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Min Wu,* Qi-man Shi,* Sai-Li Duan, Deng-jie Ou-yang, Pei Chen, Biao Tu, Peng Huang Department of General Surgery, Xiangya Hospital Central South University, Changsha, Hunan, 410008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng Huang, Email xiangyahp@csu.edu.cnPurpose: Glutamine and serine rich 1 (QSER1), as a DNA methylation modulator, play a crucial role in transforming tumor cells. Previous studies have shown that QSER1 plays a role in regulating the progression of various malignancies and that QSER1 dysfunction is connected with precancerous lesions of hepatocellular carcinoma (HCC) as well as HCC prognosis. However, little is known about the detailed contribution of QSER1 in HCC.Patients and Methods: Various statistical methods such as Kaplan–Meier method, AUC analysis, GSEA, and immune-infiltration analysis were used to evaluate the relationship between QSER1 expression and clinical features, prognostic factors, and potential functional mechanisms of QSER1.Results: QSER1 expression was negatively correlated with clinicopathological features (clinical stage, pathological grade, TP53 mutation, lymph node metastasis) and clinical outcome (overall survival versus recurrence). Functional enrichment analysis further suggested that QSER1 is involved in multiple pathways related to DNA replication and tumor immunity. TIMER analysis indicated that high QSER1 expression was significantly associated with higher macrophage infiltration and poorer macrophage-related outcomes. In particular, QSER1 was significantly more associated with M2 macrophages than M1 macrophages.Conclusion: Overall, elevated QSER1 is a potential prognostic marker for HCC and is associated with immune infiltration in HCC.Keywords: HCC, QSER1, prognosis, immune infiltration

Background: From 2004 onwards, the Chinese government has freely offered complimentary Chinese herbal medicine (CHM) to Chinese HIV/AIDS patients, alongside the prescribed first line therapy of highly active antiretroviral therapy (HAART). Thus, we aimed to explore the effectiveness and safety of CHM for patients with HIV/AIDS., Methods: The data from the Guangxi pilot database and antiviral treatment sites database have been respectively developed into two datasets in this prospective cohort real-world study, the CHM combined HAART group (the integrated group) and the HAART group. A 1:1 propensity score matching (PSM) was performed and the longitudinal data were analyzed using a generalized estimating equation (GEE) model with an autocorrelation matrix and log link function attached to the Gamma distribution., Results: A final sample of 629 patients, 455 and 174 in the integrated group and HAART group respectively, were obtained from the full dataset. As covariates for PSM, gender, age, baseline CD4+ and CD4+/ CD8+ were assessed based on the results of the logistic regression analyses. Following PSM, 166 pairs from the full dataset were matched successfully, with 98 pairs in the baseline CD4+ > 200 subgroup, and 55 pairs in the baseline CD4+ ≤ 200 subgroup. In the full dataset, HAART group achieved higher CD4+ count (OR = 1.119, 95%CI [1.018, 1.230]) and CD4+/CD8+ ratio (OR = 1.168, 95%CI [1.045, 1.305]) than the integrated group, so did in the CD4+ > 200 subgroup. For the CD4+ ≤ 200 subgroup, the CD4+ (OR = 0.825, 95%CI [0.694, 0.980]) and CD4+/CD8+ (OR = 0.826, 95%CI [0.684, 0.997]) of the integrated group were higher than those of the HAART group. The safety outcomes showed that there were no significant differences in BUN, ALT and AST levels between the groups but Cr showed significantly higher levels in HAART groups of all three datasets., Conclusions: Compared to HAART alone, CHMs combined with HAART had better effects in improving the immune function of HIV/AIDS in patients with baseline CD4+ count ≤ 200. The results of the two subgroups are in opposite directions, and chance does not explain the apparent subgroup effect. A study with larger sample size and longer follow-up period is warranted in order to increase study credibility., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Although the potential association between autoimmune thyroiditis and papillary thyroid cancer (PTC) has been acknowledged, whether the clinicopathological features of PTC will be affected by thyroid autoantibodies remains unknown., Patients and Methods: We conducted a case-control study to investigate the association of thyroid autoantibodies with clinicopathological characteristics of PTC in 15,305 patients (including 11,465 females and 3,840 males) from 3 medical centers in the central province of China. Logistic regression and restricted cubic spline models were performed to analyze the association of thyroid autoantibodies with clinicopathological features of PTC., Results: In total, out of the 15,305 patients enrolled in this study, 10,087 (65.9%) had negative thyroid autoantibodies, while 5,218(34.1%) tested positive thyroid autoantibodies. Among these individuals, 1,530(10.0%) showed positivity for TPOAb only, 1,247(8.2%) for TGAb only and a further 2,441(15.9%) exhibited dual positivity for both TPOAb and TGAb combined. Thyroid autoantibodies level demonstrated significant correlations with certain aggressive features in PTC. Specifically, TGAb level displayed a direct correlation to an increased likelihood of multifocality, bilateral tumor, extrathyroidal extension, lymph node metastasis, as well as more than five affected lymph nodes. However, TPOAb level exhibited an inverse association with the risk associated with extrathyroidal extension, lymph node metastasis, and more than five affected lymph nodes., Conclusion: Elevated level of TGAb were positively correlated with the risk of aggressive features in PTC, while high level of TPOAb were inversely associated with the risk of extrathyroidal extension and lymph node metastasis., (© 2024. The Author(s).)

Background: The aim of this study is to design a deep learning (DL) model to preoperatively predict the occurrence of central lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC)., Methods: This research collected preoperative ultrasound (US) images and clinical factors of 611 PTMC patients. The clinical factors were analyzed using multivariate regression. Then, a DL model based on US images and clinical factors was developed to preoperatively predict CLNM. The model's efficacy was evaluated using the receiver operating characteristic (ROC) curve, along with accuracy, sensitivity, specificity, and the F 1 score., Results: The multivariate analysis indicated an independent correlation factors including age ≥55 (OR = 0.309, p < 0.001), tumor diameter (OR = 2.551, p = 0.010), macrocalcifications (OR = 1.832, p = 0.002), and capsular invasion (OR = 1.977, p = 0.005). The suggested DL model utilized US images achieved an average area under the curve (AUC) of 0.65, slightly outperforming the model that employed traditional clinical factors (AUC = 0.64). Nevertheless, the model that incorporated both of them did not enhance prediction accuracy (AUC = 0.63)., Conclusions: The suggested approach offers a reference for the treatment and supervision of PTMC. Among three models used in this study, the deep model relied generally more on image modalities than the data modality of clinic records when making the predictions., Competing Interests: The authors declare there are no competing interests., (©2024 Wang et al.)

The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family includes CMTM1-8 and CKLF, and they play key roles in the hematopoietic, immune, cardiovascular, and male reproductive systems, participating in the physiological functions, cancer, and other diseases associated with these systems. CMTM family members activate and chemoattract immune cells to affect the proliferation and invasion of tumor cells through a similar mechanism, the structural characteristics typical of chemokines and transmembrane 4 superfamily (TM4SF). In this review, we discuss each CMTM family member's chromosomal location, involved signaling pathways, expression patterns, and potential roles, and mechanisms of action in pancreatic, breast, gastric and liver cancers. Furthermore, we discuss several clinically applied tumor therapies targeted at the CMTM family, indicating that CMTM family members could be novel immune checkpoints and potential targets effective in tumor treatment., Competing Interests: The authors declare that they have no competing interests., (© 2024 Duan et al.)

Although the incidence of thyroid cancer is increasing year by year, most patients, especially those with differentiated thyroid cancer, can usually be cured with surgery, radioactive iodine, and thyroid-stimulating hormone suppression. However, treatment options for patients with poorly differentiated thyroid cancers or radioiodine-refractory thyroid cancer have historically been limited. Altered energy metabolism is one of the hallmarks of cancer and a well-documented feature in thyroid cancer. In a hypoxic environment with extreme nutrient deficiencies resulting from uncontrolled growth, thyroid cancer cells utilize "metabolic reprogramming" to satisfy their energy demand and support malignant behaviors such as metastasis. This review summarizes past and recent advances in our understanding of the reprogramming of glucose metabolism in thyroid cancer cells, which we expect will yield new therapeutic approaches for patients with special pathological types of thyroid cancer by targeting reprogrammed glucose metabolism., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The tumor microenvironment (TME) is an intricate ecosystem that is actively involved in various stages of cancer occurrence and development. Some characteristics of tumor biological behavior, such as proliferation, migration, invasion, inhibition of apoptosis, immune escape, angiogenesis, and metabolic reprogramming, are affected by TME. Studies have shown that non-coding RNAs, especially long-chain non-coding RNAs and microRNAs in cancer-derived exosomes, facilitate intercellular communication as a mechanism for regulating angiogenesis. They stimulate tumor growth, as well as angiogenesis, metastasis, and reprogramming of the TME. Exploring the relationship between exogenous non-coding RNAs and tumor-associated endothelial cells, as well as their role in angiogenesis, clinicians will gain new insights into treatment as a result., 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 Duan, Fu, Jiang, Peng, Ousmane, Zhang and Wang.)

Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease with complex causes. The main pathological changes were intestinal mucosal injury. Leucine-rich repeat-containing G protein coupled receptor 5 (LGR5)-labeled small intestine stem cells (ISCs) were located at the bottom of the small intestine recess and inlaid among Paneth cells. LGR5+ small ISCs are active proliferative adult stem cells, and their self-renewal, proliferation and differentiation disorders are closely related to the occurrence of intestinal inflammatory diseases. The Notch signaling pathway and Wnt/β-catenin signaling pathway are important regulators of LGR5-positive ISCs and together maintain the function of LGR5-positive ISCs. More importantly, the surviving stem cells after intestinal mucosal injury accelerate division, restore the number of stem cells, multiply and differentiate into mature intestinal epithelial cells, and repair the damaged intestinal mucosa. Therefore, in-depth study of multiple pathways and transplantation of LGR5-positive ISCs may become a new target for the treatment of UC., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The sirtuins (SIRTs) family is a nicotinamide adenine dinucleotide (NAD+) family of dependent deacetylases, which includes SIRT1-7. This family is related to the development and progression of various tumors. However, a comprehensive analysis of the role of SIRTs in clear cell renal cell carcinoma (ccRCC) is still lacking, and there are few reports on the inhibitory role of SIRT5 in ccRCC., Methods: We used immunohistochemical analysis, and several bioinformatic databases to perform an integrated analysis of the expression and prognostic value of SIRT5 and other SIRT family members in ccRCC along with the associated immune cell infiltration. These databases include TIMER, THPA, cell culture, UALCAN, cBioPortal, WebGestalt, Metascape, DiseaseMeth, STRING database, and Cytoscape., Results: The protein expression of SIRT1, 2, 3, 6, and 7 were upregulated in ccRCC for the Human Protein Atlas database, whereas the expression of SIRT4 and SIRT5 was decreased. The expression based on tumor stage, and grade followed a similar trend. Kaplan-Meier analysis showed that high SIRT4 and SIRT5 expression was positively related to better overall survival (OS), whereas SIRT6 and SIRT7 expression was positively related to worse OS. Further, high SIRT3 expression was related to worse relapse-free survival (RFS), whereas high SIRT5 expression was related to better RFS. To explore the mechanism underlying the function of SIRTs in ccRCC, we also used several databases to perform the functional enrichment analysis and explore the relationship between infiltrating immune cells and seven SIRT family members in ccRCC. The results showed that several SIRT family members, and particularly SIRT5, are correlated with the infiltration of some important immune cells. The protein expression of SIRT5 was significantly lower in tumor tissue compared to normal tissue and was negatively related to the age of the patient ccRCC individual tumor stages, and grades. In human ccRCC samples, strong IHC staining expression of SIRT5 was displayed in adjacent normal tissue than in tumor tissues., Conclusion: SIRT5 may be a prognostic marker and a novel strategy for the treatment of ccRCC., Competing Interests: The authors declare there are no competing interests., (©2023 Peng et al.)

Purpose: Hashimoto's thyroiditis often leads to reactive hyperplasia of the central compartment lymph nodes in papillary thyroid carcinoma (PTC) patients. However, the effect and clinical significance of Hashimoto's thyroiditis (HT) on ultrasonography evaluation for cervical lymph node (LN) lesions remain unknown. This study aims to investigate the effect of Hashimoto's thyroiditis on the diagnostic efficacy of preoperative ultrasonography on cervical lymph node lesions in PTC patients., Patients and Methods: This study consecutively enrolled 1,874 PTC patients who underwent total thyroidectomy and radical cervical lymph node dissection between January 2010 and December 2021. Eligible patients were categorized as with HT and without HT. The diagnostic performance of preoperative ultrasonography for cervical LN lesions (including central LNs and lateral LNs) was evaluated between PTC patients with HT and those without HT, respectively., Results: Among the 1,874 PTC patients, 790 (42.1%) had central cN+ and 1,610 (85.9%) had lateral cN+. Compared with PTC patients without HT, the preoperative US for central LNs displays a higher false-positive rate (27.9% vs. 12.2%, p < 0.001) and a lower specificity (72.1% vs. 87.8%, p < 0.001) in PTC patients with HT. Moreover, in PTC patients with HT, the ratio of the absence of fatty hilum in central LNs without metastasis was higher than in PTC patients without HT (13.02% vs. 7.46%, p = 0.013). However, no such differences were observed in lateral LNs., Conclusion: HT will interfere with the preoperative US evaluation for central LNs and increase the incidence of the absence of fatty hilum in central benign LNs. When PTC patients have concomitant HT, clinicians should thoroughly evaluate the central LNs, thereby decreasing the incidence of misdiagnosis and unnecessary surgery., 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 Tan, Nyarko, Duan, Zhao, Chen, He, Zhang, Chang and Huang.)

Background: The GSDM family includes six members, GSDMA, GSDMB, GSDMC, GSDMD, GSDME (DFNA5), and PJVK (Pejvakin, DFNB59), which can induce pyroptosis, thereby regulating the tumorigenesis of various cancers. However, the clinical characteristics and role of the GSDM family in LUAD are not well understood., Methods: In this study, several important bioinformatics databases were used to integrate the analysis of the expression, prognostic value, and immune infiltration of GSDMs in LUAD. These databases include UALCAN, DiseaseMeth, GEPIA, THPA, cBioPortal, TIMER, WebGestalt, STRING database, and Cytoscape., Results: The findings from the UALCAN database revealed that the expression of all six GSDMs based on the tumor stage in LUAD was increased (particularly GSDMD). Our IHC results verified it. Additionally, the DiseaseMeth database showed that the methylation levels of GSDMA, GSDMB, GSDMC, and GSDMD were decreased. The expression of six GSDMs was related to shorter overall survival in patients with LUAD, according to the GEPIA database. The cBioPortal database was further used to explore the alteration rate and correlated genes in LUAD. Subsequently, these genes were subjected to functional enrichment and protein-protein interaction network analyses. We identified that the GSDM family regulate several signaling pathways, including immune-associated signaling pathways. According to tumor-infiltrating immune cell analysis from the TIMER database, GSDM family members are associated with the infiltration of important immune cells and their signature markers., Conclusions: GSDM family may be prognostic markers and novel strategies for the treatment of LUAD., 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 Peng, Duan, Li, Wang, Han, Huang, Yu, Ou and Wang.)

Gut microbiota imbalances play an important role in inflammatory bowel disease (IBD), but no single pathogenic microorganism critical to IBD that is specific to the IBD terminal ileum mucosa or can invade intestinal epithelial cells has been found. Invasive Escherichia coli ( E. coli) adhesion to macrophages is considered to be closely related to the pathogenesis of inflammatory bowel disease. Further study of the specific biological characteristics of adherent invasive E. coli (AIEC) may contribute to a further understanding of IBD pathogenesis. This review explores the relationship between AIEC and the intestinal immune system, discusses the prevalence and relevance of AIEC in Crohn's disease and ulcerative colitis patients, and describes the relationship between AIEC and the disease site, activity, and postoperative recurrence. Finally, we highlight potential therapeutic strategies to attenuate AIEC colonization in the intestinal mucosa, including the use of phage therapy, antibiotics, and anti-adhesion molecules. These strategies may open up new avenues for the prevention and treatment of IBD in the future., Competing Interests: Conflict-of-interest statement: All authors declare that there are no conflicts of interest to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease with a complex etiology. Intestinal mucosal injury is an important pathological change in individuals with UC. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5+) intestinal stem cells (ISCs) exhibit self-renewal and high differentiation potential and play important roles in the repair of intestinal mucosal injury. Moreover, LGR5+ ISCs are intricately regulated by both the Wnt/β-catenin and Notch signaling pathways, which jointly maintain the function of LGR5+ ISCs. Combination therapy targeting multiple signaling pathways and transplantation of LGR5+ ISCs may lead to the development of new clinical therapies for UC., 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 Zheng, Duan, Wen and Dai.)

Background: The purpose of this study was to define and analyze the characteristics of the top 100 most-cited articles and reviews on the topic of pheochromocytomas and paragangliomas (PPGLs) by using bibliometric methods., Methods: We explored the Web of Science Core Collection database to gather the 100 top-cited original articles and reviews of PPGL from 1985 to 20 December 2020. We conducted a bibliometric study to identify the most influential journals, authors, countries, and institutions in the PPGL field., Results: The 100 top-cited papers were cited a total number of 25,723 times, ranging from 131 to 1,144 (mean, 257.23 ± 173.64). All of these 100 top-cited papers were published between 1999 and 2017, and the number of top-cited papers published before 2008 (1999-2008) was significantly higher than that after 2008 (2009-2017) (p = 0.043). The journal with the highest number of published papers is the Journal of Clinical Endocrinology & Metabolism (n = 23). The United States was the most productive country in this topic, which published about half of these publications (n = 51). The National Institutes of Health (NIH) had the largest number of publications (n = 17). Genes or genetics is still the hottest topic in the field of PPGLs., Conclusions: We defined and analyzed the top 100 most-cited papers in the field of PPGLs by gathering detailed information. These data provided insights into the most influential studies related to PPGL. We hoped to inspire researchers and readers in this field to improve their understanding of PPGL research trends and provide ideas for future research from unique perspectives., 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 Duan, Qi, Li, Liu, Wang and Guan.)

With the development of microbiology and metabolomics, the relationship between the intestinal microbiome and intestinal diseases has been revealed. Fecal microbiota transplantation (FMT), as a new treatment method, can affect the course of many chronic diseases such as metabolic syndrome, malignant tumor, autoimmune disease and nervous system disease. Although the mechanism of action of FMT is now well understood, there is some controversy in metabolic diseases, so its clinical application may be limited. Microflora transplantation is recommended by clinical medical guidelines and consensus for the treatment of recurrent or refractory Clostridium difficile infection, and has been gradually promoted for the treatment of other intestinal and extraintestinal diseases. However, the initial results are varied, suggesting that the heterogeneity of the donor stools may affect the efficacy of FMT. The success of FMT depends on the microbial diversity and composition of donor feces. Therefore, clinical trials may fail due to the selection of ineffective donors, and not to faulty indication selection for FMT. A new understanding is that FMT not only improves insulin sensitivity, but may also alter the natural course of type 1 diabetes by modulating autoimmunity. In this review, we focus on the main mechanisms and deficiencies of FMT, and explore the optimal design of FMT research, especially in the field of cardiometabolic diseases., Competing Interests: Conflict-of-interest statement: The authors declare that there are no conflicts of interest related to this study., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Over the past two decades, it is improved gut microbiota plays an important role in the health and disease pathogenesis. Metabolites, small molecules produced as intermediate or end products of microbial metabolism, is considered as one of the major interaction way for gut microbiota with the host. Bacterial metabolisms of dietary substrates, modification of host molecules or bacteria are the major source of metabolites. Signals from microbial metabolites affect immune maturation and homeostasis, host energy metabolism as well as mucosal integrity maintenance. Based on many researches, the composition and function of the microbiota can be changed, which is also seen in the metabolite profiles of patients with inflammatory bowel disease (IBD). Additionally, some specific classes of metabolites also can trigger IBD. In this paper, definition of the key classes of microbial-derived metabolites which are changed in IBD, description of the pathophysiological basis of association and identification of the precision therapeutic modulation in the future are the major contents., Competing Interests: Conflict-of-interest statement: The authors declare that there are no conflicts of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: Aberrant DNA methylation plays a crucial role in the tumorigenesis of differentiated thyroid cancer (DTC); nevertheless, the factors leading to the local and regional recurrence of DTC are not well understood. This study aimed to establish the connection between DNA methylation-driven genes and the recurrence of DTC. Methods: RNA sequencing profiles and DNA methylation profiles of DTC were downloaded from The Cancer Genome Atlas (TCGA) database. Combined application of the methylmix R package and univariate Cox regression analyses were used to screen and distinguish prognosis-related methylation-driven genes. Multivariate Cox regression analyses were utilized to identify the target genes that were closely associated with the recurrence of DTC. Then, correlations between the expression levels of the target genes and the clinicopathological features were verified, as well as their potential biological functions. Results: A total of 168 Methylation-driven genes were differentially expressed in thyroid cancer, among which 10 genes (GSTO2, GSTM5, GSTM1, GPX7, FGF2, LIF, PLAU, BCL10, SHARPIN and TNFRSF1A) were identified as Hub genes. We selected PLAU for further analysis because PLAU was most strongly correlated with DTC recurrence and the DNA methylation levels of PLAU were closely associated with multiple clinicopathological features of DTC. PLAU was significantly upregulated in DTC, and patients with a high expression level of PLAU had a higher risk of recurrence ( p < 0.05). Functional predictions suggested that PLAU-related genes were mainly involved in the regulation of immune-related signaling pathways. Moreover, the mRNA level of PLAU was found to be positively correlated with the cell markers of neutrophils and dendritic cells. In addition, we found that two DNA methylation sites (cg06829584, cg19399285) were associated with abnormal expression of PLAU in DTC. Conclusion: The methylation-driven gene PLAU is an independent risk factor for the recurrence of DTC and it functions as an oncogene through the regulation of immune-related signaling pathways, which offers new insight into the molecular mechanisms of thyroid cancer and provides new possibilities for individualized treatment of thyroid cancer patients., 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 Wu, Wei, Duan, Liu, Ou-Yang, Huang and Chang.)

Chemical investigation of the stem bark of Ficus tsiangii led to the isolation of a new coumarin ficuscoumarin (1) and a new norlignan ficuslignan (2) by chromatographic methods. Their structures were elucidated on the basis of spectroscopic analyses.

Objective: To investigate the regulation of hypoxia-inducible factor-1α (HIF-1α) on permeability of rat vascular endothelial cells and the mechanism. Methods: Twelve male Sprague-Dawley rats aged 35 to 38 days were collected and vascular endothelial cells were separated and cultured. The morphology of cells was observed after 4 days of culture, and the following experiments were performed on the 2nd or 3rd passage of cells. (1) Rat vascular endothelial cells were collected and divided into blank control group, negative control group, HIF-1α interference sequence 1 group, HIF-1α interference sequence 2 group, and HIF-1α interference sequence 3 group according to the random number table (the same grouping method below), with 3 wells in each group. Cells in negative control group, HIF-1α interference sequence 1 group, HIF-1α interference sequence 2 group, and HIF-1α interference sequence 3 group were transfected with GV248 empty plasmid, recombinant plasmid respectively containing HIF-1α interference sequence 1, interference sequence 2, and interference sequence 3 with liposome 2000. Cells in blank control group were only transfected with liposome 2000. After transfection of 24 h, expression levels of HIF-1α mRNA and protein of cells in each group were respectively detected by reverse transcription real-time fluorescent quantitative polymerase chain reaction and Western blotting (the same detecting methods below) . The sequence with the highest interference efficiency was selected. (2) Another batch of rat vascular endothelial cells were collected and divided into blank control group, negative control group, and HIF-1α low expression group, with 3 wells in each group. Cells in blank control group were only transfected with liposome 2000, and cells in negative control group and HIF-1α low expression group were respectively transfected with GV248 empty plasmid and low expression HIF-1α recombinant plasmid selected in experiment (1) with liposome 2000. After 14 days of culture, the mRNA and protein expressions of HIF-1α in each group were detected. (3) Another batch of rat vascular endothelial cells were collected and divided into blank control group, negative control group, and HIF-1α high expression group, with 3 wells in each group. Cells in blank control group were transfected with liposome 2000, and cells in negative control group and HIF-1α high expression group were respectively transfected with GV230 empty plasmid and HIF-1α high expression recombinant plasmid with liposome 2000. After 14 days of culture, the mRNA and protein expressions of HIF-1α of cells in each group were detected. (4) After transfection of 24 h, cells of three groups in experiment (1) and three groups in experiment (2) were collected, and mRNA and protein expressions of myosin light chain kinase (MLCK), phosphorylated myosin light chain (p-MLC), and zonula occludens 1 (ZO-1) of cells were detected. Data were processed with one-way analysis of variance and t test. Results: After 4 days of culture, the cells were spindle-shaped, and rat vascular endothelial cells were successfully cultured. (1) The interference efficiencies of HIF-1α of cells in HIF-1α interference sequence 1 group, HIF-1α interference sequence 2 group, and HIF-1α interference sequence 3 group were 47.66%, 45.79%, and 62.62%, respectively, and the interference sequence 3 group had the highest interference efficiency. After transfection of 24 h, the mRNA and protein expression levels of HIF-1α of cells in interference sequence 3 group were significantly lower than those in blank control group ( t =18.404, 9.140, P <0.01) and negative control group ( t =15.099, 7.096, P <0.01). (2) After cultured for 14 days, the mRNA and protein expression levels of HIF-1α of cells in HIF-1α low expression group were significantly lower than those in blank control group ( t =21.140, 5.440, P <0.01) and negative control group ( t = 14.310, 5.210, P <0.01). (3) After cultured for 14 days, the mRNA and protein expression levels of HIF-1α of cells in HIF-1α high expression group were significantly higher than those in blank control group ( t =19.160, 7.710, P <0.01) and negative control group ( t = 19.890, 7.500, P <0.01). (4) After transfection of 24 h, the mRNA expression levels of MLCK and p-MLC of cells in HIF-1α low expression group were significantly lower than those in blank control group ( t =2.709, 4.011, P <0.05 or P <0.01) and negative control group ( t =2.373, 3.744, P <0.05 or P <0.01). The mRNA expression level of ZO-1 of cells in HIF-1α low expression group was significantly higher than that in blank control group and negative control group ( t =4.285, 5.050, P <0.01). The mRNA expression levels of MLCK and p-MLC of cells in HIF-1α high expression group were significantly higher than those in blank control group ( t =9.118, 11.313, P <0.01) and negative control group ( t =9.073, 11.280, P <0.01). The mRNA expression level of ZO-1 of cells in HIF-1α high expression group was significantly lower than that in blank control group and negative control group ( t =2.889, 2.640, P <0.05). (5) After transfection of 24 h, the protein expression levels of MLCK and p-MLC of cells in HIF-1α low expression group were significantly lower than those in blank control group ( t =2.652, 3.983, P <0.05 or P <0.01) and negative control group ( t =2.792, 4.065, P <0.05 or P <0.01). The protein expression of ZO-1 of cells in HIF-1α low expression group was significantly higher than that in blank control group and negative control group ( t =3.881, 3.570, P <0.01). The protein expression levels of MLCK and p-MLC of cells in HIF-1α high expression group were 1.18±0.24 and 0.68±0.22, which were significantly higher than 0.41±0.21 and 0.35±0.14 in blank control group ( t =5.011, 3.982, P <0.05 or P <0.01) and 0.43±0.20 and 0.36±0.12 in negative control group ( t = 4.880, 3.862, P <0.05 or P <0.01). The protein expression level of ZO-1 of cells in HIF-1α high expression group was 0.08±0.06, which was significantly lower than 0.20±0.09 in blank control group and 0.19±0.09 in negative control group ( t =4.178, 3.830, P <0.05 or P <0.01). Conclusions: HIF-1α up-regulates expressions of MLCK and p-MLC and down-regulates expression of ZO-1, thereby increasing the permeability of rat vascular endothelial cells.

Water-borne transportation plays an important role in the economic and social development and contributes greatly to air pollution in China as well. An effective regulating policy is dependent on accurate estimation in terms of sorts, quantification and location of emissions. However, there is insufficient real and reliable data source for China's marine diesel engines and vessels. In order to employ fuel-based approach and ship activity-based approach to estimate accurately the exhaust emissions from water-borne transportation sector in China, emission factors of different types of marine diesel engines were investigated. Based on statistical analysis on Parent Engine emission test reports of 76 and 113 marine diesel engines manufactured by China's engine makers in accordance with IMO NO x TierⅠ and TierⅡ standards respectively as defined in MARPOL(International Convention for the Prevention of Pollution from Ships) Annex VI, abnormal data were statistically identified and eliminated by Grubbs' criterion method, fuel-based emission factors and energy-based emission factors of NO x , CO, HC and CO 2 for 2-Stroke main engines, 4-Stroke main engines and 4-Stroke auxiliary engines were determined respectively. The results showed that fuel-based emission factors of NO x , CO, HC and CO 2 for different types of marine diesel engines were 30.67-76.55, 3.01-6.13, 1.25-2.24 and 3141.15-3165.63 kg·t -1 respectively. Energy-based emission factors of NO x , CO, HC and CO 2 for different types of marine diesel engines were 6.83-13.64, 0.61-1.35, 0.21-0.50 and 534.04-745.18 g·(kW·h) -1 respectively. In addition, the relationships of energy-based emission factors against engine load were expressed by power function or quadratic polynomial and the algorithm coefficients were determined. In addition, it is difficult to obtain the true emission levels of marine diesel engines in China through simple modification of emission factors reported by foreign institutes. In particular,considering the diversity of diesel engines onboard China's coastal and inland vessels, more samples and tests in terms of types and operational conditions are necessary to provide basic data for marine emission inventories in China. The results could provide applicable data for estimation of marine emissions in China.

In the past few years, progress being made in stem cell studies has incontestably led to the hope of developing cell replacement based therapy for diseases deficient in effective treatment by conventional ways. The induced pluripotent stem cells (iPSCs) are of great interest of cell therapy research because of their unrestricted self-renewal and differentiation potentials. Proof of principle studies have successfully demonstrated that iPSCs technology would substantially benefit clinical studies in various areas, including neurological disorders, hematologic diseases, cardiac diseases, liver diseases and etc. On top of this, latest advances of gene editing technologies have vigorously endorsed the possibility of obtaining disease-free autologous cells from patient specific iPSCs. Here in this review, we summarize current progress of stem cell therapy research with special enthusiasm in iPSCs studies. In addition, we compare current gene editing technologies and discuss their potential implications in clinic application in the future.

By repeated column chromatography, including silica gel, macroporous resin, and preparative HPLC, a new compound (1) was isolated and purified. On the basis of spectroscopic methods, the structure of 1 was elucidated as ( - ) -epiafzelechin-3, 5-di-O-beta-D-apiofuranoside (1). In the bioassay screening experiments, glucose consumption assays in IR HepG2 cells and colorimetric assay of surface GLUT4myc translocation were used to assess the effects on glucose metabolism of compound 1. Both compound 1 and its derivatives--naringin could improve glucose consumption in IR HepG2 cells and enhance GLUT4 translocation in skeletal muscle cell L6myc in a dose-dependent manner, indicating that these two compouds showed potential anti-diabetic activities in vitro.