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Shi-Chao Luo,1 Kai-Ming Duan,1 Chao Fang,1,2 Dan-Yang Li,1 Shan-Shan Zheng,1 Si-Qi Yang,1 Shu-Ting Yang,1 Mi Yang,1 Liang-Bin Zhang,1 Sai-Ying Wang1 1Department of Anesthesiology, Third Xiangya Hospital of Central South University, Changsha 410013, People’s Republic of China; 2Postdoctoral Research Workstation of Clinical Medicine, Third Xiangya Hospital of Central South University, Changsha 410013, People’s Republic of ChinaCorrespondence: Sai-Ying WangDepartment of Anesthesiology, Third Xiangya Hospital of Central South University, Changsha 410013, People’s Republic of ChinaTel +86 731 8861-8150Email 1771303488@qq.comObjective: To investigate the association of genetic polymorphisms of SIRT with postpartum depressive symptoms and analyze the risk factors for postpartum depressive symptoms in women following cesarean section.Methods: A total of 368 Chinese woman undergoing cesarean section were enrolled in this study. A cutoff of ≥ 10 for the Edinburgh Postnatal Depression Scale identified postpartum depressive symptoms. Genotypes of SIRT1, SIRT 2, and SIRT 6 were determined using Sequenom MassArray single-nucleotide polymorphism (SNP) analysis. We analyzed the contribution of genetic factors (SNPs, linkage disequilibrium, and haplotype) to postpartum depressive symptoms and performed logistic regression analysis to identify all potential risk factors for postpartum depressive symptoms and define interactions between genetic and environmental factors.Results: The incidence of postpartum depressive symptoms was 18.7% in this cohort. Univariate analysis suggested that SIRT2 polymorphism at rs2873703 (TT genotype) and rs4801933 ((TT genotype) and SIRT6 polymorphism at rs350846 (CC genotype) and rs107251 (TT genotype) were significantly correlated with the occurrence of postpartum depressive symptoms (p< 0.05). Linkage disequilibrium was identified between SIRT6 polymorphisms rs350846 and rs107251. Incidence of postpartum depressive symptoms in cesarean-section parturients with SIRT2 haplotype CCC was decreased (OR 0.407, 95% CI 0.191– 0.867; p=0.016). SIRT2 polymorphisms rs2873703 and rs4801933 were multiply collinear. Logistic regression analysis showed that SIRT2 polymorphism at rs2873703 (TT genotype) and rs4801933 (TT genotype), domestic violence, stress during pregnancy, and depressive prenatal mood were risk factors for postpartum depressive symptoms (p< 0.05).Conclusion: Pregnant women with SIRT2 genotypes rs2873703 TT and rs4801933 TT and experiencing domestic violence, stress during pregnancy, and prenatal depression are more likely to suffer from postpartum depressive symptoms.Keywords: SIRT, genetic variants, postpartum depressive symptoms, epigenetics

Yue-Lin Zhang,1,2,* Tan-Yang Zhou,1,2,* Jing Ai,3,* Sheng-Qun Chen,1,2,* Feng Chen,4 Chun-Hui Nie,1,2 Xin-Hua Chen,1,2 Guan-Hui Zhou,1,2 Hong-Liang Wang,1,2 Tong-Yin Zhu,1,2 Bao-Quan Wang,1,2 Zi-Niu Yu,1,2 Li Jing,1,2 Li-Ming Wu,1,2 Shu-Sen Zheng,1,2 Jun-Hui Sun1,2 1Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, People’s Republic of China; 2Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, People’s Republic of China; 3Eye Centre, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, People’s Republic of China; 4Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun-Hui SunHepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, People’s Republic of ChinaTel +86 571 8723 6815Email 1307005@zju.edu.cnFeng ChenDepartment of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, People’s Republic of ChinaTel +86 571 8723 6815Email chenfenghz@zju.edu.cnPurpose: Gene-targeting therapy provides a novel therapeutic approach for tumor treatment using genetically modified endothelial progenitor cells (EPCs) as cellular carriers. This study applied EPCs armed with cytosine deaminase (CD) and endostatin (ES) fusion gene in liver cancer to explore its therapeutic effect.Materials and Methods: EPCs from heart blood of male BALB/c nude mice were cultured and transfected with CD and ES fusion gene. Subsequently, these genetically modified cells were injected into mice bearing hepatoma through their tail veins. The tumor volumes and cell apoptosis were followed up.Results: Tumor volume in the group injected CD/ES-EPCs greatly decreased. The positive rate of VEGF and CD31 in the tumor tissue was lowest in the CD/ES-EPC group. Furthermore, the number of apoptotic cells was highest in the CD/ES-EPC group.Conclusion: The EPCs transfected with CD/ES inhibited tumor growth and preferentially induced tumor cell apoptosis, providing a novel methodology for cancer-targeting therapy.Keywords: gene-targeting therapy, endothelial progenitor cell, endostatin, cytosine deaminase, hepatoma, transfection

Sisi Zheng,1,* Tao Qin,2,* Yu Lu,3 Yifan Huang,2 Li Luo,1 Zhenguang Liu,1 Ruonan Bo,1 Yuanliang Hu,1 Jiaguo Liu,1 Deyun Wang1,2 1Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 2Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal, Fujian Agriculture and Forestry University, Fuzhou, 3National Veterinary Product Engineering Research Center, Jiangsu Academy of Agricultural Sciences, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: Poly lactide (PLA) was proved in the last years to be good for use in sustained drug delivery and as carriers for vaccine antigens. In our previous research, pachyman (PHY)-encapsulated PLA (PHYP) nanospheres were synthesized and their function of controlling drug release was demonstrated.Purpose: In order to modify the fast drug-release rate of PHY when inoculated alone, the maturation of bone marrow dendritic cells (BMDCs) in vitro and their immunological enhancement in vivo were explored using PHYP nanospheres.Methods: The maturation and antigen uptake of BMDCs were evaluated, both alone and with formulated antigen PHYP nanospheres, ie, ovalbumin (OVA)-loaded PHYP nanospheres, as an antigen delivery system, to investigate antigen-specific humoral and cellular immune responses.Results: The results indicated that, when stimulated by PHYP, the BMDCs matured as a result of upregulated expression of co-stimulatory molecules; the mechanism was elucidated by tracing fluorescently labeled antigens in confocal laser scanning microscopy images and observing the uptake of nanospheres by transmission electron microscopy. It was further revealed that mice inoculated with OVA-PHYP had augmented antigen-specific IgG antibodies, increased cytokine secretion by splenocytes, increased splenocyte proliferation, and activation of cluster of differentiation (CD)4+ and CD8+ T cells in vivo. Elevated immune responses were produced by OVA-PHYP, possibly owing to the activation and maturation of dendritic cells (in draining lymph nodes).Conclusion: It was corroborated that PHY- and/or OVA-encapsulated PLA nanospheres elicited prominent antigen-presenting effects on BMDCs and heightened humoral and cellular immune responses compared with other formulations. Keywords: PHYP, bone marrow dendritic cell, antigen delivery system, immune response

Hai-Yong Chen,1,2 Yao-Min Chen,3 Jian Wu,1,2 Fu-Chun Yang,1,2 Zhen Lv,1,2 Yi-Gang Qian,1,2 Shu-Sen Zheng1,2 1Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, 3Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Objective: To investigate the correlations of two hepatocyte growth factor (HGF) gene polymorphisms (rs5745652 and rs2074725) and their protein expression levels with the efficacy of transhepatic arterial chemotherapeutic embolism (TACE) and prognosis in patients with primary liver cancer (PLC). Methods: From March 2011 to June 2012, 109 PLC patients (the case group) who chose TACE as primary treatment and 80 healthy people (the control group) who had undergone physical examination in The First Affiliated Hospital, Zhejiang University were selected during the same period. Gene polymorphisms of HGF rs5745652 and HGF rs2074725 were detected. Serum HGF level, treating efficacy, survival quality, and 3-year survival rate for PLC patients who received TACE were observed. Results: There were significant differences in genotype and allele frequencies of HGF rs5745652 and HGF rs2074725, between the case and control groups (all P

Cycle-cup oaks ( Quercus section Cyclobalanopsis ) are one of the principal components of forests in the tropical and subtropical climates of East and Southeast Asia. They have experienced relatively recent increases in the diversification rate, driven by changing climates and the Himalayan orogeny. However, the evolutionary history and adaptive mechanisms at the chloroplast genome level in cycle-cup oaks remain largely unknown. Therefore, we studied this problem by conducting chloroplast genomics on 50 of the ca. 90 species. Comparative genomics and other analyses showed that Quercus section Cyclobalanopsis had a highly conserved chloroplast genome structure. Highly divergent regions, such as the ndhF and ycf1 gene regions and the petN - psbM and rpoB-trnC-GCA intergenic spacer regions, provided potential molecular markers for subsequent analysis. The chloroplast phylogenomic tree indicated that Quercus section Cyclobalanopsis was not monophyletic, which mixed with the other two sections of subgenus Cerris . The reconstruction of ancestral aera inferred that Palaeotropics was the most likely ancestral range of Quercus section Cyclobalanopsis , and then dispersed to Sino-Japan and Sino-Himalaya. Positive selection analysis showed that the photosystem genes had the lowest ω values among the seven functional gene groups. And nine protein-coding genes containing sites for positive selection: ndhA , ndhD , ndhF , ndhH , rbcL , rpl32 , accD , ycf1 , and ycf2 . This series of analyses together revealed the phylogeny, evolutionary history, and ecological adaptation mechanism of the chloroplast genome of Quercus section Cyclobalanopsis in the long river of earth history. These chloroplast genome data provide valuable information for deep insights into phylogenetic relationships and intraspecific diversity in Quercus ., Competing Interests: The authors declare that they have no conflict of interest. No approval/permission is required for the sample collection in accordance with relevant regulations and standards., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Chloroplast (cp) genome sequences have been extensively used for phylogenetic and evolutionary analyses, as many have been sequenced in recent years. Identification of Quercus is challenging because many species overlap phenotypically owing to interspecific hybridization, introgression, and incomplete lineage sorting. Therefore, we wanted to gain a better understanding of this genus at the level of the maternally inherited chloroplast genome. Here, we sequenced, assembled, and annotated the cp genomes of the threatened Quercus marlipoensis (160,995 bp) and Q. kingiana (161,167 bp), and mined these genomes for repeat sequences and codon usage bias. Comparative genomic analyses, phylogenomics, and selection pressure analysis were also performed in these two threatened species along with other species of Quercus. We found that the guanine and cytosine content of the two cp genomes were similar. All 131 annotated genes, including 86 protein-coding genes, 37 transfer RNA genes, and 8 ribosomal RNA genes, had the same order in the two species. A strong A/T bias was detected in the base composition of simple sequence repeats. Among the 59 synonymous codons, the codon usage pattern of the cp genomes in these two species was more inclined toward the A/U ending. Comparative genomic analyses indicated that the cp genomes of Quercus section Ilex are highly conserved. We detected eight highly variable regions that could be used as molecular markers for species identification. The cp genome structure was consistent and different within and among the sections of Quercus. The phylogenetic analysis showed that section Ilex was not monophyletic and was divided into two groups, which were respectively nested with section Cerris and section Cyclobalanopsis. The two threatened species sequenced in this study were grouped into the section Cyclobalanopsis. In conclusion, the analyses of cp genomes of Q. marlipoensis and Q. kingiana promote further study of the taxonomy, phylogeny and evolution of these two threatened species and Quercus., (© 2024. The Author(s).)

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. Intestinal fibrosis or stricture is one of the most prevalent complications in CD with a high recurrence rate. Manual examination of intestinal fibrosis or stricture by physicians may be biased or inefficient. A rapid development of artificial intelligence (AI) technique in recent years facilitates the detection of existing or possible intestinal fibrosis and stricture in CD through various modalities, including endoscopy, imaging examination, and serological biomarkers. We reviewed the articles on AI application in diagnosing intestinal fibrosis and stricture in CD during the past decade and categorized them into three aspects based on the detection methods, and found that AI helps accurate and expedient identification and prediction of intestinal fibrosis and stenosis in CD., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Lymphangioma is a rare cystic tumor that occurs across different locations. Retroperitoneal lymphangioma accounts for about 1% of all lymphangiomas. In this study, we report the clinicopathological features of retroperitoneal lymphangioma and describe our experience in treating this disease., Methods: We collected clinical data from all patients who were pathologically diagnosed with retroperitoneal lymphangioma at Zhejiang Provincial People's Hospital, between June 2013 and August 2022., Results: The 7 and 8 male and female patients analyzed herein had a mean age of 48.6 (SD 14.24) years at diagnosis. The mean duration of follow-up was 4.7 years. Among them, 66.67% were asymptomatic, with the rest manifesting abdominal pain, nausea, low back pain and elevated blood pressure as the main symptoms. Preoperative diagnosis and evaluation of cysts were mainly performed via computed tomography (CT) (n = 10, 66.67%) or magnetic resonance imaging (MRI) (n = 8, 53.33%). All patients were completely resected following surgery. Immunohistochemical analysis, performed on 6 patients, revealed that they were positive for D2-40. A total of 4, 4 and 3 patients were positive for CD31, CD34 and SMA, respectively. Moreover, the study cohort had an average postoperative hospital stay of 6.6 days. Follow up, after the end of the study, revealed no relapse in any of the 15 patients., Conclusions: Lymphangioma is a benign tumor of the lymphatic system. Although typical imaging features can be accurate for preoperative diagnosis, histological examination is crucial to final confirmation. Complete surgical resection is the best option to limit the risk of recurrence in cases with symptomatic lesions., (© 2024. The Author(s).)

Background: Biliary mucinous cystic neoplasms (BMCNs) are rare hepatobiliary cystic tumors, which can be divided into noninvasive and invasive types. This study aimed to investigate the diagnosis, treatment, and prognosis of BMCNs in a large single center., Methods: We analyzed 49 patients with BMCNs confirmed by postoperative pathology at the First Affiliated Hospital, Zhejiang University School of Medicine between January 2007 and December 2021., Results: Among the 49 patients, 37 were female (75.5%), and the average age was 57.04 years. Common symptoms included abdominal discomfort, jaundice and fever, while 22 patients (44.9%) had no symptoms. Serum carbohydrate antigen (CA) 19-9 and CA125 concentrations were elevated in 34.8% and 19.6% of patients, respectively. Forty-eight patients had tumors in the intrahepatic bile ducts and only one had a tumor in the extrahepatic bile duct. Forty-eight patients with noninvasive intrahepatic BMCNs were further analyzed in terms of pathological features: 34 (70.8%) had low-grade intraepithelial neoplasms (LGINs), and 14 (29.2%) had high-grade intraepithelial neoplasms (HGINs). The potential immunohistochemical markers of BMCNs were cytokeratin (CK) 19, CK7, estrogen receptor and progesterone receptor. Follow-up data for 37 patients with intrahepatic BMCNs were obtained. The median overall survival (OS) of BMCNs was not reached. The longest survival time was 137 months.The 5- and 10-year OS rates were 100% and 85.4%, respectively. The 5- and 10-year recurrence-free survival (RFS) rates were 93.9% and 80.2%, respectively., Conclusions: BMCNs are rare cystic neoplasms that commonly occur in middle-aged females. BMCNs can only be diagnosed and classified by postoperative pathology, as there are no specific clinical presentations, serological indicators or imaging modalities for preoperative diagnosis. Complete surgical resection is necessary for BMCNs, and the postoperative prognosis is favorable., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Background: Cognitive impairment and brain atrophy are common in chronic kidney disease patients. It remains unclear whether differences in renal function, even within normal levels, influence hippocampal volume (HCV) and cognition. We aimed to investigate the association between estimated glomerular filtration rate (eGFR), HCV and cognition in outpatients., Methods: This single-center retrospective study enrolled 544 nonrenal outpatients from our hospital. All participants underwent renal function assessment and 3.0 T magnetic resonance imaging (MRI) in the same year. HCV was also measured, and cognitive assessments were obtained. The correlations between eGFR, HCV, and cognitive function were analyzed. Logistic regression analysis was performed to identify the risk factors for hippocampal atrophy and cognitive impairment. Receiver-operator curves (ROCs) were performed to find the cut-off value of HCV that predicts cognitive impairment., Results: The mean age of all participants was 66.5 ± 10.9 years. The mean eGFR of all participants was 88.5 ± 15.1 mL/min/1.73 m 2 . eGFR was positively correlated with HCV and with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Univariate and multivariate logistic regression analysis showed Age ≥ 65 years, eGFR < 75 mL/min/1.73 m 2 , Glucose ≥6.1 mmol/L and combined cerebral microvascular diseases were independent risk factors for hippocampal atrophy and Age ≥ 65 years, left hippocampal volume (LHCV) <2,654 mm 3 were independent risk factors for cognitive impairment in outpatients. Although initial unadjusted logistic regression analysis indicated that a lower eGFR (eGFR < 75 mL/min/1.73 m 2 ) was associated with poorer cognitive function, this association was lost after adjusting for confounding variables. ROC curve analysis demonstrated that LHCV <2,654 mm 3 had the highest AUROC [(0.842, 95% CI: 0.808-0.871)], indicating that LHCV had a credible prognostic value with a high sensitivity and specificity for predicting cognitive impairment compared with age in outpatients., Conclusion: Higher eGFR was associated with higher HCV and better cognitive function. eGFR < 75 mL/min/1.73 m 2 was an independent risk factor for hippocampal atrophy after adjusting for age. It is suggested that even eGFR < 75 mL/min/1.73 m 2 , lower eGFR may still be associated with hippocampal atrophy, which is further associated with cognitive impairment. LHCV was a favorable prognostic marker for predicting cognitive impairment rather than age., Competing Interests: The authors declare that this study was conducted in the absence of any commercial or financial relationships that could be interpreted as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Wu, Lu, Zheng, Cui, Lu and Zhang.)

Background: As one of the leading causes of child mortality, deaths due to congenital anomalies (CAs) have been a prominent obstacle to meet Sustainable Development Goal 3.2., Objective: We conducted this study to understand the death burden and trend of under-5 CA mortality (CAMR) in Zhejiang, one of the provinces with the best medical services and public health foundations in Eastern China., Methods: We used data retrieved from the under-5 mortality surveillance system in Zhejiang from 2012 to 2021. CAMR by sex, residence, and age group for each year was calculated and standardized according to 2020 National Population Census sex- and residence-specific live birth data in China. Poisson regression models were used to estimate the annual average change rate (AACR) of CAMR and to obtain the rate ratio between subgroups after adjusting for sex, residence, and age group when appropriate., Results: From 2012 to 2021, a total of 1753 children died from CAs, and the standardized CAMR declined from 121.2 to 62.6 per 100,000 live births with an AACR of -9% (95% CI -10.7% to -7.2%; P<.001). The declining trend was also observed in female and male children, urban and rural children, and neonates and older infants, and the AACRs were -9.7%, -8.5%, -8.5%, -9.2%, -12%, and -6.3%, respectively (all P<.001). However, no significant reduction was observed in children aged 1-4 years (P=.22). Generally, the CAMR rate ratios for male versus female children, rural versus urban children, older infants versus neonates, and older children versus neonates were 1.18 (95% CI 1.08-1.30; P<.001), 1.20 (95% CI 1.08-1.32; P=.001), 0.66 (95% CI 0.59-0.73; P<.001), and 0.20 (95% CI 0.17-0.24; P<.001), respectively. Among all broad CA groups, circulatory system malformations, mainly deaths caused by congenital heart diseases, accounted for 49.4% (866/1753) of deaths and ranked first across all years, although it declined yearly with an AACR of -9.8% (P<.001). Deaths due to chromosomal abnormalities tended to grow in recent years, although the AACR was not significant (P=.90)., Conclusions: CAMR reduced annually, with cardiovascular malformations ranking first across all years in Zhejiang, China. Future research and practices should focus more on the prevention, early detection, long-term management of CAs and comprehensive support for families with children with CAs to improve their survival chances., (©Wen-Hong Dong, Jun-Xia Guo, Lei Wang, Shuang-Shuang Zheng, Bing-Quan Zhu, Jie Shao. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 03.06.2024.)

Background: The prognosis of HCC patients without MVI (so called M0) is highly heterogeneous and the need for adjuvant therapy is still controversial., Methods: Patients with HCC with M0 who underwent liver resection (LR) or liver transplantation (LT) as an initial therapy were included. The Eastern Hepatobiliary Surgery Hospital (EHBH)-M0 score was developed from a retrospective cohort to form the training cohort. The classification which was developed using multivariate cox regression analysis was externally validated., Results: The score was developed using the following factors: α-fetoprotein level, tumour diameter, liver cirrhosis, total bilirubin, albumin and aspartate aminotransferase. The score differentiated two groups of M0 patients (≤3, >3 points) with distinct long-term prognoses outcomes (median overall survival (OS), 98.0 vs. 46.0 months; p < 0.001). The predictive accuracy of the score was greater than the other commonly used staging systems for HCC. And for M0 patients with a higher score underwent LR. Adjuvant transcatheter arterial chemoembolization (TACE) was effective to prolong OS., Conclusions: The EHBH M0 scoring system was more accurate in predicting the prognosis of HCC patients with M0 after LR or LT. Adjuvant therapy is recommended for HCC patients who have a higher score., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Chromobox Homolog 1 (CBX1) plays a crucial role in the pathogenesis of numerous diseases, including the evolution and advancement of diverse cancers. The role of CBX1 in pan-cancer and its mechanism in hepatocellular carcinoma (HCC), however, remains to be further investigated., Methods: Bioinformatics approaches were harnessed to scrutinize CBX1's expression profile, its association with tumor staging, and its potential impact on patient outcomes across various cancers. Single-cell RNA sequencing data facilitated the investigation of CBX1 expression patterns at the individual cell level. The CBX1 expression levels in HCC and adjacent non-tumor tissues were quantified through Real-Time Polymerase Chain Reaction (RT-PCR), Western Blotting (WB), and Immunohistochemical analyses. A tissue microarray was employed to explore the relationship between CBX1 levels, patient prognosis, and clinicopathological characteristics in HCC. Various in vitro assays-including CCK-8, colony formation, Transwell invasion, and scratch tests-were conducted to assess the proliferative and motility properties of HCC cells upon modulation of CBX1 expression. Moreover, the functional impact of CBX1 on HCC was further discerned through xenograft studies in nude mice., Results: CBX1 was found to be upregulated in most cancer forms, with heightened expression correlating with adverse patient prognoses. Within the context of HCC, elevated levels of CBX1 were consistently indicative of poorer clinical outcomes. Suppression of CBX1 through knockdown methodologies markedly diminished HCC cell proliferation, invasive capabilities, migratory activity, Epithelial-mesenchymal transition (EMT) processes, and resistance to Tyrosine kinase inhibitors (TKIs). Contrastingly, CBX1 augmentation facilitated the opposite effects. Subsequent investigative efforts revealed CBX1 to be a promoter of EMT and a contributor to increased TKI resistance within HCC cells, mediated via the IGF-1R/AKT/SNAIL signaling axis. The oncogenic activities of CBX1 proved to be attenuable either by AKT pathway inhibition or by targeted silencing of IGF-1R., Conclusions: The broad overexpression of CBX1 in pan-cancer and specifically in HCC positions it as a putative oncogenic entity. It is implicated in forwarding HCC progression and exacerbating TKI resistance through its interaction with the IGF-1R/AKT/SNAIL signaling cascade., (© 2024. The Author(s).)

Background: Elevated preoperative γ-glutamyl transferase (GGT) levels or reduced serum albumin levels have been established as negative prognostic factors for patients with hepatocellular carcinoma (HCC) and various other tumors. Nonetheless, the prognostic significance of the GGT to serum albumin ratio (GAR) in liver transplantation (LT) therapy for HCC is still not well-defined., Methods: A retrospective analysis was conducted on the clinical data of 141 HCC patients who underwent LT at Shulan (Hangzhou) Hospital from June 2017 to November 2020. Using the receiver operating characteristic (ROC) curve, the optimal GAR cutoff value to predict outcomes following LT was assessed. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent risk factors associated with both overall survival (OS) and recurrence-free survival (RFS)., Results: A GAR value of 2.04 was identified as the optimal cutoff for predicting both OS and RFS, with a sensitivity of 63.2% and a specificity of 74.8%. Among these patients, 80 (56.7%) and 90 (63.8%) met the Milan and the University of California San Francisco (UCSF) criteria, respectively. Univariate Cox regression analysis showed that microvascular invasion (MVI), maximum tumor size (>5 cm), total tumor size (>8 cm), liver cirrhosis, TNM stage (III), and GAR (≥2.04) were significantly associated with both postoperative OS and RFS in patients with HCC (all p  < 0.05). Multivariate Cox regression analysis indicated that GAR (≥2.04) was independently linked with RFS and OS., Conclusion: Pre-transplant GAR ≥2.04 is an independent correlate of prognosis and survival outcomes after LT for HCC and can be used as a prognostic indicator for both mortality and tumor recurrence following LT., 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 Luo, Chang, Ye, Gao, Zhu, Liu, Zhou, Zheng and Yang.)

Objective: To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China. Methods: A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test. Results: A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) μg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs . 9.9% (1 057/10 680), χ 2 =5.58, P =0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ 2 =201.81, P <0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs . 8.3% (714/8 577), χ 2 =65.54, P <0.01), with statistically significant differences in the rates by region ( χ 2 =126.60, P <0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference ( χ 2 =147.71, 29.73, 773.02, all P <0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) ( χ 2 =38.62, P <0.01), while the difference in iron deficiency prevalence was not significant ( χ 2 =0.51, P =0.476). Conclusions: There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.

Quercus is a valuable genus ecologically, economically, and culturally. They are keystone species in many ecosystems. Species delimitation and phylogenetic studies of this genus are difficult owing to frequent hybridization. With an increasing number of genetic resources, we will gain a deeper understanding of this genus. In the present study, we collected four Quercus section Cyclobalanopsis species ( Q . poilanei , Q . helferiana , Q . camusiae , and Q . semiserrata ) distributed in Southeast Asia and sequenced their complete genomes. Following analysis, we compared the results with those of other species in the genus Quercus . These four chloroplast genomes ranged from 160,784 bp ( Q . poilanei ) to 161,632 bp ( Q . camusiae ) in length, with an overall guanine and cytosine (GC) content of 36.9%. Their chloroplast genomic organization and order, as well as their GC content, were similar to those of other Quercus species. We identified seven regions with relatively high variability ( rps16 , ndhk , accD , ycf1 , psbZ-trnG-GCC , rbcL-accD , and rpl32-trnL-UAG ) which could potentially serve as plastid markers for further taxonomic and phylogenetic studies within Quercus . Our phylogenetic tree supported the idea that the genus Quercus forms two well-differentiated lineages (corresponding to the subgenera Quercus and Cerris ). Of the three sections in the subgenus Cerris , the section Ilex was split into two clusters, each nested in the other two sections. Moreover, Q . camusiae and Q . semiserrata detected in this study diverged first in the section Cyclobalanopsis and mixed with Q . engleriana in the section Ilex . In particular, 11 protein coding genes ( atpF , ndhA , ndhD , ndhF , ndhK , petB , petD , rbcL , rpl22 , ycf1 , and ycf3 ) were subjected to positive selection pressure. Overall, this study enriches the chloroplast genome resources of Quercus , which will facilitate further analyses of phylogenetic relationships in this ecologically important tree genus.

The metabolic activities of microorganisms play a crucial role in the quality development of fermented sausage. This study investigated the effect of inoculation with different combinations of starter cultures (Lactiplantibacillus plantarum YR07, Latilactobacillus sakei L.48, Staphylococcus xylosus S.14, and Mammaliicoccus sciuri S.18) on the quality of sausages. Inoculation with mixed starter cultures promoted protein degradation to generate amino acids and the conversion to volatile compounds, which enhanced the flavor development in fermented sausages. The bacterial community analyses demonstrated that the inoculation of mixed starter cultures could inhibit the growth of spoilage and pathogenic bacteria, thereby reducing the total content of biogenic amines. The correlation analysis between the core bacteria and characteristic volatile compounds revealed that fermented sausages inoculated with Lactobacillus and coagulase negative staphylococci exhibited significant positive correlations with the majority of key characteristic volatile compounds. In four treatments, inoculation with L. plantarum YR07 and M. sciuri S.18 greatly promoted the formation of characteristic volatile compounds (3-hydroxy-2-butanone, hexanal, and 1- octen-3ol). Therefore, the combined inoculation of L. plantarum YR07 and M. sciuri S.18 is promising to enhance fermented sausage's flavor profile and safety., 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.)

Background: Grafts from older donors after circulatory death were associated with inferior outcome in liver transplants in the past. But it has seemed to remain controversial in the last decade, as a result of modified clinical protocols, selected recipients, and advanced technology of organ perfusion and preservation. The present study aimed to examine the impact of older donor age on complications and survival of liver transplant using grafts from donation after circulatory death (DCD)., Methods: A total of 944 patients who received DCD liver transplantation from 2015 to 2020 were included and divided into two groups: using graft from older donor (aged ≥ 65 years, n = 87) and younger donor (age < 65 years, n = 857). Propensity score matching (PSM) was applied to eliminate selection bias., Results: A progressively increased proportion of liver transplants with grafts from older donors was observed from 1.68% to 15.44% during the study period. The well-balanced older donor (n = 79) and younger donor (n = 79) were 1:1 matched. There were significantly more episodes of biliary non-anastomotic stricture (NAS) in the older donor group than the younger donor group [15/79 (19.0%) vs. 6/79 (7.6%); P = 0.017]. The difference did not reach statistical significance regarding early allograft dysfunction (EAD) and primary non-function (PNF). Older livers had a trend toward inferior 1-, 2-, 3-year graft and overall survival compared with younger livers, but these differences were not statistically significant (63.1%, 57.6%, 57.6% vs. 76.9%, 70.2%, 67.7%, P = 0.112; 64.4%, 58.6%, 58.6% vs. 76.9%, 72.2%, 72.2%, P = 0.064). The only risk factor for poor survival was ABO incompatible transplant (P = 0.008) in the older donor group. In the subgroup of ABO incompatible cases, it demonstrated a significant difference in the rate of NAS between the older donor group and the younger donor group [6/8 (75.0%) vs. 3/14 (21.4%); P = 0.014]., Conclusions: Transplants with grafts from older donors (aged ≥ 65 years) after circulatory death are more frequently associated with inferior outcome compared to those from younger donors. Older grafts from DCD are more likely to develop NAS, especially in ABO incompatible cases., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

As a major neuron type in the brain, the excitatory neuron (EN) regulates the lifespan in C. elegans. How the EN acquires senescence, however, is unknown. Here, we show that growth differentiation factor 11 (GDF11) is predominantly expressed in the EN in the adult mouse, marmoset and human brain. In mice, selective knock-out of GDF11 in the post-mitotic EN shapes the brain ageing-related transcriptional profile, induces EN senescence and hyperexcitability, prunes their dendrites, impedes their synaptic input, impairs object recognition memory and shortens the lifespan, establishing a functional link between GDF11, brain ageing and cognition. In vitro GDF11 deletion causes cellular senescence in Neuro-2a cells. Mechanistically, GDF11 deletion induces neuronal senescence via Smad2-induced transcription of the pro-senescence factor p21. This work indicates that endogenous GDF11 acts as a brake on EN senescence and brain ageing., (© 2023. The Author(s).)

Background and Aims: Understanding adaptive genetic variation and whether it can keep pace with predicted future climate change is critical in assessing the genetic vulnerability of species and developing conservation management strategies. The lack of information on adaptive genetic variation in relict species carrying abundant genetic resources hinders the assessment of genetic vulnerability. Using a landscape genomics approach, this study aimed to determine how adaptive genetic variation shapes population divergence and to predict the adaptive potential of Pterocarya macroptera (a vulnerable relict species in China) under future climate scenarios., Methods: We applied restriction site-associated DNA sequencing (RAD-seq) to obtain 8244 single-nucleotide polymorphisms (SNPs) from 160 individuals across 28 populations. We examined the pattern of genetic diversity and divergence, and then identified outliers by genetic differentiation (FST) and genotype-environment association (GEA) methods. We further dissected the effect of geographical/environmental gradients on genetic variation. Finally, we predicted genetic vulnerability and adaptive risk under future climate scenarios., Key Results: We identified three genetic lineages within P. macroptera: the Qinling-Daba-Tianmu Mountains (QDT), Western Sichuan (WS) and Northwest Yunnan (NWY) lineages, which showed significant signals of isolation by distance (IBD) and isolation by environment (IBE). IBD and IBE explained 3.7-5.7 and 8.6-12.8 % of the genetic structure, respectively. The identified GEA SNP-related genes were involved in chemical defence and gene regulation and may exhibit higher genetic variation to adapt to the environment. Gradient forest analysis revealed that the genetic variation was mainly shaped by temperature-related variables, indicating its adaptation to local thermal environments. A limited adaptive potential was suggested by the high levels of genetic vulnerability in marginal populations., Conclusions: Environmental gradient mainly shaped the population differentiation of P. macroptera. Marginal populations may be at high risk of extinction, and thus proactive management measures, such as assisted gene flow, are required to ensure the survival of these populations., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Annals of Botany Company.)

Background: Remote ischemic perconditioning (RIPerC) has been demonstrated to protect grafts from hepatic ischemia-reperfusion injury (IRI). This study investigated the role of exosomes in RIPerC of liver grafts in rats., Methods: Twenty-five rats (including 10 donors) were randomly divided into five groups (n = 5 each group): five rats were used as sham-operated controls (Sham), ten rats were for orthotopic liver transplantation (OLT, 5 donors and 5 recipients) and ten rats were for OLT + RIPerC (5 donors and 5 recipients). Liver architecture and function were evaluated., Results: Compared to the OLT group, the OLT + RIPerC group exhibited significantly improved liver graft histopathology and liver function (P < 0.05). Furthermore, the number of exosomes and the level of P-Akt were increased in the OLT + RIPerC group., Conclusions: RIPerC effectively improves graft architecture and function, and this protective effect may be related to the increased number of exosomes. The upregulation of P-Akt may be involved in underlying mechanisms., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2022. Published by Elsevier B.V.)

Background: Wernicke encephalopathy (WE) is an acute neurological disease resulting from vitamin B1 deficiency, and there are only very few case reports of WE after liver transplantation. The present study aimed to investigate the clinical characteristics, etiology, magnetic resonance imaging (MRI) features, treatment and prognosis of patients with WE after liver transplantation., Methods: Twenty-three patients with WE after liver transplantation from the First Affiliated Hospital, Zhejiang University School of Medicine and Jiangxi Provincial People's Hospital between January 2011 and December 2021 were retrospectively analyzed., Results: Among the 23 patients diagnosed with WE after liver transplantation, 6 (26%) had a classic triad of impaired consciousness, oculomotor palsy and ataxia, and 17 (74%) had two features. The misdiagnosis rate was 65%. After treatment with high-dose vitamin B1, 19 (83%) patients showed improvement, whereas 4 (17%) showed no improvement, including 3 with residual short-term memory impairments and 1 with residual spatial and temporal disorientation and ataxia., Conclusions: The misdiagnosis rate is high in the early stage of WE, and the prognosis is closely associated with whether WE is diagnosed early and treated timely. High-dose glucose or glucocorticoids can trigger WE and cannot be administered before vitamin B1 treatment. Vitamin B1 is suggested to be used as a prophylactic treatment for patients with WE after liver transplantation., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2022. Published by Elsevier B.V.)

Protein Z (PZ), a vitamin-K-dependent anticoagulant glycoprotein, is reported to be highly expressed in various malignant tissues and correlated with a poor prognosis in patients with lung cancer. This study aimed to investigate the pathological activity of PZ on lung cancer cell migration, invasion, and metastasis. PZ was assessed by Western blot in three non-small-cell lung cancer cell lines (A549, H1299, and H1975). Meanwhile,western blot was used to detect the expression of EMT pathway-related proteins (Slug, Vimentin, and N-cadherin) in the A549 cells knocked down with siRNA. The cellular proliferation, migration, and invasion were detected by Cell Counting Kit (CCK)-8, wound healing, and Transwell assays in the A549 cells. The results showed that PZ expression was higher in A549, H1299, and H1975 cells, according to Western blot. CCK-8, wound healing, and Transwell assays showed that knockdown of PZ significantly decreased cellular proliferation, migration, and invasion, as well as the protein levels of Slug, Vimentin, and N-cadherin in the A549 cells. In conclusion, the pro-metastasis activity of PZ may modulate the epithelial-mesenchymal transition pathway in lung cancer A549 cells., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter.)

Background: Hyperlipidemia is a common complication after liver transplantation (LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipidemia and favorable prognosis in patients with hepatocellular carcinoma (HCC) undergoing hepatectomy. This study aimed to evaluate the possibility of predicting prognosis in HCC patients receiving LT by early posttransplant dyslipidemia., Methods: From January 2015 to December 2017, a total of 806 HCC patients from China Liver Transplant Registry database were retrospectively enrolled. The prognostic relevance of early posttransplant hypertriglyceridemia or hypercholesterolemia was examined using survival analysis, and subgroup analysis was implemented based on LT criteria., Results: Early posttransplant hypercholesterolemia (EPHC) was independently inversely associated with the risk of recurrence [hazard ratio (HR) = 0.630; P = 0.022], but was not significantly correlated with the mortality. However, early posttransplant hypertriglyceridemia was not related to prognosis. Intriguingly, with further classification, we found that borderline EPHC (B-EPHC), instead of significant EPHC, was a predictor of lower risk for both recurrence (HR = 0.504; P = 0.006) and mortality (HR = 0.511; P = 0.023). Compared with non-EPHC patients, B-EPHC patients achieved significantly superior 1-year and 3-year tumor-free survival (89.6% and 83.7% vs. 83.8% and 72.7% respectively; P = 0.023), and 1-year and 3-year overall survival (95.8% and 84.8% vs. 94.6% and 77.6% respectively; P = 0.039). In the subgroup analysis, B-EPHC remained an independent predictor of better prognosis in patients beyond Milan criteria and those within Hangzhou criteria; whereas there was no significant relationship between B-EPHC and prognosis in patients within Milan criteria and those beyond Hangzhou criteria. More interestingly, patients beyond Milan criteria but within Hangzhou criteria were identified as the crucial subpopulation who benefited from B-EPHC (recurrence HR = 0.306, P = 0.011; mortality HR = 0.325, P = 0.031)., Conclusions: B-EPHC could assist transplant teams in dynamically evaluating prognosis after LT for HCC as a postoperative non-oncological biomarker, especially in patients beyond Milan criteria but within Hangzhou criteria., (Copyright © 2022. Published by Elsevier B.V.)

Background: Liver transplantation (LT) is the best treatment for patients with hepatocellular carcinoma (HCC). However, the surgical technique needs to be improved. The present study aimed to evaluate the "no-touch" technique in LT., Methods: From January 2018 to December 2019, we performed a prospective randomized controlled trial on HCC patients who underwent LT. The patients were randomized into two groups: a no-touch technique LT group (NT group, n = 38) and a conventional LT technique group (CT group, n = 46). Operative outcomes and survival in the two groups were analyzed., Results: The perioperative parameters were comparable between the two groups (P > 0.05). There was no significant difference between the two groups in disease-free survival (DFS) (P = 0.732) or overall survival (OS) (P = 0.891). Of 36 patients who were beyond the Hangzhou criteria for LT, the DFS of the patients in the NT group was significantly longer than that in the CT group (median 402 vs. 126 days, P = 0.025). In 31 patients who had portal vein tumor thrombosis (PVTT), DFS and OS in the NT group were significantly better than those in the CT group (median DFS 420 vs. 167 days, P = 0.022; 2-year OS rate 93.8% vs. 66.7%, P = 0.043). In 14 patients who had diffuse-type HCCs, DFS and OS were significantly better in the NT group than those in the CT group (median DFS 141 vs. 56 days, P = 0.008; 2-year OS rate 75.0% vs. 33.3%, P = 0.034). Multivariate analysis showed that for patients with PVTT and diffuse-type HCCs, the no-touch technique was an independent favorable factor for OS (PVTT: HR = 0.018, 95% CI: 0.001-0.408, P = 0.012; diffuse-type HCCs: HR = 0.034, 95% CI: 0.002-0.634, P = 0.024)., Conclusions: The no-touch technique improved the survival of patients with advanced HCC compared with the conventional technique. The no-touch technique may provide a new and effective LT technique for advanced HCCs., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2022. Published by Elsevier B.V.)

Primary liver cancer is the sixth most commonly diagnosed cancer and was the third leading cause of cancer deaths worldwide in 2020. It includes hepatocellular carcinoma (HCC) (representing 75%-85% of cases), intrahepatic cholangiocarcinoma (representing 10%-15% of cases), and other rare types. The survival rate of patients with HCC has risen with improved surgical technology and perioperative management in recent years; however, high tumor recurrence rates continue to limit long-term survival, even after radical surgical resection (exceeding 50% recurrence). For resectable recurrent liver cancer, surgical removal [either salvage liver transplantation (SLT) or repeat hepatic resection] remains the most effective therapy that is potentially curative for recurrent HCC. Thus, here, we introduce surgical treatment for recurrent HCC. Areas Covered: A literature search was performed for recurrent HCC using Medline and PubMed up to August 2022. Expert commentary: In general, long-term survival after the re-resection of recurrent liver cancer is usually beneficial. SLT has equivalent outcomes to primary liver transplantation for unresectable recurrent illness in a selected group of patients; however, SLT is constrained by the supply of liver grafts. SLT seems to be inferior to repeat liver resection when considering operative and postoperative results but has the major advantage of disease-free survival. When considering the similar overall survival rate and the current situation of donor shortages, repeat liver resection remains an important option for recurrent HCC., Competing Interests: Conflict-of-interest statement: The authors report no conflicts of interest in this work., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Myeloid cells are physiologically related to innate immunity and inflammation. Tumor-associated myeloid cells gained increasing interest because of their critical roles in tumor progression and anticancer immune responses in human malignancies. However, the associations between tumor-associated myeloid cell-related genes and hepatocellular carcinoma have yet to be revealed. Here, through the integrating analysis of bulk and single-cell RNA (scRNA) sequencing of public HCC samples, we developed a gene signature to investigate the role of HCC-specific myeloid signature genes in HCC patients. We firstly defined 317 myeloid cell marker genes through analyzing scRNA data of HCC from the GEO dataset. After selecting the differentially expressed genes, eleven genes were also proved prognostic. Then we built a gene signature from the TCGA cohort and verified further with the ICGC dataset by applying the LASSO Cox method. An eight genes signature (FABP5, C15orf48, PABPC1, TUBA1B, AKR1C3, NQO1, AKR1B10, SPP1) was achieved finally. Patients in the high risk group correlated with higher tumor stages and poor survival than those in the low-risk group. The risk score was proved to be an independent risk factor for prognosis. The high risk group had higher infiltrations of dendritic cells, macrophages and Tregs. And the APC co-inhibition, T cell co-inhibition pathways were also activated. Besides, the risk score positively correlated with multidrug resistance proteins. In conclusion, our myeloid cell marker genes related signature can predict patients' survival and may also indicate the levels of immune infiltration and drug resistance., 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 Zheng, Wu, Zhang, Huang and Xue.)

The apparent second-order rate constant with hexavalent ferrate (Fe(VI)) (k Fe(VI) ) is a key indicator to evaluate the removal efficiency of a molecule by Fe(VI) oxidation. k Fe(VI) is often determined by experiment, but such measurements can hardly catch up with the rapid growth of organic compounds (OCs). To address this issue, in this study, a total of 437 experimental second-order k Fe(VI) rate constants at a range of conditions (pH and temperature) were used to train four machine learning (ML) algorithms (lasso regression (LR), ridge regression (RR), extreme gradient boosting (XGBoost), and the light gradient boosting machine (LightGBM)). Using the Morgan fingerprint (MF)) of a range of organic compounds (OCs) as the input, the performance of the four algorithms was comprehensively compared with respect to the coefficient of determination (R 2 ) and root-mean-square error (RMSE). It is shown that the RR, XGBoost, and LightGBM models displayed generally acceptable performance k Fe(VI) (R 2 test > 0.7). In addition, the shapely additive explanation (SHAP) and feature importance methods were employed to interpret the XGBoost/LightGBM and RR models, respectively. The results showed that the XGBoost/LightGBM and RR models suggestd pH as the most important predictor and the tree-based models elucidate how electron-donating and electron-withdrawing groups influence the reactivity of the Fe(VI) species. In addition, the RR model share eight common features, including pH, with the two tree-based models. This work provides a fast and acceptable method for predicting k Fe(VI) values and can help researchers better understand the degradation behavior of OCs by Fe(VI) oxidation from the perspective of molecular structure., 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. Published by Elsevier Ltd.)

Background: Liver transplantation (LT) is an effective treatment option for end-stage liver disease. Mammalian target of rapamycin (mTOR) inhibitors, such as rapamycin, are widely used post LT., Data Sources: In this review, we focused on the anti-cancer activities and metabolic side effects of rapamycin after LT. The literature available on PubMed for the period of January 1999-September 2022 was reviewed. The key words were rapamycin, sirolimus, liver transplantation, hepatocellular carcinoma, diabetes, and lipid metabolism disorder., Results: Rapamycin has shown excellent effects and is safer than other immunosuppressive regimens. It has exhibited excellent anti-cancer activity and has the potential in preventing hepatocellular carcinoma (HCC) recurrence post LT. Rapamycin is closely related to two long-term complications after LT, diabetes and lipid metabolism disorders., Conclusions: Rapamycin prevents HCC recurrence post LT in some patients, but it also induces metabolic disorders. Reasonable use of rapamycin benefits the liver recipients., (Copyright © 2022 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Background: Studies have shown that community-based group rehabilitation activities can have a positive impact on patients., Objective: This study attempted to improve schizophrenia patients' social and self-cognition through short-term group-based cognitive behavioral therapy (G-CBT), break negative coping styles, and improve the patients' quality of life., Methods: The patients with schizophrenia who participated in long-term community-based group rehabilitation were treated with G-CBT. Training on coping styles was conducted to improve their self-cognition and social cognition, and the rehabilitation effects of G-CBT on these patients were evaluated., Results: Compared with the control group, patient scores for self-esteem, self-efficacy, and positive coping in the G-CBT group increased, while patient scores for negative coping decreased. Compared with the control group, the differences in the total scores for mental health and the five dimensions of physical functioning, general health, vitality, social functioning, and emotional role function in the short-form (SF-12) survey were statistically significant. Compared with the baseline data, the differences in self-esteem, self-efficacy, positive coping, negative coping, and quality of life scores were statistically significant., Conclusion: Short-term G-CBT had a good effect on patients with chronic schizophrenia who participated in community-based group rehabilitation for the long-term.

Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel anti-inflammatory and proresolving lipid mediator biosynthesized from docosahexaenoic acid. Excessive activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and consequent pyroptosis are involved in diverse inflammatory diseases. However, how PCTR1 affects NLRP3 inflammasome activation and pyroptosis are still unclear. Here, we demonstrated that PCTR1 inhibited NLRP3 inflammasome activation and pyroptosis. These results show that PCTR1 dose-dependently inhibited gasdermin D cleavage in lipopolysaccharide (LPS)-primed murine primary macrophages upon nigericin stimulation. Additionally, PCTR1 treatment after LPS priming inhibited caspase-1 activation and subsequent mature interleukin-1β release independent of the nuclear factor-kappa B pathway. PCTR1 exerted its inhibitory effects by blocking NLRP3-apoptosis-associated speck-like protein containing a CARD (ASC) interaction and ASC oligomerization, thereby restricting NLRP3 inflammasome assembly. However, the inhibitory effect of PCTR1 could be reversed by KH7 and H89, which are the inhibitors of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway. Moreover, PCTR1 treatment alleviated lung tissue damage and improved mouse survival in LPS-induced sepsis. Our study unveils the molecular mechanism of negative regulation of NLRP3 inflammasome activation and pyroptosis by a novel lipid mediator and suggests that PCTR1 may serve as a potential treatment option for NLRP3-inflammasome driven diseases., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Bladder cancer (BCa) is a common malignancy in the urinary system. This study aims to explore the role of miR-186 in BCa tumorigenesis., Methods: The expression of miR-186 and ADAMTS12 in clinical BCa tissues and cell lines was detected. BCa cell lines T24, 5637 and EJ were used to transfect miR-186 mimics or inhibitors. Luciferase reporter gene detection confirmed the correlation between miR-186 and ADAMTS12. MTT method and flow cytometry were used to detect cell viability and apoptosis. Cell migration and invasion ability was detected by transwell assay. The protein level of ADAMTS12, β-catenin, GSK-3β and p-GSK-3β was determined using western blot analysis., Results: MiR-186 was negatively correlated with the expression of ADAMTS12 in BCa tissues. Further research confirmed that ADAMTS12 is the direct target of miR-186. In addition, overexpression of miR-186 down-regulated the expression of ADAMTS12, inhibiting cell viability and apoptosis, while knockout of miR-186 led to the opposite result. miR-186 also inhibits the phosphorylation of GSK-3 β and β-catenin without changing the total GSK-3β level. Our study shows that miR-186 has a negative regulatory effect on the expression of ADAMTS12 in clinical specimens and in vitro. miR-186 can inhibit the proliferation and invasion of BCa cells., Conclusions: miR-186 has the potential to be used as a biomarker in the early detection of BCa., Competing Interests: All authors have no conflicts of interest or financial ties to disclose., (© 2022 Liang JF et al.)

Introduction: Lenvatinib plus an anti-PD-1 antibody has shown promising antitumor effects in patients with advanced hepatocellular carcinoma (HCC), but with clinical benefit limited to a subset of patients. We developed and validated a radiomic-based model to predict objective response to this combination therapy in advanced HCC patients., Methods: Patients ( N = 170) who received first-line combination therapy with lenvatinib plus an anti-PD-1 antibody were retrospectively enrolled from 9 Chinese centers; 124 and 46 into the training and validation cohorts, respectively. Radiomic features were extracted from pretreatment contrast-enhanced MRI. After feature selection, clinicopathologic, radiomic, and clinicopathologic-radiomic models were built using a neural network. The performance of models, incremental predictive value of radiomic features compared with clinicopathologic features and relationship between radiomic features and survivals were assessed., Results: The clinicopathologic model modestly predicted objective response with an AUC of 0.748 (95% CI: 0.656-0.840) and 0.702 (95% CI: 0.547-0.884) in the training and validation cohorts, respectively. The radiomic model predicted response with an AUC of 0.886 (95% CI: 0.815-0.957) and 0.820 (95% CI: 0.648-0.984), respectively, with good calibration and clinical utility. The incremental predictive value of radiomic features to clinicopathologic features was confirmed with a net reclassification index of 47.9% ( p < 0.001) and 41.5% ( p = 0.025) in the training and validation cohorts, respectively. Furthermore, radiomic features were associated with overall survival and progression-free survival both in the training and validation cohorts, but modified albumin-bilirubin grade and neutrophil-to-lymphocyte ratio were not., Conclusion: Radiomic features extracted from pretreatment MRI can predict individualized objective response to combination therapy with lenvatinib plus an anti-PD-1 antibody in patients with unresectable or advanced HCC, provide incremental predictive value over clinicopathologic features, and are associated with overall survival and progression-free survival after initiation of this combination regimen., Competing Interests: Hui-Chuan Sun has received honorarium or lecture fees from Roche, Bayer, MSD, Eisai, Hengrui, Innovent, TopAlliance, Abbott, Beigene, Gilead, and Zelgen during the last 5 years. Jia Fan is an Editorial Board Member of Liver Cancer. All remaining authors have no conflicts of interest to declare., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

Percutaneous coronary intervention (PCI) is the mainstream treatment to widen narrowed or obstructed coronary arteries due to pathological conditions. However, the post-operational neointimal hyperplasia occurs because of endothelium denudation during surgical procedures and the following inflammation. MicroRNAs (miRs) are new therapeutics of great potential for cardiovascular diseases. However, miRs easily degrade in vivo. A vehicle that can maintain their bioactivities and extend their retention at the site of delivery is prerequisite for miRs to play their roles as therapeutic reagents. Here, we reported the use of the Laponite hydrogels to deliver miR-22 that are modulators of phenotypes of smooth muscle cells (SMCs). The Laponite hydrogels allow a homogenous distribution of miR-22 within the gels, which had the capacity to transfect SMCs in vitro. Upon the injection of the miR-22 incorporated in the Laponite hydrogels in vivo, miR-22 could be well retained surrounding arteries for at least 7 days. Moreover, the miR-22 loading Laponite hydrogels inhibited the neointimal formation, reduced the infiltration of the macrophages, and reversed the adverse vascular ECM remodeling after the balloon-induced vascular injuries by upregulation of miR-22 and downregulation of its target genes methyl-CpG binding protein 2 (MECP2). The application of the Laponite hydrogels for miR local delivery may offer a novel strategy to treat cardiovascular diseases., Competing Interests: Declaration of competing interest The authors declare no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)