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Zhong-Tai Lin,1,2,* Shao-Ming Wei,1,3,* Jun-Yi Wu,1,3,* Zhi-Bo Zhang,4 Shuang-Jia Wang,5 Jian-Yin Zhou,6 Meng-Chao Luo,1,3 Zhen-Xin Zeng,1 Xiang-Ye Ou,1 Yang-Kai Fu,1 Han Li,1 De-Yi Liu,1 Jia-Yi Wu,1,3 Mao-Lin Yan1,3 1The Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 2Department of Gastrointestinal Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 4Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 5Department of Hepato-Biliary-Pancreatic and Vascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, People’s Republic of China; 6Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jia-Yi Wu; Mao-Lin Yan, The Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Dongjie Road 134, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86 0591-88217140, Fax +86 0591-87557768, Email tyhjwjy@163.com; yanmaolin74@163.comBackground: This study aimed to assess the effect of adjuvant therapy with different durations in patients with initially unresectable hepatocellular carcinoma (uHCC) after conversion surgery.Methods: This study included 85 patients with initially uHCC who received conversion surgery between May 2019 and November 2022. They were divided into the long duration group (n = 57) and short duration group (n = 28) based on postoperative medication duration. Recurrence-free survival (RFS) and overall survival (OS) were analyzed and compared between the cohorts.Results: No significant difference in RFS or OS was found between the two groups [RFS: hazard ratio (HR) = 0.486; 95% confidence interval (CI), 0.229– 1.034, P = 0.061; OS: HR = 0.377; 95% CI, 0.119– 1.196, P = 0.098]. Patients without major pathologic response (MPR) in the long duration group had better RFS and OS results compared to those in the short duration group (RFS: HR = 0.242; 95% CI, 0.092– 0.634, P = 0.004; OS: HR = 0.264; 95% CI, 0.079– 0.882, P = 0.031). No significant difference was detected in RFS or OS between the two groups in patients with MPR (RFS: HR = 1.250; 95% CI, 0.373– 4.183, P = 0.718; OS: HR = 7.389; 95% CI, 0.147– 372.4, P = 0.317). After propensity score matching, 25 pairs of patients were selected and the results remained consistent.Conclusion: At least 6 months of adjuvant therapy may be beneficial for patients without MPR after conversion surgery. However, in patients with MPR, the effect of adjuvant therapy remains unclear. Further studies are needed to confirm the optimal duration of adjuvant therapy.Keywords: unresectable, hepatocellular carcinoma, conversion therapy, adjuvant therapy, recurrence-free survival, overall survival

Jia-Yi Wu,1,2,* Jun-Yi Wu,1,2,* De-Yi Liu,1,* Han Li,1,* Shao-Wu Zhuang,3 Bin Li,4 Jian-Yin Zhou,5 Jing-Yao Huang,6 Zhi-Bo Zhang,7 Shu-Qun Li,8 Mao-Lin Yan,1,2 Yao-Dong Wang1,2 1Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 2Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 3Department of Interventional Radiology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, People’s Republic of China; 4Department of Hepato-Biliary-Pancreatic and Vascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, People’s Republic of China; 5Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province, People’s Republic of China; 6Department of Interventional Radiology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, People’s Republic of China; 7Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 8Department of Hepatobiliary Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mao-Lin Yan; Yao-Dong Wang, The Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Dongjie Road 134, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86 591-88217140 ; +86 591-88217130, Fax +86 591-87557768, Email yanmaolin74@163.com; wangyaodongfjsl@163.comBackground: This study aimed to determine whether salvage hepatectomy offers prognostic advantages for unresectable hepatocellular carcinoma (uHCC) patients with clinical complete response (cCR) after conversion therapy.Methods: A total of 74 consecutive uHCC patients with cCR after conversion therapy at seven major cancer centers in China between October 2018 and December 2021 were included. One-to-one propensity score matching (PSM) was performed to minimize the influence of potential confounders. Disease-free survival (DFS) and overall survival (OS) rates were compared between the surgical group and the non-surgical group.Results: Before PSM, 45 patients received salvage hepatectomy, and 29 patients received nonsurgical treatment. The 1-, 2-, and 3-year DFS rates were 77.8%, 61.5%, and 61.5% in the surgical group and 81.2%, 60.9%, and 60.9% in the non-surgical group, respectively. The 1-, 2-, and 3-year OS rates were 92.9%, 92.9%, and 69.7% in the surgical group and 100%, 70%, and 70% in the non-surgical group, respectively. There were no statistical differences in DFS and OS between groups [hazard ratio (HR)=0.715, 95% confidence interval (CI): 0.250– 2.043, p=0.531; HR=0.980, 95% CI: 0.177– 5.418, p=0.982, respectively]. After PSM, 26 pairs of patents were selected; there remained no significant differences in DFS and OS between these two groups (HR=1.547, 95% CI: 0.512– 4.669, p=0.439; HR=1.024, 95% CI: 0.168– 6.242, p=0.979, respectively).Conclusion: Through the study, it tend to show that salvage hepatectomy may be not essential for uHCC patients with cCR, especially for patients with a high risk of surgical complications. Prospective trials with long term follow-up are warranted to evaluate this treatment option.Plain Language Summary: To date, there is limited evidence on the prognosis of the unresectable hepatocellular carcinoma (uHCC) patients with clinical complete response (cCR), and the necessity of salvage surgery remains controversial. In this study, they compare and evaluate therapeutic benefits of salvage hepatectomy and nonsurgical treatment in the management of uHCC patients with cCR after conversion therapy. Finally, a total of 74 consecutive uHCC patients with cCR after conversion therapy at seven major cancer centers in China were included. There were no statistically significant differences for disease-free survival and overall survival were observed before and after propensity score matching. They revealed that cCR after conversion therapy led to a good prognosis for patients with uHCC. Furthermore, nonsurgical treatment provided similar survival benefits to those of salvage hepatectomy, suggesting that salvage hepatectomy may be not essential for uHCC patients with cCR.Keywords: conversion therapy, hepatocellular carcinoma, overall survival, disease-free survival, salvage surgery

Zhi-Bi Zhang,1 Tian-Yong Xu,2 Ding-Yun You,3 Shuai Yi,4 Qing Liu,4 Huifang-Jie Li,4 Jin-Yun Gu5 1Biomedical Engineering Center, Kunming Medical University, Kunming, People’s Republic of China; 2Experiment Center for Medical Science Research, Kunming, People’s Republic of China; 3Department of Science and Technology, Kunming Medical University, Kunming, People’s Republic of China; 4School of Forensic Medicine, Kunming Medical University, Kunming, People’s Republic of China; 5Zhanyi Branch of Qujing Public Security Bureau, Qujing, People’s Republic of China Background: A number of studies have demonstrated the significant and rapid antidepressant effects of ketamine, which is also known as a neurotoxic and illicit drug. Ketamine and alcohol are increasingly used together in clubs by teenagers and young adults. Previous studies have proven that chronic ketamine consumption induces a delayed and persistent activation of the dopamine (DA) system. However, the rewarding properties of recreational ketamine abuse remain unclear, and the underlying mechanisms of the effects on the DA system after administration of ketamine with ethanol are yet to be explored. Methods: Here, we evaluated the effects of two different doses of ketamine (30 mg/kg and 60 mg/kg) with and without ethanol (0.3156 g/kg) on DA concentration in the rat’s ventral tegmental area (VTA), a vital region in the reward and motivation system. We explored the effects of the combined drug treatment on the expression profiling of the DA metabolism genes, tyrosine hydroxylase, dopa decarboxylase, vesicular monoamine transporter 2, and synaptosomal-associated protein 25, as well as protein expression level of brain-derived neurotrophic factor in the rat’s VTA. Results: We found that administration of ketamine with ethanol led to a significant increase of DA in the VTA associated with differential regulation of mRNA levels of the four DA metabolism genes and protein levels of brain-derived neurotrophic factor. Moreover, the rewarding properties of coadministration of ketamine and ethanol were related to dopaminergic neuron activation in the VTA. Conclusion: These results indicated the possibility that combined drug treatment might positively affect the mesencephalic DA reward system. Keywords: ketamine, ethanol, TH, DDC, dopamine, ventral tegmental area

Chronic diarrhea is a common bowel disorder; disturbance of intestinal microorganisms may play a role in its pathogenesis. This study assessed the clinical efficacy of lyophilized, heat-killed Lactobacillus acidophilus LB versus living lactobacilli in the treatment of chronic diarrhea. One hundred thirty-seven patients with chronic diarrhea were randomly allocated to receive either a 4-week course of 2 capsules of Lacteol Fort twice a day (Lacteol group, 69 patients) or a 4-week course of 5 chewable tablets of Lacidophilin three times a day (Lacidophilin group, 64 patients). The frequency of stools was recorded quantitatively, and semiquantitative parameters such as stool consistency, abdominal pain, distention, and feeling of incomplete evacuation were evaluated. At the second and fourth week of treatment, mean bowel frequency was significantly lower in the Lacteol group than in the Lacidophilin group (1.88 +/- 1.24 vs 2.64 +/- 1.12, 1.39 +/- 0.92 vs 2.19 +/- 1.05; P<.05). At the end of the treatment, the clinical symptoms were markedly improved in the Lacteol group, indicating that L. acidophilus LB is more effective than living lactobacilli in the treatment of chronic diarrhea. [ABSTRACT FROM AUTHOR]

Geminal and vicinal borosilanes have unique applications in functional materials and synthetic transformations. Herein, a convenient method for the synthesis of geminal and vicinal borosilanes is developed via photoredox metal-free hydrosilylation of vinylboronic esters. This strategy features the advantages of high atom economy, environmental friendliness, and excellent functional group compatibility. The mechanism studies reveal that the catalytic reaction goes through photoredox HAT catalysis and a radical addition pathway.

Objective: To analyze the clinical and histopathological features of uveal leiomyoma. Methods: A retrospective study was performed on 19 patients with uveal leiomyoma confirmed by histopathological examination in Beijing Tongren Hospital from January 2018 to May 2023. All patients underwent local resection of the tumor. Clinical data of the patients, such as gender, age, clinical manifestations, tumor location, size, and B-scan ultrasound examinations were collected. The pathological morphological characteristics of the tissue (cell type) and the expression of the immune markers, including smooth muscle actin, actin, and neural cell adhesion molecule (CD56), were evaluated. Results: Among the 19 intraocular leiomyoma patients, there were 5 males and 14 females. The average age was (38.9±13.7) years, ranging from 14 to 64 years. The course of the disease ranged from 1 to 36 months with an average of (9.3±8.7) months. The most common clinical manifestation was blurred vision (12/19), followed by decreased vision (4/19), increased IOP (2/19), and visual occlusion (1/19) in patients. The tumor was located in the ciliary body in 10 female and 5 male patients, including 2 patients with the iris involved, and in the choroid in 4 female patients. Two patients with a history of breast fibronenoma had uveal leiomyoma in the ciliary body and the choroid, respectively. One patient with a history of uterine leiomyoma suffered uveal leiomyoma in the ciliary body. B-scan ultrasonography showed that the tumor was a solid and medium-low echoic lesion with a clear boundary in all eyes. We divided these leiomyomas into two histopathological types: spindle cell type (15/19) and round cell type (4/19). Immunohistochemical staining disclosed smooth muscle actin and actin were expressed in all tumor cells (19/19, 100%), and CD56 was positive in 16 of 19 eyes (84.2%). The positive expression rates of estrogen and progesterone were 0/19 and 2/19. During the follow-up of 7 to 71 months after surgery, no tumor metastasis occurred. Only 1 male patient had tumor recurrence. Conclusions: The most common site of uveal leiomyoma is the ciliary body, the major clinical manifestation is blurred vision, and the prognosis is good. Most of the tumors are spindle cell tumors, with myogenic and neurogenic histological characteristics. Although uveal leiomyoma is more frequently found in women of reproductive age, it shows no significant correlation with estrogen and progestational hormones.

Background: ATP citrate lyase (Acly) is widely expressed in many tissues, has been proved to be involved in the pathogenesis of many inflammatory diseases. So far, the importance of Acly in acute pancreatitis(AP) has not been clearly determined. The purpose of this study is to clarify whether Acly can evoke inflammatory cascades in the progression of AP and hamper the subsequent regeneration process of pancreas., Methods: Experimental pancreatitis in mice with a specific deficiency of Acly in the pancreas and in control mice through repetitive cerulein injections in vivo. The pancreas pathological grading, cell proliferative potential and the formation of acinar-to-ductal metaplasia (ADM) were evaluated. The levels of inflammatory cytokines in plasma were qualified by enzyme-linked immuno sorbent assay (ELISA). Pancreatic malondialdehyde (MDA), superoxide dismutase (SOD) activity and reduced glutathione (GSH) contents were measured for oxidative stress. The infiltration of macrophages and neutrophils, the expression of Toll like receptor 4 (TLR4), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and the activation of nuclear factor kappaB (NF-κB) and cleaved Caspase-3, were measured using immunostaining. The mRNA transcription levels of TLR4, TNF-α, and IL-1β in pancreatic tissues were detected by quantitative real-time PCR as well. Additionally, inhibition of TLR4 signaling by TAK-242 in AP mice with a pancreas-specific deletion of Acly was conducted in vivo., Results: The results demonstrated that the elimination of pancreatic Acly not only exacerbated the severity of pancreatitis in mice during the initial inflammatory phase, as evidenced by more severe pathological damage, but also impeded the healing process of the exocrine pancreas by enhancing the formation of ADM and decreasing the ability of acinar cells to proliferate. In addition, deficiency of Acly increased the circulating TNF-α, IL-1β and IL-6, the infiltration of macrophages and neutrophils, agumented the activation of nuclear factor kappaB (NF-κB) p65, the expression of TLR4, TNF-α, IL-1β and cleaved Caspase-3, and exacerbated excessive oxidative stress in the pancreas at specific time points of AP mice. However, TLR4 inhibition significantly attenuated the structural and functional damage of the pancreas induced by AP in mice with a pancreas-specific deletion of Acly, as indicated by improvement of the above indexes., Conclusions: The present study demonstrated that ablation of pancreatic Acly intensified inflammatory reaction and cell death, and dampened exocrine regeneration following AP, due to the positive regulation of TLR4/NF-κB signaling activation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Numerous experiments and clinical practices have demonstrated the effectiveness of Qishen Yiqi dripping pills (QSYQ) on myocardial ischemia (MI). However, the bioactive ingredients and mechanisms remain unclear, leading to huge gaps between quality control and biological effect of QSYQ. Discovering quality markers (Q-markers) based on effective components is crucial for ensuring stable quality and clinical effectiveness of QSYQ., Purpose: To explore Q-markers of QSYQ against MI by a stepwise strategy integrating serum pharmacochemistry, network pharmacology, metabolomics, quantitative analysis, and cell experiments., Methods: Firstly, liquid/gas chromatography-mass spectrometry was applied to characterize chemical profiles of QSYQ in vitro and in vivo. Based on the serum migrating constituents, a component-target-MI interaction network was constructed. Subsequently, pharmacodynamics and metabolomics were conducted to evaluate cardioprotective effect and potential mechanism of QSYQ. Next, conjoint analysis of network pharmacology and metabolomics was performed to screen candidate Q-markers. Finally, the measurability and bioactivity were validated to justify their usage as Q-markers., Results: A total of 97 components were identified in QSYQ, 24 prototypes of which were detected in serum. The "component-target-disease" interaction network was constructed based on serum migrating constituents. Pharmacodynamic results showed that QSYQ effectively improved cardiac function, attenuated inflammatory cell infiltration, alleviated myocardial fibrosis, and reduced the levels of myocardial enzymes and oxidative stress in MI rats. Metabolomics study demonstrated that 59 metabolites were markedly altered in MI rats, 25 of which were significantly reversely regulated by QSYQ. After integrative analysis of network pharmacology and metabolomics, 12 components were selected as candidate Q-markers of QSYQ, and the contents were quantified. These candidate Q-markers displayed synergistic protective effects against H 2 O 2 -induced injury in H9c2 cells. Taken together, 12 components with properties of transitivity and traceability, effectiveness, measurability, and compatibility contribution were defined as representative Q-markers of QSYQ, including Astragaloside IV, Ononin, Calycosin, Formononetin, Rosmarinic acid, Cryptotanshinone, Salvianolic acid A, Tanshinol, Ginsenoside Rb1, Ginsenoside Rg1, Nerolidol, and Santalol., Conclusion: In this study, a novel stepwise integrated strategy was presented for discovering Q-markers related to therapeutic effects of traditional Chinese medicine prescriptions. Twelve comprehensive and representative Q-markers of QSYQ were identified for the first time to improve its quality control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Basal-like breast cancer (BLBC) is the most malignant subtype of breast cancer because of its aggressive clinical behaviour and lack of effective targeted agents. Krüppel-like factor 5 (KLF5) is an oncogenic transcription factor that is highly expressed in BLBC. The deubiquitinase (DUB) BRCA1-associated protein 1 (BAP1) stabilizes KLF5 and promotes BLBC growth and metastasis. Therefore, pharmacological inhibition of the BAP1‒KLF5 axis is an effective therapeutic strategy for BLBC. Here, through screening, we identified a series of tetrahydro-β-carboline derivatives that effectively reduced the protein expression of KLF5 and exhibited strong antitumour activity. Among the investigated compounds, the lead compound LN-439A presented the strongest antitumour activity and inhibitory effect on KLF5 expression. LN-439A suppressed the proliferation and migration of BLBC cells, induced G2/M arrest, and induced apoptosis. Mechanistically, LN-439A functions as a small molecule catalytic inhibitor of BAP1 by binding to the catalytic pocket of BAP1, leading to the ubiquitination and degradation of KLF5. Consistent with this finding, the overexpression of KLF5 suppressed the antitumour effects of LN-439A. In summary, LN-439A is a promising therapeutic agent for BLBC that functions by targeting the BAP1‒KLF5 axis., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia ( n =4), fatigue ( n =3), fever ( n =2), abdominal discomfort ( n =2), osteolytic lesions ( n =2), dizziness ( n =1), skin flushing ( n =1), and weight loss ( n =1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) μg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

Background: Biliary atresia (BA) is a devastating neonatal cholangiopathy with an unclear pathogenesis, and prompt diagnosis of BA is currently challenging., Methods: Proteomic and immunoassay analyses were performed with serum samples from 250 patients to find potential BA biomarkers. The expression features of polymeric immunoglobulin receptor (PIGR) were investigated using human biopsy samples, three different experimental mouse models, and cultured human biliary epithelial cells (BECs). Chemically modified small interfering RNA and adenovirus expression vector were applied for in vivo silencing and overexpressing PIGR in a rotavirus-induced BA mouse model. Luminex-based multiplex cytokine assays and RNA sequencing were used to explore the molecular mechanism of PIGR involvement in the BA pathogenesis., Findings: Serum levels of PIGR, poliovirus receptor (PVR), and aldolase B (ALDOB) were increased in BA patients and accurately distinguished BA from infantile hepatitis syndrome (IHS). Combined PIGR and PVR analysis distinguished BA from IHS with an area under the receiver operating characteristic curve of 0.968 and an accuracy of 0.935. PIGR expression was upregulated in the biliary epithelium of BA patients; Th1 cytokines TNF-α and IFN-γ induced PIGR expression in BECs via activating NF-κB pathway. Silencing PIGR alleviated symptoms, reduced IL-33 expression, and restrained hepatic Th2 inflammation in BA mouse model; while overexpressing PIGR increased liver fibrosis and IL-33 expression, and boosted hepatic Th2 inflammation in BA mouse model. PIGR expression promotes the proliferation and epithelial-mesenchymal transition, and reduced the apoptosis of BECs., Interpretation: PIGR participated in BA pathogenesis by promoting hepatic Th2 inflammation via increasing cholangiocytes derived IL-33; PIGR has the value as a diagnostic and therapeutic biomarker of BA., Funding: This study was financially supported by the National Natural Science Foundation of China (82170529), the National Key R&D Program (2021YFC2701003), and the National Natural Science Foundation of China (82272022)., Competing Interests: Declaration of interests The authors do not have any disclosures to report., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: The objective of this study is to develop a novel diagnostic tool using deep learning and radiomics to distinguish bone tumors on CT images as metastases from breast cancer. By providing a more accurate and reliable method for identifying metastatic bone tumors, this approach aims to significantly improve clinical decision-making and patient management in the context of breast cancer., Methods: This study utilized CT images of bone tumors from 178 patients, including 78 cases of breast cancer bone metastases and 100 cases of non-breast cancer bone metastases. The dataset was processed using the Medical Image Segmentation via Self-distilling TransUNet (MISSU) model for automated segmentation. Radiomics features were extracted from the segmented tumor regions using the Pyradiomics library, capturing various aspects of tumor phenotype. Feature selection was conducted using LASSO regression to identify the most predictive features. The model's performance was evaluated using ten-fold cross-validation, with metrics including accuracy, sensitivity, specificity, and the Dice similarity coefficient., Results: The developed radiomics model using the SVM algorithm achieved high discriminatory power, with an AUC of 0.936 on the training set and 0.953 on the test set. The model's performance metrics demonstrated strong accuracy, sensitivity, and specificity. Specifically, the accuracy was 0.864 for the training set and 0.853 for the test set. Sensitivity values were 0.838 and 0.789 for the training and test sets, respectively, while specificity values were 0.896 and 0.933 for the training and test sets, respectively. These results indicate that the SVM model effectively distinguishes between bone metastases originating from breast cancer and other origins. Additionally, the average Dice similarity coefficient for the automated segmentation was 0.915, demonstrating a high level of agreement with manual segmentations., Conclusion: This study demonstrates the potential of combining CT-based radiomics and deep learning for the accurate detection of bone metastases from breast cancer. The high-performance metrics indicate that this approach can significantly enhance diagnostic accuracy, aiding in early detection and improving patient outcomes. Future research should focus on validating these findings on larger datasets, integrating the model into clinical workflows, and exploring its use in personalized treatment planning., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier GmbH.)

Territorial spatial planning could achieve the integration of various plans, resulting in a unified "multi-plan integration" map. Such planning emphasizes the efficient use of territorial spatial patterns and structures to ensure functional perfection, and serves as the spatial framework for building a modern socialist country, particularly in the areas of ecological security and ecological civilization. The past few decades have seen rapid advances in the development of landscape ecology in China. The core concept of "pattern-process-function" has gained significant progress and been widely applied in the initial phase of territorial spatial planning at various levels. We outlined the advancements in the territorial spatial planning system and the core research theories and technologies in landscape ecology. We discussed the progress and shortcomings of key theories and methods of landscape ecology in practical applications of territorial spatial planning, such as ecological security patterns, pattern and process, and scale effects. We proposed the future application of landscape ecology theories and technologies in territorial spatial planning, including overall ecological effects, scale effects, and regional ecological network optimization. Future developments in landscape ecology, especially research on the "human-place-ecology" coupling based on the latest Big Data and AI technology for sustainable development, will provide robust theoretical and methodological supports for the scientific formulation of territorial spatial planning in China.

Aims: β3-AR (β3-adrenergic receptor) is essential for cardiovascular homeostasis through regulating adipose tissue function. Perivascular adipose tissue (PVAT) has been implicated in the pathogenesis of aortic dissection and aneurysm (AD/AA). Here, we aim to investigate β3-AR activation-mediated PVAT function in AD/AA., Methods and Results: Aortas from patients with thoracic aortic dissection (TAD) were collected to detect β3-AR expression in PVAT. ApoE-/- and β-aminopropionitrile monofumarate (BAPN)-treated C57BL/6 mice were induced with Angiotensin II (AngII) to simulate AD/AA, and subsequently received either placebo or mirabegron, a β3-AR agonist. The results demonstrated an up-regulation of β3-AR in PVAT of TAD patients and AD/AA mice. Moreover, activation of β3-AR by mirabegron significantly prevented AngII-induced AD/AA formation in mice. RNA-sequencing analysis of adipocytes from PVAT revealed a notable increase of the lymphangiogenic factor VEGF-C in mirabegron-treated mice. Consistently, enhanced lymphangiogenesis was found in PVAT with mirabegron treatment. Mechanistically, the number of CD4+/CD8+ T cells and CD11c+ cells was reduced in PVAT but increased in adjacent draining lymph nodes (LNs) of mirabegron-treated mice, indicating the improved draining and clearance of inflammatory cells in PVAT by lymphangiogenesis. Importantly, adipocyte-specific VEGF-C knockdown by the adeno-associated virus system restrained lymphangiogenesis and exacerbated inflammatory cell infiltration in PVAT, which ultimately abolished the protection of mirabegron on AD/AA. In addition, the conditional medium derived from mirabegron-treated adipocytes activated the proliferation and tube formation of lymphatic endothelial cells (LECs), which was abrogated by the silencing of VEGF-C in adipocytes., Conclusions: Our findings illustrated the therapeutic potential of β3-AR activation by mirabegron on AD/AA, which promoted lymphangiogenesis by increasing adipocyte-derived VEGF-C and, therefore, ameliorated PVAT inflammation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Hypoxia-ischemia (HI) is one of the main causes of neonatal brain injury. Mitophagy has been implicated in the degradation of damaged mitochondria and cell survival following neonatal brain HI injury. Pleckstrin homology-like domain family A member 1 (PHLDA1) plays vital roles in the progression of various disorders including the regulation of oxidative stress, the immune responses and apoptosis. In the present study we investigated the role of PHLDA1 in HI-induced neuronal injury and further explored the mechanisms underlying PHLDA1-regulated mitophagy in vivo and in vitro. HI model was established in newborn rats by ligation of the left common carotid artery plus exposure to an oxygen-deficient chamber with 8% O 2 and 92% N 2 . In vitro studies were conducted in primary hippocampal neurons subjected to oxygen and glucose deprivation/-reoxygenation (OGD/R). We showed that the expression of PHLDA1 was significantly upregulated in the hippocampus of HI newborn rats and in OGD/R-treated primary neurons. Knockdown of PHLDA1 in neonatal rats via lentiviral vector not only significantly ameliorated HI-induced hippocampal neuronal injury but also markedly improved long-term cognitive function outcomes, whereas overexpression of PHLDA1 in neonatal rats via lentiviral vector aggravated these outcomes. PHLDA1 knockdown in primary neurons significantly reversed the reduction of cell viability and increase in intracellular reactive oxygen species (ROS) levels, and attenuated OGD-induced mitochondrial dysfunction, whereas overexpression of PHLDA1 decreased these parameters. In OGD/R-treated primary hippocampal neurons, we revealed that PHLDA1 knockdown enhanced mitophagy by activating FUNDC1, which was abolished by FUNDC1 knockdown or pretreatment with mitophagy inhibitor Mdivi-1 (25 μM). Notably, pretreatment with Mdivi-1 or the knockdown of FUNDC1 not only increased brain infarct volume, but also abolished the neuroprotective effect of PHLDA1 knockdown in HI newborn rats. Together, these results demonstrate that PHLDA1 contributes to neonatal HI-induced brain injury via inhibition of FUNDC1-mediated neuronal mitophagy., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: The aim of this study is to assess the clinical efficacy of minimally invasive surgical interventions in addressing spontaneous intracranial hemorrhage among neonates aged 0-3 months., Methods: A retrospective analysis was conducted on a cohort of 30 neonates diagnosed with spontaneous intracranial hemorrhage, who underwent minimally invasive cranial trepanation and drainage procedures at our department between 2011 and 2015., Results: A comprehensive follow-up, spanning a duration of 1-5 years, was conducted for all 30 neonates, revealing a 100% survival rate among the pediatric cohort., Conclusion: The findings suggest that minimally invasive cranial trepanation and drainage exhibit efficacy in neonates aged 0-3 months experiencing spontaneous intracranial hemorrhage, leading to a reduction in both mortality and disability rates. It is recommended that surgery be promptly performed upon definitive diagnosis and identification of operation indications to prevent severe brain damage resulting from prolonged intracranial hypertension and potential fatal outcomes in neonates. Furthermore, the surgical procedure is characterized by its simplicity, involving minimal trauma.

In order to facilitate technical personnel related to occupational health and safety production to search, obtain, and master information on the hazard classification and health effects of chemical hazards, this article surveyed 14 commonly used foreign databases and 9 commonly used domestic databases, analyzed the characteristics, main content, scope of application, and network resources of each database, and considered the development of database for occupational health hazard of chemical hazards.

The concept of a healthy lifestyle is receiving increasing attention. This study sought to identify an optimal healthy lifestyle profile associated with sleep health in general population of China. An online cross-sectional survey was conducted from June to July 2022. Six healthy lifestyle factors were assessed: healthy diet, regular physical exercise, never smoking, never drinking alcohol, low sedentary behavior, and normal weight. Participants were categorized into the healthy lifestyle (5-6 factors), average (3-4 factors), and unhealthy lifestyle groups (0-2 factors). The study's primary outcome was sleep health, which included sleep quality, duration, pattern, and the presence of any sleep disorder or disturbance, including insomnia, excessive daytime sleepiness, obstructive apnea syndrome, and narcolepsy. Multivariable logistic regression analysis was applied to explore lifestyles associated with the selected sleep health outcomes. 41,061 individuals were included, forming 18.8% healthy, 63.8% average, and 17.4% unhealthy lifestyle groups. After adjusting for covariates, participants with healthy lifestyle were associated with a higher likelihood of good sleep quality (OR = 1.56, 95% CI = 1.46-1.68), normal sleep duration (OR = 1.60, 95% CI = 1.49-1.72), healthy sleep pattern (OR = 2.15, 95% CI = 2.00-2.31), and lower risks of insomnia (OR = 0.66, 95% CI = 0.61-0.71), excessive daytime sleepiness (OR = 0.66, 95% CI = 0.60-0.73), and obstructive apnea syndrome (OR = 0.40, 95% CI = 0.37-0.43), but not narcolepsy (OR = 0.92, 95% CI = 0.83-1.03), compared to those with unhealthy lifestyle. This large cross-sectional study is the first to our knowledge to quantify the associations of a healthy lifestyle with specific aspects of sleep health. The findings offer support for efforts to improve sleep health by modulating lifestyle., (© 2024. The Author(s).)

Nitrophenols, a versatile intermediate, have been widely used in leather, medicine, chemical synthesis, and other fields. Because these components are widely applied, they can enter the environment through various routes, leading to many hazards and toxicities. There has been a recent surge in the development of simple, rapid, environmentally friendly, and effective techniques for determining these environmental pollutants. This review provides a comprehensive overview of the latest research progress on the pretreatment and analysis methods of nitrophenols since 2017, with a focus on environmental samples. Pretreatment methods include liquid-liquid extraction, solid-phase extraction, dispersive extraction, and microextraction methods. Analysis methods mainly include liquid chromatography-based methods, gas chromatography-based methods, supercritical fluid chromatography. In addition, this review also discusses and compares the advantages/disadvantages and development prospects of different pretreatment and analysis methods to provide a reference for further research., Competing Interests: Declaration of Competing Interest The authors declared that they have no conflicts of interest to this work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the pivotal role of the immune response in determining the progression and severity of viral infections. In this paper, we review the most recent studies on the complicated dynamics between SARS-CoV-2 and the host immune system, highlight the importance of understanding these dynamics in developing effective treatments and formulate potent management strategies for COVID-19. We describe the activation of the host's innate immunity and the subsequent adaptive immune response following infection with SARS-CoV-2. In addition, the review emphasizes the immune evasion strategies of the SARS-CoV-2, including inhibition of interferon production and induction of cytokine storms, along with the resulting clinical outcomes. Finally, we assess the efficacy of current treatment strategies, including antiviral drugs, monoclonal antibodies, and anti-inflammatory treatments, and discuss their role in providing immunity and preventing severe disease., Competing Interests: The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the West China School of Medicine & West China Hospital of Sichuan University.)

Nirmatrelvir, a pivotal component of the oral antiviral Paxlovid for COVID-19, targets the SARS-CoV-2 main protease (M pro ) as a covalent inhibitor. Here, we employed combined computational methods to explore how the prevalent Omicron variant mutation P132H, alone and in combination with A173V (P132H-A173V), affects nirmatrelvir's efficacy. Our findings suggest that P132H enhances the noncovalent binding affinity of M pro for nirmatrelvir, whereas P132H-A173V diminishes it. Although both mutants catalyze the rate-limiting step more efficiently than the wild-type (WT) M pro , P132H slows the overall rate of covalent bond formation, whereas P132H-A173V accelerates it. Comprehensive analysis of noncovalent and covalent contributions to the overall binding free energy of the covalent complex suggests that P132H likely enhances M pro sensitivity to nirmatrelvir, while P132H-A173V may confer resistance. Per-residue decompositions of the binding and activation free energies pinpoint key residues that significantly affect the binding affinity and reaction rates, revealing how the mutations modulate these effects. The mutation-induced conformational perturbations alter drug-protein local contact intensities and the electrostatic preorganization of the protein, affecting noncovalent binding affinity and the stability of key reaction states, respectively. Our findings inform the mechanisms of nirmatrelvir resistance and sensitivity, facilitating improved drug design and the detection of resistant strains.

Lysine (K) is widely used in the design of lysine-targeted crosslinkers, structural elucidation of protein complexes, and analysis of protein-protein interactions. In "shotgun" proteomics, which is based on liquid chromatography-tandem mass spectrometry (LC-MS/MS), proteins from complex samples are enzymatically digested, generating thousands of peptides and presenting significant challenges for the direct analysis of K-containing peptides. In view of the lack of effective methods for the enrichment of K-containing peptides, this work developed a method which based on a hydrophobic-tag-labeling reagent C10-S-S-NHS and reversed-phase chromatography (termed as HYTARP) to achieve the efficient enrichment and identification of K-containing peptides from complex samples. The C10-S-S-NHS synthesized in this work successfully labeled standard peptides containing various numbers of K and the labeling efficiency achieved up to 96% for HeLa cell protein tryptic digests. By investigating the retention behavior of these labeled peptides in C18 RP column, we found that most K-labeled peptides were eluted once when acetonitrile percentage reached 57.6% (v/v). Further optimization of the elution gradient enabled the efficient separation and enrichment of the K-labeled peptides in HeLa digests via a stepwise elution gradient. The K-labeled peptides accounted for 90% in the enriched peptides, representing an improvement of 35% compared with the number of peptides without the enrichment. The dynamic range of proteins quantified from the enriched K-containing peptides spans 5-6 orders of magnitude, and realized the detection of low-abundance proteins in the complex sample. In summary, the HYTARP strategy offers a straightforward and effective approach for reducing sample complexity and improving the identification coverage of K-containing peptides and low-abundance proteins.

As an important force in promoting the transformation and upgrading of the national economy, the occupational health of the Internet industry's employees has received widespread attention. This paper examines the current situation of occupational health risks and management in the Internet industry at home and abroad, and on this basis reveals the physical and mental health problems of Internet industry employees. Combining the existing regulations, policies and standard documents at home and abroad, countermeasures are proposed to improve the relevant laws and regulations and their guidelines, implement relevant job design requirements, build a healthy working environment, optimise the work management system and carry out workplace health promotion, in order to provide ideas to accelerate the improvement of occupational health issues in the Internet industry.

Abstract: We aimed to develop and validate a nomogram based on conventional ultrasound (CUS) radiomics model to differentiate radial scar (RS) from invasive ductal carcinoma (IDC) of the breast. In total, 208 patients with histopathologically diagnosed RS or IDC of the breast were enrolled. They were randomly divided in a 7:3 ratio into a training cohort (n = 145) and a validation cohort (n = 63). Overall, 1316 radiomics features were extracted from CUS images. Then a radiomics score was constructed by filtering unstable features and using the maximum relevance minimum redundancy algorithm and the least absolute shrinkage and selection operator logistic regression algorithm. Two models were developed using data from the training cohort: one using clinical and CUS characteristics (Clin + CUS model) and one using clinical information, CUS characteristics, and the radiomics score (radiomics model). The usefulness of nomogram was assessed based on their differentiating ability and clinical utility. Nine features from CUS images were used to build the radiomics score. The radiomics nomogram showed a favorable predictive value for differentiating RS from IDC, with areas under the curve of 0.953 and 0.922 for the training and validation cohorts, respectively. Decision curve analysis indicated that this model outperformed the Clin + CUS model and the radiomics score in terms of clinical usefulness. The results of this study may provide a novel method for noninvasively distinguish RS from IDC., Competing Interests: Conflict of interest disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The selective separation of small molecules at the sub-nanometer scale has broad application prospects in the field, such as energy, catalysis, and separation. Conventional polymeric membrane materials (e.g., nanofiltration membranes) for sub-nanometer scale separations face challenges, such as inhomogeneous channel sizes and unstable pore structures. Combining polymers with metal-organic frameworks (MOFs), which possess uniform and intrinsic pore structures, may overcome this limitation. This combination has resulted in three distinct types of membranes: MOF polycrystalline membranes, mixed-matrix membranes (MMMs), and thin-film nanocomposite (TFN) membranes. However, their effectiveness is hindered by the limited regulation of the surface properties and growth of MOFs and their poor interfacial compatibility. The main issues in preparing MOF polycrystalline membranes are the uncontrollable growth of MOFs and the poor adhesion between MOFs and the substrate. Here, polymers could serve as a simple and precise tool for regulating the growth and surface functionalities of MOFs while enhancing their adhesion to the substrate. For MOF mixed-matrix membranes, the primary challenge is the poor interfacial compatibility between polymers and MOFs. Strategies for the mutual modification of MOFs and polymers to enhance their interfacial compatibility are introduced. For TFN membranes, the challenges include the difficulty in controlling the growth of the polymer selective layer and the performance limitations caused by the "trade-off" effect. MOFs can modulate the formation process of the polymer selective layer and establish transport channels within the polymer matrix to overcome the "trade-off" effect limitations. This review focuses on the mechanisms of synergistic construction of polymer-MOF membranes and their structure-nanofiltration performance relationships, which have not been sufficiently addressed in the past., Competing Interests: Author Q.C., M.L., and S.S.; was employed by the company Nanjing Membrane Materials Industrial Technology Research Institute Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Health traits have high economic values in dairy cattle breeding, which can cause considerable financial loss through involuntary culling. In this study, fourteen health traits were analysed, including five composite health traits: reproductive disorders, udder health (UH), digestive disorders, metabolic disorders, locomotory diseases (LD), and nine independent health traits: gestation disorders and peripartum disorders, irregular estrus cycle and sterility, metritis (ME), mastitis (MA), abomasal displacement (AD), enteritis (EN), and ketosis, claw diseases (CD), laminitis complex. This study analysed variance components for health traits through both single and bivariate repeatability animal models. All health traits showed low heritability, ranging from 0.001 to 0.025. Most of the health traits in five categories showed negative genetic correlations, ranging from -0.012 (CD and EN) to -0.634 (ME and EN). Strong positive genetic correlations appeared within the same category, ranging from 0.469 (EN and AD) to 0.994 (UH and MA, LD and CD). Furthermore, approximate genetic correlations were evaluated between health traits and routinely collected traits (longevity, fertility, production, and conformation). In general, the low to moderate approximate genetic correlations were estimated between health traits and routinely collected traits. The estimated correlations between health traits and longevity, fertility, production, and conformation traits could provide an indirect reference for disease-resistance breeding in Holstein cattle., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Biological materials, although composed of meager minerals and biopolymers, often exhibit amazing mechanical properties far beyond their components due to hierarchically ordered structures. Understanding their structure-properties relationships and replicating them into artificial materials would boost the development of bulk structural nanocomposites. Layered microstructure widely exists in biological materials, serving as the fundamental structure in nanosheet-based nacres and nanofiber-based Bouligand tissues, and implying superior mechanical properties. High-efficient and scalable fabrication of bioinspired bulk structural nanocomposites with precise layered microstructure is therefore important yet remains difficult. Here, one straightforward bottom-up film-to-bulk assembly strategy is focused for fabricating bioinspired layered bulk structural nanocomposites. The bottom-up assembly strategy inherently offers a methodology for precise construction of bioinspired layered microstructure in bulk form, availability for fabrication of bioinspired bulk structural nanocomposites with large sizes and complex shapes, possibility for design of multiscale interfaces, feasibility for manipulation of diverse heterogeneities. Not limited to discussing what has been achieved by using the current bottom-up film-to-bulk assembly strategy, it is also envisioned how to promote such an assembly strategy to better benefit the development of bioinspired bulk structural nanocomposites. Compared to other assembly strategies, the highlighted strategy provides great opportunities for creating bioinspired bulk structural nanocomposites on demand., (© 2024 Wiley‐VCH GmbH.)

We report a novel organic photoredox catalysis to achieve unprecedented γ-(hetero)aryl/alkenyl-δ-silyl aliphatic amines via silyl-mediated distal (hetero)aryl/alkenyl migration of aromatic/alkenyl amines bearing unactivated alkenes with hydrosilanes. This protocol features mild and metal-free reaction conditions, high atom economy, excellent selectivity, and functional group compatibility. Mechanistic studies suggest that silylation and (hetero)aryl/alkenylation involve photoredox hydrogen atom transfer catalysis and subsequent 1,4-migration of a remote (hetero)aryl/alkenyl group from nitrogen to carbon.

Xuezheng Quanji («») written by Sun Guangyu, a doctor in the Ming Dynasty, is the first known book on blood disorders in China. The book mainly deals with bleeding. The book begins with a collection of the Neijing and the treatises of the sages, focusing on systematically summarizing the theories and experiences of the past dynasties in the treatment of bleeding, interspersed with Sun's own opinions.The main part discusses four types of bleeding, summarizing Sun's profound experience in clinical practice, and many of his personal creative opinions.In terms of causes,Sun believed that there are three causes of bleeding and more due to heat. In terms of treatment,he opposed the abuse of bitter cold and attached great importance to nourishing yin and strengthening kidney and proposed four treatment methods of dispelling stasis, nourishing Yin and suppressing Yang, regulating Qi and blood, and tonifying deficiency. He advocated that bleeding should not be treated quickly, and emphasized that the disease should be judged according to the bleeding location and bleeding color to use herbs flexibly.Special attention should be paid to daily life care during and after illness as well.

Rapid processing of tactile information is essential to human haptic exploration and dexterous object manipulation. Conventional electronic skins generate frames of tactile signals upon interaction with objects. Unfortunately, they are generally ill-suited for efficient coding of temporal information and rapid feature extraction. In this work, we report a neuromorphic tactile system that uses spike timing, especially the first-spike timing, to code dynamic tactile information about touch and grasp. This strategy enables the system to seamlessly code highly dynamic information with millisecond temporal resolution on par with the biological nervous system, yielding dynamic extraction of tactile features. Upon interaction with objects, the system rapidly classifies them in the initial phase of touch and grasp, thus paving the way to fast tactile feedback desired for neuro-robotics and neuro-prosthetics.

Background: Combination treatment with transcatheter arterial chemoembolization (TACE), lenvatinib, and anti-programmed death-1 (anti-PD-1) antibodies (triple therapy) has a high rate of tumor response and converted resection for initially unresectable hepatocellular carcinoma (uHCC) patients. This study aimed to assess the outcomes of salvage surgery in uHCC patients after conversion therapy with triple therapy., Methods: uHCC patients who met the criteria for hepatectomy after receiving triple therapy as first-line treatment were eligible for inclusion in this study. The overall survival (OS) and progression-free survival (PFS) rates in patients who received salvage surgery (SR group) and those who did not (non-SR group) were compared., Results: Of the 144 patients assessed, 91 patients underwent salvage surgery and 53 did not. The OS rates in the SR group were significantly better than those in the non-SR group. The 1- and 2-year OS rates in the SR group were 92.0% and 79.9%, respectively, whereas those in the non-SR group were 85.5% and 39.6 %, respectively (p = 0.007); however, there was no significant difference in the PFS rates. Upon further stratification, OS and PFS were significantly better in the SR group than in the non-SR group in patients who were assessed as partial responses (PR), while there was no significant difference in patients who were assessed as complete response (CR)., Conclusions: Salvage surgery is recommended and is associated with a favorable prognosis for uHCC patients who were assessed as PR after conversion therapy, however it may not be necessary for uHCC if CR was achieved., (© 2024. Society of Surgical Oncology.)

Objectives: Preoperative identification of different stromal subtypes of pleomorphic adenoma (PA) of the salivary gland is crucial for making treatment decisions. We aimed to develop and validate a model based on histogram analysis (HA) of ultrasound (US) images for predicting tumour stroma ratio (TSR) in salivary gland PA., Methods: A total of 219 PA patients were divided into low-TSR (stroma-low) and high-TSR (stroma-high) groups and enrolled in a training cohort (n = 151) and a validation cohort (n = 68). The least absolute shrinkage and selection operator regression algorithm was used to screen the most optimal clinical, US, and HA features. The selected features were entered into multivariable logistic regression analyses for further selection of independent predictors. Different models, including the nomogram model, the clinic-US (Clin + US) model, and the HA model, were built based on independent predictors using logistic regression. The performance levels of the models were evaluated and validated on the training and validation cohorts., Results: Lesion size, shape, cystic areas, vascularity, HA&#95;mean, and HA&#95;skewness were identified as independent predictors for constructing the nomogram model. The nomogram model incorporating the clinical, US, and HA features achieved areas under the curve of 0.839 and 0.852 in the training and validation cohorts, respectively, demonstrating good predictive performance and calibration. Decision curve analysis and clinical impact curves further confirmed its clinical usefulness., Conclusions: The nomogram model we developed offers a practical tool for preoperative TSR prediction in PA, potentially enhancing clinical decision-making., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology and the International Association of Dentomaxillofacial Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The occupational health issues of shift workers has received increasing attention in the field of occupational health, and discussed in this article through literature review on the health risks and management of shift work both domestically and internationally. Based on this, a series of impacts of shift work on the physiological and psychological health of workers, as well as their family and social life, are revealed. Combined with relatively mature regulations and policies in foreign countries, it is proposed that China should fully learn from the relevant experience of health management in shift work abroad, Strengthen research and explore effective management intervention measures to provide ideas for accelerating the development of scientifically feasible regulations and policies related to occupational health in shift work in China.

Proteins containing domain of unknown function (DUF) are prevalent in eukaryotic genome. The DUF1216 proteins possess a conserved DUF1216 domain resembling to the mediator protein of Arabidopsis RNA polymerase II transcriptional subunit-like protein. The DUF1216 family are specifically existed in Brassicaceae, however, no comprehensive evolutionary analysis of DUF1216 genes have been performed. We performed a first comprehensive genome-wide analysis of DUF1216 proteins in Brassicaceae. Totally 284 DUF1216 genes were identified in 27 Brassicaceae species and classified into four subfamilies on the basis of phylogenetic analysis. The analysis of gene structure and conserved motifs revealed that DUF1216 genes within the same subfamily exhibited similar intron/exon patterns and motif composition. The majority members of DUF1216 genes contain a signal peptide in the N-terminal, and the ninth position of the signal peptide in most DUF1216 is cysteine. Synteny analysis revealed that segmental duplication is a major mechanism for expanding of DUF1216 genes in Brassica oleracea, Brassica juncea, Brassica napus, Lepidium meyneii, and Brassica carinata, while in Arabidopsis thaliana and Capsella rubella, tandem duplication plays a major role in the expansion of the DUF1216 gene family. The analysis of Ka/Ks (non-synonymous substitution rate/synonymous substitution rate) ratios for DUF1216 paralogous indicated that most of gene pairs underwent purifying selection. DUF1216 genes displayed a specifically high expression in reproductive tissues in most Brassicaceae species, while its expression in Brassica juncea was specifically high in root. Our studies offered new insights into the phylogenetic relationships, gene structures and expressional patterns of DUF1216 members in Brassicaceae, which provides a foundation for future functional analysis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact., Main Text: This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation., Conclusions: By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health., (© 2024. The Author(s).)

Objective: To identify a novel reassortant H3N2 avian influenza virus using nanopore sequencing technology and analyze its genetic characteristics. Methods: The positive samples of the H3N2 avian influenza virus, collected from the external environment in the farmers' market of Guangzhou, were cultured in chicken embryos. The whole genome was sequenced by targeted amplification and nanopore sequencing technology. The genetic characteristics were analyzed using bioinformatics software. Results: The phylogenetic trees showed that each gene fragment of the strain belonged to the Eurasian evolutionary branch, and the host source was of avian origin. The HA gene was closely related to the origin of the H3N6 virus. The NA gene was closely related to the H3N2 avian influenza virus from 2017 to 2020. The PB1 gene was closely related to the H5N6 avian influenza virus in Guangxi Zhuang Autonomous Region and Fujian Province from 2016 to 2022 and was not related to the PB1 gene of the H5N6 avian influenza epidemic strain in Guangzhou. The other internal gene fragments had complex sources with significant genetic diversity. Molecular characteristics indicated that the strain exhibited the molecular characteristics of a typical low pathogenic avian influenza virus and tended to bind to the receptors of avian origin. On important protein sites related to biological characteristics, this strain had mutations of PB2-L89V, PB1-L473V, NP-A184K, M1-N30D/T215A, and NS1-P42S/N205S. Conclusions: This study identified a novel reassortant H3N2 avian influenza virus by nanopore sequencing, with the PB1 gene derived from the H5N6 avian influenza virus. The virus had a low ability to spread across species, but further exploration was needed to determine whether its pathogenicity to the host was affected.

Background: Portal vein tumor thrombus (PVTT) seriously affects the prognosis of hepatocellular carcinoma (HCC). However, whether bile duct tumor thrombus (BDTT) significantly affects the prognosis of HCC as much as PVTT remains unclear. We aimed to compare the long-term surgical outcomes of HCC with macroscopic PVTT (macro-PVTT) and macroscopic BDTT (macro-BDTT)., Methods: The data of HCC patients with macro-BDTT or macro-PVTT who underwent hemihepatectomy were retrospectively reviewed. A propensity score matching (PSM) analysis was performed to reduce the baseline imbalance. The recurrence-free survival (RFS) and overall survival (OS) rates were compared between the cohorts., Results: Before PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.043 and P = 0.008, respectively). Multivariate analyses identified PVTT (hazard ratio [HR] = 1.835, P = 0.016) and large HCC (HR = 1.553, P = 0.039) as independent risk factors for poor OS and RFS, respectively. After PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.037 and P = 0.004, respectively). The 3- and 5-year OS rates were significantly higher in the BDTT group (59.5% and 52.1%, respectively) than in the PVTT group (33.3% and 20.2%, respectively)., Conclusion: Aggressive hemihepatectomy provides an acceptable prognosis for HCC patients with macro-BDTT. Furthermore, the long-term surgical outcomes of HCC patients with macro-BDTT were significantly better than those of HCC patients with macro-PVTT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Wei, Fu, Zeng, Huang, Lv, Chen, Wei, Zhang, Zhou, Wu and Yan.)

Background and Aims: Transcatheter arterial chemoembolization combined with lenvatinib and PD-1 inhibitors (triple therapy) exhibits promising efficacy for unresectable hepatocellular carcinoma (uHCC). We aimed to evaluate the prognosis of patients with uHCC who received triple therapy and develop a prognostic scoring model to identify patients who benefit the most from triple therapy., Methods: A total of 246 patients with uHCC who received triple therapy at eight centers were included and assigned to the training and validation cohorts. Prognosis was evaluated by the Kaplan-Meier curves. The prognostic model was developed by utilizing predictors of overall survival (OS), which were identified through the Cox proportional hazards model., Results: In the training cohort, the 3-year OS was 52.0%, with a corresponding progression-free survival (PFS) of 30.6%. The median PFS was 13.2 months [95% confidence interval, 9.7-16.7]. Three variables (total bilirubin ≥ 17 μmol/L, alpha-fetoprotein ≥ 400 ng/mL, and extrahepatic metastasis) were predictors of poor survival and were used for developing a prognostic model (TAE score). The 2-year OS rates in the favorable (0 points), intermediate (1 point), and dismal groups (2-3 points) were 96.9%, 61.4%, and 11.4%, respectively (p < 0.001). The PFS was also stratified according to the TAE score. These findings were confirmed in an external validation cohort., Conclusions: Triple therapy showed encouraging clinical outcomes, and the TAE score aids in identifying patients who would benefit the most from triple therapy., (© 2023. Asian Pacific Association for the Study of the Liver.)

Antibiotics have attracted global attention because of their potential ecological and health risks. The emission, multimedia fate and risk of 18 selected antibiotics in the entire Yangtze River basin were evaluated by using a level Ⅳ fugacity model. High antibiotic emissions were found in the middle and lower reaches of the Yangtze River basin. The total antibiotic emissions in the Yangtze River basin exceeded 1600 tons per year between 2013 and 2021. The spatial distribution of antibiotics concentration was the upper Yangtze River > middle Yangtze River > lower Yangtze River, which is positively correlated with animal husbandry size in the basin. Temperature and precipitation increases may decrease the antibiotic concentrations in the environment. Transfer fluxes showed that source emission inputs, advection processes, and degradation fluxes contributed more to the total input and output. High ecological risks in the water environment were found in 2018, 2019, 2020, and 2021. The comprehensive health risk assessment through drinking water and fish consumption routes showed that a small part of the Yangtze River basin is at medium risk, and children have a relatively high degree of health risk. This study provides a scientific basis for the pollution control of antibiotics at the basin scale., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To understand the infection status and molecular types of rhinovirus (RV) among cases of Acute Respiratory Infections (ARIs) in Luohe City, Henan Province, from 2017 to 2022. Methods: From October 2017 to June 2022, clinical and epidemiological data were collected from 2 270 cases of ARIs at Luohe Central Hospital in Henan Province. Throat swab specimens were obtained from these cases. Real-time quantitative polymerase chain reaction (qPCR) was used to screen for RV-positive specimens. Subsequently, the positive samples were subjected to nested reverse transcription polymerase chain reaction (nested RT-PCR) to amplify the full-length VP1 region. Using the MEGA software, along with 169 RV reference strains recommended by the International Committee on Taxonomy of Viruses, a phylogenetic tree was constructed to determine RV types. Results: Among the 2 270 cases of ARIs, there were 1 283 male cases (56.52%). The median age ( Q 1 , Q 3 ) was 3 (1, 6) years, with the population under 5 years old accounting for 68.59% (1 557/2 270). RV was detected in 137 cases (6.04%), of which 68 cases (49.64%) showed co-detection with other viruses, with the most common being co-detection with enterovirus, accounting for 14.60% (20/137). The RV detection rates in the age groups of 0~4 years, 5~14 years, 15~59 years, and≥60 years were 6.42% (100/1 557), 4.69% (21/448), 3.80% (6/158), and 9.35% (10/107), respectively, with no statistically significant differences ( χ 2 =5.310, P =0.150). The overall detection rates of RV before (2017-2019) and during (2020-2022) the COVID-19 pandemic showed no statistically significant difference ( χ 2 =1.823, P =0.177). A total of 109 VP1 sequences were obtained, including 62 types. Among them, RV-A, RV-B, and RV-C had 42, 3, and 17 types respectively. Conclusion: RV is one of the predominant pathogens in ARIs cases in Luohe City, Henan Province, from 2017 to 2022. Multiple types of RV co-circulate without any apparent dominant type.

Background: This study evaluates the efficacy of alpha-fetoprotein (AFP) response as a surrogate marker for determining recurrence-free survival (RFS) in patients with unresectable hepatocellular carcinoma (uHCC) who undergo salvage hepatectomy following conversion therapy with tyrosine kinase inhibitor (TKI) and anti-PD-1 antibody-based regimen., Methods: This multicenter retrospective study included 74 patients with uHCC and positive AFP (>20 ng/mL) at diagnosis, who underwent salvage hepatectomy after treatment with TKIs and anti-PD-1 antibody-based regimens. The association between AFP response-defined as a ≥ 80% decrease in final AFP levels before salvage hepatectomy from diagnosis-and RFS post-hepatectomy was investigated., Results: AFP responders demonstrated significantly better postoperative RFS compared to non-responders ( P <0.001). The median RFS was not reached for AFP responders, with 1-year and 2-year RFS rates of 81.3% and 70.8%, respectively. In contrast, AFP non-responders had a median RFS of 7.43 months, with 1-year and 2-year RFS rates at 37.1% and 37.1%, respectively. Multivariate Cox regression analysis identified AFP response as an independent predictor of RFS. Integrating AFP response with radiologic tumor response facilitated further stratification of patients into distinct risk categories: those with radiologic remission experienced the most favorable RFS, followed by patients with partial response/stable disease and AFP response, and the least favorable RFS among patients with partial response/stable disease but without AFP response. Sensitivity analyses further confirmed the association between AFP response and improved RFS across various cutoff values and in patients with AFP ≥ 200 ng/mL at diagnosis (all P <0.05)., Conclusion: The "20-80" rule based on AFP response could be helpful for clinicians to preoperatively stratify the risk of patients undergoing salvage hepatectomy, enabling identification and management of those unlikely to benefit from this procedure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lin, Zhang, Lin, Chen, Luo, Chen, Wang, Tai, Zhang, Wang, Li, Wang, Zheng, Zheng, Wu, Lin, Yang and Zeng.)

Background: B56ε is a regulatory subunit of the serine/threonine protein phosphatase 2A, which is abnormally expressed in tumors and regulates various tumor cell functions. At present, the application of B56ε in pan-cancer lacks a comprehensive analysis, and its role and mechanism in hepatocellular carcinoma (HCC) are still unclear., Aim: To analyze B56ε in pan-cancer, and explore its role and mechanism in HCC., Methods: The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Profiling Interactive Analysis, and Tumor Immune Estimation Resource databases were used to analyze B56ε expression, prognostic mutations, somatic copy number alterations, and tumor immune characteristics in 33 tumors. The relationships between B56ε expression levels and drug sensitivity, immunotherapy, immune checkpoints, and human leukocyte antigen (HLA)-related genes were further analyzed. Gene Set Enrichment Analysis (GSEA) was performed to reveal the role of B56ε in HCC. The Cell Counting Kit-8, plate cloning, wound healing, and transwell assays were conducted to assess the effects of B56ε interference on the malignant behavior of HCC cells., Results: In most tumors, B56ε expression was upregulated, and high B56ε expression was a risk factor for adrenocortical cancer, HCC, pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma (all P < 0.05). B56ε expression levels were correlated with a variety of immune cells, such as T helper 17 cells, B cells, and macrophages. There was a positive correlation between B56ε expression levels with immune checkpoint genes and HLA-related genes (all P < 0.05). The expression of B56ε was negatively correlated with the sensitivity of most chemotherapy drugs, but a small number showed a positive correlation (all P < 0.05). GSEA analysis showed that B56ε expression was related to the cancer pathway, p53 downstream pathway, and interleukin-mediated signaling in HCC. Knockdown of B56ε expression in HCC cells inhibited the proliferation, migration, and invasion capacity of tumor cells., Conclusion: B56ε is associated with the microenvironment, immune evasion, and immune cell infiltration of multiple tumors. B56ε plays an important role in HCC progression, supporting it as a prognostic marker and potential therapeutic target for HCC., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)