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Ying Chen,1,2,* Wen-Xia Li,1,2,* Jia-Hua Wu,1,2 Geng-Hang Chen,2 Chun-Min Yang,1,2 Hai Lu,1,2 Xi Wang,3 Shu-Sen Wang,4 Heng Huang,5 Li Cai,6 Li Zhao,7 Rou-Jun Peng,8 Ying Lin,9 Jun Tang,3 Jian Zeng,10 Le-Hong Zhang,11 Yong-Li Ke,12 Xian-Ming Wang,13 Xin-Mei Liu,14 An-Qin Zhang,15 Fei Xu,4 Xi-Wen Bi,4 Jia-Jia Huang,4 Ji-Bin Li,16 Dan-Mei Pang,17 Cong Xue,4 Yan-Xia Shi,4 Zhen-Yu He,18 Huan-Xin Lin,18 Xin An,4 Wen Xia,4 Ye Cao,16 Ying Guo,16 Ruo-Xi Hong,4 Kui-Kui Jiang,4 Yong-Yi Zhong,4 Ge Zhang,19 Piyawan Tienchaiananda,20 Masahiro Oikawa,21 Zhong-Yu Yuan,4 Qian-Jun Chen22,23 1Department of Breast Surgery, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Breast Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Department of Breast Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 4Department of Medical Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 5Department of Breast Oncology, Lianjiang People’s Hospital, Lianjiang, People’s Republic of China; 6Department of Medical Oncology, The Affiliated Tumour Hospital of Harbin Medical University, Harbin, People’s Republic of China; 7Department of Breast Oncology, Guangzhou First People Hospital, Guangzhou, People’s Republic of China; 8Department of Integrated Therapy in Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 9Department of Breast Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 10Department of Breast Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 11Department of Breast Oncology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 12Department of Breast Oncology, General Hospital of PLA Guangzhou Military Area, Guangzhou, People’s Republic of China; 13Department of Breast Oncology, Shenzhen Second People’s Hospital, Shenzhen, People’s Republic of China; 14Department of Breast Oncology, Haikou People’s Hospital, Haikou, People’s Republic of China; 15Department of Breast Oncology, Maternal and Child Health Care Hospital of Guangdong Province, Guangzhou, People’s Republic of China; 16Department of Good Clinical Practice, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 17Department of Medical Oncology, Foshan First People’s Hospital, Foshan, People’s Republic of China; 18Department of Radiotherapy, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 19Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases (TMBJ), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong; 20Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Rangsit University, Rajavithi Hospital, Bangkok, Thailand; 21The Department of Breast Surgery, New-wa-kai Oikawa Hospital, Fukuoka, Japan; 22State Key Laboratory of Traditional Chinese Medicine Syndrome/Departments of Gynecologic Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 23State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian-Jun Chen, 55N, Neihuanxi Road, Guangzhou, Guangdong, 510006, People’s Republic of China, Tel +86 1868883505, Email cqj55@163.com Zhong-Yu Yuan, 651 Dongfeng Road, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86 13798027658, Email yuanzhy@sysucc.org.cnPurpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not.Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into “consistent” (standard acceptable dose) and “inconsistent” (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes.Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the “inconsistent” dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the “inconsistent” dose of anthracycline and taxane did not affect DFS compared with the “consistent” dose. Moreover, in the capecitabine group, the “inconsistent” anthracycline dose did not affect DFS compared with the “consistent” dose. However, patients with “consistent” taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06).Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.Keywords: adjuvant chemotherapy, capecitabine, SYSUCC-001, triple-negative breast cancer, TNBC

Kai Zhang,* Ruoxi Hong,* Fei Xu, Wen Xia, Lee Kaping, Ge Qin, Qiufan Zheng, Qianyi Lu, Yan Xia Shi, Zhong Yu Yuan, Shusen Wang Sun Yat-Sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this work Background: The clinical implication of plasma ESR1 mutations in the estrogen receptor (ER)-positive metastatic breast cancer (MBC) patients who had progressed after prior aromatase inhibitor (AI)-based therapy remains controversial. We conducted the first meta-analysis to investigate the prognostic significance and predictive role of plasma ESR1 mutations in MBC patients with prior exposure to AI therapy. Materials and methods: We searched PubMed, Embase, and Cochrane Library databases for eligible studies. Meta-analysis was conducted to calculate combined hazard ratios (HRs) with 95% CIs for progression-free survival (PFS) and overall survival (OS). Subgroup and sensitivity analyses were also performed. Results: This study enrolled a total of 1,530 patients with ER-positive MBC cases from six articles, including 429 ESR1 mutation carriers (28.04%). Meta-analysis demonstrated that plasma ESR1 mutation carriers had significantly worse PFS (HR: 1.40, 95% CI: 1.17–1.66; P

Xiaoli Li,1 Jingjing Li,2 Yanxia Shi,2 Ting Wang,2 Aling Zhang,2 Na Shao,2 Zhenghui Wang2 1Department of Dermatology, 2Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of China Background: The purpose of this study is to examine the effect of psychological intervention on the life quality of patients with laryngeal cancer.Methods: Two hundred and ten patients with laryngeal cancer were randomly assigned to the study group receiving psychological intervention and control group receiving routine nursing care. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and the Europe Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) were used to evaluate life quality.Results: There were no significant differences in the scores of HAMD, HAMA, and EORTC QLQ-C30 between the 2 groups before treatment (P>0.05). After treatment, the scores in the study group were significantly different to those in the control group (P

Inflammatory signals lead to recruitment of circulating monocytes and induce their differentiation into pro-inflammatory macrophages. Therefore, whether blocking inflammatory monocytes can mitigate disease progression is being actively evaluated. Here, we employ multiple lineage-tracing models and show that monocyte-derived macrophages (mo-mac) are the major population of immunosuppressive, liver metastasis-associated macrophages (LMAM), while the proportion of Kupffer cells (KC) as liver-resident macrophages is diminished in metastatic nodules. Paradoxically, genetic ablation of mo-macs results in only a marginal decrease in LMAMs. Using a proliferation-recording system and a KC-tracing model in a monocyte-deficient background, we find that LMAMs can be replenished either via increased local macrophage proliferation or by promoting KC infiltration. In the latter regard, KCs undergo transient proliferation and exhibit substantial phenotypic and functional alterations through epigenetic reprogramming following the vacating of macrophage niches by monocyte depletion. Our data thus suggest that a simultaneous blockade of monocyte recruitment and macrophage proliferation may effectively target immunosuppressive myelopoiesis and reprogram the microenvironment towards an immunostimulatory state., (© 2024. The Author(s).)

Patients carrying mutations in polymerase epsilon/polymerase delta have shown positive responses to immune checkpoint inhibitors. Yet, prospective trials exploring the efficacy in those with polymerase epsilon/polymerase delta mutations are still lacking. A phase II clinical trial was initiated to evaluate the efficacy of toripalimab, a humanized IgG4K monoclonal antibody to human PD-1, in patients with advanced solid tumors with unselected polymerase epsilon/polymerase delta mutations but without microsatellite instability-high. A total of 15 patients were enrolled, 14 of whom were assessed for treatment efficacy. There was a 21.4% overall response rate, with a disease control rate of 57.1%. The median overall survival and median progression-free survival were 17.9 (95% CI 13.5-not reach) months and 2.5 (95% CI 1.4-not reach) months, respectively. For patients with exonuclease domain mutations, the objective response rate was 66.7% (2/3), with a disease control rate of 66.7% (2/3). For those with non-exonuclease domain mutations, the rates were 9.1% (1/11) and 54.5% (6/11), respectively. Notably, patients with PBRM1 gene mutations exhibited a high response rate to toripalimab at 75.0% (3/4). This study showed that neither the exonuclease domain mutations nor non-exonuclease domain mutations could fully predict the efficacy of immunotherapy, urging the need for more investigations to clarify potential immune sensitization differences within polymerase epsilon/polymerase delta mutation variants., (© 2024. The Author(s).)

Objective: To evaluate the long-term outcomes of lower extremity arteriovenous graft (AVG) in hemodialysis patients. Methods: Hemodialysis patients with lower extremity AVG from August 2015 to July 2023 in the Department of Vascular Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine were enrolled. Therapeutic effects and complications of AVG were retrospectively analyzed. Results: A total of 83 cases aged (58.9±13.3) years were enrolled, including 25 males and 58 females. The success rate of the operation was 100% (83/83), and no perioperative complications occurred. The follow-up time [ M ( Q 1 , Q 3 )] was 38.4 (22.6, 55.3) months, with a follow-up rate of 92.8% (77/83). There were 9 cases (11.7%) of puncture site infection, 5 cases (6.5%) of pseudoaneurysm, 2 cases (2.6%) of seroma, 3 cases (3.9%) of lower limb ischemia, 48 cases (62.3%) of stenosis and 24 cases (31.2%) of thrombosis during the follow-up period. The 6-month, 1-year, 2-year, 3-year and 5-year primary patency rates after surgery were 78.9%, 61.2%, 39.0%, 27.0% and 16.3%, respectively, assisted primary patency rates were 93.5%, 82.5%, 74.9%, 68.0% and 53.0%, respectively, and secondary patency rates were 96.1%, 94.7%, 93.1%, 91.3% and 75.3%, respectively. Conclusion: For patients whose vascular resources of upper limbs are exhausted, lower extremity AVG is a safe and effective hemodialysis vascular access.

Background: Colorectal cancer significantly impacts global health, with unplanned reoperations post-surgery being key determinants of patient outcomes. Existing predictive models for these reoperations lack precision in integrating complex clinical data., Aim: To develop and validate a machine learning model for predicting unplanned reoperation risk in colorectal cancer patients., Methods: Data of patients treated for colorectal cancer ( n = 2044) at the First Affiliated Hospital of Wenzhou Medical University and Wenzhou Central Hospital from March 2020 to March 2022 were retrospectively collected. Patients were divided into an experimental group ( n = 60) and a control group ( n = 1984) according to unplanned reoperation occurrence. Patients were also divided into a training group and a validation group (7:3 ratio). We used three different machine learning methods to screen characteristic variables. A nomogram was created based on multifactor logistic regression, and the model performance was assessed using receiver operating characteristic curve, calibration curve, Hosmer-Lemeshow test, and decision curve analysis. The risk scores of the two groups were calculated and compared to validate the model., Results: More patients in the experimental group were ≥ 60 years old, male, and had a history of hypertension, laparotomy, and hypoproteinemia, compared to the control group. Multiple logistic regression analysis confirmed the following as independent risk factors for unplanned reoperation ( P < 0.05): Prognostic Nutritional Index value, history of laparotomy, hypertension, or stroke, hypoproteinemia, age, tumor-node-metastasis staging, surgical time, gender, and American Society of Anesthesiologists classification. Receiver operating characteristic curve analysis showed that the model had good discrimination and clinical utility., Conclusion: This study used a machine learning approach to build a model that accurately predicts the risk of postoperative unplanned reoperation in patients with colorectal cancer, which can improve treatment decisions and prognosis., Competing Interests: Conflict-of-interest statement: All authors declare that there is no conflict of interest involved in this study., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Egl-9 family hypoxia-inducible factor 3 (EGLN3) is involved in the regulation of tumor microenvironment and tumor progression. However, its biological function and clinical significance in various cancers remain unclear., Methods: RNA-seq, immunofluorescence, and single-cell sequencing were used to investigate the expression landscape of EGLN3 in pan-cancer. The TISCH2 and CancerSEA databases were used for single-cell function analysis of EGLN3 in tumors. TIMER2.0 database was used to explain the relationship between EGLN3 expression and immune cell infiltration. In addition, the LinkedOmics database was used to perform KEGG enrichment analysis of EGLN3 in pan-cancer. siRNA was used to silence gene expression. CCK8, transwell migration assay, flow cytometry analysis, RT-PCR, and western blotting were used to explore biological function of EGLN3., Results: The results showed that EGLN3 was highly expressed in a variety of tumors, and was mainly localized to the cytosol. EGLN3 expression is associated with immunoinfiltration of a variety of immune cells, including macrophages in the tumor immune microenvironment and tumor-associated fibroblasts. Functional experiments revealed that EGLN3 knockdown could inhibit cell proliferation, migration, and promote cell apoptosis. In addition, we found that Bax expression was up-regulated and Bcl-2 expression was down-regulated in the si-EGLN3 group. Taken together, as a potential oncogene, EGLN3 is involved in the regulation of tumor malignant process, especially tumor cell apoptosis., Conclusion: We comprehensively investigated the expression pattern, single-cell function, immune infiltration level and regulated signaling pathway of EGLN3 in pan-cancer. We found that EGLN3 is an important hypoxia and immune-related gene that may serve as a potential target for tumor immunotherapy., 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.)

Lead (Pb) is a major source of heavy metal contamination, and poses a threat to biodiversity and human health. Elevated levels of Pb can hinder insect growth and development, leading to apoptosis via mechanisms like oxidative damage. The midgut of silkworms is the main organ exposed to heavy metals. As an economically important lepidopteran model insect in China, heavy metal-induced stress on silkworms causes considerable losses in sericulture, thereby causing substantial economic damage. This study aimed to investigate Pb-induced detoxification-related genes in the midgut of silkworms using high-throughput sequencing methods to achieve a deeper comprehension of the genes' reactions to lead exposure. This study identified 11,567 unigenes and 14,978 transcripts. A total of 1265 differentially expressed genes (DEGs) were screened, comprising 907 upregulated and 358 downregulated genes. Subsequently, Gene Ontology (GO) classification analysis revealed that the 1265 DEGs were distributed across biological processes, cellular components, and molecular functions. This suggests that the silkworm midgut may affect various organelle functions and biological processes, providing crucial clues for further exploration of DEG function. Additionally, the expression levels of 12 selected detoxification-related DEGs were validated using qRT-PCR, which confirmed the reliability of the RNA-seq results. This study not only provides new insights into the detoxification defense mechanisms of silkworms after Pb exposure, but also establishes a valuable foundation for further investigation into the molecular detoxification mechanisms in silkworms.

Diffusive gradients in thin films technique (DGT) is recognized as a more reliable method for determining labile heavy metal (HM) concentration in soil than traditional destructive methods. However, the current DGT measurement index, C DGT , theoretically underestimates the true labile concentration (C labile ) of HMs in soil and lacks direct comparability with the conventional soil HM content indices due to unit differences. Here, we proposed C DGT-W , a new simple index which is defined as the HM accumulation in the binding layer, normalized to the weight of soil (optimized water content = 100% of the maximum water holding capacity) filled in the open cavity-type DGT device over a specified deployment time (optimized time = 24 h). The procedure for measuring C DGT-W is analogous to that of C DGT but includes precise determination of water content (water/dry soil) and the mass of soil filled in the cavity. We conducted measurements of Cu, Pb, Cr(Ⅵ) and As(V) as C DGT-W , C DGT , solution concentration (C soln ), and CaCl 2 extractable concentration (C CaCl2 ) on three soils with a diverse range of HM concentrations. C DGT-W showed significant linear correlations with all other tested indexes. The ratios of C DGT-W to C CaCl2 varied between 0.30 and 0.98 for all HM-soil combinations with only one exception, a range much greater than C DGT /C soln (typically <0.1) but lower than 1. This suggested that C DGT-W may more accurately reflect C labile than C DGT (theoretically underestimates C liable ) and C CaCl2 (likely overestimates C liable ). Additionally, C DGT-W measurements for these four HMs exhibited a broad measure concentration range and a low detection limit (mg/kg level). Consequently, C DGT-W may offer a more reliable alternative to C DGT for characterizing C labile in unsaturated soils., 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 Ltd. All rights reserved.)

2,6-pyridine dicarboxylic acid (DPA) is an exceptional biomarker of notorious anthrax spores. Therefore, the rapid, sensitive, and selective quantitative detection of DPA is extremely significant and urgent. This paper reports a Zn(II) metal-organic framework with the formula of {[Zn 6 (NDA) 6 (DPBT) 3 ] 2H 2 O·3DMF} n (MOF-1), which consists of 2,6-naphthalenedicarboxylic acid (2,6-NDA), 4,7-di(4-pyridyl)-2,1,3-benzothiadiazole (DPBT), and Zn(II) ions. Structural analysis indicated that MOF-1 is a three-dimensional (3D) network which crystallized in the monoclinic system with the C 2/c space group, revealing high pH, solvent, and thermal stability. Luminescence sensing studies demonstrated that MOF-1 had the potential to be a highly selective, sensitive, and recyclable fluorescence sensor for the identification of DPA. Furthermore, fluorescent test paper was made to detect DPA promptly with color changes. The enhancement mechanism was established by the hydrogen-bonding interaction and photoinduced electron transfer transition between MOF-1 and DPA molecules.

Background: The active ingredients of the Chinese medical herb Paris polyphylla, P. polyphylla ethanol extract (PPE) and polyphyllin I (PPI), potentially inhibit epithelial-mesenchymal transition (EMT) in tumors. However, the roles of these ingredients in inhibiting EMT in adenomyosis (AM) remain to be explored., Purpose: The primary goal of the study was to uncover the underlying molecular processes through which PPE and PPI suppress EMT in AM, alongside assessing the safety profiles of these substances., Methods: To assess the suppressive impact of PPE on adenomyosis-derived cells (AMDCs), we employed Transwell and wound healing assays. The polyphyllins (PPI, PPII, PPVII) contained in PPE were characterized using high-performance liquid chromatography (HPLC). Then, bioinformatics techniques were performed to pinpoint potential PPI targets that could be effective in treating AM. Immunoblotting was used to verify the key proteins and pathways identified via bioinformatics. Furthermore, we examined the efficacy of PPE and PPI in treating Institute of Cancer Research (ICR) mice with AM by observing the morphological and pathological features of the uterus and performing immunohistochemistry. In addition, we assessed safety by evaluating liver, kidney and spleen pathologic features and serum test results., Results: Three major polyphyllins of PPE were revealed by HPLC, and PPI had the highest concentration. In vitro experiments indicated that PPE and PPI effectively prevent AMDCs invasion and migration. Bioinformatics revealed that the primary targets E-cadherin, N-cadherin and TGFβ1, as well as the EMT biological process, were enriched in PPI-treated AM. Immunoblotting assays corroborated the hypothesis that PPE and PPI suppress the TGFβ1/Smad2/3 pathway in AMDCs to prevent EMT from progressing. Additionally, in vivo studies showed that PPE (3 mg/kg and 6 mg/kg) and PPI (3 mg/kg and 6 mg/kg), successfully suppressed the EMT process through targeting the TGFβ1/Smad2/3 signaling pathway. Besides, it was observed that lower doses of PPE (3 mg/kg) and PPI (3 mg/kg) exerted minimal effects on the liver, kidneys, and spleen., Conclusions: PPE and PPI efficiently impede the development of EMT by inhibiting the TGFβ1/Smad2/3 pathway, revealing an alternative pathway for the pharmacological treatment of AM., Competing Interests: Declaration of competing interest There are no known conflicts of interest in this publication., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Tuberculosis (TB) remains one of the major infectious diseases in the world with a high incidence rate. Drug-resistant tuberculosis (DR-TB) is a key and difficult challenge in the prevention and treatment of TB. Early, rapid, and accurate diagnosis of DR-TB is essential for selecting appropriate and personalized treatment and is an important means of reducing disease transmission and mortality. In recent years, imaging diagnosis of DR-TB has developed rapidly, but there is a lack of consistent understanding. To this end, the Infectious Disease Imaging Group, Infectious Disease Branch, Chinese Research Hospital Association; Infectious Diseases Group of Chinese Medical Association of Radiology; Digital Health Committee of China Association for the Promotion of Science and Technology Industrialization, and other organizations, formed a group of TB experts across China. The conglomerate then considered the Chinese and international diagnosis and treatment status of DR-TB, China's clinical practice, and evidence-based medicine on the methodological requirements of guidelines and standards. After repeated discussion, the expert consensus of imaging diagnosis of DR-PB was proposed. This consensus includes clinical diagnosis and classification of DR-TB, selection of etiology and imaging examination [mainly X-ray and computed tomography (CT)], imaging manifestations, diagnosis, and differential diagnosis. This expert consensus is expected to improve the understanding of the imaging changes of DR-TB, as a starting point for timely detection of suspected DR-TB patients, and can effectively improve the efficiency of clinical diagnosis and achieve the purpose of early diagnosis and treatment of DR-TB., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1223/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

The present study investigated the bioaccumulation and translocation of mercury (Hg) and chromium (Cr) in Yunyan 87 flue-cured tobacco (Nicotiana tabacum) and assessed the influence of soil pH on the metal uptake by plant organs at the field scale. The study was conducted in 4 different regions selected from Sichuan Province, China: Guangyuan, Luzhou, Panzhihua, and Yibin. The results revealed that Hg highly contaminated Yibin soils at 0.29 mg kg -1 and by Cr at 147 mg kg -1 , which is above the permissible limit. The levels of Hg in tobacco plant organs were predominantly in the order of leaves > root > stem. The overall trend for Cr contents in tobacco organs was in the order of root > leaves > stem. The results of an index of bioaccumulation (IBA) and translocation factor (TF) showed that the values observed in Panzhihua and Guangyuan tobacco leaves were generally higher, despite the low levels of soil contamination. The linear mixed model (LMM) demonstrated that the log of Hg IBA in tobacco organs was likely to decrease with soil pH increase, whereas the log of Cr IBA only decreased in the root but gradually increased in the aerial parts with soil pH increase. The total random variation in the log of metals' IBA due to regions indicated that for Hg, 33.42% of the variation was explained by regional differences, while for Cr, only 13% was accounted. The results suggested that Yibin and Luzhou need to correct the soil acidity if they are set to reduce Hg contamination in tobacco-growing soils. Guangyuan and Panzhihua need efforts to keep the soil pH on track to avoid high contamination levels, and effective measures of soil nutrients supply are required to produce high tobacco leaf quality free from heavy metal content. The findings of this study may be used to ascertain regional differences in heavy metals, particularly Hg and Cr uptake by tobacco plant organs, and to prevent the cultivation areas contamination through soil pH monitoring., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Hexavalent chromium (Cr(VI)) is a toxic heavy metal and its mobility and bioaccessibility in soils are influenced by soil properties. In this study, the soil pH and organic carbon contents of Ultisol, Alfisol, and Inceptisol were adjusted before they were polluted with 230 mg kg -1 Cr(VI). Alkaline digestion, sequential extraction, and an in vitro experiment were conducted to study the valence state, species, and bioaccessibility of Cr in the soils. The results showed that a high soil pH was not favorable for reduction of Cr(VI); therefore the Cr(VI) and exchangeable Cr contents were positively related to soil pH. Soil organic carbon promoted the reduction of Cr(VI). Almost all Cr(VI) was reduced to Cr(III) when the soil organic carbon content reached 10 g kg -1 . Chromium bioaccessibility in simulated gastric and intestinal phase solutions was influenced by Cr(VI) and Cr(III) adsorption/desorption, dissolution/precipitation, and redox reactions. Chromium bioaccessibility differences between the gastric and intestinal phases were associated with the Cr(VI)/Cr(III) ratio. Acidic conditions and a high organic carbon content promoted the conversion of Cr(VI) to Cr(III). When soil pH was increased from 4.01 to 5.85, Cr(VI) in Alfisol without the addition of humic acid increased from 96.38 to 174.78 mg kg -1 , the exchangeable Cr proportion increased from 9.7% to 22.6%, and Cr bioaccessibility increased from 41.29% to 49.14% in the gastric phase and from 41.32% to 48.24% in the intestinal phase. When the organic carbon content increased from 3.95 to 9.28 g kg -1 in Alfisol, Cr(VI) content decreased from 167.66 to 20.52 mg kg -1 , which led to a decrease in Cr bioaccessibility from 49.15% to 13.8% in the gastric phase and from 45.85% to 7.67% in the intestinal phase. Therefore, acidic conditions and increasing soil organic carbon levels can reduce the health risk posed by Cr in soils., 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 Ltd. All rights reserved.)

Uremic toxins are chemicals, organic or inorganic, that accumulate in the body fluids of individuals with acute or chronic kidney disease and impaired renal function. More than 130 uremic solutions are included in the most comprehensive reviews to date by the European Uremic Toxins Work Group, and novel investigations are ongoing to increase this number. Although approaches to remove uremic toxins have emerged, recalcitrant toxins that injure the human body remain a difficult problem. Herein, we review the derivation and elimination of uremic toxins, outline kidney-gut axis function and relative toxin removal methods, and elucidate promising approaches to effectively remove toxins., 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 © 2023 Xu, Bi, Shi, Liang, Wang, Lai, Bian and Guo.)

Background: More and more studies have demonstrated that potassium channel tetramerization domain-containing 5 (KCTD5) plays an important role in the development of cancer, but there is a lack of comprehensive research on the biological function of this protein in pan-cancer. This study systematically analyzed the expression landscape of KCTD5 in terms of its correlations with tumor prognosis, the immune microenvironment, programmed cell death, and drug sensitivity., Methods: We investigated a number of databases, including TCGA, GEPIA2, HPA, TISIDB, PrognoScan, GSCA, CellMiner, and TIMER2.0. The study evaluated the expression of KCTD5 in human tumors, as well as its prognostic value and its association with genomic alterations, the immune microenvironment, tumor-associated fibroblasts, functional enrichment analysis, and anticancer drug sensitivity. Real-time quantitative PCR and flow cytometry analysis were performed to determine the biological functions of KCTD5 in lung adenocarcinoma cells., Results: The results indicated that KCTD5 is highly expressed in most cancers and that its expression is significantly correlated with tumor prognosis. Moreover, KCTD5 expression was related to the immune microenvironment, infiltration by cancer-associated fibroblasts, and the expression of immune-related genes. Functional enrichment analysis revealed that KCTD5 is associated with apoptosis, necroptosis, and other types of programmed cell death. In vitro experiments showed that knockdown of KCTD5 promoted apoptosis of A549 cells. Correlation analysis confirmed that KCTD5 was positively correlated with the expression of the anti-apoptotic genes Bcl-xL and Mcl-1. Additionally, KCTD5 was significantly associated with sensitivity to multiple antitumor drugs., Conclusion: Our results suggest that KCTD5 is a potential molecular biomarker that can be used to predict patient prognosis, immunoreactions and drug sensitivity in pan-cancer. KCTD5 plays an important role in regulating programmed cell death, especially apoptosis., (© 2023. The Author(s).)

Background: During mitosis and meiosis, centromere proteins (CENPs) play a key role in proper chromosome segregation. Abnormal expression of CENPs leads to chromosome instability, which is the main cause of tumorigenesis., Methods: To elucidate the functional characteristics of CENPs in pan-cancer, we comprehensively analyzed the expression landscape of CENPs and their relationships with patient survival, genomic alterations, tumor immunity, tumor microenvironment, and anticancer drug sensitivity. The expression patterns and signaling pathways of CENPs were identified through multiple bioinformatics mining and experimental verification. GEPIA2 and PrognoScan were implemented to evaluate the prognostic value of CENPs. The molecular functions of CENPs in pan-cancer were comprehensively assessed using cBioPortal, GSCA, ImmuCellAI, CellMiner, the ROC plotter tool and TIDE., Results: The results showed that CENPs were upregulated in most tumors compared with normal tissues. We confirmed this conclusion by immunohistochemistry and real-time quantitative PCR. Survival analysis revealed a significant association between high CENP expression and a poor prognosis. CENP expression is related to genome alterations, copy number variation, single nucleotide variation and methylation. Among CENP family genes, CENPF and CENPE are mutated at high frequencies in various tumors, while CENPM and CENPA are less frequently mutated. Furthermore, CENPs regulate the tumor mutational burden, stemness, and microsatellite instability, and are associated with tumor immunity. Most importantly, we revealed that CENP family gene expression was correlated with chemosensitivity and immunotherapy responses., Conclusion: These findings may clarify the role of CENPs in cancer progression and antitumor drug sensitivity and provide evidence for CENPs as a potential target in pan-cancer., Competing Interests: Declaration of Competing Interest There are no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Ganoderic acids (GAs) are well recognized as important pharmacological components of the medicinal species belonging to the basidiomycete genus Ganoderma. However, transcription factors directly regulating the expression of GA biosynthesis genes remain poorly understood. Here, the genome of Ganoderma lingzhi is de novo sequenced. Using DNA affinity purification sequencing, we identify putative targets of the transcription factor sterol regulatory element-binding protein (SREBP), including the genes of triterpenoid synthesis and lipid metabolism. Interactions between SREBP and the targets are verified by electrophoretic mobility gel shift assay. RNA-seq shows that SREBP targets, mevalonate kinase and 3-hydroxy-3-methylglutaryl coenzyme A synthetase in mevalonate pathway, sterol isomerase and lanosterol 14-demethylase in ergosterol biosynthesis, are significantly upregulated in the SREBP overexpression (OE::SREBP) strain. In addition, 3 targets involved in glycerophospholipid/glycerolipid metabolism are upregulated. Then, the contents of mevalonic acid, lanosterol, ergosterol and 13 different GAs as well as a variety of lipids are significantly increased in this strain. Furthermore, the effects of SREBP overexpression on triterpenoid and lipid metabolisms are recovered when OE::SREBP strain are treated with exogenous fatostatin, a specific inhibitor of SREBP. Taken together, our genome-wide study clarify the role of SREBP in triterpenoid and lipid metabolisms of G. lingzhi., (© 2023. The Author(s).)

Phosphorus (P) availability in highly weathered soils is significantly influenced by the contents of iron (Fe)/aluminum (Al) oxides, clay minerals, and organic matter. With the increasing interest in biofertilizers (e.g. chitosan), it is important to understand how they affect P adsorption profiles on colloids of weathered soils rich in Fe/Al oxides. Thus, the effect of chitosan on the adsorption of P to colloids of hematite, gibbsite, Oxisol, and Ultisol was studied through electrokinetic measurements, spectroscopic analysis, and adsorption edge/isotherm profiles. The presence of chitosan significantly improved the surface positive charge and the decreasing trend of surface positive charge was slower for chitosan-treated colloids compared to the control with increasing pH. At pH 5.0, all the colloids were positively charged, with the oxides containing more positve charges than the soil colloids. At this pH value, the surface coverage capacity of P was 99.1, 61.6, 50.5, and 37.5 mmol kg⁻ 1 for Oxisol, Ultisol, hematite, and gibbsite, respectively. This suggests that clay minerals in soil colloids were vital in enhancing P adsorption. In the presence of chitosan, the surface coverage capacity of P was increased by 111%, 173%, 647%, and 488% for Oxisol, Ultisol, gibbsite, and hematite, respectively. Drawing inferences from spectroscopic analysis, citric acid desorption profile, and zeta potential analysis, we suggest that chitosan (CH) enhanced P adsorption by promoting the formation of (i) citric acid "undisplaceable" inner-sphere P complexes such as [Colloid-OP-O-CH] and [Colloid-OP-N-CH], (ii) citric acid "displaceable" outer-sphere P complexes such as {[Colloid-O-CH]-OP} and {[Colloid-N-CH]-OP}, and (iii) water "leachable or soluble" P complexes such as {[Colloid-CH] + PO 4 ³⁻} and {[Colloid-OP]⁻CH + }. Thus, applying chitosan as a biofertilizer (source of N) along with P in highly weathered soils could improve P availability while reducing P leaching., 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 © 2022 Elsevier Ltd. All rights reserved.)

PIK3CA mutations are highly prevalent in solid tumors. Targeting phosphatidylinositol 3-kinase α is therefore an attractive strategy for treating cancers harboring PIK3CA mutations. Here, we report the results from a phase Ia, open label, dose-escalation and -expansion study (NCT03544905) of CYH33, a highly selective PI3Kα inhibitor, in advanced solid tumors. The primary outcomes were the safety, tolerability, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of CYH33. The secondary outcomes included evaluation of pharmacokinetics, preliminary efficacy and changes in pharmacodynamic biomarkers in response to CYH33 treatment. The exploratory outcome was the relationship between the efficacy of CYH33 treatment and tumor biomarker status, including PIK3CA mutations. A total of 51 patients (19 in the dose escalation stage and 32 in the dose expansion stage) including 36 (70.6%) patients (4 in the dose escalation stage and 32 in the dose expansion stage) with PIK3CA mutations received CYH33 1-60 mg. The MTD of CYH33 was 40 mg once daily, which was also selected as the RP2D. The most common grade 3/4 treatment-related adverse events were hyperglycemia, rash, platelet count decreased, peripheral edema, and fatigue. Forty-two out of 51 patients were evaluable for response, the confirmed objective response rate was 11.9% (5/42). Among 36 patients harboring PIK3CA mutations, 28 patients were evaluable for response, the confirmed objective response rate was 14.3% (4/28). In conclusion, CYH33 exhibits a manageable safety profile and preliminary anti-tumor efficacy in solid tumors harboring PIK3CA mutations., (© 2022. The Author(s).)

Medium-chain acyl-CoA dehydrogenase (MCAD) is one of the significant enzymes involved in the β-oxidation of mitochondrial fatty acids. MCAD deficiency affects the β-oxidation of fatty acid and leads to lipid deposition in multiple organs, but little is known about its importance in nonalcoholic steatohepatitis (NASH). Empagliflozin is revealed to effectively improve NASH by increasing research, whereas the specific mechanism still has to be explored. Human liver tissues of patients with or without NASH were obtained for proteomic analysis to screen proteins of interest. db/db mice were given empagliflozin by gavage for 8 weeks. The expression of MCAD and signaling molecules involved in hepatic lipid metabolism was evaluated in human liver, mice and HL7702 cells. We found that the MCAD levels in the liver were significantly reduced in NASH patients compared to patients without NASH. Protein-protein interaction network analysis showed that MCAD was highly correlated with forkhead box A2 (FOXA2) and protein kinase AMP-activated catalytic subunit alpha (PRKAA). AMPK/FOXA2/MCAD signaling pathway was detected to be inhibited in the liver of NASH patients. Decreased expression of MCAD was also observed in the livers of db/db mice and hepatocyte treated with palmitic acid and glucose. Of note, empagliflozin could upregulate MCAD expression by activating AMPK/FOXA2 signaling pathway, reduce lipid deposition and improve NASH in vivo and in vitro. This research demonstrated that MCAD is a key player of hepatic lipid deposition and its targeting partially corrects NASH. MCAD thus may be a potential therapeutic target for the treatment of NASH.

To explore the effects of the increases in pH and pH buffering capacity (pHBC) induced by crop residue biochars on the changes in soil available Cd content, six acidic paddy soils developed from different parents were amended with seeded sunflower plate biochar (SSPBC), peanut straw biochar (PSBC) and corn straw biochar (CSBC). The pH, pHBC, and available Cd of the soils were measured after laboratory incubation. The results showed that the incorporation of crop residue biochars led to the increases in soil pH and pHBC, but a decrease in soil available Cd content. The decreasing order of available Cd content was SSPBC > PSBC > CSBC and was consistent with the changes in soil pH induced by the biochars. During submerging and draining, soil pH increased first and then declined, however the content of available Cd decreased first and then increased significantly. Soil pH in the treatments with biochars showed little change during draining, which was different from the control without the biochars added. This was attributed to the enhancing effect of the biochars on soil pHBC. Also, there was a significant negative correlation between the change in available Cd content and soil pHBC during submerging/draining alternation and suggested that higher pHBC corresponded to smaller soil available Cd content. Consequently, the amount of Cd absorbed by rice was reduced, thereby reducing the potential risk of soil Cd to humans. These results can provide useful references for the remediation of Cd-contaminated paddy soils., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Urolithiasis or kidney stones is a common and frequently occurring renal disease; calcium oxalate (CaOx) crystals are responsible for 80% of urolithiasis cases. Phyllanthus niruri L. (PN) has been used to treat urolithiasis. This study aimed to determine the potential protective effects and molecular mechanism of PN on calcium oxalate-induced renal injury. Methods: Microarray data sets were generated from the calcium oxalate-induced renal injury model of HK-2 cells and potential disease-related targets were identified. Network pharmacology was employed to identify drug-related targets of PN and construct the active ingredient-target network. Finally, the putative therapeutic targets and active ingredients of PN were verified in vitro and in vivo . Results: A total of 20 active ingredients in PN, 2,428 drug-related targets, and 127 disease-related targets were identified. According to network pharmacology analysis, HMGCS1, SQLE, and SCD were identified as predicted therapeutic target and ellagic acid (EA) was identified as the active ingredient by molecular docking analysis. The increased expression of SQLE, SCD, and HMGCS1 due to calcium oxalate-induced renal injury in HK-2 cells was found to be significantly inhibited by EA. Immunohistochemical in mice also showed that the levels of SQLE, SCD, and HMGCS1 were remarkably restored after EA treatment. Conclusion: EA is the active ingredient in PN responsible for its protective effects against CaOx-induced renal injury. SQLE, SCD, and HMGCS1 are putative therapeutic targets of EA., 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 © 2022 Li, Liu, Zhou, Huang, Shi, Hou, Lu, Yu, Chen and Guo.)

Recently, the albumin-bilirubin (ALBI) score, a continuous index consisting of only albumin and bilirubin, has been developed for objectively assessing liver function in patients with hepatocellular carcinoma (HCC). However, the ALBI score was arbitrarily categorized into three ALBI grades based on two artificially predetermined cutoff points with no explanation and statistical grounds, causing a considerable loss of discriminatory ability. This study aims to propose a modified ALBI (mALBI) grade for offering a detailed evaluation of hepatic reserve and specify its role during clinical practice in the HCC setting. The study population comprised 3540 HCC patients treated with mainstream therapies including hepatectomy (n=2056), thermal ablation (n=550), and transcatheter arterial chemoembolization (n=934) from 2002 to 2017. The ALBI score was stratified into four mALBI grades through a recently proposed statistical method aiming to select the optimal cutoff points of a continuous predictive variable by maximizing the discriminative ability in a multivariable Cox regression model. The mALBI grade had an overall better discriminatory ability than the ALBI grade in predicting overall survival through Harrell's C-index (0.614 vs. 0.598, P<0.001). Both visual inspections of Kaplan-Meier curves and calculation of hazard ratios displayed a more subtle evaluation of liver function using the mALBI grade. Moreover, the newly identified cut-point (ALBI score = -2.29) between the mALBI grade 2a and 2b was much closer to a 30% retention rate of indocyanine green at 15 minutes, an indicator for the performance of a subsegmentectomy. The newly proposed mALBI grade provides a more subtle assessment of liver function to guide clinical decision-making and predicts the prognosis of HCC patients more accurately than the original ALBI grade., Competing Interests: None., (AJCR Copyright © 2022.)

To obtain novel insights into the tumor biology and therapeutic targets of LUAD, we performed a comprehensive analysis of the KCTD family genes. The expression patterns and clinical significance of the KCTD family were identified through multiple bioinformatics mining. Moreover, the molecular functions and potential mechanisms of differentially expressed KCTDs were evaluated using TIMER 2.0, cBioPortal, GeneMANIA, LinkedOmics and GSEA. The results indicated that the mRNA and protein expression levels of KCTD9, KCTD10, KCTD12, KCTD15 and KCTD16 were significantly decreased in LUAD, while those of KCTD5 were significantly increased. High KCTD5 expression was significantly associated with advanced tumor stage, lymph node metastasis, TP53 mutation and poor prognosis. In addition, KCTD5 was positively correlated with CD8 + T cell, neutrophil, macrophage and dendritic cell infiltration. Additionally, KCTDs demonstrate promising prospects in the diagnosis of LUAD. Importantly, high KCTD5 expression was enriched in signaling pathways associated with the malignant progression of tumors, including the inflammatory response, the IL6/JAK/STAT3 signaling pathway, EMT and hypoxia. Further association analysis showed that KCTD5 was positively correlated with hypoxia-related genes such as HIF1. Overall, KCTDs can be used as molecular targets for the treatment of LUAD, as well as effective molecular biomarkers for diagnosis and prognosis prediction., (© 2022. The Author(s).)

Background: Patients who achieve a tumor pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) have better outcomes than patients with residual tumor. However, tumors still recur in the pCR patients. Therefore, we aim to explore factors associated with tumor recurrence in this patient population., Methods: A total of 1,913 patients diagnosed with breast cancer between 1995 and 2020 and received NAC were included in this analysis. Clinicopathological data of the patients were retrospectively collected. We used Cox regression analysis to assess the associations of clinicopathological factors with patients' outcome. Proteomic study of tumors was applied to identify differentially expressed proteins (DEPs) between tumors from the pCR patients with tumor recurrence and tumors from those without tumor recurrence. PPI network analysis of the corresponding genes of DEPs was used to identify the hub genes. The prognostic value of the corresponding genes of DEPs was evaluated using two online databases, Kaplan-Meier Plotter and bc-GenExMiner. The genes that were significantly associated with patients' survival in both databases, as well as being identified as hub genes, were considered as potential prognostic markers for pCR patients. Publicly available data from Gene Expression Omnibus (GEO) was used to verify the prognostic value of the identified marker., Results: Among the 1,913 included patients, 420 had tumor pCR. The median follow-up for the pCR patients was 32.6 months (IQR, 16.3-55.5). Overall estimated 5-year risk of tumor recurrence for the pCR patients was 11%. Multivariable analysis showed that a higher pre-NAC clinical T stage and N stage were independent predictors for increased risk of tumor recurrence (hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.01-6.51, P=0.047 for clinical T stage and HR 3.48, 95%CI 1.37-8.83, P=0.009 for clinical N stage). NAC regimens, the type of breast and axillary surgery, and adjuvant chemotherapy were not associated with tumor recurrence. Finally, aldehyde dehydrogenase (ALDH) 3A2 was identified by the proteomic study and was verified as a potential predictor for tumor recurrence in the pCR patients (with a median follow up of 3.78 years for dataset GSE32603 and 2.74 years for dataset GSE25066 from GEO, tumor recurrence rate: low versus high expression, 20.7% versus 4.5% [data from GSE32603]; 10.9% versus 0% [data from GSE25066])., Conclusions: Clinical T stage, clinical N stage and tumor expression of ALDH3A2 were potential markers for predicting tumor recurrence in the pCR patients after NAC., 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 © 2022 Xie, Wang, Chen, Shi, Zhang, Lin, Liang, Xiao, Wu, Yuan and Qiu.)

Purpose: There is no research evidence demonstrate which is the better partner strategy, endocrine therapy or chemotherapy, to combine with anti-HER2 therapy as the first-line management of hormone receptor (HR)-positive (HR+) and HER2-positive (HER2+) metastatic breast cancer (MBC). We wished to ascertain if trastuzumab plus endocrine therapy is noninferior to trastuzumab plus chemotherapy., Patients and Methods: We conducted an open-label, noninferiority, phase III, randomized, controlled trial (NCT01950182) at nine hospitals in China. Participants, stratified by previous adjuvant endocrine therapy and disease status (recurrent disease vs. de novo metastasis), were assigned randomly (1:1) to receive trastuzumab plus endocrine therapy (per investigator's choice of oestrogen-receptor modulators or aromatase inhibitor, with/without concurrent ovarian suppression) or chemotherapy (per investigator's choice of taxanes, capecitabine, or vinorelbine). The primary endpoint was progression-free survival (PFS) with a noninferiority upper margin of 1.35 for the HR. The intention-to-treat population was used in primary and safety analyses., Results: A total of 392 patients were enrolled and assigned randomly to receive trastuzumab plus endocrine therapy (ET group, n = 196) or trastuzumab plus chemotherapy (CT group, n = 196). After a median follow-up of 30.2 months [interquartile range (IQR) 15.0-44.7], the median PFS was 19.2 months [95% confidence interval (CI), 16.7-21.7)] in the ET group and 14.8 months (12.8-16.8) in the CT group (hazard ratio, 0.88; 95% CI, 0.71-1.09; Pnoninferiority < 0.0001). A significantly higher prevalence of toxicity was observed in the CT group compared with the ET group., Conclusions: Trastuzumab plus endocrine therapy was noninferior to trastuzumab plus chemotherapy in patients with HR+HER2+ MBC., (©2021 The Authors; Published by the American Association for Cancer Research.)

There are varying definitions of women at high risk of breast cancer across different institutions, and there are reports suggesting that the breast cancer risk assessment tools have not been well integrated into clinical practice. In this study, we tried to investigate the perceived importance of different breast cancer risk factors by physicians in China. A cross-sectional survey involving 386 anonymous physicians was conducted using a 20-item, 5-point Likert scale questionnaire. The Kruskal-Wallis test and post-hoc pairwise comparisons were used to compare the differences in response. Most of the respondents were either breast surgeons/specialists (n=161; 41.7%) or medical oncologists (n=151; 39.1%), and the results showed that the breast cancer risk factors were not perceived as equally important. The weighting of each risk factor also varied depending on the physician's medical specialty, location of practice, and the number of years of clinical experience.  This study provides a more updated insight into the perceptions of physicians in China toward the breast cancer risk factors, as well as underlines the potential improvements in breast cancer risk assessment strategies that can be done.

Islet β cell dedifferentiation is one of the most important mechanisms in the occurrence and development of diabetes. We studied the possible effects of chemokine stromal cell-derived factor-1 (SDF-1) in the dedifferentiation of islet β cells. It was noted that the number of dedifferentiated islet β cells and the expression of SDF-1 in pancreatic tissues significantly increased with diabetes. In islet β cell experiments, inhibition of SDF-1 expression resulted in an increase in the number of dedifferentiated cells, while overexpression of SDF-1 resulted in a decrease. This seemed to be contradicted by the effect of diabetes on the expression of SDF-1 in pancreatic tissue, but it was concluded that this may be related to the loss of SDF-1 activity. SDF-1 binds to CXCR4 to form a complex, which activates and phosphorylates AKT, subsequently increases the expression of forkhead box O1 (FOXO1), and inhibits the dedifferentiation of islet β cells. This suggests that SDF-1 may be a novel target in the treatment of diabetes., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Non-muscle-invasive bladder cancer (NMIBC) still poses a heavy load for resulting in many new cases which contribute significantly to medical costs. Although many NMIBC guidelines have been developed, their implementation remains deficient., Objective: This study was conducted in order to analyze the knowledge of and compliance with the guidelines for NMIBC of Chinese urologists and to identify associated factors., Methods: We conducted an online survey between August 2019 and January 2021. Respondents who were more than 65 years old or did not give informed consent were excluded. Linear/logistic regressions were performed to identify factors associated with the knowledge of and compliance with the guidelines of urologists, respectively. McNemar's tests were used to explore the divergence between knowledge and compliance., Results: A total of 814 responses were received, and 98.77% of urologists acknowledged the positive effects of high-quality guidelines. The average knowledge score was 6.10 ± 1.28 (out of a full score of 9), and it was positively associated with educational level and the number of guidelines consulted. Only 1.61% and 39.36% of the respondents realized that the guidelines did not recommend further chemotherapy or BCG infusion for low-risk patients. There were 38.87% and 51.84% respondents "often" or more frequently utilizing BCG therapy for intermediate- and high-risk NMIBC patients, respectively. Divergence between knowledge and compliance in performing a second TURBT after incomplete initial resection reached statistical significance ( p < 0.001)., Conclusions: Although the vast majority of urologists acknowledged the positive effects of guidelines, knowledge of and compliance with some recommendations of NMIBC guidelines are still inadequate. Factors associated with guidelines, individual professionals, patients, organizations, and the environment jointly contributed to the non-compliance., 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 © 2021 Wang, Huang, Huang, Jin, Wang, Shi, Yan, Yang, Li, Liu and Zeng.)

Objectives: To study the association of amplitude-integrated electroencephalogram (aEEG) and the quantitative indices biparietal width (BPW) and interhemispheric distance (IHD) of cranial magnetic resonance imaging (cMRI) with short-term neurodevelopment in moderately and late preterm infants., Methods: A total of 104 moderately and late preterm infants who were admitted to the neonatal intensive care unit from September 2018 to April 2020 were selected as the subjects for this prospective study. The Naqeeb method and sleep-wake cycling (SWC) were used for aEEG assessment within 72 hours after birth. cMRI was performed at the corrected gestational age of 37 weeks. BPW and IHD were measured at the T2 coronal position. At the corrected age of 6 months, the Developmental Screening Test for Child Under Six (DST) was used to follow up neurodevelopment. According to developmental quotient (DQ), the infants were divided into a normal DST group (78 infants with DQ≥85) and an abnormal DST group (26 infants with DQ<85). Related indices were compared between the two groups. The association between aEEG and cMRI was evaluated., Results: Compared with the normal DST group, the abnormal DST group had significantly lower aEEG normal rate and SWC maturation rate ( P <0.05), as well as a significantly larger IHD and a significantly smaller BPW ( P <0.05). Immature SWC, aEEG abnormality, and a relatively large IHD were the risk factors for abnormal DST ( P <0.05), and a relatively large BPW was a protective factor against abnormal DST ( P <0.05)., Conclusions: For moderately and late preterm infants, aEEG within 72 hours after birth and the quantitative indices BPW and IHD of cMRI at the corrected gestational age of 37 weeks may affect their neurodevelopmental outcome at the corrected age of 6 months.

Objective: The health-related quality of life (HRQoL) of donors deserves attention and must be considered for a long time. Many of the published studies had small sample sizes, and research from mainland China, in particular, is scant. Thus, this study aimed to investigate the HRQoL of living liver donors and identify the influencing factors of the HRQoL in mainland China. Methods: This is a cross-sectional study. The data were collected from the liver transplantation center, the Tianjin First Center Hospital, China. Living liver donors older than 18 years and at a minimum of 1-month, post-donation was included. The HRQoL was evaluated using the Medical Outcome Study Short form 36 (SF-36). Sociodemographic and clinical-related variables, HRQoL status, and its potential impact factors were analyzed. Results: A total of 382 living liver donors completed the survey. The median number of months post-donation was 25, and parental donors (99.2%) were the most frequent relationship. The majority of the participants (372, 97.4%) donated their left lateral lobes. Thirty-two (8.4%) donors suffered complications, and of them, 7 suffered from biliary leakage (1.8%), which was the most common one in this study. The physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH), social functioning (SF), role-emotional (RE), and mental health (MH) scores among the living liver donors were significantly better than those of the Chinese norms. Short-time post-donation [odds ratio ( OR ): 0.008; p < 0.001] and male recipients ( OR :0.195; p = 0.024) were associated with the likelihood of a poor physical related quality of life. Conclusions: Despite, in general, good HRQoL outcomes, we also believed that liver donation has an obvious influence on the physical functions of liver donors. More attention and long-term follow-ups are necessary for donors at higher risk based on identified influencing factors and correlates., 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 © 2021 Shi, Zhang, Chen, Huang, Yu, Jin, Wang and Gao.)

Lung cancer is a major public health problem worldwide, with a high associated incidence and mortality. In the present study, novel epigenetic signatures were identified through genome-wide DNA methylation microarrays. The results revealed that tripartite motif containing 58 (TRIM58), a potential tumor suppressor gene exhibited high methylation and low expression in lung cancer tissue samples compared with normal tissues. Receiver operating characteristic curve analysis demonstrated that TRIM58 may be a promising early diagnostic indicator of lung cancer. In addition, the present study analyzed the role of TRIM58 in tumorigenesis and development in lung cancer A549 cells. Wound healing assay and transwell migration assay were used to investigate cell migration, and flow cytometry analysis was used to detect apoptosis. Silencing TRIM58 accelerated the proliferation and migration of lung cancer cells. In contrast, the overexpression of TRIM58 significantly inhibited the proliferation and migration of lung cancer cells and promoted apoptosis. Gene set enrichment analysis revealed that TRIM58 expression was negatively correlated with MYC targets, G 2 M checkpoints and the mTORC1 signaling pathway. These results of the present study suggested that TRIM58, a potential tumor suppressor gene may serve as a novel diagnostic biomarker and therapeutic target in human lung cancer., Competing Interests: The author declares that he has no competing interests., (Copyright: © Shi et al.)

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and its prognosis remains dismal. Hence, it is important to identify the diagnostic and prognostic biomarkers for HCC. Urokinase plasminogen activator (uPA), an extracellular matrix (ECM)-degrading protease, plays a pivotal role in the invasion and metastasis of HCC., Methods: To confirm the clinical significance of uPA in HCC, we explored uPA expression in HCC in The Cancer Genome Atlas (TCGA) database. The expression level of uPA was further verified by quantitative reverse transcription polymerized chain reaction (qRT-PCR) in 133 pairs of primary HCC samples. A survival analysis was conducted with the Kaplan-Meier method in the HCC samples and TCGA database., Results: Our results showed that uPA was overexpressed in HCC and was significantly associated with HCC tumor size (P=0.015), differentiation grade (P=0.028), and absence of tumor encapsulation (P=0.010). Patients with high uPA expression levels had a poor outcome (P=0.026). TCGA database analysis was also consistent with our experimental results., Conclusions: In conclusion, our findings revealed that uPA was overexpressed in HCC and was related to HCC malignant features including tumor size, differentiation grade and absence of tumor encapsulation. High uPA expression had a shorter survival time. It is a potential prognostic biomarker of HCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jgo-21-343). The authors have no conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

Aims: In order to determine acute cardiac involvement in patients with COVID-19, we quantitatively evaluated tissue characteristics and mechanics by non-invasive cardiac magnetic resonance (CMR) in a cohort of patients within the first 10 days of the onset of COVID symptoms., Methods and Results: Twenty-five patients with reverse transcription polymerase chain reaction confirmed COVID-19 and at least one marker of cardiac involvement [cardiac symptoms, abnormal electrocardiograph (ECG), or abnormal cardiac biomarkers] and 25 healthy age- and gender-matched control subjects were recruited to the study. Patients were divided into those with elevated (n = 8) or normal TnI (n = 17). There were significant differences in global longitudinal strain among patients who were positive and negative for hs-TnI, and controls [-12.3 (-13.3, -11.5)%, -13.1 (-14.2, -9.8)%, and -15.7 (-18.3, -12.7)%, P = 0.004]. Native myocardial T1 relaxation times in patients with positive and negative hs-TnI manifestation (1169.8 ± 12.9 and 1113.2 ± 31.2 ms) were significantly higher than the normal (1065 ± 57 ms) subjects, respectively (P < 0.001). The extracellular volume (ECV) of patients who were positive and negative for hs-TnI was higher than that of the normal controls [32 (31, 33)%, 29 (27, 30)%, and 26 (24, 27.5)%, P < 0.001]. In our study, quantitative T2 mapping in patients who were positive and negative for hs-TnI [51 (47.9, 52.8) and 48 (47, 49.4) ms] was significantly higher than the normal [42 (41, 45.2) ms] subjects (P < 0.001)., Conclusion: In patients with early-stage COVID-19, myocardial oedema, and functional abnormalities are a frequent finding, while irreversible regional injury such as necrosis may be infrequent., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Objectives: Both coronavirus disease 2019 (COVID-19) pneumonia and influenza A (H1N1) pneumonia are highly contagious diseases. We aimed to characterize initial computed tomography (CT) and clinical features and to develop a model for differentiating COVID-19 pneumonia from H1N1 pneumonia. Methods: In total, we enrolled 291 patients with COVID-19 pneumonia from January 20 to February 13, 2020, and 97 patients with H1N1 pneumonia from May 24, 2009, to January 29, 2010 from two hospitals. Patients were randomly grouped into a primary cohort and a validation cohort using a seven-to-three ratio, and their clinicoradiologic data on admission were compared. The clinicoradiologic features were optimized by the least absolute shrinkage and selection operator (LASSO) logistic regression analysis to generate a model for differential diagnosis. Receiver operating characteristic (ROC) curves were plotted for assessing the performance of the model in the primary and validation cohorts. Results: The COVID-19 pneumonia mainly presented a peripheral distribution pattern (262/291, 90.0%); in contrast, H1N1 pneumonia most commonly presented a peribronchovascular distribution pattern (52/97, 53.6%). In LASSO logistic regression, peripheral distribution patterns, older age, low-grade fever, and slightly elevated aspartate aminotransferase (AST) were associated with COVID-19 pneumonia, whereas, a peribronchovascular distribution pattern, centrilobular nodule or tree-in-bud sign, consolidation, bronchial wall thickening or bronchiectasis, younger age, hyperpyrexia, and a higher level of AST were associated with H1N1 pneumonia. For the primary and validation cohorts, the LASSO model containing above eight clinicoradiologic features yielded an area under curve (AUC) of 0.963 and 0.943, with sensitivity of 89.7 and 86.2%, specificity of 89.7 and 89.7%, and accuracy of 89.7 and 87.1%, respectively. Conclusions: Combination of distribution pattern and category of pulmonary opacity on chest CT with clinical features facilitates the differentiation of COVID-19 pneumonia from H1N1 pneumonia., Competing Interests: Y-HT was employed by Winning Health Technology Group Co., Ltd., Shanghai, China. 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., (Copyright © 2021 Shi, Hu, Zhang, Liu, Zhou, Tang, Zhang, Shi, Zhang, Xiong and Shan.)

Background: 6-Phosphofructo-2-kinase/fructose-2,6-biphosphate-4 (PFKFB4) is a key factor that plays an important role in tumorigenesis. However, its role in triple-negative breast cancer (TNBC) progression needs to be further validated. We investigated whether PFKFB4 is directly involved in the oncogenic signaling networks of TNBC., Methods: First, we assessed the expression level of PFKFB4 in tumor tissue specimens by immunohistochemistry and evaluated its prognostic value. Next, the effect of PFKFB4 on TNBC cell growth and associated mechanisms were investigated. Finally, the results were further verified in vivo., Results: We found that PFKFB4 overexpression was associated with an unfavorable prognosis in TNBC patients. PFKFB4 was overexpressed in TNBC cell lines in hypoxic environments, and its overexpression promoted tumor progression in vitro and in vivo. Further analyses demonstrated that the possible mechanism might be that PFKFB4 overexpression facilitates TNBC progression by enhancing the G1/S phase transition by increasing the protein level of CDK6 and phosphorylation of Rb., Conclusions: These data suggest that PFKFB4 plays significant roles in the tumorigenesis and development of TNBC., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Yu-Chen Cai et al.)

Fischdiabietane A ( 1 ), a novel asymmetric diterpenoid dimer with a unique nonacyclic 6/6/6/5/7/6/6/6/6 ring system possessing unprecedented 2-oxaspiro[4.5]decane-1-one and 2-oxabicyclo[3.2.2]nonane frameworks in D/E/F rings, was isolated from the roots of Euphorbia fischeriana . Its structure was determined by spectroscopic techniques, electronic circular dichroism calculations, and X-ray diffraction experiments. Notably, 1 is the first abietane-type [4 + 2] Diels-Alder dimer identified from nature. The IC 50 of 1 against T47D cells was about sixfold higher than that of cisplatin (the positive control). Furthermore, 1 induced apoptosis in T47D cells through the activation of caspase-3 and the degradation of poly(ADP-ribose) polymerase.

The oomycete genus Phytophthora includes devastating plant pathogens that are found in almost all ecosystems. We sequenced the genomes of two quarantined Phytophthora species- P. fragariae and P. rubi . Comparing these Phytophthora species and related genera allowed reconstruction of the phylogenetic relationships within the genus Phytophthora and revealed Phytophthora genomic features associated with infection and pathogenicity. We found that several hundred Phytophthora genes are putatively inherited from red algae, but Phytophthora does not have vestigial plastids originating from phototrophs. The horizontally-transferred Phytophthora genes are abundant transposons that "transmit" exogenous gene to Phytophthora species thus bring about the gene recombination possibility. Several expansion events of Phytophthora gene families associated with cell wall biogenesis can be used as mutational targets to elucidate gene function in pathogenic interactions with host plants. This work enhanced the understanding of Phytophthora evolution and will also be helpful for the design of phytopathological control strategies., (© 2021 The Authors. Published by Elsevier Ltd.)

Background: A significant positive association was found in previous studies among obesity, visceral fat accumulation, and hyperuricemia. The purpose of this study was to explore the association between the ratio of visceral fat area to leg muscle mass (VFA-to-LMM) and hyperuricemia, and verify the role of gender differences in the association., Methods: A total of 3393 (43.3% are men) participants from Tianjin Union Medical Center-Health Management Center were recruited for this cross-sectional study. The VFA-to-LMM ratio was used as the independent variable. Hyperuricemia, a serum uric acid level ≥ 416 μmol/L in men and in menopausal women and ≥ 357 μmol/L in premenopausal women, was used as the dependent variable. Multiple logistic regression analysis was used to estimate the odds ratio and the 95% confidence interval between the VFA-to-LMM ratio and hyperuricemia., Results: The overall prevalence of hyperuricemia was 14.8% (8.9% in women, and 22.5% in men). After adjustment by age, smoking status (for males), menopause status (for females), drinking status, exercise frequency, blood pressure, alanine aminotransferase, fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, creatinine, and history of diseases, a strong positive association was found between the VFA-to-LMM ratio and hyperuricemia in both men (4th vs. 1st quartile 1.60, 95%CI: 1.03-2.49) and women (4th vs. 1st quartile 5.22, 95%CI: 2.44-12.56). After additional adjustment by BMI, there was still a significant positive association in women (4th vs. 1st quartile 2.57, 95%CI: 1.06-6.77). The results of subgroup analysis showed that pre-menopausal women (4th vs. 1st quartile OR: 3.61) have a higher risk of hyperuricemia than postmenopausal women (4th vs. 1st quartile OR: 1.94) with the increase of the VFA-to-LMM ratio. Besides, the interaction analysis results showed the highest risk of hyperuricemia when VFA and LMM were both in the highest quantile (OR: 11.50; 95% CI: 4.86-31.98)., Conclusion: The VFA-to-LMM ratio was positively associated with the risk of hyperuricemia in women after adjustment by confounders. Pre-menopausal women have a higher risk of hyperuricemia than postmenopausal women with the increase of the VFA-to-LMM ratio. In addition, the highest risk of hyperuricemia was demonstrated when both VFA and LMM were at the highest quartile.