in our institution between July 2018 and June 2021 were collected. The outcomes of MDP with stapler and hand-sewn closure were compared. The primary outcome was clinically relevant postoperative pancreatic fistula (CR-POPF) per the International Study Group of Pancreatic Surgery definition. Results:. Of the 384 patients (stapler closure, 339; hand-sewn closure, 45) enrolled, 249 developed CR-POPF (grades B and C: 242 and 7 patients, respectively). The rates of grade B and grade C POPF in the stapler group were similar to the corresponding rates in the hand-sewn group (64.6% and 1.5% vs 51.1% and 4.4%, P = .078 and P = .223, respectively). No differences between the stapler and hand-sewn groups were observed regarding the median operation time (207 vs 222 minutes, P = .139), incidence of major complications (16.5% vs 20.0%, P = .559), and mortality (0.2% vs 0%, P = 1.000). The independent risk factors of CR-POPF were abdominal abscess, prolonged operation time, and transection site (P = .004, .006, and .001, respectively). Conclusion:. The incidence and severity of CR-POPF by stapler closure of the pancreatic stump were comparable to those associated with hand-sewn closure in MDP in this retrospective cohort. Randomized controlled trials are needed to verify this finding.

Abstract Purpose Since May 2022, Mpox has spread extensively outside of Africa, posing a serious threat to the health of people globally, and particularly to the men who have sex with men (MSM) population. Chongqing, a province in Southwest China, has relatively large MSM and people living with HIV (PLWH) populations, presenting conditions conducive to the wide dissemination of Mpox. In this study, we investigated the clinical characteristics of Mpox patients among MSM and PLWH in Chongqing, aiming to inform the development of targeted prevention, control, and treatment strategies for Mpox. Method We evaluated the clinical characteristics, travel history, time of onset, distribution and number of skin lesions of Mpox patients admitted to the Chongqing Public Health Medical Center between September 2022 and October 2023. Meanwhile, a series of clinical samples were collected and the pathogen of interest was identified as Mpox virus using quantitative polymerase chain reaction (qPCR). The results were presented in the form of cycle thresholds (Ct), which help to approximate the quantification of viral load. Results As of October 11, 2023, the Chongqing Public Health Medical Center reported a total of nine Mpox virus infections. All the patients identified were male and belonged to the MSM population, among whom seven (77.8%) were living with HIV, and maintained a preserved immune system while achieving viral suppression via effective ART. We observed no discernible clinical differences between MSM with Mpox with or without HIV, and no fatalities were recorded. Viral loads were observed to be higher in samples taken from the skin than those from the throat, nasopharynx, blood, or semen. Conclusion In this retrospective study, the clinical manifestations of MPXV infection appeared consistent among MSM patients, regardless of HIV status. Elevated MPXV viral loads in the skin and mucosal tissues, particularly at genital and anal sites, indicate that transmission is more likely to occur via direct physical contact as opposed to respiratory pathways or through exposure to bodily fluids.

Uranium-bearing particle analysis is an important technology in the field of nuclear safeguards. In uranium-related nuclear activities, especially in the processes of uranium enrichment, uranium-bearing aerosols are unavoidable released into the environment. There are significant differences between the uranium particles formed by uranium-bearing aerosols after drying and that from nature in terms of isotopic ratio, elemental composition, and impurity composition. Therefore, we can provide a judgment basis for the monitoring of nuclear facilities and activities by analyzing the characteristic information of micrometer or submicron sized uranium-bearing particle. After nearly 30 years of development, some relatively mature methods for the analysis of uranium-bearing particles have been developed. In this review, the process of particle analysis including sample collection, preliminary screen, particle recovery, identification and localization, and measurement is briefly introduced. The advantages and disadvantages of the commonly used technical in each process are compared. At the same time, according to the different purposes of analysis, uranium-bearing particle analysis is divided into three research directions: uranium isotope analysis, morphology and elemental composition analysis, and age-dating. Recent progress of each direction is discussed. Finally, based on the progress of the research, combined with the Development and Implementation Support Program for Nuclear Verification of the IAEA, the future research direction of uranium-bearing particle analysis technology is prospected.