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Hongmei Xu,1 Ningning Wu,2 Hui Yu,3 Chuanqing Wang,4 Jikui Deng,5 Hongmei Wang,5 Chunzhen Hua,6 Yinghu Chen,6 Xuejun Chen,7 Ting Zhang,8 Hong Zhang,9 Yiping Chen,10 Shifu Wang,11 Qing Cao,12 Huiling Deng,13 Sancheng Cao,14 Jianhua Hao,15 Wei Gao,16 Chunmei Jing2 1Infectious Disease Department, Children’s Hospital of Chongqing Medical University; National Clinical Research Center for Child Health and Disorders; Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, People’s Republic of China; 2Department of Clinical Laboratory, Children’s Hospital of Chongqing Medical University; National Clinical Research Center for Child Health and Disorders; Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, People’s Republic of China; 3Infectious Disease Department, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, People’s Republic of China; 4Department of Clinical Microbiology Laboratory, Nosocomial Infection Control Department, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, People’s Republic of China; 5Infectious Disease Department, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 6Infectious Disease Department, Children’s Hospital of Zhejiang University, Zhejiang, People’s Republic of China; 7Department of Medical Laboratory, Children’s Hospital of Zhejiang University, Zhenjiang, People’s Republic of China; 8Digestive and Infectious Disease Department, Children’s Hospital of Shanghai Jiaotong University, Shanghai, People’s Republic of China; 9Department of Medical Laboratory, Children’s Hospital of Shanghai Jiaotong University, Shanghai, People’s Republic of China; 10Pediatric Infectious Disease Department, Second Affiliated Hospital, and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 11Department of Medical Laboratory, Qilu Children’s Hospital, Shandong University, Shandong, People’s Republic of China; 12Infectious Disease Department, Shanghai Children’s Medical Center, Shanghai, People’s Republic of China; 13Infectious Disease Department, Xi’an Children’s Hospital, Xi’an, People’s Republic of China; 14Department of Medical Laboratory, Xi’an Children’s Hospital, Xi’an, People’s Republic of China; 15Infectious Disease Department, Children’s Hospital of Kaifeng City, Kaifeng, People’s Republic of China; 16Department of Medical Laboratory, Children’s Hospital of Kaifeng City, Kaifeng, People’s Republic of ChinaCorrespondence: Chunmei Jing, Department of Clinical Laboratory, Children’s Hospital of Chongqing Medical University, Chongqing Medical University, No. 136 Zhongshan Er Road, Yu Zhong District, Chongqing, 400014, People’s Republic of China, Email jcm791203@163.comObjective: Aim to investigate the pathogens distribution and drug resistance of gram-negative bacteria causing bloodstream infection (BSIs) in Infectious Disease Surveillance of Pediatric from 2016 to 2022. The prevalence of four important drug resistance phenotypes was studied: difficult-to-treat resistance, fluoroquinolone resistance, carbapenem resistance, and extended-spectrum cephalosporin resistance, and to provide reference basis for preventing and treating BSIs diseases in children.Methods: Strain identification and antimicrobial susceptibility tests were independently performed at each hospital. Data were analyzed using Whonet 5.6 and GraphPad Prism 8 software. The Mann–Whitney U-test was used to examine and compare temporal changes.Results: A total of 39977 BSIs strains were isolated, with 27.1% of the negative bacteria causing BSIs (10824 strains). The highest bacteria detected were E. coli and S. maltophilia in the neonatal and pediatric groups. The detection rate of carbapenem-resistant-K. pneumoniae (CRKPN) in neonate group was 31.4%, significantly increased compared with pediatric group, whose detection rate was 24.7%. The rates of resistance to levofloxacin and trimethoprim/sulfamethoxazole were significantly lower in neonatal groups than pediatric groups in BSIs caused by K. pneumoniae. To imipenem and meropenem were 3.6% and 3.9% among neonatal isolates, which was lower than 4.7% and 5.8 among pediatric BSIs caused by E. coli. Isolated from neonatal BSIs caused by A. baumannii showed lower resistance ratios to all the agents tested than those from pediatric. However, only the prevalence of piperacillin/tazobactam resistance was statistically lower than that in pediatric BSIs caused by P. aeruginosa. The average detection rates of carbapenem resistance, extended-spectrum cephalosporin resistance, and fluoroquinolone resistance for K. pneumoniae and E. coli were 28.1%,41.4%,11.6% and 4.0%,24.3%,31.1%, respectively.Conclusion: The detection rate of gram-negative pathogens showed an increasing trend among the bloodstream infection. The detection rate of CRKPN assumed a downward trend in 2018. There are differences types of pathogens between the neonatal group and the pediatric group, The detection rate of CRKPN in the neonate group was significantly higher than pediatric group. The first average detection rates for carbapenem resistance, extended-spectrum cephalosporin resistance, and fluoroquinolone resistance were obtained for A. baumannii, K. pneumoniae, and Escherichia coli, respectively. Those data showed a high level of antimicrobial resistance, which has posed an urgent threat to Children’s health, suggested that effective monitoring of antimicrobial resistance and antimicrobial stewardship among children in China are required.Keywords: bloodstream infection, pathogenic bacterium, difficult-to-treat resistance, carbapenem resistance, extended-spectrum cephalosporin resistance, fluoroquinolone resistance

Zesi Liu,1 Chunli Jing2 1Department of Gynecology and Obstetrics, The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Department of Ultrasound of Gynecology and Obstetrics, The Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of ChinaCorrespondence: Chunli Jing, Department of Ultrasound of Gynecology and Obstetrics, The Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China, Tel +86-133-522-31070, Fax +86-82866055, Email tg980927@126.comBackground: Retroperitoneal ectopic pregnancy (REP) is an extremely rare type of ectopic pregnancy that can be life threatening. The pathogenesis of REP remains inconclusive and the diagnosis and treatment modalities are unclear.Case Presentation and Review of the Literature: A 27-year-old woman (gravida: 3; parturition: 0) underwent transvaginal ultrasound (TVS) 40 days after in vitro fertilization-embryo transfer (IVF-ET); no intrauterine gestational sac was detected. The patient was asymptomatic and had no abnormalities on physical examination. β-HCG and progesterone were 18.210 mIU/mL and 10.891 ng/mL, respectively. Transabdominal ultrasound (TAS) showed that the gestational sac had implanted adjacent to the abdominal aorta and near a branch of the iliac artery. Laparoscopic exploration was performed under general anesthesia; intraoperative findings showed that the gestational sac was approximately 2.5 cm in diameter and in the same location as suggested by preoperative ultrasound. Histopathological examination confirmed the diagnosis of EP. On day three post-surgery, the levels of β-HCG had fallen to 911 mIU/mL. We further systematically reviewed the REP cases reported in the English literature and performed a review on the diagnosis and treatment of REP.Conclusion: Clinicians should be alert to the occurrence of REP. Combined radiological examinations including ultrasonography (TAS and TVS), CT, and MRI are essential for the early diagnosis of REP. Once a definitive diagnosis is made, appropriate treatment should be administered immediately. Although there are cases of successful drug treatment described in the literature, surgery remains as the primary treatment option for REP.Keywords: retroperitoneal ectopic pregnancy, ultrasound, surgery, diagnosis, review

The genetic factors involved in disease progression and drug resistance in multiple myeloma (MM) are varied and complex. Here, genomic and transcriptomic profiling of 511 relapsed and refractory MM patients reveals genetic alterations in several oncogenic pathways contributing to progression and resistance to MM therapies.

Lei Yang,1,2,* Xiafei Li,3,* Yiting Wu,4 Pengchong Du,1,5 Lulu Sun,1 Zhenyang Yu,2 Shuang Song,1 Jianshen Yin,1 Xianfen Ma,1 Changqin Jing,1 Junqiang Zhao,3 Hongli Chen,1 Yuzhen Dong,2 Qiqing Zhang,1 Liang Zhao1,6,7 1College of Life Science and Technology, Xinxiang Medical University, Xinxiang, People’s Republic of China; 2Department of Orthopedics, First Affiliated Hospital, Xinxiang Medical University, Xinxiang, People’s Republic of China; 3College of Medical Engineering, Xinxiang Medical University, Xinxiang, People’s Republic of China; 4Xiacun Community Health Service Center, Shenzhen Hospital, University of Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 5Department of Cardio-Thoracic Surgery, Third Affiliated Hospital, Xinxiang Medical University, Xinxiang, People’s Republic of China; 6Key Laboratory of Cardiac Structure Research, Zhengzhou Seventh People’s Hospital, Zhengzhou, People’s Republic of China; 7The Central Lab, The Third People’s Hospital of Datong, Datong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang Zhao; Yuzhen Dong Email zhaoliang4321@163.com; dongyuzhen1998@163.comPurpose: The development of tissue-engineered blood vessels provides a new source of donors for coronary artery bypass grafting and peripheral blood vessel transplantation. Fibrin fiber has good biocompatibility and is an ideal tissue engineering vascular scaffold, but its mechanical property needs improvement.Methods: We mixed polyurethane (PU) and fibrin to prepare the PU/fibrin vascular scaffolds by using electrospinning technology in order to enhance the mechanical properties of fibrin scaffold. We investigated the morphological, mechanical strength, hydrophilicity, degradation, blood and cell compatibility of PU/fibrin (0:100), PU/fibrin (5:95), PU/fibrin (15:85) and PU/fibrin (25:75) vascular scaffolds. Based on the results in vitro, PU/fibrin (15:85) was selected for transplantation in vivo to repair vascular defects, and the extracellular matrix formation, vascular remodeling, and immune response were evaluated.Results: The results indicated that the fiber diameter of the PU/fibrin (15:85) scaffold was about 712nm. With the increase of PU content, the mechanical strength of the composite scaffolds increased, however, the degradation rate decreased gradually. The PU/fibrin scaffold showed good hydrophilicity and hemocompatibility. PU/fibrin (15:85) vascular scaffold could promote the adhesion and proliferation of mesenchymal stromal cells (MSCs). Quantitative RT-PCR experimental results showed that the expression of collagen, survivin and vimentin genes in PU/fibrin (15:85) was higher than that in PU/fibrin (25:75). The results in vivo indicated the mechanical properties and compliance of PU/fibrin grafts could meet clinical requirements and the proportion of thrombosis or occlusion was significantly lower. The graft showed strong vasomotor response, and the smooth muscle cells, endothelial cells, and ECM deposition of the neoartery were comparable to that of native artery after 3 months. At 3 months, the amount of macrophages in PU/fibrin grafts was significantly lower, and the secretion of pro-inflammatory and anti-inflammatory cytokines decreased.Conclusion: PU/fibrin (15:85) vascular scaffolds had great potential to be used as small-diameter tissue engineering blood vessels.Keywords: PU/fibrin scaffold, small diameter, in vitro biocompatibility, biomechanical properties, vascular remodeling

Context Patients treated with maintenance hemodialysis experience significant symptom burden resulting in impaired quality of life. However, the association of patient reported symptom burden and the risk of healthcare use for patients with end stage kidney disease on hemodialysis has not been fully explored. Objectives To investigate if higher symptom burden, assessed by the Edmonton Symptom Assessment System-revised (ESASr), is associated with increased healthcare use in patients with end stage kidney disease on hemodialysis. Methods Prospective, single-center, study of adult patients on HD. Participants completed the ESASr questionnaire at enrollment. Baseline demographic, clinical information as well as healthcare use events during the 12-month following enrollment were extracted from medical records. The association between symptom burden and healthcare use was examined with a multivariable adjusted negative binomial model. Results Mean (SD) age of the 80 participants was 71 (13) years, 56% diabetic, and 70% male. The median (IQR) dialysis vintage was 2 (1–4) years. In multivariable adjusted models, higher global [incident rate ratio (IRR) 1.02, 95% confidence interval (CI) 1.00–1.04, p = .025] and physical symptom burden score [IRR 1.03, CI 1.00–1.05, p = .034], but not emotional symptom burden score [IRR 1.05, CI 1.00–1.10, p = .052] predicted higher subsequent healthcare use. Conclusions Our preliminary evidence suggests that higher symptom burden, assessed by ESASr may predict higher risk of healthcare use amongst patients with end stage kidney disease on hemodialysis. Future studies need to confirm the findings of this preliminary study and to assess the utility of ESASr for systematic symptom screening.

Jiajia Lin,1,* Tingting Fang,1,* Mengxuan Zhu,1,* Xin Xu,1 Juan Zhang,1 Susu Zheng,1 Chuyu Jing,1 Meixia Zhang,1 Binbin Liu,1 Boheng Zhang1,2 1The Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China; 2Center for Evidence-Based Medicine, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Boheng Zhang; Binbin LiuThe Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai 200032, People’s Republic of ChinaTel +86 216 403 8038Fax +86 216 403 8038Email zhang.boheng@zs-hospital.sh.cn; liu.binbin@zs-hospital.sh.cnObjective: Prognostic performance of inflammation-based prognostic scores, including the Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), Prognostic Index (PI) and Prognostic Nutritional Index (PNI) has been explored in patients with varied types of cancer, though little data is available in intrahepatic cholangiocarcinoma (ICC). This study sought to evaluate the impact of systemic inflammation on the overall survival (OS) of ICC patients, and to identify more optimal prognostic indices.Patients and methods: The prognostic power of all the scores mentioned above was compared in 123 patients underwent curative surgery for ICC using Kaplan–Meier curves, COX regression models and the receiver operating characteristics (ROC) curves. The results were validated in a cohort of 95 ICC patients.Results: Multivariate analysis identified LMR as the only independent inflammation-based predictor for OS in the training cohort (P=0.007, HR 2.082, 95% CI 1.218–3.558). More importantly, the combined score of LMR and pTNM designated the inflammation-based pathological stage (IPS) outperformed other established scores in terms of discriminatory ability, monotonicity and homogeneity in the training and validation cohorts.Conclusion: This study reveals that preoperative LMR is an independent predictor of OS in ICC patients after hepatectomy, and the IPS can be applied as a novel prognostic indicator in these patients.Keywords: inflammation-based prognostic score, the lymphocyte to monocyte ratio, intrahepatic cholangiocarcinoma, prognostic marker, staging system

Zeqiang Zhan,1 Xuebin Xu,2 Zhen Gu,3 Jianghong Meng,4 Xiayidan Wufuer,5 Mingliu Wang,6 Meilian Huang,7 Jianhui Chen,8 Chunmei Jing,9 Zhiying Xiong,1 Mei Zeng,10 Ming Liao,1 Jianmin Zhang1 1National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Key Laboratory of Zoonoses, Ministry of Agriculture, Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Animal Infectious Diseases Laboratory, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China; 2Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China; 3Emerging Infections Program China Office, Beijing, 102206, China; 4Department of Food Science and Nutrition, University of Maryland, College Park, Maryland 20742, USA; 5Xinjiang Uygur Autonomous Region Center for Disease Control and Prevention, Urumchi 830001, China; 6Guangxi Zhuang Autonomous Region Disease Prevention and Control Center, Nanning 530028, China; 7Xiamen City Children’s Hospital, Xiamen 361006, China; 8Fujian Provincial Center for Disease Control and Prevention, Fuzhou 350001, China; 9Chongqing City Children’s Hospital, Chongqing 400014, China; 10Department of Infectious Diseases, Children’s Hospital of Fudan University, Shanghai 200336, ChinaCorrespondence: Mei ZengDepartment of Infectious Diseases, Children’s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102, ChinaEmail zengmeigao@aliyun.comJianmin ZhangCollege of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, ChinaTel +86 20 8528 0240Fax +86 20 8528 5282Email junfeng-v@163.comPurpose: Human infections caused by invasive non-typhoidal Salmonella (iNTS) are highly prevalent worldwide. However, data for such infections in China are scarce. This study reports the epidemiology of iNTS in China.Methods: INTS isolates were recovered from blood and other clinical specimens collected during 2007–2016 across five provinces (Shanghai, Xinjiang, Fujian, Guangxi, and Chongqing) in China. Antimicrobial susceptibility was performed using the agar dilution method and molecular epidemiology was performed using standard microbiological techniques.Results: A total of 178 iNTS isolates were recovered from approximately 9700 patient specimens during 2007–2016. The predominant serovars were Salmonella Enteritidis (57/178, 32%), Salmonella Choleraesuis (47/178, 26.4%), and Salmonella Typhimurium (24/178, 13.5%). Up to 50 isolates (28.1%) were from patients who were ≤1 year of age, while 28 (15.7%) were from patients who were ≥60 years. Among these isolates, high rates of resistance to nalidixic acid (114/178, 64%), sulfisoxazole (59%), ciprofloxacin (15.2%), and cefotaxime (8.4%) were found. Moreover, 53.4% (95/178) exhibited multidrug resistance, and 3.9% (7/178) showed co-resistance to third-generation cephalosporins and ciprofloxacin. Steadily increasing numbers of nalidixic acid, cefotaxime, and ciprofloxacin-resistant isolates, but decreasing numbers of multidrug resistance isolates were detected during the study period. Detection of quinolone genes in 114 nalidixic acid-resistant isolates showed that 58.3% (67/114) harbored plasmid-mediated quinolone resistance (PMQR) genes [aac(6´)-Ib-cr, qnrA, qnrB, oqxAB, qepA, qnrS, and qnrD] and 98.2% (112/114) exhibited mutations in quinolone resistance determining regions [gyrA, parC, and parE]. Furthermore, we detected beta-lactamases genes in the ceftriaxone-resistant isolates. The most common were blaTEM-1 (93.3%), followed by blaCTX-M-55 (40%), blaCMY-2 (33.3%), and blaOXA-1 (33.3%). Finally, a range of pulsed-field gel electrophoresis patterns were detected among the Salmonella Enteritidis and Salmonella Typhimurium isolates.Conclusion: High rates of multidrug resistance and steadily increasing cefotaxime and ciprofloxacin-resistant iNTS could pose a significant challenge for the effective treatment of salmonellosis in China.Keywords: invasive non-typhoidal Salmonella, fluoroquinolones, multidrug resistant, beta-lactamases, pulsed field gel electrophoresis, China

We report an index case of histiocytic sarcoma arising in a 70-year-old patient with long-standing chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The patient presented in 2017 with painful, enlarging swelling of the left neck. He had remote history of cutaneous squamous cell carcinoma with no sign of recurrence, and his CLL/SLL was thought to be in remission. Computed tomography showed mild splenomegaly and multifocal lymphadenopathy including a 3-cm left neck mass. Biopsy of the left neck mass showed CLL/SLL with associated histiocytic sarcoma. Flow cytometry demonstrated a B cell neoplasm with CLL/SLL phenotype. Despite radiation therapy, he expired 3 months after presentation. Two similar cases (CLL/SLL and histiocytic sarcoma, follicular lymphoma and Langerhans cell sarcoma) from another institution are also illustrated. The pathological features of combined tumors in lymphoid neoplasms, a general framework to the work-up to determine interrelatedness of tumor components, and the clinical relevance are discussed.

Background: Hypochondroplasia (HCH) is a prevalent form of dwarfism linked to mutations in the fibroblast growth factor receptor 3 (FGFR3) gene, causing missense alterations. We previous report was the first to identify FGFR3(G382D) gain-of-function variants with a positive family history as a novel cause of HCH. However, the precise contribution of FGFR3 to the pathogenesis of HCH remains elusive. Methods: We generated an Fgfr3 (V376D) mutation mouse model using CRISPR/Cas9 technology and performed proteomic analyses to investigate the molecular mechanisms and potential therapeutic targets of HCH. Radiography and micro-computed tomography were employed to assess the bone-specific phenotype in Fgfr3 (V376D)mutant mice. Immunofluorescence, western blotting, and flow cytometry were used to systematically investigate the underlying mechanisms and therapeutic targets. Results: We observed that Fgfr3 (V376D) mutant mice exhibit a bone-specific phenotype, with symmetrically short limb bones, partially resembling the dwarfism phenotype of patients with HCH. We demonstrated that the mutant-activated FGFR3 promotes heat shock protein B 6 (HSPB6)-mediated cuproptosis by inhibiting chondrocyte autophagy both in vivo and in vitro. Additionally, we revealed that FGFR3 (G382D) mutation leads to enhanced ERK signaling, increased Drp1-mediated mitochondrial fission, and upregulated cuproptosis-related protein ferredoxin 1 (FDX1). Furthermore, genetic and pharmacological inhibition of the HSPB6-ERK-Drp1-FDX1 pathway partially alleviate the phenotypes of FGFR3 mutants. Conclusions: Our study provides the first evidence for the pathogenicity of a gain-of-function mutation in FGFR3 (G382D) using mouse and cell models, and it underscores the potential of targeting the HSPB6-ERK-Drp1-FDX1 axis as a novel therapeutic approach for HCH. Translational potential of this article: We first demonstrate that impaired autophagy and enhanced cuproptosis are pivotal in the pathogenesis of HCH. This study not only enlarged the therapeutic potential of targeting cuproptosis for treating FGFR3 mutation-related HCH but also provided a novel perspective on the role of the HSPB6-ERK-Drp1-FDX1 signaling pathway in the development of HCH. Consequently, this article provides valuable insights into the mechanisms and treatment strategies for FGFR3 mutation-related chondrodysplasia.

The interfacial bonding between graphene and Al critically influences the composite's strengthening efficiency. In this paper, nickel oxide nanoparticle-coated reduced graphene oxide (NiO@rGO) reinforcements were synthesized by alcohol-thermal and annealing process. Subsequently, NiO@rGO/Al composites were fabricated through intermittent ball milling and hot-press sintering. The presence of NiO leads to a thermite reaction during the high-temperature sintering process, forming a distinctive graded interface structure of graphene/Al2O3/Al, which boosts the interface bonding strength and enhances the load-transfer ability. Concurrently, the thermal effect generated by the Al thermal reaction would facilitate the long-distance diffusion of Ni atoms, contributing to the generation of intragranular Al3Ni, which avoids premature fracture due to stress concentration at the interface. Consequently, the composite demonstrates excellent mechanical properties. Compared to pure Al, the composite's ultimate tensile strength has increased by 66% (143.1 ± 2.3 MPa). Theoretical modeling analysis indicates that the primary enhancements in the NiO@rGO/Al composite material stem from load transfer and interface thermal mismatch.

Abstract Recent research highlights the pivotal role of N6-methyladenosine (m6A) modification and ferroptosis in the evolution of various cancers. This study aimed to establish a prognostic framework centered on genes associated with m6A and ferroptosis to enhance the accuracy of prognosis predictions for neuroblastoma (NB) patients, thereby improving targeted therapeutic strategies. Patient data, including expression profiles and clinical information from NB cases, were acquired from The Cancer Genome Atlas. Genes related to m6A modification and ferroptosis were identified, and those significant for prognosis were pinpointed using a combination of Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression. For further validation, the study utilized external datasets GSE62564 and GSE85047. A prognostic index was computed for each NB patient, followed by analyses of immune cell infiltration and potential drug responsiveness based on the prognostic model. Additionally, enrichment analysis was conducted on the prognostic scores. These scores showed a strong association with the tumor immune environment and the efficacy of prevalent cancer therapies. Moreover, the model’s prognostic score emerged as an independent predictive marker for NB. This research succeeded in creating and confirming a prognostic model rooted in m6A and ferroptosis-linked genes, promising to enrich the prognostic understanding and treatment approaches for NB.

Abstract Programmable metasurfaces (PMs), also called reconfigurable intelligent surfaces (RISs), are planar structures capable of dynamically manipulating electromagnetic waves in real-time. Regarded as a key enabling technology for implementing smart wireless propagation environments, PMs/RISs also serve as an ideal supporting platform for integrated sensing and communication (ISAC). Here, we propose two ISAC schemes based on a special type of PMs/RISs: space-time-coding metasurfaces (STCMs). By leveraging space-time-coding strategies, STCMs simultaneously control the propagation at the fundamental (carrier) frequency for reliable wireless communication and generate spatially distributed harmonics for sensing. The proposed schemes seamlessly integrate both communication and sensing on a shared hardware platform, eliminating the need for additional sensors. For experimental validation, we implemented an ISAC system using a 2-bit STCM operating at microwave frequencies. Experimental results align with theoretical predictions, confirming the practical viability and effectiveness of the proposed ISAC schemes for applications in communication, imaging, radar, and sensing systems.

In the present research, the nanosecond short-pulsed laser with rotary drilling method was designed to process carbon fiber-reinforced polymer (CFRP) composite plate. The hole dimension, surface morphology, heat-affected zone (HAZ), and mechanical properties were analyzed. The results reveal that the CFRP composite plate could be rapidly drilled with highly qualified processing surface by the nanosecond short-pulsed laser with rotary drilling method. The figures such as circle, square, triangle, and regular hexagon could be processed with minimum hole diameter of 0.1 mm. The changing of laser scanning speed and laser power could result in the variation in diameter of hole entrance and exit, which fluctuates in scope of 35 μm. The calculated biggest taper angle is about 0.43°, but the smallest taper angle is about 0.12°. The laser drilling on CFPR composite decreases the tensile strength by about 9%, which should be ascribed to the damage of continuous carbon fiber, but it is still acceptable. The nanosecond short-pulsed laser with rotary drilling method generates a small HAZ on hole entrance but almost no HAZ in hole exit. The surface roughness of laser processed CFRP ranges from 2.925 to 4.226 μm. Comparatively, the laser scanning speed between 800 and 1,000 mm/s and laser power around 28 W would be the optimal choice, which could realize the best balance between surface quality and efficiency.

Abstract To study the effect and mechanism of coal-rock underground impact pressure prevention and control under the influence of upper protective layer mining. In this paper, the research is carried out based on four factors, namely, the mining stress environment, the mechanical strength of coal and rock, the dynamic load disturbance effect of mining, and the energy loss space of coal and rock. Theoretical calculation and analysis, rock mechanics test, physical similar simulation test and on-site industrial experiments are adopted to study the stress distribution of the coal rock below the influence of the mining of the upper protective layer, overlying strata migration, and the law of mine pressure behavior. The results show that after the mining of the upper protective layer, the vertical stress of the coal rock body under the mined-out area increases with the depth, and the horizontal compressive stress in the shallow area gradually decreases with the increase of depth. In contrast, the horizontal tensile stress in deep areas gradually increases with the depth increase. The uniaxial compressive strength and impact energy index of the coal rock both decrease with the increase of the mining intensity of the upper protective layer. The mining of the upper protected layer will weaken the overburden structure of the mining field of the protected layer, and will reduce the breaking span and disturbance intensity of the key layer in the protected layer. The mining coal rock body in the process of upper protected mining experienced three stages of advanced stress concentration, the rapid growth of pressure relief, and the slow recovery of pressure relief, and the stress release rates all decreased with the increase of depth. The results of the study can provide an important reference value for the prevention and control of underground impact pressure and other disasters in the upper protective layer mining of closed-distance coal seam groups.

Abstract To evaluate the effect of recombinant human thrombopoietin (rhTPO) on platelet engraftment after autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (NDMM) patients. Clinical data of 40 NDMM patients who underwent high-dose melphalan conditioning and ASCT were analyzed, with 26 receiving rhTPO and 14 in the control group. The primary study endpoint was the median time to platelet engraftment. The secondary study endpoints included the median time to neutrophil engraftment, number of blood cells transfused, treatment-related adverse events, long-term hematopoietic reconstitution, and economic cost-effectiveness. The median time to neutrophil engraftment was 10.92 and 11.14 days in the rhTPO and control groups, respectively (p = 0.405). The median time to platelet engraftment (11.5 vs. 11.36 days, p = 0.776), median number of erythrocyte infusions (0.23 vs. 0 units, p = 0.326), and median number of platelet infusions (1.615 vs. 1.5 units, p = 0.721) did not significantly differ between the groups. The median hospitalization duration was 27.08 and 25.07 days in the rhTPO and control groups, respectively (p = 0.193). The median hospitalization cost was RMB 73,846 and RMB 54,136 in the rhTPO and control groups, respectively (p

Abstract Various risks often exist in metro construction and building, and how to assess the risk when metro is constructed by shield method and establish the construction risk indicator system has become a hot research topic nowadays. In this paper, HHM (hierarchical holography method) is firstly used to list the initial 26 risk indicators, and the risk list is optimized by using vague set theory to get 13 risk indicators. Then, the risk indicators are assigned by a combination of the G1 method (order-relationship hierarchy method) and the COWA method (order-weighted average operator) to determine the weights of the construction safety risk evaluation indicators of the shield construction method of metro tunnels. At the same time, to reduce the influence of the uncertainty, randomness and ambiguity of the shield construction of metro tunnels and more intuitively represent the risk weights of the indicators, and the cloud theory is used to objectively display the risk weights of the indicators. Finally, the subway tunnel shield method construction safety risk evaluation model introduced into the Tianjin Metro an interval case for risk assessment, and test of the scientific nature of the model, applicability, the evaluation results obtained, and the actual results are consistent with the validation of this paper to build the subway tunnel shield method construction safety risk evaluation model of scientific applicability and reliability, enriching the subway tunnel engineering construction safety risk evaluation method for subway tunnels. Construction safety risk evaluation provides a scientific basis for decision-making, but also for the further development of risk prevention measures, reduces the risk of construction of subway tunneling projects to provide a basis for promoting the healthy and rapid development of the construction of urban subways, and provides guidance for similar projects.

Abstract Background Enhanced recovery after surgery (ERAS) has been widely used in several surgical fields. This meta-analysis compared the clinical outcomes of the ERAS protocol and standard care (SC) in patients who underwent lumbar interbody fusion surgery. Materials and methods The PubMed, Web of Science, Cochrane Library, and Embase databases were systematically searched to identify studies reporting the effects of the ERAS protocol on clinical outcomes in patients who underwent lumbar interbody fusion surgery. Results Overall, 15 studies involving 17 865 patients were included in the final analysis. With the ERAS protocol, the length of hospitalization (SMD: − 0.47, 95% CI − 0.56 to –0.38), postoperative complications (OR = 0.62; 95% CI 0.50 to 0.77), operation time (SMD = − 0.26; 95% CI − 0.44 to –0.09), postoperative pain (SMD = − 0.35; 95% CI − 0.64 to –0.07) and duration of ambulation (SMD = − 0.80; 95% CI − 1.02 to − 0.58) were significantly reduced. The rates of readmission (OR = 0.63; 95% CI 0.38 to 1.04), estimated blood loss (SMD = − 0.31; 95% CI − 0.69 to 0.06) and hospitalization costs (SMD: − 0.56, 95% CI − 1.27 to 0.14) did not significantly differ between the ERAS and SC groups. Conclusions The present meta-analysis indicated that the ERAS protocol could be safely and feasibly implemented in the perioperative management of patients receiving lumbar interbody fusion surgery. The protocol significantly reduced the length of hospitalization, incidence of postoperative complications, operation time, duration of 1st ambulation and duration of postoperative pain. However, no differences were observed in estimated blood loss, readmission rates or hospitalization costs.

Abstract Objective This study aims to investigate the relationships between living and neighborhood environmental factors and anxiety symptoms among older adults residing in urban and rural areas of Anhui Province, China. Methods Data were collected from 5876 participants in a cross-sectional study carried out in four cities located in Anhui, China. Anxiety symptoms were evaluated via the Generalized Anxiety Disorder scale (GAD-7), and participants with scores of 5 and above were defined as having anxiety symptoms. The presence of dust and noise in the context of daily life was used to evaluate the living environment of the participants. The neighborhood environment was assessed by the availability of barrier-free facilities, proximity to facilities (supermarkets, restaurants, hospitals, and parks), and green and blue space near participants’ dwellings. Multilevel linear and logistic regression analyses were used to estimate the associations between these environmental factors and anxiety symptoms. Results The participants who lived in dusty environments had elevated GAD-7 scores and higher odds of anxiety (dust: β = 0.754, 95% CI: 0.337, 1.171; OR = 1.451, 95% CI: 1.164, 1.809). Having barrier-free facilities and the existence of a neighboring park decreased the GAD-7 scores and the likelihood of having anxiety symptoms (barrier-free facilities: β=-0.503, 95% CI: -0.992, -0.085; OR = 0.768, 95% CI: 0.656, 0.899; park: β=-0.478, 95% CI: -0.830, -0.125; OR = 0.599, 95% CI: 0.440, 0.816). However, participants residing in close proximity to the hospital presented an increased likelihood of experiencing anxiety symptoms (OR = 1.377, 95% CI: 1.162, 1.631). Conclusions Participants who lived in dusty and noisy environments were more likely to suffer from anxiety, whereas those who lived near barrier-free facilities and parks were at lower risk. The findings emphasize the need for targeted interventions to create age-friendly communities, suggesting an integrated approach that combines environmental health strategies with mental health strategies for older adults.

Abstract Background Radiomics has shown promise in the diagnosis and prognosis of lung cancer. Here, we investigated the performance of computed tomography-based radiomic features, extracted from gross tumor volume (GTV), peritumoral volume (PTV), and GTV + PTV (GPTV), for predicting the pathological invasiveness of pure ground-glass nodules present in lung adenocarcinoma. Methods This was a retrospective, cross-sectional, bicentric study with data collected from January 1, 2018, to June 1, 2022. We divided the dataset into a training cohort (n = 88) from one center and an external validation cohort (n = 59) from another center. Radiomic signatures (rad-scores) were obtained after features were selected through correlation and least absolute shrinkage and selection operator analysis. Three machine learning models, a support vector machine model, a random forest model, and a generalized linear model, were then applied to build radiomic models. Results Invasive adenocarcinoma had a higher rad-score (P

The Gaoligong Mountains lie at the intersection of three global biodiversity hotspots. In recent years, with the continuous deepening of fieldwork in the region, studies have increasingly indicated that the amphibian diversity of this region remains poorly understood. During herpetological surveys in 2023, a series of Amolops specimens were collected from the Gaoligong Mountains of Yunnan Province, China. The integrated results of morphological and molecular phylogenetic analyses indicate the presence of a separate and previously unknown lineage in the A. viridimaculatus group, which we herein confirm as a new species, Amolops gudao Yu, Wu, Lu & Che, sp. nov. Our discovery increases the number of Amolops species recorded in China to 59, and the total number of Amolops species to 86. The discovery of a new species in the Gaoligong Mountains further highlights the underestimated amphibian diversity in the region, emphasizing the need for continued fieldwork and research. Furthermore, Amolops gudao Yu, Wu, Lu & Che, sp. nov. exhibits obvious intraspecific variation in color patterns, a phenomenon also reported in several species within the A. viridimaculatus group, such as A. viridimaculatus and A. kaulbacki. Future studies on the taxonomy of A. viridimaculatus group should be careful with the use of color patterns as a diagnostic characteristic.

The chest X-ray (CXR) imaging has been the most frequently performed radiographic examination for decades, and its demand continues to grow due to their critical role in diagnosing various diseases. However, the image quality of CXR has long been a factor limiting their diagnostic accuracy. As a post-processing procedure, image enhancement can cost-effectively improve image quality. Recently, the successful application of deep learning (DL) algorithms in medical image analysis has prompted researchers to propose and design DL-based CXR image enhancement algorithms. This review examines advancements in CXR image enhancement methods from 2018 to 2023, categorizing them into four groups: bone suppression, image denoising, super-resolution reconstruction, and contrast enhancement. For each group, the unique approaches, strengths, and challenges are analyzed. The review concludes by discussing shared challenges across these methods and proposing directions for future research.

During operation, wind turbine systems are affected by external wind speed disturbances and the dynamic coupling of the system, which can lead to significant resonance phenomena within certain frequency ranges. Resonance causes a dramatic increase in the system’s dynamic response at specific frequencies, resulting in unstable power output and exacerbating the accumulation of fatigue loads, posing a threat to the safety and operational reliability of the wind turbine. To address this issue, this study proposes a multi-objective H $_{\mathrm {\infty }}$ /generalized H2 additional damping control method, which improves control precision by minimizing the integral of time-weighted absolute error of state variables, effectively suppressing the resonance peaks at critical frequencies and reducing the resulting power and load fluctuations. Experimental results show that, compared to reference open-source controller tuning, the proposed strategy reduces the standard deviations of output power, tower-top fore-aft displacement, and tower base roll moment by 19.97%, 18.90%, and 30.13%, respectively. This approach significantly enhances the power stability of the wind turbine system and effectively reduces load fluctuations, providing an efficient solution for improving the operational reliability and lifespan of wind turbines.

Epigenetic regulation is critical to multiple physiological and pathological processes. However, little is known regarding the epigenetic changes during neonatal skin development and skin aging, and in response to ultraviolet (UV) exposure. The transcriptomes of human skin samples from different ages or irradiated with different types and doses of UV light were analyzed using R (version 4.0.3) software. The epigenetic landscape of the skin, including histone modifications, genetic imprinting and m6A modification, which are mainly involved in collagen formation, extracellular matrix organization, immune function and keratinization, underwent significant changes during neonatal to adult development. Epigenetic effectors such as IGF2BP2, GATA2, GATA3, CPA4 and CDK1 were significantly correlated with extracellular matrix organization, and VEGFA, CDK1 and PRKCB with skin immune function. The m6A readers such as IGF2BP2, IGF2BP3, HNRNPA2B1 and EIF3G showed significant correlation with extracellular matrix organization, metabolism, or antigen processing and presentation. Small doses of UV exposure only induced changes in the expression levels of some epigenetic effectors, without any significant effect on the overall epigenetic landscape. However, the minimal erythema dose of UV exposure altered multiple epigenetic effectors regulating extracellular matrix organization, cell-matrix adhesion, innate immune response, mitochondrial function and mRNA processing. In addition, epigenetic changes following UV exposure were more pronounced in the elderly skin compared to the younger skin. In conclusion, histone modifications, genetic imprinting and m6A modification play critical roles during skin development, and a large dose of UV exposure can significantly change the expression of multiple epigenetic effectors.

Abstract Background Insulin resistance (IR) plays a pivotal role in the interplay between metabolic disorders and heart failure with preserved ejection fraction (HFpEF). Various non-insulin-based indices emerge as reliable surrogate markers for assessing IR, including the triglyceride-glucose (TyG) index, the TyG index with body mass index (TyG-BMI), atherogenic index of plasma (AIP), and the metabolic score for insulin resistance (METS-IR). However, the ability of different IR indices to predict outcome in HFpEF patients has not been extensively explored. Methods Patients having HFpEF were recruited from January 2012 and December 2023. The outcome was defined as major adverse cardiovascular event (MACE), encompassing all-cause mortality and rehospitalization for heart failure. The potential linear relationship was visualized by the restricted cubic spline (RCS) curve. Both univariable and multivariable Cox proportional hazards models were employed to examine the association between the IR indexes and MACE. Furthermore, to assess the incremental prognostic value of the TyG index, we conducted comprehensive analyses using area under the curve (AUC), the continuous net reclassification index (cNRI), and the integrated discrimination index (IDI). Results A total of 8693 patients met the inclusion criteria and were included in the final analysis. The mean age of the patients was 70.59 ± 10.6 years, with 5045 (58.04%) being male. The Kaplan-Meier survival analysis revealed that higher degree of the four IR indexes was associated with higher risk of MACE (all log-rank P

Abstract Background The C-repeat binding factor (CBF)/dehydration-responsive element binding (DREB1) belongs to a subfamily of the AP2/ERF (APETALA2/ethylene-responsive factor) superfamily, which can regulate many physiological and biochemical processes in plants, such as plant growth and development, hormone signal transduction and response to abiotic stress. Although the CBF/DREB1 family has been identified in many plants, studies of the CBF/DREB1 family in alfalfa are insufficient. Results In this study, 25 MsCBF genes were identified in the genome of alfalfa (“Zhongmu No. 4”). These genes were distributed on chromosomes 1, 5, 6 and unassembled scaffolds. Phylogenetics divided the CBF members of Medicago sativa, Arabidopsis thaliana, and Medicago truncatula into six groups, of which group VI had the most MsCBFs members, reaching 52% (13/25). Gene duplication analysis showed that 64% (16/25) of MsCBFs formed tandem duplications, and 32% (8/25) formed segment duplications. The expression pattern of MsCBF9 under different hormone treatments was verified by RT-qPCR, and it was found that MsCBF9 responded to GA3, IAA, SA, and MeJA. Overexpression of MsCBF9 in Arabidopsis significantly delayed the flowering time of Arabidopsis. In contrast, the flowering time of the cbfs mutant was earlier, and overexpression of MsCBF9 also increased the number and size of Arabidopsis rosette leaves. Conclusion In this study, the CBF/DREB1 family of alfalfa was comprehensively identified and analyzed, and the function of MsCBF9 in regulating flowering time was studied. This study laid a foundation for further analysis of the function of the CBF family in alfalfa. Clinical trial number Not applicable.

Abstract This study investigates the role of flavonoid Icaritin (ICT) in estrogen-deficient ovariectomized (OVX) female mice by activating the Estrogen receptor (ER)/ Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (Akt) signaling pathway, potentially delaying Parkinson’s disease (PD) progression post-castration. Seventy-five 8-week-old C57BL/6J female mice underwent ovariectomy, followed by MPTP (20 mg/kg) injection for 7 days. ICT (20 mg/kg) was administered for 14 days, and motor function was assessed using various behavioral tests. Serum estradiol, FSH, LH levels were measured by ELISA, and the expression of PI3K/Akt signaling and apoptosis proteins was analyzed by Western blot. Bone mineral density was assessed via dual-energy X-ray absorption, and histology of the uterus and femur was performed. Results showed that ICT alleviated MPTP-induced motor deficits, increased serum estradiol, and improved uterine atrophy. At the molecular level, ICT activated the PI3K/Akt pathway, reduced apoptosis, and mitigated PD symptoms and osteoporosis induced by OVX. These findings suggest ICT may offer therapeutic potential in managing OVX-induced motor dysfunction and PD.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy, and current postoperative prognostic assessment methods remain unsatisfactory, underlining the urgent to develop a reliable approach for precision medicine. Given the similarities with gametogenesis, cancer/testis genes (CTGs) are acknowledged for regulation unrestrained multiplication and immune microenvironment during oncogenic processes. These processes are associated with advanced disease and poorer prognosis, indicating that CTGs could serve as ideal prognostic biomarkers in ESCC. The purpose of this study is to develop a novel clinically prognostic prediction system to facilitate the individualized postoperative care. Methods We conducted LASSO regression analysis of protein-coding CTGs and clinical characteristics from 119 pathologically confirmed ESCC patients to recognize powerful predictive variables. We employed nine supervised machine learning classifiers and integrated best predictive machine learning classifiers by weighted voting method to construct an ensemble model called PPMESCC. Additionally, functional assay was conducted to examine the potential effect of top-ranking CTG HENMT1 in ESCC. Results LASSO regression identified five CTGs and TNM stage as optimized prognostic features. Six machine learning classifiers were integrated to construct an ensemble model, PPMESCC, which exhibited outstanding performance in ESCC prediction. The AUC for PPMESCC was 0.9828 (95% confidence interval: 0.9608 to 0.9926), with an accuracy of 98.32% (95% CI: 96.64–99.16%) in the discovery cohort and 0.9057 (95% CI: 0.8897 to 0.9583) of AUC with an accuracy of 90% (95% CI: 89.08–93.28%) in validation cohort. In addition, the top-ranking CTG HENMT1 encodes 2’-O-methyltransferase of piRNAs that was confirmed positively correlated with the proliferation capacity of ESCC cells. Then we systematically screen piRNAs associated with esophageal carcinoma based on GWAS, eQTL-piRNA, and i2OM databases, and successfully discovered 8 piRNAs potentially regulated by HENMT1. Conclusion The study highlights the clinical utility of PPMESCC algorithm in prognostic prediction that may facilitate to establish the personalized screening and management strategies for postoperative ESCC patients.

Abstract Background Primary healthcare (PHC) plays a key role in hyperlipidemia (HL) management yet lacks adequate monitoring and feedback. This study aims at identifying pragmatic measures out from routinely collected electronic records to enable automatic monitoring and inform continuous optimization of HL-management at PHC settings. Methods The study used randomly selected electronic records of PHC (from the province-wide data center of Anhui-province, China) as the main data source and generated both procedure-based and encounter-based measures for assessing HL-management. The procedure-based measures were derived from specific quality-facts of 21 stages/procedures (e.g., lipid lowering medication prescription) using self-designed algorithms. While the encounter-based measures included number or rate of visits for HL, currently-noticed hyperlipidemia (CNHL, or HL noticed during the current consultation), and ever-diagnosed hyperlipidemia (EDHL). Analysis of these measures employed mainly simple descriptives and linear regression modeling. Results The study revealed interesting findings including: low and varied rates of visits for HL(from 0.01 to 1.43%) and visits by patients with EDHL/CNHL(from 0.13 to 20.54% or from 0.02 to 2.99%) between regions; large differences (5.14 to 22.20 times) between the mean or cumulative proportions of visits by patients with EDHL versus CNHL among clinician groups; consistent increase in the ratio of visits for HL in all cause visits over the study period (from 0.087 to 1.000%) accompanied with relatively stable proportions of patients with CNHL/EDHL; Relatively low scores in the procedure-based measures (ranged from 0.00 to 36.08% for specific procedures by seasons). Conclusions The measures identified are not only feasible from real-world PHC records but also give some useful metrics about how well current HL-management is going and what future actions are needed.

Abstract Photoimmunotherapy, which combines phototherapy with immunotherapy, exhibits significantly improved therapeutic effects compared with mono-treatment regimens. However, its use is associated with drawbacks, such as insufficient reactive oxygen species (ROS) production and uneven photosensitizer distribution. To address these issues, we developed a controllable, targeted nanosystem that enhances oxidative stress through multiple pathways, achieving synergistic photothermal, photodynamic, and immunotherapy effects for tumor treatment. These nanoparticles (D/I@HST NPs) accurately target overexpressed transferrin receptors (TfRs) on the surface of tumor cells through surface-modified transferrin (Tf). After endocytosis, D/I@HST NPs generate ROS under 808-nm laser irradiation, breaking the ROS-responsive crosslinking agent and increasing drug release and utilization. Tf also carries Fe3+, which is reduced to Fe2+ by iron reductase in the acidic tumor microenvironment (TME). Consequently, the endoperoxide bridge structure in dihydroartemisinin is cleaved, causing additional ROS generation. Furthermore, the released IR-780 exerts both photodynamic and photothermal effects, enhancing tumor cell death. This multi-pathway oxidative stress amplification and photothermal effect can trigger immunogenic cell death in tumors, promoting the release of relevant antigens and damage-associated molecular patterns, thereby increasing dendritic cell maturation and sensitivity of tumor cells to immunotherapy. Mature dendritic cells transmit signals to T cells, increasing T cells infiltration and activation, facilitating tumor growth inhibition and the suppression of lung metastasis. Furthermore, the myeloid-derived suppressor cells in the tumor decreases significantly after treatment. In summary, this multi-pathway oxidative stress-amplified targeted nanosystem effectively inhibits tumors, reverses the immunosuppressive tumor microenvironment, and provides new insights into tumor immunotherapy combined with phototherapy.