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Abstract Body composition assessment is very useful for evaluating a patient’s status in the clinic, but recognizing, labeling, and calculating the body compositions would be burdensome. This study aims to develop a web-based service that could automate calculating the areas of skeleton muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) according to L3 computed tomography (CT) images. 1500 L3 CT images were gathered from Xuzhou Central Hospital. Of these, 70% were used as the training dataset, while the remaining 30% were used as the validating dataset. The UNet framework was combined with attention gate (AG), Squeeze and Excitation block (SEblock), and Atrous Spatial Pyramid Pooling (ASSP) modules to construct the segmentation deep learning model. The model’s efficacy was externally validated using two other test datasets with multiple metrics, the consistency test and manual result checking. A graphic user interface was also created and deployed using the Streamlit Python package. The custom deep learning model named L3 Body Composition Segmentation Model (L3BCSM) was constructed. The model’s Median Dice is 0.954(0.930, 0.963)(SATA), 0.849(0.774,0.901)(VATA), and 0.920(0.901, 0.936)(SMA), which is equal to or better than classic models, including UNETR and AHNet. L3BCSM also achieved satisfactory metrics in two external test datasets, consistent with the qualified label. An internet-based application was developed using L3BCSM, which has four functional modules: population analysis, time series analysis, consistency analysis, and manual result checking. The body composition assessment application was well developed, which would benefit the clinical practice and related research.

Abstract In order to prevent leakage of pyrolysed oil and gas and the release of contaminants from the top and bottom strata, it is essential to carry out a comprehensive study of the seepage behaviour of these strata under high temperature triaxial stress conditions. The findings of this study will contribute to the development of effective strategies for the containment and integrity monitoring of subsurface reservoirs and storage environments. Mudstone, serving as both the upper and lower strata, offers an effective barrier due to its inherently low permeability. In order to explore the change rule of mudstone sealing performance under high temperature triaxial stress, an air-heated low permeability rock mass air permeability measurement system is used to measure the ground stress buried 500 m deep and the temperature variation characteristics of mudstone permeability on the roof and floor of Jimsar oil shale in Xinjiang under 100 °C. It was found that the permeability of stressed mudstone decreased with the temperature rising up to 100 °C. The primary factor influencing the outcome was the thermal expansion of the mudstone. The magnitude of the drop value was contingent upon the triaxial stresses that could potentially be induced by the application of significant tensile forces, resulting in a relatively minor drop value. The average hydraulic radius of pore in the mudstone was also calculated, which also exhibited continuous reduction as heating up to 100 °C and the degree of reduction could reach 68%. The capacity, that prevent oil & gas and contaminant from moving cross strata as a barrier, would be strengthened when the mudstone strata from roof and floor experienced the temperature low than 100 °C. The barrier performance of mudstone as a pollutant migration barrier layer to gas pollutant migration during in-situ heat injection mining of oil shale was further evaluated.

Abstract In clinical nursing, neonatal pain assessment is a challenging task for preventing and controlling the impact of pain on neonatal development. To reduce the adverse effects of repetitive painful treatments during hospitalization on newborns, we propose a novel method (namely pain concept-cognitive computing model, PainC3M) for evaluating facial pain in newborns. In the fusion system, we first improve the attention mechanism of vision transformer by revising the node encoding way, considering the spatial structure, edge and centrality of nodes, and then use its corresponding encoder as a feature extractor to comprehensively extract image features. Second, we introduce a concept-cognitive computing model as a classifier to evaluate the level of pain. Finally, we evaluate our PainC3M on various open pain data sets and a real clinical pain data stream, and the experimental results demonstrate that our PainC3M is very effective for dynamic classification and superior to other comparative models. It also provides a good approach for pain assessment of individuals with aphasia (or dementia).

Abstract Accurate detection of asphalt pavement distress is crucial for road maintenance and traffic safety. However, traditional convolutional neural networks usually struggle with this task due to the varied distress patterns and complex background in the images. To enhance the accuracy of asphalt pavement distress identification across various scenarios, this paper introduces an improved model named SMG-YOLOv8, based on the YOLOv8s framework. This model integrates the space-to-depth module and the multi-scale convolutional attention mechanism, while optimizing the backbone’s C2f structure with a more efficient G-GhostC2f structure. Experimental results demonstrate that SMG-YOLOv8 outperforms the YOLOv8s baseline model, achieving P macro and mAP50 scores of 81.1% and 79.4% respectively, marking an increase of 8.2% and 12.5% over the baseline. Furthermore, SMG-YOLOv8 exhibits clear advantages in identifying various types of pavement distresses, including longitudinal cracks, transverse cracks, mesh cracks, and potholes, when compared to YOLOv5n, YOLOv5s, YOLOv6s, YOLOv8n, and SSD models. This enhancement optimizes the network structure, reducing the number of parameters while maintaining excellent detection performance. In real-world scenarios, the SMG-YOLOv8 model, when applied to image data collected from projects, achieves a P macro of 80.5% and an R macro of 86.2%. This result demonstrates its excellent generalization capability and practicality. The model provides significant technical support for the intelligent detection of pavement distress.

"Objective To analyze multimodal ultrasonic characteristics of human epidermal growth factor receptor 2 (HER-2) positive breast cancer patients in different hormone receptor (HR) expression states, so as to provide a reference for the early diagnosis and treatment of HER-2 positive breast cancer. Methods The clinical data of 160 patients with HER-2 positive breast cancer who were diagnosed and treated in the First Affiliated Hospital with Nanjing Medical University and Jurong Peoples Hospital from January 2017 to December 2023 were collected retrospectively. According to immunohistochemical results, patients were divided into HR positive group (n=89) and HR negative group (n=71). General data, pathological characteristics and multimodal ultrasonic characteristics of the two groups were compared. Logistic regression analysis was performed to analyze the relationship between multimodal ultrasonic characteristics and HR expression in HER-2 positive breast cancer. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of multimodal ultrasonic characteristics for HR expression in HER-2 positive breast cancer patients. Results Compared with HR negative group, proportions of routine ultrasound signs (irregular shape, edge anomaly or fuzziness, microcalcification, internal uneven echo) significantly decreased in HR positive group, and proportions of contrast-enhanced ultrasound signs (irregular shape, fuzzy boundary and non-filling defect after enhancement) significantly decreased (P＜0.05). Compared with HR negative group, difference value of lesion diameter in contrast-enhanced ultrasound sign ［(3.29±0.36) mm vs (4.30±0.44) mm, t=15.971, P＜0.01］, elasticity score ［(3.15±0.33) points vs (4.56±0.47) points, t=21.416, P＜0.01］ and hardness ratio ［(0.24±0.04) points vs (0.33±0.05) points, t=12.340, P＜0.01］ in elastography signs significantly decreased in HR positive group. Logistic regression analysis showed that difference value of lesion diameter, elasticity score and hardness ratio after enhancement were closely related to HR expression (P＜0.05). ROC curve analysis showed that the area under the curve of three characteristics of ultrasoud multimodality combined to predict the HR expression status in patients with HER-2 positive breast cancer (0.895) was larger than that of the lesion diameter difference (0.641), elasticity score (0.833) and hardness ratio (0.783) (Z=7.524, 3.405, 4.420, P＜0.05), and the specificity and Youden index of combined prediction were also the highest. Conclusion HR positive expression in patients with HER-2 positive breast cancer is closely related to multimodal ultrasonic characteristics. Multimodal ultrasonic characteristics have a high predictive value for HR positive expression in HER-2 positive patients."

Abstract We present the theory, concept and design of an efficient, megawatt coherent Cherenkov radiation source based on a two-dimensional periodic surface lattice (2D-PSL) cavity combined with a novel energy recovery system for the generation of highly efficient (> 50%) single-frequency radiation. We demonstrate the scalability of the transverse dimension of the 2D-PSL cavity of the Cherenkov source and thus the potential for efficient, continuous-wave, high-power (> 1 MW) operation; fundamental to the eventual realization of clean, fusion energy. These new sources, with the capacity to operate in the 0.1-10THz range, hold strong promise to address the long-standing “Terahertz gap”. By combining a Cherenkov oscillator driven by a non-gyrating beam with an innovative four-stage depressed collector energy recovery system, the overall device efficiency can be increased to be competitive with gyrotrons in the requirements for heating and current drive in fusion plasma. In these Cherenkov devices, the frequency independence of the magnetic guide field enables advantageous frequency scaling without deployment constraints, making them especially attractive for high-impact applications in fusion science, turbulence diagnostics, non-destructive testing and biochemical spectroscopy. The novel energy recovery techniques presented in this paper have broad applicability to many electron-beam driven devices, bringing revolutionary potential to future THz source technologies.

Abstract With the rapid development of Internet of Things (IoT) services, technologies that leverage multimedia computer communication for information sharing in embedded systems have become a research focus. To address the challenges of low spectral efficiency and poor network flexibility in multimedia computer communications, this paper proposes a resource allocation scheme based on parallel Convolutional Neural Network (CNN). The scheme optimizes the base station beamforming vector and the Reconfigurable Intelligent Surface (RIS) phase shifts to maximize the secure transmission rate for cellular users (CUs), while ensuring normal and secure communication for device-to-device (D2D) users. First, to mitigate interference caused by D2D users reusing CU spectrum resources, the RIS phase shifts and beamforming vectors are optimized to suppress interference and enhance system secrecy rates. Second, to maximize the CU secrecy rate, the paper proposes a parallel CNN-based resource allocation model that considers base station transmission power, RIS reflection coefficients, and D2D communication rate constraints, incorporating multi-scale residual modules in the convolutional layers of the model. Simulation results demonstrate that the proposed CNN-based resource allocation scheme significantly improves the secrecy rate of embedded system communications, ensuring secure multimedia computing, and outperforms traditional methods.

Abstract Aiming at the requirements of strong mobility and high flexibility of rescue and relief mobile pump trucks, this paper designs a new type of mobile pump truck frame based on existing mobile vehicle frame models. The materials used for the frame are 40Cr and Q235, and the finite element method is utilized to carry out static mechanical analysis and dynamic characteristic analysis. Simultaneously utilizing topology optimization and multi-objective genetic algorithm to optimize the design of the frame structure. The results show that the optimized pump truck frame can meet the strength design requirements of four typical working conditions: full load bending, full load torsion, emergency turning and emergency braking, while avoiding resonance phenomena caused by road surface and diesel engine vibration. Compared with the original frame model, the weight of the optimized frame is reduced by 87.88 kg, with a weight reduction rate of 10.89%, realizing the lightweight design requirements.

Abstract The small Extracellular vesicles (sEV) has been recognized to be significant for intercellular communication due to their ability to transfer important cellular cargoes like miRNAs through circulation. The pituitary gland has not been clearly known about the role of its secreted sEV under normal physiological conditions. And Liver disease is a global public health burden. The present study is the first to investigate the effect of pituitary sEV on the liver. Sequencing and qRT-PCR revealed miR-143-3p is one of the richest in the pituitary sEV. MiR-143 Knockout (KO) mice resulted in a remarkable decrease in insulin-like growth factor 1 (IGF-1) levels and a significant increase in insulin-like growth factor binding protein 5 (IGFBP5) levels along with a reduction in liver primary cell growth. More importantly, compared with miR-143-KO-sEV, WT-sEV possesses a more robust capacity to improve miR-143 KO mice liver repair through the Wnt/β-catenin pathway after an acute injury caused by carbon tetrachloride (CCl4). Our results indicate that pituitary-derived sEV promotes hepatocyte proliferation and liver repair by its cargo miR-143-3p and provides new insight into the regulation mechanism of the pituitary-liver axis, and open a new window for endocrine regulation by using sEV.

Abstract To evaluate the clinical significance of PLT, MPV, and PDW in monitoring malaria treatment efficacy and predicting disease progression. A total of 31 patients with imported malaria were selected as the observation group, while 31 non-malaria patients with fever were selected as controls. The observation group was subdivided into a complication group and a non-complication group according to the occurrence of complications during treatment. Additionally, on the 1st day (within 24 h), the 3rd day, and the 5th day following admission, a comprehensive blood routine examination, Plasmodium microscopic examination, and colloidal gold assay were conducted. The blood routine examination results were compared before and after treatment among patients in the observation group and the control group. Moreover, the study involved dynamic monitoring and analysis of the levels and variations in PLT, MPV, and PDW within both the complication group and the non-complication group. The Plasmodium density was negatively correlated with PLT before treatment. There were significant differences were observed in PLT, MPV, and PDW (P 0.05) within the observation group before and after treatment. The PLT, MPV, and PDW levels in the complication group and the non-complication group exhibited an upward trend after treatment. Further, the PLT of patients in the complication group was significantly lower than that in the non-complication group. Additionally, the PLT, MPV, and PDW levels in the complication group and the non-complication group increased gradually from the time of admission to the 3rd and 5th day of treatment. Notably, the PLT in the complication group was consistently lower than that in the non-complication group. The continuous monitoring of PLT, MPV, and PDW changes plays a crucial role in assessing malaria treatment efficacy and prognosis in these individuals.

Objective To investigate the mid-term efficacy and patency rate of TurboHawk peripheral plaque excision system in the treatment of femoral popliteal artery lesions with different Global Limb Anatomic Staging System (GLASS) grades. Methods The clinical data of 141 patients with femoral popliteal arteriosclerosis obliterans who were treated with TurboHawk from January 2018 to July 2022 in our institution were retrospectively analyzed. There were 109 male patients and 32 female patients. Recordings were made of the patient’s symptoms of limb ischemia, technical success rate, primary patency rate of target vessels, ankle brachial index (ABI), GLASS grades, postoperative complications, and a statistical analysis with the patient’s preoperative treatment was conducted. Results All patients had improved limb ischemia symptoms to varying degrees after surgery, with a technical success rate of 100% (femoral artery puncture and superficial femoral artery recanalization) without bleeding, hematoma, pseudoaneurysm, arteriovenous fistula or other complications. The follow-up period was 1-24 months, during which the severity of claudication, resting pain, and toe ulcers significantly improved. The primary patency rate of the target vessel was 98.58% (139/141), and the ABI significantly increased on the second day, three months, and six months after surgery compared to before surgery. No major adverse events were found during follow-up. The patency rates at 1, 6, 12 and 24 months after intervention were 100%, 80%, 75% and 60% respectively. Conclusion The mid-term efficacy and patency rate of TurboHawk in the treatment of femoral popliteal artery lesions with GLASS I patients have the best mid-term prognosis, the highest mid-term survival rate, and the highest vascular patency. The plaque removal system has proven to be an effective treatment for individual localized chronic total occlusion lesions. Additionally, the TurboHawk system provides a safe and minimally invasive treatment alternative for superficial femoral artery conditions, achieving significant therapeutic results within a brief period.

Objective(s): Investigating the impact of cadmium (Cd) on annulus fibrosus (AF) cells and its potential mechanism was the purpose of the current study.Materials and Methods: Cd was cultivated in different concentrations (0, 1, 5, 10, and 20 μM) on AF cells and the potential effects of the metal were assessed. Using the CCK-8 method, cell viability and proliferation were identified. Using transcriptome analysis, the annulus fibrosus cells were sequenced both with and without cadmium chloride. The EdU method was used to determine the rate of cell proliferation; senescence-associated β-galactosidase (SA-β-Gal) staining was used to determine the number of positive cells; and western blot, RT-PCR, and immunofluorescence were used to determine the protein and mRNA expression of senescence-associated proteins (p16, p21, and p53) and c-Jun N-terminal kinase (JNK).Results: According to the findings, Cd has the ability to increase the production of senescence-associated genes (p16 and p21) and senescence-associated secreted phenotype (SASP), which includes IL-1β and IL-6. Through the JNK/p53 signal pathway, Cd exposure simultaneously accelerated AF cell senescence and promoted SASP. Following JNK inhibitor (SP600125) treatment, the expression of p53, JNK, and senescence-associated indices were all down-regulated.Conclusion: By activating the JNK/p53 signaling pathway, Cd can induce oxidative stress damage and AF cell senescence. These findings could provide a new approach for treating and preventing intervertebral disc degeneration (IVDD) caused by Cd exposure.

Abstract Background Renal cell carcinoma (RCC) is a malignant tumor. Radix Actinidiae chinensis (RAC) is the root of Actinidia arguta (Sieb. et Zucc) Planch. ex Miq. In clinical research, RAC was confirmed to have a certain anti-tumor effect, including liver cancer and cholangiocarcinoma. This study investigated the anticancer effect and mechanism of RAC in RCC cells. Methods The 786-O and A498 cells were intervened with varying concentrations of RAC (0–100 mg/mL) to detect the half maximal inhibitory concentration (IC50) of RAC. The cells were then co-cultured with 0–50 mg/mL RAC for 0–72 h to assess the effect of RAC on cell viability using the cell counting kit-8. The effects on cell proliferation, cell cycle or apoptosis, migration or invasion, and autophagy were detected using cloning, flow cytometry, Transwell, AOPI assay and Western blot. The number of autophagolysosomes was quantified using a transmission electron microscope. PI3K/AKT/mTOR pathway-related proteins were detected by Western blot. Additionally, an autophagy inhibitor 3-MA was used to explore the underlying mechanism of RAC. Results IC50 values of RAC in 786-O and A498 were 14.76 mg/mL and 13.09 mg/mL, respectively. RAC demonstrated the ability to reduce the cell malignant phenotype of RCC cells, blocked the S phase of cells, promoted apoptosis and autophagy in cells. Furthermore, RAC was observed to increase autophagy-related proteins LC3II/I and Beclin-1, while decreasing the level of P62. The expression of apoptosis-related proteins was increased, while the ratios of p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, p-P38/P38 and p-ERK/ERK were reduced by RAC. However, the addition of 3-MA reduced the apoptosis and autophagy- promotion effects of RAC on RCC cells. Conclusion RAC induced the apoptosis and autophagy, to inhibit the progression of RCC cells. This study may provide a theoretical and experimental basis for clinical anti-cancer application of RAC for RCC.

Abstract To investigate the flow characteristics in front chamber and rear chamber in pump mode and pump as turbine mode, a 3D computational model of a centrifugal pump was established, including the front and rear chamber. Based on Realizable k-ε turbulence model, numerical calculations of incompressible flow were carried out for internal viscous flow in two operating modes. Further analysis was conducted on the flow stability and hydraulic losses under two modes using energy gradient theory and entropy production theory. The numerical simulation results are within reasonable error compared to the experimental results in pump operation mode, which ensures the reliability of the numerical calculation method. The results indicate that the volumetric efficiency in both two modes is on an upward trend with increasing flow, but the volumetric efficiency of the pump mode is more significantly affected by changes in flow; the distribution patterns of dimensionless circumferential velocity and dimensionless radial velocity in the front and rear chambers under two operating modes are similar, but the distribution pattern of dimensionless radial velocity in the front chamber in turbine mode is significantly different from other operating conditions; flow instability is most likely to occur at the outlet of impeller, and the energy loss in clearance of wear-rings is greater than that in the pump chamber.

Abstract Antitumor therapies based on adoptively transferred T cells or oncolytic viruses have made significant progress in recent years, but the limited efficiency of their infiltration into solid tumors makes it difficult to achieve desired antitumor effects when used alone. In this study, an oncolytic virus (rVSV-LCMVG) that is not prone to induce virus-neutralizing antibodies was designed and combined with adoptively transferred T cells. By transforming the immunosuppressive tumor microenvironment into an immunosensitive one, in B16 tumor-bearing mice, combination therapy showed superior antitumor effects than monotherapy. This occurred whether the OV was administered intratumorally or intravenously. Combination therapy significantly increased cytokine and chemokine levels within tumors and recruited CD8+ T cells to the TME to trigger antitumor immune responses. Pretreatment with adoptively transferred T cells and subsequent oncolytic virotherapy sensitizes refractory tumors by boosting T-cell recruitment, down-regulating the expression of PD-1, and restoring effector T-cell function. To offer a combination therapy with greater translational value, mRNA vaccines were introduced to induce tumor-specific T cells instead of adoptively transferred T cells. The combination of OVs and mRNA vaccine also displays a significant reduction in tumor burden and prolonged survival. This study proposed a rational combination therapy of OVs with adoptive T-cell transfer or mRNA vaccines encoding tumor-associated antigens, in terms of synergistic efficacy and mechanism.

Background: Metastatic neuroendocrine carcinoma (NEC) is associated with short survival. Other than platinum-based chemotherapy, there is no clear standard regimen. Current guidelines suggest that combination treatment with BRAF-inhibitors should be considered for patients with BRAF V600E-mutated NEC. However, since only eight such patients have been reported in the literature, our object was to confirm the validity of this recommendation. Methods: This was a single-center retrospective cohort study conducted at Uppsala University Hospital. The included patients 1) had a histopathologically confirmed diagnosis of NEC, 2) were diagnosed between January 1st, 2018 and December 31st, 2023, 3) had tumor tissue genetically screened by a broad next-generation sequencing (NGS) panel, and 4) showed a tumor mutation for which there is a currently available targeted therapy. Results: We screened 48 patients diagnosed with NEC between January 1st, 2018 and December 31st, 2023. Twelve had been analyzed with a broad NGS-panel, and two had a targetable mutation. Both these patients harbored a BRAF V600E-mutated colon-NEC and were treated with BRAF- and MEK-inhibitors dabrafenib and trametinib in second-line. At first radiological evaluation (RECIST 1.1), both patients had a reduction of tumor size, which decreased by 31 and 40%. Both had short response periods, and their overall survival was 12 and 9 months. Conclusions: BRAF-mutated NEC is sensitive to treatment with BRAF- and MEK-inhibitor combination. These results further support that DNA sequencing should be considered as standard of care in NECs to screen for potential treatment targets.

In the new era, the health needs of residents are constantly increasing, and how community health services adapt to the needs of the times and achieve comprehensive transformation urgently needs to be answered. Firstly, the article reviewed the development process of community health service (CHS) in China and found that it is functionally defective. Secondly, the article summarized the challenges faced by the optimization of CHS in China and pointed out that the current health needs of the population are undergoing structural changes. Finally, the article proposed the optimization paths of CHS in China in terms of changing the focus of work, improving the sense of value for contracted doctors and the sense of achievement for residents, building a collaborative and complementary CHS network, and establishing a demand-oriented health information platform.

Abstract Using the unsteady Bernoulli equation for the piping system and the angular momentum equation for the rotor, derives here a theoretical model to predict the startup performance of a pump as turbine (PAT). This model is effective for predicting the instantaneous evolution characteristics of the main performance parameters of PAT during startup, and these changings are initially faster and then slowly as a whole. The effect of the rotor moment of inertia and the final stabilized rotational speed of PAT on evolution characteristics of parameters is opposite. The rotational speed, head, hydraulic power, and conversion efficiency show a upward rising trend with the startup time, whereas the flow rate and hydraulic head loss display a downward trend.

Abstract The presence of heterotopic ossification (HO) after primary total knee replacement (TKR) is rare and associated with limited mobility and stiffness of the knee. This study aimed to identify if the arthroscopic debridement after TKR could decrease HO and improve the function and range of motion. Thirty HO patients after TKR were retrospectively separated into 2 cohorts. 15 patients of group A accepted the arthroscopic debridement, while 15 patients of group B only had non-operative treatment, mainly including oral nonsteroidal anti-inflammatory drugs (NSAIDs) and rehabilitative treatment. Visual analog scale (VAS) scores, knee society knee scores (KSS), range of motion (knee flexion and knee extension) were obtained before treatment and at 1 month, 3 months, and 6 months after treatment. Radiography of after-treatment was also evaluated to assess the changes in HO. There were 3 males and 27 females with a mean age of 67.4 ± 0.8 years in group A and 68.2 ± 1.3 in group B. The onset time of HO was 3–6 months. The maximum size of the ossification was 5 cm in 1 knee. The size of HO decreased gradually in all knees by X-ray film at the last follow-up. There were no significant differences in VAS scores after replacement between two groups (p > 0.05). The average range of motion preoperatively in group A was − 15.2–90.6°, which postoperatively increased to − 4.2–110.0°. Meanwhile, the KSS scores and average range of motion of the group A were better than those of the group B at each follow-up time after treatment. Arthroscopic debridement can decrease HO seen from postoperative X-rays, improve the function and range of motion, as well as the pain remission between two groups are comparable. Consequently, arthroscopic resection of HO after TKR is recommended as soon as there is aggravating joint stiffness.

Abstract This single-arm, multi-center clinical trial aimed to evaluate the safety, tolerability, DLT, recommended dose (RD), preliminary efficacy, and pharmacokinetics (PK) characteristics of lurbinectedin, a selective inhibitor of oncogenic transcription, in Chinese patients with advanced solid tumors, including relapsed SCLC. Patients with advanced solid tumors were recruited in the dose-escalation stage and received lurbinectedin in a 3 + 3 design (two cohorts: 2.5 mg/m2 and 3.2 mg/m2, IV, q3wk). The RD was expanded in the following dose-expansion stage, including relapsed SCLC patients after first-line platinum-based chemotherapy. The primary endpoints included safety profile, tolerability, DLT, RD, and preliminary efficacy profile, while the secondary endpoints included PK characteristics. In the dose-escalation stage, ten patients were included, while one patient had DLT in the 3.2 mg/m2 cohort, which was also the RD for the dose-expansion stage. At cutoff (May 31, 2022), 22 SCLC patients were treated in the ongoing dose-expansion stage, and the median follow-up was 8.1 months (range 3.0–11.7). The most common grade ≥ 3 treatment-related adverse events (TRAEs) included neutropenia (77.3%), leukopenia (63.6%), thrombocytopenia (40.9%), anemia (18.2%), and ALT increased (18.2%). The most common severe adverse events (SAEs) included neutropenia (27.3%), leukopenia (22.7%), thrombocytopenia (18.2%), and vomiting (9.1%). No treatment-related deaths occurred. The Independent Review Committee (IRC)-assessed ORR was 45.5% (95% CI 26.9–65.3). Lurbinectedin at the RD (3.2 mg/m2) showed manageable safety and acceptable tolerability in Chinese patients with advanced solid tumors, and demonstrates promising efficacy in Chinese patients with SCLC as second-line therapy. Trial registration: This study was registered with ClinicalTrials.gov NCT04638491, 20/11/2020.

Abstract Severe trauma could induce sepsis due to the loss of control of the infection, which may eventually lead to death. Accurate and timely diagnosis of sepsis with severe trauma remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis. We compared the diagnostic characteristics of routinely used biomarkers of sepsis alone and in combination, trying to define a biomarker panel to predict sepsis in severe patients. This prospective observational study included patients with severe trauma (Injury severity score, ISS = 16 or more) in the emergency intensive care unit (EICU) at a university hospital. Blood samples were collected and plasma levels of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) were measured using commercial enzyme linked immunosorbent assay (ELISA) kits. A total of 100 patients were eligible for analysis. Of these, 52 were diagnosed with sepsis. CRP yielded the highest discriminative value followed by PCT. In multiple logistic regression, SAA, CRP, and PCT were found to be independent predictors of sepsis. Bioscore which was composed of SAA, CRP, and PCT was shown to be far superior to that of each individual biomarker taken individually. Therefore, compared with single markers, the biomarker panel of PCT, CRP, and SAA was more predictive of sepsis in severe polytrauma patients.

Abstract Background Postinfarction cardiac remodeling presents a compensatory mechanism aimed at mitigating congestive heart failure. It is distinguished by progressive dilatation and hypertrophy of the ventricular chambers, fibrotic alterations, and prolonged apoptosis of cardiomyocytes. The primary objective of this study was to assess the effects of icariin on myocardial fibrosis and ventricular remodeling in rats subjected to myocardial infarction (MI). Methods Male Sprague‒Dawley (SD) rats were subjected to randomization and subsequently divided into distinct groups: the control group, the sham group (undergoing sham operation), the MI group (experiencing ligation of the left anterior descending artery), and the icariin group. Within the icariin group, rats were further categorized into three different dose groups based on the administered icariin dosage: the MI30 group (30 mg/kg/day), the MI60 group (60 mg/kg/day), and the MI120 group (120 mg/kg/day). Cardiac function evaluation was carried out using echocardiography. Histological examinations, including hematoxylin and eosin (HE) staining, Masson staining, and immunohistochemistry studies, were conducted 90 days after the occurrence of MI. Additionally, Western blotting was employed to assess TGF‐β1, p-Smad2, and p-Smad3 levels. Results The administration of icariin revealed a noteworthy enhancement in cardiac function among rats afflicted with left anterior descending coronary artery (LAD) ligation. In comparison to the icariin groups, the MI group exhibited reduced EF and FS, along with elevated LVEDD and LVESD. Furthermore, the cardiac fibrosis levels in the MI group rats exhibited a considerable increase compared to those in the icariin group. Notably, the levels of Collagen I, Collagen III, MMP2, and MMP9 were significantly higher in the MI group than in the icariin group, with evident distinctions. Moreover, the expression levels of TGF-β, IL-13, p-Smad2, and p-Smad3 were notably upregulated in the MI group compared to the icariin group. Conclusions In an experimental rat model of MI, the administration of icariin resulted in the amelioration of both cardiac function and remodeling processes, operating through the intricate TGF-β1/Smad signaling pathway.

Abstract Background To analyze the global burden of headache disorders in adolescents and young adults (AYAs). Methods Data of headache disorders in the 15–39 age groups were extracted from GBD 2019. The age-standardized rates (ASRs) of incidence, prevalence, and years lived with disability (YLDs) rate were used to describe the burden. Estimated Annual Percentage Changes (EAPCs) were used to describe the trend from 1990 to 2019. Results In 2019, the age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), and age-standardized YLDs rate (ASYR) in AYAs were 42,473.18 (95% CI: 34,836.35, 50,858.30) per 100,000, 12,566.18 (95% CI: 8542.10, 16,915.68) per 100,000 and 790.32 (95% CI: 129.56, 1786.52) per 100,000, respectively. From 1990 to 2019, the ASRs showed increasing trends, with EAPCs of 0.04 (95% CI: 0.03, 0.06), 0.05 (95% CI: 0.03, 0.07), and 0.08 (95% CI: 0.07, 0.10). Migraine accounted for 91.54% of headache-related YLDs. The burdens in females were higher than those in males, especially for ASYR. This burden was greatest in the high sociodemographic index (SDI) super region. In the temporal trend of ASIR, 127 (62.25%) countries showed upward trends, mainly distributed in East Asia, Central Asia, West Africa, and Western Latin America. Conclusions The burden of headache disorders in the global population aged 15–39 is severe, especially among females and in countries with high SDI. Furthermore, this burden has been steadily increasing over the past three decades. Those findings assist in implementing targeted intervention measures.

Abstract Video-assisted thoracoscopic surgery (VATS) provides better option concerning pathological diagnosis and curative intention of small pulmonary nodules (SPNs) that are sometimes challenging to localize. We assess the safety and feasibility of a new localization technique for SPNs, and report experience accumulated over time. A retrospective review of the new claw-suture localization cases between February 2018 and May 2023 was performed. Nodules were localized by a novel system that has an anchor claw and a tri-colored suture, guided by computed tomography (CT). Localization and operative procedure outcomes were then assessed. A total of 590 SPNs were localized from 568 patients before operation. The median nodule size was 0.70 cm (range, 0.3–2.0 cm). The claw-suture localization was successful without dislodgment or device fracture in 574 of 590 lesions (97.3%). Failures included not meeting target distance between claw and lesion (n = 13 [2.2%]), and device displacement (n = 3 [0.5%]). Complications requiring no further medical intervention included asymptomatic pneumothorax (n = 68 [11.5%]), parenchymal hemorrhage (n = 51 [8.6%]), and hemothorax (n = 1 [0.2%]) with the exception of pleural reaction observed in 2 cases (0.3%). Additionally, the depth of pulmonary nodules was significantly associated with the occurrence of pneumothorax (P = 0.036) and parenchymal hemorrhage (P = 0.000). The median duration of the localization was 12 min (range, 7–25 min). No patient complained of remarkable pain during the entire procedure. Retrieve of device after operation was 100%. The new localization technique is a safe, feasible, and well-tolerated method to localize SPNs for VATS resection.

Abstract Atherosclerosis, which is a vascular pathology characterized by inflammation and plaque build-up within arterial vessel walls, acts as the important cause of most cardiovascular diseases. Except for a lipid-depository and chronic inflammatory, increasing evidences propose that epigenetic modifications are increasingly associated with atherosclerosis and are of interest from both therapeutic and biomarker perspectives. The chronic progressive nature of atherosclerosis has highlighted atherosclerosis heterogeneity and the fact that specific cell types in the complex milieu of the plaque are, by far, not the only initiators and drivers of atherosclerosis. Instead, the ubiquitous effects of cell type are tightly controlled and directed by the epigenetic signature, which, in turn, is affected by many proatherogenic stimuli, including low-density lipoprotein, proinflammatory, and physical forces of blood circulation. In this review, we summarize the role of DNA methylation and histone post-translational modifications in atherosclerosis. The future research directions and potential therapy for the management of atherosclerosis are also discussed. Video Abstract

Abstract Background Roxadustat is a novel oral medication used to treat anemia in CKD patients. Several studies have shown that Roxadustat can alleviate anemia in CKD patients by increasing hemoglobin levels and regulating iron metabolism. We aimed to evaluate the effect of Roxadustat on ventricular repolarization in PD patients. This study may provide a new integrated approach to the assessment and treatment of CKD. Methods The present prospective cohort study enrolled 65 CKD patients who were treated with Roxadustat and 31 CKD patients who received conventional therapy between January 2021 and June 2022. All patients were examined for ECG in the absence of clinical symptoms and compared the ECG indicators. Demographic and clinical data of all patients were collected. All data used SPSS 18.0 for statistical analyses. Results The T peak-to-end (Tpe) of PD patients in the Roxadustat group was remarkably slower than that of patients in the conventional group. Additionally, the Tpe/QT ratio in the conventional group was significantly elevated than that in the Roxadustat group. The results of logistic regression analysis showed that Tpe (95%CI 1.191 ~ 2.141, P = 0.002) and Roxadustat treatment (95%CI 1.357 ~ 42.121, P = 0.021) were the risk factors of PD patients with high Tp-e/QT ratio. Conclusion In summary, we found that Roxadustat could improve ventricular repolarization in peritoneal dialysis patients, which indicated a potential cardiovascular protective effect of Roxadustat. This study might provide a new integrated approach to the assessment and treatment of CKD.

Abstract In order to improve the efficiency of the self-priming pump in the outdoor emergency rescue mobile pump truck, this paper took the key energy conversion component-impeller as the target and used the orthogonal experimental design method to optimize its hydraulic performance. Firstly the numerical calculations were compared with the experimental results to confirm the reliability of the calculation method. Then, L 9 (34) orthogonal design was applied to investigate the influence of the impeller diameter, the blade outlet width, the blade wrap angle and the number of blades on the hydraulic performance of the self-priming pump. Through range analysis, the order of influence of each influencing factor on the head and efficiency of the self-priming pump was determined, and finally obtained the optimal parameter combination scheme. The results show that the optimized self-priming pump exceeds the head of the prototype pump at all flow conditions, and the efficiency curve at high flow conditions is significantly improved and has a wide high efficiency zone.

Abstract Background As the most lethal gynecologic cancer, ovarian cancer (OV) holds the potential of being immunotherapy-responsive. However, only modest therapeutic effects have been achieved by immunotherapies such as immune checkpoint blockade. This study aims to propose a generalized stroma-immune prognostic signature (SIPS) to identify OV patients who may benefit from immunotherapy. Methods The 2097 OV patients included in the study were significant with high-grade serous ovarian cancer in the III/IV stage. The 470 immune-related signatures were collected and analyzed by the Cox regression and Lasso algorithm to generalize a credible SIPS. Correlations between the SIPS signature and tumor microenvironment were further analyzed. The critical immunosuppressive role of stroma indicated by the SIPS was further validated by targeting the major suppressive stroma component (CAFs, Cancer-associated fibroblasts) in vitro and in vivo. With four machine-learning methods predicting tumor immune subtypes, the stroma-immune signature was upgraded to a 23-gene signature. Results The SIPS effectively discriminated the high-risk individuals in the training and validating cohorts, where the high SIPS succeeded in predicting worse survival in several immunotherapy cohorts. The SIPS signature was positively correlated with stroma components, especially CAFs and immunosuppressive cells in the tumor microenvironment, indicating the critical suppressive stroma-immune network. The combination of CAFs’ marker PDGFRB inhibitors and frontline PARP inhibitors substantially inhibited tumor growth and promoted the survival of OV-bearing mice. The stroma-immune signature was upgraded to a 23-gene signature to improve clinical utility. Several drug types that suppress stroma-immune signatures, such as EGFR inhibitors, could be candidates for potential immunotherapeutic combinations in ovarian cancer. Conclusions The stroma-immune signature could efficiently predict the immunotherapeutic sensitivity of OV patients. Immunotherapy and auxiliary drugs targeting stroma could enhance immunotherapeutic efficacy in ovarian cancer.

Abstract To explore the strain rate effect of deformation and failure of impact prone coal rock, uniaxial compression tests and triaxial compression tests with different strain rates were carried out. The mechanical properties and impact tendency of impact-prone coal rock were studied, and the energy evolution law and pre-peak energy self-promotion-inhibition mechanism of impact-prone coal rock were obtained. The results show that with the increase of strain rate, the peak strength of coal rock under uniaxial compression decreases gradually, and the peak strength of coal rock under triaxial compression increases first and then decreases, and the impact tendency of coal rock increases first and then decreases. The energy evolution of coal rock under uniaxial compression is mainly divided into four stages: initial energy damage, energy hardening, energy softening and failure. With the increase of strain rate, the total energy and elasticity at the peak point of coal rock under uniaxial compression decrease gradually, and the total energy, elastic energy and dissipation energy at the peak point under triaxial compression increase first and then decrease. The elastic energy promotion coefficient of impact-prone coal rock is much larger than the inhibition coefficient, and the increase of strain rate will promote the generation of elastic energy inside coal rock. The research results can provide reference for the prevention and early warning of dynamic disasters of coal and rock mass with impact tendency.

Abstract To study the effect of the width-to-narrow ratio on the forward and reverse flow characteristics of the Tesla valve, five different models of the Tesla valve with different width-to-narrow ratios are established in this paper. The numerical calculations of forward and reverse flow under different working conditions are carried out by the CFD method in the laminar flow regime, and the reliability of the numerical calculation method is verified by comparing it with the experimental results. The results show that: in forward flow, the main flow-through channel is not related to the width-to-narrow ratio, the flow rate of the straight channel increases with the increase of the width-to-narrow ratio, and the static pressure in the diversion section is in the shape of “∞”; while in reverse flow, the main flow-through channel is weakly related to the width-to-narrow ratio, the flow rate of the arc channel is not increased with the increase of the width-to-narrow ratio, and the static pressure in the diversion section is in the shape of “bench”. As the width-to-narrow ratio decreases, the pressure drop during forward and reverse flow becomes more significant.

Abstract Background National standardized training for resident doctors (STRD) in mainland China has been formally established since 2014 as a kind of postgraduate education. The purpose of this survey was to assess the satisfaction of the training residents in Guangdong Province on the ophthalmology STRD program after a duration of 5 years. Method A 48-item survey was sent to all postgraduate ophthalmology residents from bases in Guangdong Province to inquire about their attitude towards the program. The survey contained questions about demographic and work-related information, job satisfaction, psychological resilience, and job performance. All responses were verified, and invalid questionnaires were excluded. Statistical analyses were performed using SPSS software version 22.0 (SPSS, Inc., Chicago, IL). Multiple logistic regression analysis was used to evaluate the factors (demographic information, working environment, clinical exposure, supervision and hands-on training opportunities, and involvement in academic activities) impacting the overall satisfaction. P

Abstract The cisterna magna has been defined as the space between the inferior margin of the cerebellar vermis to the level of the foramen magnum, while an enlarged dorsal subarachnoid space at the occipito-cervical junction extending from the foramen magnum to the upper border of the axis (C2) is still ignored. Recently, the myodural bridge complex is proved to drive the cerebral spinal fluid flowing via this region, we therefore introduce the “occipito-atlantal cistern (OAC)” to better describe the subarachnoid space and provide a detailed rationale. The present study utilized several methods, including MRI, gross anatomical dissection, P45 sheet plastination, and three-dimensional visualization. OAC was observed to be an enlarge subarachnoid space, extending from the foramen magnum to the level of the C2. In the median sagittal plane, OAC was a funnel shape and its anteroposterior dimensions were 15.92 ± 4.20 mm at the level of the C0, 4.49 ± 1.25 mm at the level of the posterior arch of the C1, and 2.88 ± 0.77 mm at the level of the arch of the C2, respectively. In the median sagittal plane, the spino-dural angle of the OAC was calculated to be 35.10 ± 6.91°, and the area of OAC was calculated to be 232.28 ± 71.02 mm2. The present study provides OAC is a subarachnoid space independent from the cisterna magna. Because of its distinctive anatomy, as well as theoretical and clinical significance, OAC deserves its own name.

BackgroundThe increasing prevalence of nonalcoholic fatty liver disease (NAFLD) in China presents a significant public health concern. Traditional ultrasound, commonly used for fatty liver screening, often lacks the ability to accurately quantify steatosis, leading to insufficient follow-up for patients with moderate-to-severe steatosis. Transient elastography (TE) provides a more quantitative diagnosis of steatosis and fibrosis, closely aligning with biopsy results. Moreover, machine learning (ML) technology holds promise for developing more precise diagnostic models for NAFLD using a variety of laboratory indicators. ObjectiveThis study aims to develop a novel ML-based diagnostic model leveraging TE results for staging hepatic steatosis. The objective was to streamline the model’s input features, creating a cost-effective and user-friendly tool to distinguish patients with NAFLD requiring follow-up. This innovative approach merges TE and ML to enhance diagnostic accuracy and efficiency in NAFLD assessment. MethodsThe study involved a comprehensive analysis of health examination records from Suzhou Municipal Hospital, spanning from March to May 2023. Patient data and questionnaire responses were meticulously inputted into Microsoft Excel 2019, followed by thorough data cleaning and model development using Python 3.7, with libraries scikit-learn and numpy to ensure data accuracy. A cohort comprising 978 residents with complete medical records and TE results was included for analysis. Various classification models, including logistic regression (LR), k-nearest neighbor (KNN), support vector machine (SVM), random forest (RF), light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost), were constructed and evaluated based on the area under the receiver operating characteristic curve (AUROC). ResultsAmong the 916 patients included in the study, 273 were diagnosed with moderate-to-severe NAFLD. The concordance rate between traditional ultrasound and TE for detecting moderate-to-severe NAFLD was 84.6% (231/273). The AUROC values for the RF, LightGBM, XGBoost, SVM, KNN, and LR models were 0.91, 0.86, 0.83, 0.88, 0.77, and 0.81, respectively. These models achieved accuracy rates of 84%, 81%, 78%, 81%, 76%, and 77%, respectively. Notably, the RF model exhibited the best performance. A simplified RF model was developed with an AUROC of 0.88, featuring 62% sensitivity and 90% specificity. This simplified model used 6 key features: waist circumference, BMI, fasting plasma glucose, uric acid, total bilirubin, and high-sensitivity C-reactive protein. This approach offers a cost-effective and user-friendly tool while streamlining feature acquisition for training purposes. ConclusionsThe study introduces a groundbreaking, cost-effective ML algorithm that leverages health examination data for identifying moderate-to-severe NAFLD. This model has the potential to significantly impact public health by enabling targeted investigations and interventions for NAFLD. By integrating TE and ML technologies, the study showcases innovative approaches to advancing NAFLD diagnostics.

Abstract The prognostic value of the left atrial function index (LAFI) in acute ST segment elevation myocardial infarction (STEMI) patients treated with percutaneous coronary intervention (PCI) is unknown. This study sought to determine whether the LAFI predicts prognosis in STEMI patients treated with PCI. Patients with newly diagnosed STEMI who were treated with PCI in Hunan Provincial People's Hospital from March 2020 to October 2020 were prospectively enrolled. All patients underwent transthoracic echocardiography at baseline and follow-up. The endpoint events included rehospitalization due to unstable angina, nonfatal myocardial infarction, rehospitalization due to heart failure and cardiovascular death. A total of 156 STEMI patients treated with PCI were studied with a median follow-up of 14 months. Forty-eight patients had endpoint events. The LAFI had the highest area under the receiver operating characteristic curve (AUC) predicting the endpoint events, with an AUC of 0.90 (95% CI 0.84–0.94). Multivariate Cox analysis demonstrated that only the LAFI (HR: 0.91, 95% CI 0.87–0.96, P 42.25 cm/cc/m2 (HR: 19.15, 95% CI 8.90–41.21, P

Abstract In order to reveal the influence of starting acceleration on starting process of a pump as turbine system, this paper carries out a numerical calculation of the three-dimensional viscous unsteady flow of pump as turbine circulating piping system under three starting acceleration conditions, and obtains the external and internal flow characteristics of each overflow component during the starting process, and also analyzes the energy loss of each component in the piping system in depth with the help of entropy production method and Q criterion method. The results show that during system start-up, the flow rate and outlet static pressure curves of the pump as turbine are hysteresis relative to the rotational speed, the head curve is similar to a linear rise during slow and medium speed start-up, while it shows a parabolic rise during rapid start-up, the entropy production and vorticity in the impeller domain of the pump as turbine are mainly distributed between the blades, and the distribution decreases during start-up. In addition, the pump similarity law does not apply to the performance prediction during the transient start of the pump as turbine.

Objective This study aims to identify potential prognostic and therapeutic biomarkers in papillary renal cell carcinoma (pRCC). Methods Two microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified. The protein-protein interaction (PPI) networks and functional annotations of DEGs were established. Survival analysis was utilized to evaluate the prognostic significance of the DEGs and the association between the expression level of candidate biomarkers and various tumour-infiltrating immune cells was explored. The role of PTTG1 in tumour microenvironments (TME) was further explored using Single-cell RNA-seq and its prognostic and therapeutic significance was validated in Fudan University Shanghai Cancer Centre (FUSCC) cohort. Results Eight genes, including BUB1B, CCNB1, CCNB2, MAD2L1, TTK, CDC20, PTTG1, and MCM were found to be negatively associated with patients’ prognosis. The expression level of PTTG1 was found to be significantly associated with lymphocytes, immunomodulators, and chemokine in the TCGA cohort. Single-cell RNA-seq information indicated that PTTG1 was strongly associated with the proliferation of T cells. In the FUSCC cohort, the expression level of PTTG1 was also statistically significant for both progression-free survival (PFS) and overall survival (OS) prediction (HR = 2.683, p

Background As healthcare gatekeepers, the competency of community general practitioners (GPs) will directly determine the quality of their services. However, the requirements for the competency of community GPs are still unclear and relevant applied research is scarce. Objective To construct a competency assessment system for community GPs. Methods An item pool of the first draft of the Onion Model-based Competency Assessment System for Community General Practitioners (OMCASCGP) was created by use of literature review in January 2021, then items in which were screened and improved in accordance with the results of two rounds of email-based expert consultation conducted with a purposive sample of 52 experts in general medicine and general medical management from February to March 2021. The weight of each index was determined by using the Analytic Hierarchy Process. Results The response rate, authority coefficient, judgment coefficient and the degree of familiarity with the index for both rounds of consultation were 100.0% (52/52) , 0.91, 0.904, and 0.916, respectively. The formal system is composed of 6 first-level indices, 15 second-level indices and 48 third-level indices. The 6 first-level indices with corresponding weights are basic information (0.085 7) , clinical capability (0.436 1) , public health capability (0.244 5) , humanistic literacy (0.110 4) , career development (0.082 7) , and other aspects (0.040 6) . The Kendall's W measuring inter-expert agreement on the first-, second- and third-level indices was 0.254, 0.302, and 0.341, respectively (P

Abstract Previous palaeoenvironmental reconstructions have implied that East Asia was dominated by a zonal climate pattern during the Eocene, with an almost latitudinal arid/semiarid band at ~ 30° N. However, this long-standing model has recently been challenged by growing body of multidisciplinary evidence. Some studies indicated that central China was characterized by climatic fluctuations between humid and drier conditions during the Early Eocene, akin to the present East Asian monsoon (EAM) regime. Using palynological assemblages in the Tantou Basin, central China, we quantitatively reconstructed climate changes from the Late Palaeocene to Early Eocene to better understand climate change in central China. Palynological assemblages revealed that the coniferous and broad-leaved mixed forest in this area received no less than 800 mm of annual precipitation and experienced a climate change from warm and wet to relatively cool and dry. According to palaeoclimate curves, a sudden climate change occurred in the Early Eocene, with the mean annual temperature and precipitation decreasing by 5.1 °C and 214.8 mm, respectively, and the climate became very similar to the present climate, which is controlled by the monsoon. Therefore, this significant climate change during the Early Eocene may signal the emergence of the EAM in East Asia.

Abstract Skeletal muscle atrophy is prevalent and remarkably increases the risk of cardiovascular (CV) events and mortality in hemodialysis (HD) patients. However, whether diaphragm dysfunction predicts clinical outcomes in HD patients is unknown. This was a prospective cohort study of 103 HD patients. After assessment of diaphragm function by ultrasonography and collection of other baseline data, a 36-month follow-up was then initiated. Participants were divided into diaphragm dysfunction (DD+) group and normal diaphragm function (DD−) group, according to cutoff value of thickening ratio (i.e. the change ratio of diaphragm thickness) at force respiration. The primary endpoint was the first nonfatal CV event or all-cause mortality. A secondary endpoint was less serious CV events (LSCEs, a composite of heart failure readmission, cardiac arrhythmia or myocardial ischemia needed pharmacological intervention in hospital). 98 patients were eligible to analysis and 57 (58.16%) were men. 28 of 44 patients(63.64%) in DD+ group and 23 of 54 patients (42.59%) in DD− group had at least one nonfatal CV event or death (p = 0.038). Compared to DD− group, DD+ group had significantly higher incidence of LSCEs (21 vs.14, p = 0.025) and shorter survival time (22.02 ± 12.98 months vs. 26.74 ± 12.59 months, p = 0.046). Kaplan–Meier analysis revealed significantly higher risks of primary endpoint (p = 0.039), and LSCEs (p = 0.040) in DD+ group. Multivariate hazard analysis showed that DD+ group had significantly higher risk of primary endpoint [hazard ratio (HR) 1.59; 95% confident interval (CI) 1.54–1.63], and LSCEs (HR 1.47; 95%CI 1.40–1.55). Ultrasound-assessed diaphragm dysfunction predicts clinical outcomes in HD patients. Trial registration: This study was registered with Chinese Clinical Trials Registry ( www.chictr.org.cn ) as ChiCTR1800016500 on Jun 05, 2018.

Objective To explore the effect of lnc000727 on the differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) into osteoblasts. Methods Real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the expression of lnc000727. The alkaline phosphatase (ALP) method was used to determine the differentiation of osteoblasts. The expression of lnc000727 in hBM-MSCs was over-expressed or inhibited by liposome transfection. The osteogenic differentiation markers Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and pontin were detected by RT-qPCR and Western blot. Pontin (OPN) mRNA and protein expression. The expression of key proteins in the Wnt/β-catenin pathway was analyzed. Results During the differentiation of hBM-MSCs osteoblasts, the expression of lnc000727 and ALP activity increased significantly(P＜0.05). Inhibition of lnc000727 could down-regulate ALP activity and inhibit the expression of osteogenic differentiation markers RUNX2, OCN, OPN and the expression of Wnt and β-catenin (P＜0.05); over-expression of lnc000727 could up-regulate ALP activity and promote the expressions of osteogenic differentiation markers RUNX2, OCN and OPN, and the expressions of Wnt and β-catenin (P＜0.05). Conclusions Lnc000727 promotes the differentiation of hBM-MSCs into osteoblasts, thereby inhibits the occurrence and development of osteoporosis.

Aortic dilation disease, represented by aortic dissection and aortic aneurysm, is the most dangerous disease in vascular surgery. The pathogenesis of this disease is not very clear. Single-cell RNA sequencing (scRNA-seq) technology can study cell heterogeneity and identify new cell states and populations at the single cell level, which provides a new tool for studying the occurrence and development mechanism of aortic disease.

Abstract Background Recent studies have shown that the fox family plays a vital role in tumorigenesis and progression. Forkhead Box S1 (FOXS1), as a newly identified subfamily of the FOX family, is overexpressed in certain types of malignant tumors and closely associated with patient's prognosis. However, the role and mechanism of the FOXS1 in colorectal cancer (CRC) remain unclear. Method FOXS1 level in CRC tissues and cell lines was analyzed by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) was used to detect the relationship between FOXS1 expression and clinicopathological features in 136 patients in our unit. The expression of FOXS1 was knocked down in CRC cells using small interfering RNA (siRNA) technology. Cell proliferation was assessed by CCK8 assay, colony formation, and 5-Ethynyl-20-deoxyuridine (EdU) incorporation assay. Flow cytometry detected apoptosis and wound healing, and Transwell assays determined cell migration and invasion. Western blotting was used to detect the levels of proteins associated with the Wnt/β-catenin signaling pathway. Then, we used short hairpin RNA (shRNA) to knock down FOXS1 to see the effect of FOXS1 on the proliferation, migration, invasion, and metastasis of CRC cells in vivo. Finally, we investigated the impact of Wnt activator LiCl on the proliferation, migration, invasion, and metastasis of CRC cells after FOXS1 knockdown. Result Compared to those in normal groups, FOXS1 overexpressed in CRC tissues and CRC cells (P

Abstract In this paper, a bilateral haptic virtual surgery simulation system under a hybrid controller was studied. An analogue controller realized by a field programmable analogue array (FPAA) was paralleled in the operator robot side, which reduced the impact of controller discretisation on the system. A system stability conditions under hybrid control with multiple-operators were deduced. The stability analysis indicates that the addition of analogue derivative term widens the range of haptic controls gains that satisfy the multiple-users’ stability conditions. Finally, the human’s performance of a stiffness discrimination task was studied in an independently developed minimally invasive surgical (MIS) platform. The experiment results show that, human operators under the hybrid controller achieve the highest task success rates.

Abstract Perovskite solar cells have become the most promising third-generation solar cells because of their superior physical–chemical properties and high photoelectric conversion efficiency. However, the current obstacles to commercialization of perovskite solar cells are their poor stability and harmful elements. How to find high-efficiency, high-stability and non-toxic perovskite materials from thousands of possible perovskite crystals is the key to solve this problem. In this paper, the inorganic halide double perovskite A2BX6 and its crystal structure are considered, and the data mining algorithm in informatics is introduced into the high-throughput computing data to analyze various elements in nature to study the perovskite materials that can meet the requirements of high performance. The photoelectric conversion properties and stability of 42 inorganic double perovskite materials are studied based on density functional theory (DFT). The results show that the tolerance factors of 39 crystals are between 0.8 and 1.10, indicating that these crystals have stable perovskite structure. In addition, the dielectric function, PDOS, elastic modulus, shear modulus and poison’s ratio of these crystals are analyzed. According to the above theoretical simulation results, three candidate materials for ideal light absorption are presented. This can provide a theoretical basis for the industrial application of perovskite solar cells.

Summary: Background: Long-term treatment with immunosuppressants is necessary to attenuate allograft rejection following organ transplantation (OT). Consequently, the overall survival of OT recipients with malignancies has been substantially compromised by tumour recurrence. Rapamycin (RAPA) is a clinically approved immunosuppressive agent with antitumour activity that is considered beneficial in preventing posttransplant tumour recurrence. However, the clinical outcome of RAPA is impeded by acquired drug resistance and its poor oral bioavailability. Methods: A nanotherapeutic strategy was developed by supramolecular assembly of RAPA into a polymer cytotoxic 7-ethyl-10-hydroxycamptothecin (SN38) prodrug nanoparticle (termed SRNP) for simultaneous codelivery of cytotoxic/immunosuppressive agents. Cell-based experiments were used to evaluate the cytotoxicity of SRNPs against hepatocellular carcinoma (HCC). The therapeutic efficacy of SRNPs was evaluated in multiple preclinical models including an orthotopic HCC mouse model, an orthotopic liver transplantation (OLT) rat model and a clinically relevant cancer-transplant model to examine its antitumour and immunosuppressive activity. Findings: The combination of SN38 with RAPA resulted in synergetic effects against HCC cells and alleviated RAPA resistance by abrogating Akt/mTOR signalling activation. SRNPs exhibited potent antitumour efficiency in the orthotopic HCC model while substantially prolonging the survival of allografts in the OLT model. In the cancer-transplant model that simultaneously bears tumour xenografts and skin allografts, SRNPs not only effectively inhibited tumour growth but also attenuated allograft damage. Interpretation: The nanotherapy presented here had enhanced efficacy against tumours and maintained satisfactory immunosuppressive activity and thus has great potential to improve the survival outcomes of patients with a high risk of tumour recurrence following OT. Funding: This work was supported by the National Natural Science Foundation of China (32171368 and 31671019), the Zhejiang Provincial Natural Science Foundation of China (LZ21H180001), the Zhejiang Province Preeminence Youth Fund (LR19H160002), and the Jinan Provincial Laboratory Research Project of Microecological Biomedicine (JNL-2022039c).

Background The level of exercise self-efficacy of lung cancer patients affects the establishment of exercise goals and the belief of overcoming difficulties. Understanding the current situation has a good predictive effect on the exercise behavior of lung cancer patients, but there is no norm for exercise self-efficacy assessment tools for lung cancer patients in China, which makes the measurement results lack of reference standards. Objective To establish the norm of Exercise Self-efficacy Scale for lung cancer patients in Anhui Province. Methods Anhui Province was divided into northern, central and southern regions according to its geographical location. A total of 1 600 lung cancer patients were selected by regional stratified random sampling from January to August in 2021, and Exercise Self-efficacy Scale was used to investigate them, the mean, percentile and demarcation norm of the scale were established. Results A total of 1 600 questionnaires were distributed, 1 459 valid questionnaires were recovered, with an effective recovery rate of 91.19%. The total score of Exercise Self-efficacy Scale for lung cancer patients in Anhui Province was (67.66±14.90) , and the score of efficacy expectation dimension was (63.09±18.13) , the outcome expectation dimension score was (73.48±14.10) . In this study, the mean norm of Exercise Self-efficacy Scale for lung cancer patients in Anhui Province was established according to gender and age groups (young group of 19-35 years old, middle-aged group of 36-59 years old, and elderly group of ≥60 years old) . The results of multiple linear regression analysis showed that gender, age, education level, occupation, regular exercise habits, concomitant diseases, hospital level, department, BMI and regional division were the influencing factors for the total score of exercise self-efficacy in lung cancer patients (P

Abstract Objective This paper explores the effect of blood sample storage temperature and time on the erythrocyte sedimentation rate (ESR) by using the Weiss method. Methods Whole blood samples were collected from 80 patients and diluted 1:9 with sodium citrate solution. Each sample was split into two tubes. Using the Weiss method, ESR was tested within 1 h of collection, and one sample was placed at 4 °C and the other at room temperature (23 ± 2 °C). ESR was then measured at 2, 4, 6, 8, 12, and 24 h. The data were statistically analyzed with consideration for temperature and time. Results ESR decreased gradually over 6 h at room temperature, but the results were not statistically significant. Similarly, there was no significant difference in the decline of ESR within 8 h at 4 °C. However, ESR results decreased significantly after the samples were stored at room temperature for more than 6 h or at 4 °C for more than 8 h. ESR reduction was lower in the samples stored at 4 °C than in those stored at room temperature over the same time period. Conclusion Blood sample storage temperature and duration can affect the measurement of ESR using the Weiss method. ESR testing should be completed within 4 h of sample collection in clinical work.