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The role of aquaculture systems in the global carbon cycle is poorly understood to date. We investigated the carbon budgets in 2 polyculture systems (PM: swimming crab Portunus trituberculatus with kuruma shrimp Marsupenaeus japonicus; and PMR: crab, shrimp and short-necked clam Ruditapes philippinarum) during the farming season (125 d in total). The main carbon input occurred via water (PM: 55.06%; PMR: 62.50%), followed by that via feed. PM absorbed 21.55 g C m-2 across the air-water interface, accounting for 13.27% of the total input. The carbon output via water was the main output in both PM (89.17%) and PMR (46.43%). PMR emitted 53.00 g C m-2 into the atmosphere during the farming season, accounting for 32.53% of the total output. The carbon output by harvested animals in PMR accounted for 19.48% of the total output, which was much higher than that in PM (5.71%). Carbon accumulation in the sediment was significantly higher in PM than in PMR (p < 0.05), but the value of both represented a small portion of the total output. Clam farming in the polyculture system profoundly altered the carbon budgets by changing the CO2 flux direction, reducing carbon accumulation in water and sediments and increasing the carbon output by harvested animals. In terms of the global warming potential, which was calculated from the results of CO2 and CH4 fluxes across the air-water interface, PM had the potential for mitigating the greenhouse effect on the 20 yr horizon, whereas PMR exacerbated global warming. Our results suggest that PM acted as a net carbon sink in the global carbon cycle, while PMR acted as a carbon source.

Methane (CH4) fluxes at the water-air interface in 2 typical seawater polyculture systems were determined during the farming season. The mean CH4 fluxes were 66.0 ± 44.1 µg m-2 h-1 in the bispecies polyculture system of swimming crab Portunus trituberculatus with kuruma shrimp Marsupenaeus japonicus (PM) and 68.7 ± 39.5 µg m-2 h-1 in the trispecies polyculture system of swimming crab with shrimp and short-necked clam Ruditapes philippinarum (PMR), and no significant differences were observed between them. CH4 emissions showed temporal variability during the farming season, peaking in mid-August. The linear mixed-effect model demonstrated that air temperature was the main regulator of CH4 fluxes rather than the internal physical and chemical properties of the systems. Air, water and sediment temperatures explained 58.9, 61.4 and 55.3% of the CH4 flux variations in the PM and 64.6, 57.1 and 60.8% of the variations in the PMR, respectively. Reducing organic matter accumulation in the sediment by means of improving feeding efficiency and the application of integrated aquaculture are likely to be effective in reducing CH4 emissions from aquaculture systems.

To estimate the carbon source-sink function of mariculture ponds without a food supply, we analyzed carbon budgets and gaseous carbon fluxes in shrimp Marsupenaeus japonicus-sea cucumber Apostichopus japonicus polyculture seawater ponds (PSPs) without feeding. Over a 1 yr cycle, the total organic carbon outflow accounted for 78.6% of the inflow organic carbon in PSPs. Approximately 1558.1 kg ha-1 of organic carbon accumulated in PSPs, and the ratio of gaseous carbon exchange to carbon burial ranged from 0.73 to 1.45. The PSPs acted as a purification system where organic carbon is eliminated from the inflow water, and carbon retention in the sediment of such systems could offset their carbon emissions into the atmosphere.

There is a growing trend towards culturing fish in intensive recirculating aquaculture systems, which have a reduced need for water exchange compared to many other systems. However, it is unknown whether these intensive aquaculture operations facilitate bioaccumulation of trace elements in fish tissue. The present study therefore evaluated and compared the accumulation of 20 trace elements in the flesh of marbled eel Anguilla marmorata reared in 3 different systems: a recirculating aquaculture system (RAS), a biofloc technology system (BFT), and a concrete pond (CP; traditional method). In the BFT system fish were also raised in polyculture with tilapia Oreochromis niloticus and water spinach Ipomoea aquatica Forsk. Fish were fed the same feed and reared in water from the same source. The trace elements (Al, As, Ba, Be, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Pb, Sb, Se, Sn, Sr, Ti, V, and Zn) in the fish flesh were analyzed by inductively coupled plasma-optical emission spectrometry. Fish reared in the RAS had elevated concentrations of only a single element (Al) compared with CP fish. This element was also elevated in BFT fish and was probably related to the high Al concentration in the fish feed. Fish reared in the BFT system also showed significantly higher levels of As, Ba, Cr, Fe, Mn, Ni, Se, Sn, Sr, Ti, and Zn compared to both CP and RAS fish. The observed levels of (1) As in fish from BFT systems and (2) Pb in fish from both RAS and BFT systems exceeded national and international legislatory limits. Our results suggest that regular monitoring of trace element concentrations in BFT and RAS should be implemented in the future for this species.

Benthic fluxes of carbon dioxide (CO2) and methane (CH4) were evaluated in grass carp Ctenopharyngodon idella (G), silver carp Hypophthalmichthys molitrix (S), and bighead carp Aristichthys nobilis (B) polyculture systems, to which topmouth culter Erythroculter ilishaeformis (T), Pacific white shrimp Litopenaeus vannamei (P), or common carp Cyprinus carpio (C) were added. These systems, GSBT, GSBP, and GSBC, respectively, were monitored over 5 mo (May to September 2014). The presence of L. vannamei and C. carpio increased CO2 and CH4 emissions in GSBP and GSBC, respectively. From June to August, CO2 and CH4 fluxes increased in the 3 systems, and in July and August these fluxes were significantly higher in GSBC than in GSBP and GSBT, and significantly higher in GSBP than in GSBT. The metabolisms of L. vannamei and C. carpio contributed to decrease dissolved oxygen, pH, and oxidation-reduction levels, and the bioturbation of the upper sediment layers caused by these species increased organic matter degradation rate, resulting in a significant increase in particulate and dissolved organic carbon in the overlying water. Our results indicate that improving feeding efficiency and reducing organic carbon accumulation on the bottom of aquaculture ponds, as well as increasing dissolved oxygen and decreasing bioturbation across the sediment-water interface during farming seasons, is likely to reduce CO2 and CH4 release from aquaculture pond sediment, especially in July and August.

Qimei Wei,1,&ast; Wenxia Zuo,2,&ast; Rong Cong,1 Kun Luo,1 Shanshan Dong1 1Department of Clinical Laboratory, Wuhan Asia Heart Hospital, Wuhan, 430022, People’s Republic of China; 2Department of Cardiac Critical Care Medicine, Wuhan Asia Heart Hospital, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanshan Dong, Department of Clinical Laboratory, Wuhan Asia Heart Hospital, No. 753 Jinghan Avenue, Jianghan District, Wuhan, 430022, People’s Republic of China, Tel +86 18162516279, Email 18162516279@163.comAbstract: Elizabethkingia anophelis is an opportunistic pathogen that causes serious life-threatening infections. In this report, we describe a case of pulmonary infection caused by E. anophelis in a young female patient, following cardiac surgery, which was successfully treated with a combination of trimethoprim-sulfamethoxazole (TMP-SMZ) and eravacycline. Additionally, this report provides a summary of high-risk factors for E. anophelis infection, clinical manifestations, and therapeutic options. Given the high degree of antimicrobial drug resistance of the organism and the fact that inappropriate empirical antimicrobial therapy constitutes a risk factor for mortality, our case serves as a valuable reference for similar cases, highlighting potential strategies for effective management.Keywords: Elizabethkingia anophelis, pulmonary infections, trimethoprim-sulfamethoxazole, eravacycline

Qingyang Yu,1,2 Yuanyuan Cui,1 Shuwen Dong,1 Yanqing Ma,1 Yi Xiao,1 Li Fan,1 Shiyuan Liu1 1Department of Radiology, Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, People’s Republic of China; 2Department of Neurosurgery, Changhai Hospital, Navy Military Medical University, Shanghai, 200433, People’s Republic of ChinaCorrespondence: Shiyuan Liu, Department of Radiology, Changzheng Hospital, Navy Military Medical University, 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Fax +86 2181886012, Email radiology_cz@163.comObjective: Hemifacial spasm (HFS) is a clinical neurosurgical disease, which brain structural alterations caused by HFS remain a topic of debate. We evaluated changes in brain microstructure associated with HFS and observed their relevance to clinical characteristics.Methods: We enrolled 72 participants. T1-weighted structural and diffusion tensor images were collected from all participants using 3.0T magnetic resonance equipment. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to identify changes in gray matter volume (GMV) and disruptions in white matter (WM) integrity. The severity of the spasms was graded using the Cohn scale.Results: VBM analysis revealed that the GMV was significantly reduced in the left Thalamus and increased GMV in the right Cerebellum IV-V of the HFS group. TBSS analysis showed that FA in the left superior longitudinal fasciculus (SLF) of the HFS group was significantly increased. GMV in the thalamus showed a negative correlation with disease duration and Cohn grade, while FA in the left SLF had a positive correlation with both the disease duration and Cohn grade.Conclusion: We identified regions with altered GMV in HFS patients. Additionally, we determined that FA in the left SLF might serve as a significant neural indicator of HFS.Keywords: hemifacial spasm, voxel-based morphometry, diffusion tensor imaging, tract-based spatial statistics, Cohn grading

Weixin Bei,1,2,&ast; Shuhui Dong,1,2,&ast; Guoying Liu,1,3,4,&ast; Lanfeng Lin,2,5,&ast; Yaofei Jiang,1,2 Nian Lu,1,2 Wangzhong Li,1,2 Hu Liang,1,2 Yanqun Xiang,1,2 Weixiong Xia1,2 1Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 4Department of Radiation Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 5Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanqun Xiang; Weixiong Xia, Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People’s Republic of China, Tel +86-20-87343643, Fax +86-20-87343392, Email xiangyq@sysucc.org.cn; xiawx@sysucc.org.cnBackground: We aim to evaluate the efficacy and safety of anti-PD1 rechallenge in combination with chemotherapy in patients with metastatic nasopharyngeal carcinoma (mNPC) who have progressed on prior anti-PD1 therapy.Patients and Methods: We enrolled patients with mNPC who received chemotherapy combined with PD-1 immune-checkpoint inhibitors (ICIs) or chemotherapy alone after prior progression of anti-PD1 therapy. The primary endpoint was progress-free survival (PFS), and the secondary endpoints included overall survival (OS), disease control rate (DCR) and objective response rate (ORR).Results: A total of 96 patients were eligible between January 2015 and December 2020. Thirty-seven (38.5%) were in the PD-1 ICIs re-challenge group, while the remaining 59 patients (61.5%) were in the chemotherapy group. The ORR and DCR of PD-1 ICIs group and chemotherapy group were 37.8% vs 23.7% and 86.5% vs.74.5%, respectively. After a median follow-up period of 21.1 months (IQR 16.1– 28.7), the log-rank analysis demonstrated a significantly improved PFS in the PD-1 ICIs re-challenge group compared to the chemotherapy group (8.4 months [95% CI 4.3– 14.0] vs 5.0 months [95% CI 2.8– 7.2], P = 0.03). However, no significant difference in OS was observed between the two groups (28.3 vs 24.1 months, P = 0.09). The two groups had similar adverse reactions, but the incidence of grade 3 or 4 thrombocytopenia was significantly higher in the PD-1 ICIs re-challenge group (18.9% vs 3.4%, P = 0.025).Conclusion: mNPC patients who progressed from prior anti-PD1 therapy could benefit from the anti-PD1 rechallenge in combination with chemotherapy. However, further validation is needed.Keywords: metastatic nasopharyngeal carcinoma, chemotherapy, PD-1 immune checkpoint inhibitors, second-line treatment strategies

Di Wang,1,2 Qiqi Li,1,2 Chunsheng Xiao,2 Hao Wang,2 Shujun Dong1 1The First Outpatient Department, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of ChinaCorrespondence: Hao Wang, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Chaoyang District, Changchun, 130022, People’s Republic of China, Tel +86-431-85262110, Email wangh@ciac.ac.cn Shujun Dong, The First Outpatient Department, Hospital of Stomatology, Jilin University, Room 101, Building G5, Phase 3, China Resources Ziyun Mansion, the Intersection of Jinhu Road and Nanhu Middle Street, Nanguan District, Changchun, 130021, People’s Republic of China, Tel +86-431-80621155, Email dsj@jlu.edu.cnAbstract: Periodontitis is a disease of inflammation that affects the tissues supporting the periodontium. It is triggered by an immunological reaction of the gums to plaque, which leads to the destruction of periodontal attachment structures. Periodontitis is one of the most commonly recognized dental disorders in the world and a major factor in the loss of adult teeth. Scaling and root planing remain crucial for managing patients with persistent periodontitis. Nevertheless, exclusive reliance on mechanical interventions like periodontal surgery, extractions, and root planning is insufficient to halt the progression of periodontitis. In response to the problem of bacterial resistance, some researchers are committed to finding alternative therapies to antibiotics. In addition, some scholars focus on finding new materials to provide a powerful microenvironment for periodontal tissue regeneration and promote osteogenic repair. Nanoparticles possess distinct therapeutic qualities, including exceptional antibacterial, anti-inflammatory, and antioxidant properties, immunomodulatory capacities, and the promotion of bone regeneration ability, which made them can be used for the treatment of periodontitis. However, there are many problems that limit the clinical translation of nanoparticles, such as toxic accumulation in cells, poor correlation between in vitro and in vivo, and poor animal-to-human transmissibility. In this paper, we review the present researches on nanoparticles in periodontitis treatment from the perspective of three main categories: inorganic nanoparticles, organic nanoparticles, and nanocomposites (including nanofibers, hydrogels, and membranes). The aim of this review is to provide a comprehensive and recent update on nanoparticles-based therapies for periodontitis. The conclusion section summarizes the opportunities and challenges in the design and clinical translation of nanoparticles for the treatment of periodontitis. Keywords: anti-inflammatory, antibacterial, guided tissue regeneration, nanofibers, hydrogel, films

Zhenyi Wang, Shimin Dong, Yanjun Qin Department of Emergency, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Yanjun Qin; Shimin Dong, Department of Emergency, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 05000, People’s Republic of China, Email qyj778899@163.com; dsm_123@163.comPurpose: The aim of this study was to investigate the relationship between ARF and coagulopathy in patients with sepsis and to explore the prognostic value of these conditions.Patients and Methods: The data of 271 patients with sepsis-associated coagulopathy admitted from June 2021 to June 2022 were reviewed. The patients were divided into a survival group and a nonsurviving group according to patient prognosis. Independent sample t tests were utilized to compare laboratory parameters within 24 hours of admission, as well as the APACHE II and SOFA scores, between the two patient groups. According to the sepsis-associated coagulation dysfunction (SAC) grading criteria for grading, Spearman correlation analysis was used to study the relationship between blood creatinine and SAC grading and assignment scores, and receiver operating characteristic (ROC) curves and Cox’s proportional risk regression model were used to explore the factors affecting the prognosis of SAC patients.Results: Spearman correlation analysis revealed strong associations between serum creatinine (Scr) concentration, SAC classification, and SAC score, with coefficients above 0.7. SAC classification outcomes varied significantly with severity: mild severity had a 77.6% survival rate versus 22.4% mortality; moderate severity had 21.5% survival versus 78.5% mortality; and severe cases had a 0.7% survival rate versus 99.3% mortality (P< 0.01 for all). Multivariate analysis revealed significant predictors of outcome, including multiple organ dysfunction syndrome (MODS), with an OR of 2.070 (P=0.019); the SOFA score (OR=1.200, P< 0.01); the international normalized ratio (INR) (OR=0.72, P=0.013); and the Scr level (OR=0.995, P< 0.01). The areas under the ROC curves for the SOFA score, APACHE II score, and SAC classification were > 0.8, all P < 0.05.Conclusion: In patients with sepsis, SAC grade 3 or a SAC score of 4 or higher is associated with poorer prognosis, and the interaction of acute kidney injury exacerbates the degree of SAC, consequently affecting prognosis.Plain Language Summary: To investigate the relationship between acute renal dysfunction and coagulation dysfunction in patients with sepsis and to explore the prognostic value of these conditions. We collected information and laboratory indicators from 271 patients, classified these two groups of patients according to the grading criteria for sepsis-associated coagulation dysfunction (SAC), and compared the differences between them. We utilized Spearman correlation analysis to investigate the relationship between blood creatinine and the severity of sepsis-associated coagulation dysfunction (SAC). Additionally, we employed a Cox proportional hazards regression model to study the factors influencing the prognosis of SAC patients. This study revealed a significant positive correlation between blood creatinine levels and SAC grade. Furthermore, the presence of MODS, INR, blood creatinine, and SOFA score can serve as independent predictive factors for mortality. We can infer that there is a significant correlation between coagulation function parameters and blood creatinine levels, which play a crucial role in the diagnosis and prognostic analysis of sepsis. In patients with sepsis, a higher grade of SAC or an SAC score of 4 or higher indicates a poorer prognosis. Additionally, the interaction with acute kidney injury exacerbates the severity of SAC, thereby impacting patient prognosis.Keywords: sepsis, sepsis shock, acute kidney injury, sepsis-induced coagulopathy, multiple organ dysfunction syndrome

Xianmin Zhu,1 Shuang Dong,1 Jing Tang,1 Rong Xie,1 Huijing Wu,1 Jun Guan,2 Sheng Hu1 1Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Hematology, Wuhan NO.1 Hospital, Wuhan, People’s Republic of ChinaCorrespondence: Sheng Hu, Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, 116 South Road, Wuhan, 430079, People’s Republic of China, Email ehusmn@163.comAbstract: In recent years, there have been limited reports on the efficacy of later-line anti-programmed cell death − 1 (PD-1) therapy in achieving prolonged and complete remission in patients with hepatocellular carcinoma (HCC). Tislelizumab, a humanized anti-PD-1 monoclonal IgG4 antibody, has shown promising results in the treatment of HCC. This report highlights the case of a patient with HCC who experienced the development of lung metastatic lesions following HCC resection and chemotherapy, but achieved a prolonged complete response (CR) after receiving tislelizumab treatment. In April 2017, a 56-year-old male diagnosed with primary HCC underwent hepatectomy and hepatic arterial infusion pump placement. Following the surgery, the patient received adjuvant hepatic arterial infusion chemotherapy (HAIC) with 4 cycles of cisplatin+5-fluorouracil (PF) regimen starting in June 2017. In May 2018, lung metastatic lesions were detected, and the patient underwent 4 cycles of oxaliplatin+leucovorin+5-fluorouracil (FOLFOX) chemotherapy. However, the disease progressed in August 2018, leading to the administration of arsenic trioxide treatment. Despite this, further progression was observed in October 2018, prompting the patient’s enrollment in a clinical trial for tislelizumab therapy. Initially, the patient achieved a partial response (PR) to tislelizumab, which was followed by a CR that lasted for almost 4 years. Unfortunately, tislelizumab treatment had to be discontinued due to immune-related adverse events (AE). Subsequently, the patient received lenvatinib and maintained a CR until July 2023. Tislelizumab monotherapy, when used as a third-line treatment, has demonstrated remarkable efficacy in facilitating patients with advanced HCC to attain a durable CR.Keywords: hepatocellular carcinoma, complete response, immune checkpoint inhibitor, tislelizumab, chemotherapy failure, metastasis

Ziqin Zhao,1 Shuhui Dong,1 Yong Yang,1 Haibo Yin,1 Guangyi Xiong,1 Jianxiong Ma2 1Department of Pathology, Tianjin Hospital, Tianjin University, Tianjin, People’s Republic of China; 2Institute of Orthopaedic Surgery, Tianjin Hospital, Tianjin University, Tianjin, People’s Republic of ChinaCorrespondence: Jianxiong Ma, Institute of Orthopaedic Surgery, Tianjin Hospital, Tianjin University, Tianjin, People’s Republic of China, Email majianxiong_tjh@yeah.netIntroduction: Chondrocyte degeneration and senescence are characteristics of osteoarthritis (OA) and other joint degenerative diseases, and ferroptosis has been observed to regulate the development of OA. However, the role of the N6-methyladenosine (m6A) modification in OA ferroptosis remains unclear.Methods: This study performed series of assays to investigate the function of the m6A reader IGF2BP1 in OA ferroptosis, including m6A quantitative analysis, Iron (Fe2+) release analysis, Malondialdehyde (MDA) measurement, lipid peroxidation (ROS) detection and Glutathione (GSH) measurement. The molecular interaction and mechanism analysis was performed by Luciferase reporter assay, mRNA stability analysis and RNA immunoprecipitation (RIP) assay.Results: These results indicate that IGF2BP1 is upregulated in IL-1β-induced chondrocytes. Functionally, IGF2BP1 silencing represses ferroptosis, including iron (Fe2+) accumulation, malondialdehyde, and reactive oxygen species (ROS). Mechanistically, among the potential downstream targets, matrix metalloproteinase-3 (MMP3) was observed to harbor a significant m6A modified site in the 3’-UTR. IGF2BP1 combines with MMP3 through the binding of m6A sites, thereby enhancing MMP3 mRNA stability.Discussion: In conclusion, our findings revealed the functions and mechanisms of m6A regulator IGF2BP1 in OA chondrocyte’s ferroptosis, providing a novel target for OA treatment.Keywords: osteoarthritic cartilage, IGF2BP1, ferroptosis, MMP3

Yuqing Bu,1,&ast; Junye Wen,2,&ast; Fayan Wang,1,3 Shibo Dong,4 Liya He,1 Yang Li,1,5 Jinlong Liang,1,3 Hongzhen Zhang1,3,5 1Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 2Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 3Department of Medicine, Hebei North University, Zhangjiakou, Hebei Province, 075000, People’s Republic of China; 4Department of Imaging, Hebei General Hospital, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 5Department of Medicine, North China University of Science and Technology, Tangshan, Hebei Province, 063210, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhen Zhang, Email hongzhenzhang456@sohu.comAbstract: This study presents a case of dual primary liver cancer involving small cell neuroendocrine carcinoma and hepatocellular carcinoma. The 58-year-old Chinese male patient, who has a medical history of viral hepatitis B, presented with right upper abdominal pain persisting for one month. Imaging studies indicated the presence of multiple liver masses in segments V and VII–VIII, as well as a mass in the left lung. Subsequent hepatic biopsy performed on both segments confirmed the presence of hepatocellular carcinoma in segment V and small cell neuroendocrine carcinoma in segment VII–VIII. After undergoing one cycle of chemotherapy, the lung mass exhibited a reduction in size, while the liver masses showed an inadequate response. Subsequently, the patient underwent Transcatheter Arterial Chemoembolization (TACE) and Hepatic Artery Infusion Chemotherapy (HIAC), resulting in partial remission (PR). However, the patient was diagnosed with brain metastasis and subsequently treated with Sorafenib and Tirelizumab, a Programmed Death 1 (PD-1) immune checkpoint inhibitor. The efficacy evaluation indicated stability, and no severe adverse effects were observed at the time of writing. The patient’s survival time was 16 months.Keywords: synchronous tumor, liver tumor, primary tumor, small cell neuroendocrine carcinoma, hepatocellular carcinoma

Yan Ding,1,&ast; Banqin Wang,2,&ast; Yongjun Liu,1 Shengjie Dong,1 Xuri Sun,1 Zhilin Cao,1 Leisheng Wang1 1Department of Orthopedics, Yantaishan Hospital, Yantai, People’s Republic of China; 2Department of Blood Transfusion, Shandong Provincial Qianfoshan Hospital Affiliated with Shandong First Medical University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leisheng Wang, Department of Orthopedics, Yantaishan Hospital, No. 10087 Keji Road, Yantai, 264003, People’s Republic of China, Tel +86-13792566016 ; +86-0535-6863898, Email 37724148@qq.comPurpose: Percutaneous pedicle screw fixation is a common minimally invasive treatment for traumatic thoracolumbar and lumbar fractures; however, research on hardware removal after successful healing is limited. We aimed to introduce a rapid, safe, minimally invasive, and cost-effective method for percutaneous pedicle screw removal.Patients and Methods: We conducted a retrospective analysis of demographic (age, sex, body mass index, alcohol use, and current smoking), clinical (hypertension and diabetes mellitus), surgical (affected levels, number of screws, time of surgery, and blood loss), and treatment cost characteristics of 92 patients who had undergone percutaneous pedicle screw removal between May 2016 and February 2023. The first 57 patients underwent the conventional method, and the remaining 35 underwent the modified method. Independent-sample t-tests and chi-square tests were used to compare continuous and categorical variables, respectively, between the two groups.Results: No significant differences were observed in the demographic parameters, complications, or affected levels between the groups. However, the average surgical time (P=0.000) was significantly shorter, and the average blood loss volume (P=0.002) and total cost (P=0.000) were significantly lower in the modified group than in the conventional group.Conclusion: Compared with the conventional method, our modified method can shorten the surgical time, reduce blood loss, and reduce the total cost of treatment. It is a quick and safe minimally invasive method that does not require additional surgical instruments and is suitable for implementation in primary hospitals.Keywords: bone screw, device, Kirschner wire, surgery, control

Juan Wang, Shuangyong Dong, Mengjuan Fang, Zhiyan Fan, Yuansheng Xu Department of Emergency, Affiliated Hangzhou First People`s Hospital, School of Medicine, Westlake University, Hangzhou, People’s Republic of ChinaCorrespondence: Yuansheng Xu, Department of Emergency, Affiliated Hangzhou First People`s Hospital, School of Medicine, Westlake University, No. 261 Huansha Road, Hangzhou, Zhejiang Province, 310006, People’s Republic of China, Email xys0912@163.comBackground: Chlamydia psittaci (C. psittaci) is a pathogen that is seldom implicated in community-acquired pneumonia and is rarely linked to severe pneumonia. Reports of severe C. psittaci pneumonia accompanied by Guillain-Barre syndrome (GBS) are scarce. Tetracyclines are the preferred therapeutic approach for psittacosis. Omadacycline, a novel tetracycline, demonstrates strong antibacterial efficacy against typical bacteria and atypical pathogens, including C. psittaci. However, its application in the treatment of psittacosis pneumonia remains constrained.Case Presentation: A 77-year-old female patient was admitted to the hospital presenting with symptoms of fever, low back pain, and headache. The diagnosis of C. psittaci was established through the utilization of metagenomic next-generation sequencing (mNGS). Initial administration of moxifloxacin, meropenem, piperacillin-tazobactam, and doxycycline proved to be ineffective. Subsequent omadacycline leaded to the successful resolution of fever and dyspnea. However, after the endotracheal tube was removed, the patient experienced a rapid decline in symmetrical limb strength, leading to a diagnosis of GBS based on clinical manifestations, cerebrospinal fluid analysis, and electromyography. Following a 5-day course of immunoglobulin therapy and nutritional nerve treatment, the patient’s condition ameliorated, culminating in an uncomplicated discharge.Conclusion: This case provides evidence supporting the potential use of omadacycline as a therapeutic option for the treatment of severe C. psittaci pneumonia. The utilization of mNGS technology is of paramount importance in the prompt identification of uncommon pathogens, including C. psittaci. Nevertheless, the occurrence of GBS should be taken into consideration when C. psittaci pneumonia is accompanied by symmetrical limb weakness. These findings have important implications for the diagnosis, treatment, and management of patients with C. psittaci pneumonia.Keywords: Chlamydia psittaci pneumonia, Guillain-Barre syndrome, omadacycline, metagenomic next‑generation sequencing

Abstract Among the most prevalent neurodevelopmental disorders, Autism Spectrum Disorder (ASD) is highly diverse showing a broad phenotypic spectrum. ASD also couples with a broad range of mutations, both de novo and inherited. In this study, we used a proprietary SNP genotyping chip to analyze the genomic DNA of 250 Vietnamese children diagnosed with ASD. Our Single Nucleotide Polymorphism (SNP) genotyping chip directly targets more than 800 thousand SNPs in the genome. Our primary focus was to identify pathogenic/likely pathogenic mutations that are potentially linked to more severe symptoms of autism. We identified and validated 23 pathogenic/likely pathogenic mutations in this initial study. The data shows that these mutations were detected in several cases spanning multiple biological pathways. Among the confirmed SNPs, mutations were identified in genes previously known to be strongly associated with ASD such as SLCO1B1, ACADSB, TCF4, HCP5, MOCOS, SRD5A2, MCCC2, DCC, and PRKN while several other mutations are known to associate with autistic traits or other neurodevelopmental disorders. Some mutations were found in multiple patients and some patients carried multiple pathogenic/likely pathogenic mutations. These findings contribute to the identification of potential targets for therapeutic solutions in what is considered a genetically heterogeneous neurodevelopmental disorder.

Tongguo Miao,1 Xianzhe Lou,2 Shiming Dong,1 Xiaoxiao Zhang,1 Weiwei Guan,1 Ying Zhang,1 Lu Li,1 Xiwei Yuan,1 Dong Ma,2,&ast; Yuemin Nan1,&ast; 1Department of Traditional and Western Medical Hepatology, Hebei Medical University Third Hospital & Hebei International Joint Research Center for Liver Cancer Molecular Diagnosis, Hebei International Science and Technology Cooperation Base, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, Hebei Province, 050017, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuemin Nan, Department of Traditional and Western Medical Hepatology, Hebei Medical University Third Hospital & Hebei International Joint Research Center for Liver Cancer Molecular Diagnosis, Hebei International Science and Technology Cooperation Base, No. 139, Ziqiang Road, Shijiazhuang, Hebei Province, 050051, People’s Republic of China, Tel +86 18533112266, Email nanyuemin@163.com Dong Ma, Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, No. 361, Zhongshan East Road, Shijiazhuang, Hebei Province, 050017, People’s Republic of China, Tel +86 15081650349, Email madong119@hebmu.edu.cnPurpose: The incidence of non-B and non-C hepatocellular carcinoma (NBNC-HCC) is increasing globally. Metabolically associated fatty liver disease (MAFLD) has been a contributing factor to this rising trend in NBNC-HCC incidence. The monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) is a new prognostic marker that connects systemic inflammation with disorders of lipid metabolism. Therefore, MHR may be a potential prognostic predictor of patients with MAFLD-related HCC (MAFLD-HCC). This study aims to investigate the relationship between the MHR and prognosis of patients with MAFLD-HCC and construct a novel prognostic prediction tool for MAFLD-HCC.Patients and Methods: This retrospective study of patients with MAFLD-HCC included training (n = 112) and internal validation (n = 37) cohorts. Univariate and multivariate Cox proportional hazard regression analysis was conducted to identify independent risk factors of survival. A visual nomogram was constructed to assess the performance of the two groups. Furthermore, receiver operating characteristic (ROC) curves and calibration curves were used to verify the prognostic discriminative ability of this nomogram, even in the MHR, ALBI grade, and MHR–ALBI model.Results: Univariate and multivariate analyses revealed that extrahepatic metastases, Vascular invasion, Barcelona staging B, C, D, elevated ALBI Grade 3, C-reactive protein (CRP), and MHR were independent risk factors for the prognosis of MAFLD-HCC. Moreover, calibration plots showed good discrimination and consistency when the significant factors were entered into the nomogram. Meanwhile, the MHR strongly correlated with the prognosis of cancer under a background of MAFLD-HCC, with a sensitivity of 88.89% and a specificity of 79.61%. Importantly, the performance of the MHR alone (AUC = 86.2) was not only superior to the ALBI grade (AUC = 63.8) but was comparable to the combination of MHR and ALBI (AUC = 88.5).Conclusion: The novel nomogram demonstrated good value in predicting the overall survival of patients with MAFLD-HCC. The MHR may be a potential predictor of prognosis.Keywords: lipid metabolism, MAFLD-HCC, prognostic prediction, nomogram, MHR

Kailin Xing,1,&ast; Xinyu Bian,2,&ast; Dongmin Shi,3,&ast; Shuangshuang Dong,1 Hongxin Zhou,1 Shuxiu Xiao,4 Jinjin Bai,4 Weizhong Wu1,4 1Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Shanghai, 200032, People’s Republic of China; 2Department of Radiation Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210000, People’s Republic of China; 3Department of Medical Oncology, Shanghai Changzheng Hospital, Shanghai, 200072, People’s Republic of China; 4Clinical Center for Biotherapy, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weizhong Wu, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, People’s Republic of China, Tel +86-21-60268628, Fax +86-21-64037181, Email wu.weizhong@zs-hospital.sh.cnBackground: MicroRNA-612 (miR-612) has been proven to suppress the formation of invadopodia and inhibit hepatocellular carcinoma (HCC) metastasis by hydroxyacyl-CoA dehydrogenase alpha subunit (HADHA)-mediated lipid reprogramming. However, its biological roles in HCC cell ferroptosis remain unclear.Methods and Results: In this study, we found that HCC cells with high metastatic potential were more resistant to ferroptosis, indicating that ferroptosis is related to HCC metastasis. The levels of lipid reactive oxygen species (ROS) were found to be much lower in HCC cells with high metastatic potential by flow cytometry (FCM). We used HCC cells with miR-612 overexpression/knockout and HADHA overexpression/knockdown to test cell viability after stimulation with RSL3. HCC cells overexpressing miR-612 were more sensitive to ferroptosis, and miR-612 could increase lipid ROS levels. Furthermore, colony formation assays and Transwell assays showed that miR-612 could inhibit the proliferation and metastasis of HCC cells by promoting ferroptosis. We next confirmed that miR-612 influenced HCC cell ferroptosis by regulating HADHA. HADHA could upregulate the expression of key enzymes in the mevalonate (MVA) pathway. HADHA overexpression upregulated the expression of CoQ10 and decreased polyunsaturated fatty acid (PUFA) levels and lipid peroxide abundance. miR-612 also suppressed HCC cell proliferation and metastasis by enhancing RSL3- and lovastatin-induced ferroptosis in vivo.Conclusion: Overall, miR-612 promotes ferroptosis in HCC cells and affects HCC proliferation and metastasis by downregulating CoQ10 and increasing cellular PUFA levels and lipid peroxides via the HADHA-mediated MVA pathway.Keywords: HCC, Ferroptosis, miR-612, HADHA, MVA pathway

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion.

The GRAS (gibberellic acid insensitive, repressor of GAI, and scarecrow) proteins are a family of plant-specific transcription factors that regulate plant growth, development, and stress response. Currently, the role of GRAS transcription factors in various abiotic stress responses has not been systematically studied in cucumber (Cucumis sativus L.), a popular vegetable crop. Here, we provide a comprehensive bioinformatics analysis of the 35 GRAS genes identified in the cucumber genome. In this study, cucumber genotypes, i.e., “CG104”, which is stress-tolerant, and genotype “CG37”, which is stress-sensitive, were examined to provide insight on potential differences in the GRAS-regulated abiotic stress pathways. Transcriptional analysis by RNA-seq or qRT-PCR of these two genotypes revealed common and divergent functions of CsGRAS genes regulated by low and high temperatures, salinity, and by exposure to the phytohormones gibberellin (GA) and abscisic acid (ABA). Notably, CsGRAS2 (DELLA) and CsGRAS26 (LISCL) were regulated by all abiotic stresses and hormone treatments, suggesting that they may function in the biological cross-talk between multiple signaling pathways. This study provides candidate genes for improving cucumber tolerance to various environmental stresses.

ABSTRACT M31-LRN-2015 is a likely stellar merger discovered in the Andromeda Galaxy in 2015. We present new optical to mid-infrared photometry and optical spectroscopy for this event. Archival data show that the source started to brighten ∼2 yr before the nova event. During this precursor phase, the source brightened by ∼3 mag. The light curve at 6 and 1.5 months before the main outburst may show periodicity, with periods of 16 ± 0.3 and 28.1 ± 1.4 d, respectively. This complex emission may be explained by runaway mass-loss from the system after the binary undergoes Roche lobe overflow, leading the system to coalesce in tens of orbital periods. While the progenitor spectral energy distribution shows no evidence of pre-existing warm dust in the system, the remnant forms an optically thick dust shell at approximately four months after the outburst peak. The optical depth of the shell increases dramatically after 1.5 yr, suggesting the existence of shocks that enhance the dust formation process. We propose that the merger remnant is likely an inflated giant obscured by a cooling shell of gas with mass ∼0.2 M⊙ ejected at the onset of the common envelope phase.

After the identification of the gamma-ray blazar TXS 0506+056 as the first compelling IceCube neutrino source candidate, we perform a systematic analysis of all high-energy neutrino events satisfying the IceCube realtime trigger criteria. We find one additional known gamma-ray source, the blazar GB6 J1040+0617, in spatial coincidence with a neutrino in this sample. The chance probability of this coincidence is 30% after trial correction. For the first time, we present a systematic study of the gamma-ray flux, spectral and optical variability, and multiwavelength behavior of GB6 J1040+0617 and compare it to TXS 0506+056. We find that TXS 0506+056 shows strong flux variability in the Fermi-Large Area Telescope gamma-ray band, being in an active state around the arrival of IceCube-170922A, but in a low state during the archival IceCube neutrino flare in 2014/15. In both cases the spectral shape is statistically compatible (≤2σ) with the average spectrum showing no indication of a significant relative increase of a high-energy component. While the association of GB6 J1040+0617 with the neutrino is consistent with background expectations, the source appears to be a plausible neutrino source candidate based on its energetics and multiwavelength features, namely a bright optical flare and modestly increased gamma-ray activity. Finding one or two neutrinos originating from gamma-ray blazars in the given sample of high-energy neutrinos is consistent with previously derived limits of neutrino emission from gamma-ray blazars, indicating the sources of the majority of cosmic high-energy neutrinos remain unknown.