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Yan Cui, Xuena Li, Bulin Du, Yao Diao, Yaming Li Department of Nuclear Medicine, The First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Yaming LiDepartment of Nuclear Medicine, The First Hospital of China Medical University, North Nanjing Street 155, Shenyang, Liaoning 110001, People’s Republic of ChinaTel +86-24-83282142Fax +86-24-83282671Email ymli2001@163.comPurpose: This study aimed to evaluate the role of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in expression of tumor programmed death ligand-1 (PD-L1) expression and prognostic significance of 18F-FDG PET/CT at different PD-L1 status in patients with lung adenocarcinoma.Patients and Methods: Seventy-three patients with primary lung adenocarcinoma who received 18F-FDG PET/CT before treatment were retrospectively included in this study. Expression of tumor PD-L1, programmed death-1 (PD-1) and glucose metabolic parameters were evaluated.Results: Tumor PD-L1 expression was positively correlated with maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), hexokinase II (HK-II) and glucose transporter 1 (GLUT-1) (P< 0.0001 for all). SUVmax was a unique independent predictor of tumor PD-L1 expression, with an optimal cut-off value of 9.5. For all the patients, tumor stage (P< 0.001) and SUVmax (P=0.009) were independent prognostic indicators of disease-free survival (DFS)/progression-free survival (PFS) while carcino-embryonic antigen (CEA) (P=0.003), Ki67 (P=0.042), PD-L1 (P=0.048) and TLG (P=0.004) were independent prognostic indicators of overall survival (OS). Tumor stage (P=0.004) and SUVmax (P=0.022) were independent prognostic indicators of DFS/PFS while TLG (P=0.012) and CEA (P=0.045) were independent prognostic indicators of OS in the PD-L1-positive group. In the PD-L1-negative group, tumor stage (P=0.002) and CEA (P=0.006) were unique independent prognostic indicators of DFS/PFS and OS, respectively.Conclusion: 18F-FDG PET/CT may potentially predict tumor PD-L1 expression and play a role in predicting prognosis of PD-L1/PD-1 immunotherapy in lung adenocarcinoma.Keywords: 18F-fluorodeoxyglucose, positron emission tomography, programmed death ligand-1, lung adenocarcinoma, prognosis

Yifan Diao,1 Mingshuang Li,1 Zhiran Huang,1 Jing Sun,1 Yoke Ling Chee,2 Yunali Liu1 1School of Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, People’s Republic of China; 2Third World Network, George Town 10400, Penang, MalaysiaCorrespondence: Jing Sun; Yunali LiuSchool of Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, 5 Dongdansantiao, Dongcheng District, Beijing 100730, People’s Republic of ChinaTel/Fax +86-10-65105537Email sunjing@sph.pumc.edu.cn; yliu@pumc.edu.cnAbstract: China’s healthcare reform aims to provide affordable and equitable basic healthcare for all by 2020. Access to medicines is an essential part of the healthcare. The efforts of promoting access to medicines have been moving from meeting the needs of the basic healthcare, towards increasingly dedicated resources to offer breakthrough therapies. Looking at access to novel medicines from a health system perspective, and placing the changes China has made into that system context, this paper makes a comprehensive review of the progress of access to novel medicines in China. The review drew on two sources of information, which included desk review of published and grey literature, and key informant interview. Five hurdles were identified which create barriers of access to novel medicines, ranging from regulation and financing of medicines, intellectually property rights protection, and development of innovation capacity, to other health system components. Multiple policies have been implementing in China to remove the multiple access barriers gradually. Universal access to medicines has been moving from towards the basic common conditions to the world breakthrough technologies. We see cause for optimism, but recognize that there is a long way to go. Achieving broader and better access to modern medicines for Chinese patients will require multiple and coordinated government efforts, which would need to target the whole lifecycle regulation of novel medicines with a health system perspective, from balancing IP protection, strengthening R&D and public health, to appropriate regulatory approach and financing mechanism, and to supply chain management, as well as smart use.Keywords: access to novel medicines, regulatory, affordability, IP, R&D, health system

Flavonoids from mulberry leave (FML) are natural flavonoids, and Candida tropicalis (CT) is yeast like microbe. In this study, forty-eight male calves were selected with born weight (40.5±0.7 kg) and 20±2 days age, divided into 4 groups randomly. FML was supplemented in a dairy calf starter at 2 g/d per calf before weaning, or 4 g/d per calf after weaning (FML group), while CT was added in a dairy calf starter at 1 g/d per calf (CT group). Our results showed that FML could be used to enhance body weight (BW) of calves through enhancing apparent digestibility of ether extract (EE) of the diet, and increased the levels of serum growth hormone (GH) and insulin-like growth factors 1 (IGF-1) in calves after the age of 56 days. CT enhanced the BW of calves before weaning through increasing the apparent digestibility of neutral detergent fiber (NDF) of the diet, and elevated the apparent digestibility of EE of the diet of calves after weaning through increasing the level of serum IGF-1 in calves. Furthermore, the mixture of FML and CT plays a synergistic role in enhancing growth, improving feed intake and nutriment digestibility. In conclusion, FML and CT could be used as additives to increase growth and nutrient digestibility in calves.

Trypanosomatida parasites, such as Trypanosoma and Leishmania, are the cause of deadly diseases in many third world countries. The three dimensional structure of their mitochondrial DNA, known as kinetoplast DNA (kDNA), is unique since it is organized into several thousands of minicircles that are topologically linked. How and why the minicircles form such a network have remained unanswered questions. In our previous work we have presented a model of network formation that hypothesizes that the network is solely driven by the confinement of minicircles. Our model shows that upon confinement a percolation network forms. This network grows into a space filling network, called saturation network, upon further confinement of minicircles. Our model also shows, in agreement with experimental data, that the mean valence of the network (that is, the average number of minicircles topologically linked to any minicircle in the network) grows linearly with minicircle density. In our previous studies however we disregarded DNA flexibility and used rigid minicircles to model DNA, here we address this limitation by allowing minicircles to be flexible. Our numerical results show that the topological characteristics that describe the growth and topology of the minicircle networks have similar values to those observed in the case of rigid minicircles suggesting that these properties are robust and therefore a potentially adequate description of the networks observed in Trypanosomatid parasites.

It is well known that genomic materials (long DNA chains) of living organisms are often packed compactly under extreme confining conditions using macromolecular self-assembly processes but the general DNA packing mechanism remains an unsolved problem. It has been proposed that the topology of the packed DNA may be used to study the DNA packing mechanism. For example, in the case of (mutant) bacteriophage P4, DNA molecules packed inside the bacteriophage head are considered to be circular since the two sticky ends of the DNA are close to each other. The DNAs extracted from the capsid without separating the two ends can thus preserve the topology of the (circular) DNAs. It turns out that the circular DNAs extracted from bacteriophage P4 are non-trivially knotted with very high probability and with a bias toward chiral knots. In order to study this problem using a systematic approach based on mathematical modeling, one needs to introduce a DNA packing model under extreme volume confinement condition and test whether such a model can produce the kind of knot spectrum observed in the experiments. In this paper we introduce and study a model of equilateral random polygons con_ned in a sphere. This model is not meant to generate polygons that model DNA packed in a virus head directly. Instead, the average topological characteristics of this model may serve as benchmark data for totally randomly packed circular DNAs. The difference between the biologically observed topological characteristics and our benchmark data might reveal the bias of DNA packed in the viral capsids and possibly lead to a better understanding of the DNA packing mechanism, at least for the bacteriophage DNA. The purpose of this paper is to provide information about the knot spectrum of equilateral random polygons under such a spherical confinement with length and confinement ratios in a range comparable to circular DNAs packed inside bacteriophage heads.

Understanding the failure mechanism of geosynthetic-reinforced embankments on soft foundations is crucial for ensuring safety in design. This study aimed to investigate the failure mechanism and stability of embankments reinforced with varying layers and lengths of geosynthetic reinforcements utilising centrifuge testing and numerical modelling. The results show that a foundation under construction exhibits a progressive shear failure coupled with a tensile failure of the geosynthetic reinforcement. The plastic shear strain in the soft clay layer initiates at the centreline, shoulder and embankment toe and propagates both forward and backward until a critical slip surface develops. The tensile failure of the geosynthetic was observed at the embankment centre. Comparatively, implementing two shorter layers of geosynthetics proved more advantageous for overall stability than using a single layer with the entire length. By analysing the strain distribution in the foundation, the deformation modes of the embankment reinforced by different numbers of geosynthetic layers were clarified. It was found that increasing the number of geosynthetic layers extended the active shear zone in soft clay. [ABSTRACT FROM AUTHOR]

Older people often face varied and vicious abuse from care workers. Situations are typically more pronounced for older people who live with additional cognitive or physical difficulties, such as dementia and disabilities, the prevalence of which has been on the rise in China and elsewhere. Recent reported discoveries of elder abuse in China, which span alarming levels of verbal, physical, psychological, financial, and sexual abuse, have almost all been caused by nannies or 'bao mu'. Different from Western countries, the word nanny is often used to refer to people who offer caregiving help in residential settings at large, regardless of the age of the care recipients. What is also different is the lack of regulations or even rigorous training and evaluation processes for nannies in China: almost anyone can become a nanny—even though a background check is often required for nannies, this process is often highly variable and dependent on the specific labour agencies that nannies are registered with. Yet without structured studies and systematic data, little is known about the extent and severity of nanny-induced elder abuse in China. To this end, this article aims to discuss the unique elderly care environment—such as the '721 Rule'—in China, particularly in the post-COVID era, and highlight the critical need for timely and rigorous studies on the potential prevalence and severity of nannies' abuse and neglect of older people. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aims to explore the risk factors for stone remnants and recurrence after lateral decubitus percutaneous nephrolithotomy (PCNL), providing insights to enhance the stone-free rate and reduce the stone recurrence rate. PATIENTS AND METHODS: A retrospective analysis was conducted on 356 patients with renal or upper ureteral stones who underwent lateral decubitus PCNL from January 2015 to August 2022. Among them, 271 patients had complete clinical and follow-up data. General clinical information, perioperative data, and follow-up data were collected. Univariate and multivariate logistic regression analyses were performed to identify risk factors for stone remnants and recurrence after lateral decubitus PCNL. RESULTS: The stone-free rate after lateral decubitus PCNL was 88.6% (195/271), and the stone recurrence rate within three years was 28.1% (76/271). Stone size (p<0.001) and stone co-infection (p=0.047) were identified as independent risk factors for stone remnants after lateral decubitus PCNL. Multiple stones (p=0.003) were an independent risk factor for stone recurrence after lateral decubitus PCNL. CONCLUSIONS: Stone size and stone co-infection are independent risk factors for stone remnants after lateral decubitus PCNL. Multiple stones are an independent risk factor for stone recurrence after lateral decubitus PCNL. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease(COPD)is a group of lung diseases characterized by persistent airflow limitation, often accompanied by chronic hypoxia. This chronic hypoxia can lead to structural and functional changes in the walls of blood vessels throughout the body, causing vascular injury and altered vascular reactivity. The retina and choroid are key ocular structures with rich blood supply and are particularly prone to microstructural changes due to ischemia and hypoxia. Optical coherence tomography(OCT), an ideal tool for observing these microstructural changes, serves as a non-invasive method for assessing retinal microstructures and microvascular pathology. Currently, there is a lack of comprehensive reviews summarizing OCT-based morphological changes in the eyes of COPD patients. This paper provides an in-depth review of existing studies on ocular OCT in COPD patients, focusing on structural and blood flow changes in the retina and choroid. The primary goal of this review is to summarize the impact of COPD on ocular microstructures, explore the underlying mechanisms of these morphological changes, and offer new perspectives for assessing eye diseases in COPD patients.

Abstract Background This study retrospectively compared short-term clinical outcomes and complications of minimally invasive surgery transforaminal lumbar interbody fusion(MIS-TLIF)and endoscopic lumbar interbody fusion(Endo-LIF))for two-segmental lumbar degenerative disease, aiming to guide spine surgeons in selecting surgical approaches. Methods From January 2019 to December 2023, 30 patients were enrolled,15 in the MIS-TLIF group and 15 in the Endo-LIF group. All patients were followed up for more than 3 months after surgery and the following information was recorded: (1)surgery time, difference in hemoglobin between preoperative and postoperative, surgical costs, first time out of bed after operation, postoperative hospitalization time, postoperative complication; (2) ODI score (The Oswestry Disability Index), leg and back VAS score (Visual Analogue Scale), and lumbar vertebra JOA score (Japanese Orthopaedic Association Scores); (3) MacNab score at final follow-up to assess clinical outcome, CT to evaluate lumbar fusion. Results There were significant differences between the two groups regarding operation time and cost, with the MIS-TLIF group performing significantly better. Intraoperative bleeding was considerably less in the Endo-LIF group compared to the MIS-TLIF group. However, there were no significant differences in the time of the first postoperative ambulation, postoperative hospitalization time, and postoperative complications. There was no significant difference in preoperative VAS, ODI, and JOA between the two surgical groups There were no significant differences in VAS(leg), ODI, and JOA scores between the two groups before and at 1 day,7 days, 1 month, 3 months and final follow-up. However, at 1 day postoperatively, the VAS( back)score in the Endo-LIF group was lower than that in the MIS-TLIF group, and the difference was statistically significant. At the final follow-up, all patients achieved grade III and above according to the Bridwell criteria, and there was no significant difference between the two surgical groups compared to each other. According to the MacNab score at the final follow-up, the excellent rate was 80.00% in the Endo-LIF group and 73.33% in the MIS-TLIF group, with no significant difference between the two groups. Conclusion There was no significant difference in short-term efficacy and safety between Endo-LIF and MIS-TLIF for two-segment degenerative lumbar diseases. MIS-TLIF has a shorter operative time and lower costs, while Endo-LIF causes less tissue damage, blood loss, and early postoperative pain, aiding long-term recovery. Both MIS-TLIF and Endo-LIF are promising for treating two-segment lumbar degenerative disease. The choice of a surgical procedure depends on the patient’s financial situation, their ability to tolerate surgery, and the surgeon’s expertise.

An increasing number of catastrophic progressive collapses of deep excavations have occurred throughout the world. However, the research on progressive collapse mechanisms is limited. In this paper, two categories of model tests were conducted to investigate the mechanism of partial collapse (sudden failures of certain retaining piles) and progressive collapse. The model test results show that partial collapse can cause a sudden increase in the bending moments of adjacent piles via an arching effect. The load-transfer coefficients are defined to be equal to the peak increase ratios of the maximum bending moments in adjacent piles (peak moments caused by collapse over the values before the collapse). When the maximum load-transfer coefficient is larger than the bearing capacity safety factor of the piles, the partial failure will lead to progressive collapse. The influential factors of the progressive collapse mechanism, such as the partial collapse extent, excavation depth, and capping beam, were also investigated. During progressive collapse, the previous failed pile could cause new stress arching; simultaneously, the soil behind certain nearest intact piles could become loosened and destroy the arch springing of the stress arching, causing the progressive collapse to cease gradually. Key words: deep excavation, progressive collapse, arching effect, retaining piles, trapdoor. Un nombre croissant d'effondrements catastrophiques progressifs des excavations profondes ont eu lieu dans le monde entier. Cependant, la recherche sur les mecanismes de l'effondrement progressif est limitee. Dans cet article, deux categories d'essais sur modele ont ete menees pour etudier le mecanisme d'effondrement partiel (echecs soudains de certains pieux retenus) et l'effondrement progressif. Les resultats de test du modele montrent que l'effondrement partiel peut causer une augmentation soudaine dans les moments de flexion des pieux adjacents par un effet de voute. Les coefficients de transfert de charge sont definis comme etant egaux aux rapports d'augmentation maximale du maximum des moments de flexion dans les pieux adjacents (moments de pointe causes par l'effondrement sur les valeurs avant l'effondrement). Lorsque le coefficient de transfert de charge maximale est plus grand que le coefficient de securite de capacite portante des pieux, l'echec partiel conduira a l'effondrement progressif. Les facteurs d'influence du mecanisme d'effondrement progressif, tels que l'ampleur de l'effondrement partiel, la profondeur de l'excavation et la poutre de couronnement, ont aussi ete examines. Au cours de l'effondrement progressif, le pieu defaillant precedent pourrait causer une nouvelle arche de contrainte; simultanement, le sol derriere certains pieux intacts pourrait devenir decompacte et detruire l'arc jaillissant de l'arche de contrainte, faisant en sorte que l'effondrement progressif cesse graduellement. [Traduit par la Redaction] Mots-cles : excavation profonde, effondrement progressif, effet de voute, pieux de retenue, porte d'acces., Introduction The design of retaining structures of excavations generally proceeds element-by-element (Zheng et al. 2011). Therefore, retaining systems always lack integrity and sufficient redundancy. Consequently, a partial failure of a [...]

ObjectivesThe demand for energy in outdoor work and survival is increasing, and there are some significant shortcomings in the existing conventional energy supply methods, such as the need to carry a large amount of fuel for conventional generators and heavy weight of cells. Solar photovoltaic/thermal (PV/T) technology can effectively solve the problem of lack of energy for outdoor survival and field work. However, most of the existing PV/T collectors are rigid structures with large weight and are not easy to carry.MethodsA light and thin PV/T module based on the combination of a Cu(In,Ga)Se2(CIGS) thin film battery and a piece of capillary network were proposed. The energy collection performance of the module and the impact of water flow rate on the photoelectric and photothermal conversion efficiency of the module were studied experimentally.ResultsUnder the typical Shanghai climate conditions, the all-day electrical efficiency and thermal efficiency of the module are 13.04% and 22.50%, respectively. Under experimental conditions with an average irradiance of 760 ‍W/m², the optimal energy collection performance of this PV/T is achieved when the water flow rate is 2.1 ‍L/min. The cooling water in the capillary network can effectively reduce the cell temperature (by 10 ℃) and improve the energy utilization efficiency (by 23.94%).ConclusionsThe module has the characteristics of high power density, light weight and flexibility, and can be used for energy supply during outdoor work and survival, providing a new idea for the design of outdoor energy equipment.

Abstract Objective This study analyzes the safety and efficacy of percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) treatments for Stage III Kummell’s disease without neurological symptoms, comparing the advantages and disadvantages of these two minimally invasive surgical methods. Methods A retrospective analysis was conducted on 53 patients with non-neurological Stage III Kummell’s disease treated with PVP and PKP at our hospital from December 2018 to January 2023. Patients were divided into PVP (25 cases) and PKP (28 cases) groups based on the surgical method. There were no significant differences in general preoperative data between the two groups (all p > 0.05), ensuring comparability. The study compared surgical duration, volume of bone cement injected, distribution pattern of bone cement, rate of bone cement leakage, and preoperative, postoperative, and final follow-up scores of Visual analogue scale(VAS) and Oswestry disability index(ODI). Additionally, relative anterior height of the injured vertebrae, and Cobb angle of deformity, along with their changes at preoperative, postoperative, and final follow-up stages were calculated and analyzed. Results No significant preoperative differences were observed between the groups (p > 0.05). The PKP group had longer surgeries, higher cement volumes (p 0.05) but improved significantly from preoperative (p 0.05). Conclusion The study evaluates the safety and efficacy of PVP and PKP for Stage III Kummell’s disease without neurological symptoms, comparing the merits of both minimally invasive techniques.

Acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) represents a primary cause of treatment failure in non-small cell lung cancer (NSCLC) patients. Chemokine (C-C motif) ligand 2 (CCL2) is recently found to play a pivotal role in determining anti-cancer treatment response. However, the role and mechanism of CCL2 in the development of EGFR-TKIs resistance have not been fully elucidated. In the present study, we focus on the function of CCL2 in the development of acquired resistance to EGFR-TKIs in NSCLC cells. Our results show that CCL2 is aberrantly upregulated in EGFR-TKIs-resistant NSCLC cells and that CCL2 overexpression significantly diminishes sensitivity to EGFR-TKIs. Conversely, CCL2 suppression by CCL2 synthesis inhibitor, bindarit, or CCL2 knockdown can reverse this resistance. CCL2 upregulation can also lead to enhanced migration and increased expressions of epithelial-mesenchymal transition (EMT) markers in EGFR-TKI-resistant NSCLC cells, which could also be rescued by CCL2 knockdown or inhibition. Furthermore, our findings suggest that CCL2-dependent EGFR-TKIs resistance involves the AKT-EMT signaling pathway; inhibition of this pathway effectively attenuates CCL2-induced cell migration and EMT marker expression. In summary, CCL2 promotes the development of acquired EGFR-TKIs resistance and EMT while activating AKT signaling in NSCLC. These insights suggest a promising avenue for the development of CCL2-targeted therapies that prevent EGFR-TKIs resistance in NSCLC.

Surface cracks in gun bore may exacerbate rifling ablation and wear and in turn shorten barrel life. Thermomechanical coupling finite element (FE) models of bore are established and the dynamic responses of the bore under high-temperature and high-pressure are numerically simulated. The stress distribution characteristics on the inner surface are analyzed and the effects of autofrettage, number of firings and harden layer on the stress distribution are discussed. Based on the stress distribution characteristics, FE models with two initial cracks on the ledge of land surface are set up and the propagation, interaction and intersection of the cracks are numerically simulated, considering the effect of the distance between the two cracks. Based on simulation results, the initiation and propagation pattern and mechanism of the cracks on the inner surface are analyzed. An ablation test system was designed and produced, and used to experimentally verify the initiation and propagation mechanism of the cracks. The observed crack patterns on the inner surface of a real gun bore are also used to illustrate the mechanism obtained in this work. Understanding of the initiation and propagation mechanism of cracks in gun bore can be applied to improve and optimize the design of barrels.

The purpose of this study is to investigate the risk factors for postoperative deep vein thrombosis (DVT) in patients with traumatic spinal fractures complicated with Spinal Cord Injury(SCI). We conducted a retrospective analysis of 110 patients with traumatic spinal fractures and SCI admitted to our hospital from March 2021 to April 2024. DVT was diagnosed using ultrasound. Patient history, general data, surgical data, laboratory tests, and thromboelastogram (TEG) results were collected. The patients were divided into a DVT group and a non-DVT group according to the results of ultrasound one week after surgery. The risk factors and diagnostic value were analyzed using binary logistic regression and receiver operating characteristic (ROC) curves in both univariate and multivariate analyses. Multivariate and ROC analysis results showed that D-dimer, lower extremity, duration of bedrest, and MA values of TEG were independent risk factors for DVT in SCI, with D-dimer having the highest diagnostic value (AUC = 0.883). The AUC values for lower extremity, duration of bedrest, and MA were 0.731, 0.750, and 0.625. In conclusion, Postoperative D-dimer > 5.065 mg/l, lower extremity