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Fubin Wang,* Aijun Wang,* Xiaoyan Leng, Lin Yong Department of Ophthalmology, Shanghai Bright Eye Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fubin Wang, Shanghai Bright Eye Hospital, 899 Maotai Road, Changning District, Shanghai, 200336, People’s Republic of China, Email wfb_528@163.comIntroduction: This study presents a rare case of multiple evanescent white dot syndrome (MEWDS) with atypical electrooculogram (EOG) findings, as well as abnormal en-face images of minimum intensity projection (Min-IP) and the en-face inner segment/outer segment-ellipsoid complex.Methods: A 25-year-old female patient presented with painless visual impairment and photopsia in her right eye for a duration of two days. Multimodal imaging was employed including color fundus photography (CFP), fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT), and optical coherence tomography angiography (OCTA), and en-face images of Min-IP and the en-face inner segment/outer segment-ellipsoid complex were performed.Results: In the right eye, multifocal small white spots were observed surrounding the posterior pole and optic disc of retina with the granular appearance of the fovea. FAF displayed of hyperfluorescence. SD-OCT appearance of MEWDS demonstrated primarily disrupted ellipsoid zone (EZ), photoreceptor outer segments, and interdigitation zone (IZ) complex within the fovea. The en-face images of the inner segment/outer segment-ellipsoid complex and Min-IP exhibited hyperreflective spots in the right eye. In the left eye, interestingly, hyperreflective spots were also observed on the en-face image of the inner segment/outer segment-ellipsoid complex. EOG revealed an Arden ratio of 2.5 for the right eye, while the left eye exhibited an Arden ratio of 1.7.Conclusion: The en-face image of the inner segment/outer segment-ellipsoid complex in MEWDS exhibits aberrant features and it is noteworthy that a similar alteration may occur in the fellow eye. Further investigation is required to explore the relationship between MEWDS and EOG. The en-face images of the inner segment/outer segment-ellipsoid complex and Min-IP may help to elucidate the pathogenesis of MEWDS.Keywords: multiple evanescent white dot syndrome, EOG, inner segment/outer segment-ellipsoid complex, minimum intensity projection, multimodal imaging

Lang Liu,1,* Binghua Zhang,1,* Zhenwei Zhou,2 Jie Yang,1 Ailin Li,1 Yongji Wu,1 Zeyu Peng,1 Xiangyan Li,2 Zhonghua Liu,3 Xiangyang Leng,1 Changwei Zhao,4 Haisi Dong,2 Wenhai Zhao4 1College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 2Northeast Asia Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 3Department of Orthopaedics, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 4Affiliated Hospital of Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haisi Dong, Northeast Asia Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, People’s Republic of China, Tel/Fax +86 431-18604361976, Email adonghaisi@163.com Wenhai Zhao, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130021, People’s Republic of China, Tel/Fax +86 431-86177836, Email zwh9899@163.comBackground: Knee osteoarthritis (KOA) is a persistent degenerative condition characterized by the deterioration of cartilage. The Chinese herbal formula Radix Rehmanniae Praeparata- Angelica Sinensis-Radix Achyranthis Bidentatae (RAR) has often been used in effective prescriptions for KOA as the main functional drug, but its underlying mechanism remains unclear. Therefore, network pharmacology and verification experiments were employed to investigate the impact and mode of action of RAR in the treatment of KOA.Methods: The destabilization of the medial meniscus model (DMM) was utilized to assess the anti-KOA effect of RAR by using gait analysis, micro-computed tomography (Micro-CT), and histology. Primary chondrocytes were extracted from the rib cartilage of a newborn mouse. The protective effects of RAR on OA cells were evaluated using a CCK‐8 assay. The antioxidative effect of RAR was determined by measuring reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione (GSH) production. Furthermore, network pharmacology and molecular docking were utilized to propose possible RAR targets for KOA, which were further verified through experiments.Results: In vivo, RAR significantly ameliorated DMM-induced KOA characteristics, such as subchondral bone sclerosis, cartilage deterioration, gait abnormalities, and the degree of knee swelling. In vitro, RAR stimulated chondrocyte proliferation and the expression of Col2a1, Comp, and Acan. Moreover, RAR treatment significantly reduced ROS accumulation in an OA cell model induced by IL-1β and increased the activity of antioxidant enzymes (SOD and GSH). Network pharmacology analysis combined with molecular docking showed that Mapk1 might be a key therapeutic target. Subsequent research showed that RAR could downregulate Mapk1 mRNA levels in IL-1β-induced chondrocytes and DMM-induced rats.Conclusion: RAR inhibited extracellular matrix (ECM) degradation and oxidative stress response via the MAPK signaling pathway in KOA, and Mapk1 may be a core target.Keywords: knee osteoarthritis, RAR, cartilage degeneration, network pharmacology, Mapk1

Danyang Wang,1,2 Jianfeng Xing,2 Ying Zhang,2 Ziyang Guo,2 Shujing Deng,2 Zelin Guan,2 Binyang He,2 Ruirui Ma,2 Xue Leng,2 Kai Dong,2 Yalin Dong1 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2School of Pharmacy, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Kai Dong, School of Pharmacy, Xi’an Jiaotong University, 76 Yanta West Road, Xi’an, Shaanxi, 710061, People’s Republic of China, Tel/Fax +86-29-82655139, Email dongkai120@xjtu.edu.cn Yalin Dong, Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China, Te1 +86-29-85323241, Fax +86-29-85323240, Email dongyalin@mail.xjtu.edu.cn; donglyalin@medmail.com.cnAbstract: Chronic wounds are recalcitrant complications of a variety of diseases, with pathologic features including bacterial infection, persistent inflammation, and proliferation of reactive oxygen species (ROS) levels in the wound microenvironment. Currently, the use of antimicrobial drugs, debridement, hyperbaric oxygen therapy, and other methods in clinical for chronic wound treatment is prone to problems such as bacterial resistance, wound expansion, and even exacerbation. In recent years, researchers have proposed many novel materials for the treatment of chronic wounds targeting the disease characteristics, among which metal–phenolic networks (MPNs) are supramolecular network structures that utilize multivalent metal ions and natural polyphenols complexed through ligand bonds. They have a flexible and versatile combination of structural forms and a variety of formations (nanoparticles, coatings, hydrogels, etc.) that can be constructed. Functionally, MPNs combine the chemocatalytic and bactericidal properties of metal ions as well as the anti-inflammatory and antioxidant properties of polyphenol compounds. Together with the excellent properties of rapid synthesis and negligible cytotoxicity, MPNs have attracted researchers’ great attention in biomedical fields such as anti-tumor, anti-bacterial, and anti-inflammatory. This paper will focus on the composition of MPNs, the mechanisms of MPNs for the treatment of chronic wounds, and the application of MPNs in novel chronic wound therapies.Keywords: metal–phenolic networks, chronic wounds, antimicrobial, antioxidant, reactive oxygen species scavenging, revascularization

Kai Dong,1,2 Shu-Jing Deng,2 Bin-Yang He,2 Zi-Yang Guo,2 Ze-Lin Guan,2 Xue Leng,2 Rui-Rui Ma,2 Dan-Yang Wang,2 Jian-Feng Xing,2 Cui-Yu You1 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2School of Pharmacy, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Jian-Feng Xing, School of Pharmacy, Xi’an Jiaotong University, 76 Yanta West Road, Xi’an, 710061, Shaanxi, People’s Republic of China, Tel +86-29-82655139, Fax +86-29-82655139, Email xajdxjf@mail.xjtu.edu.cn Cui-Yu You, Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China, Tel +86-29-85323241, Fax +86-29-85323240, Email ycy720123@163.comBackground: As the first-line drug to treat ulcerative colitis (UC), long-term use of glucocorticoids (GCs) produces severe toxic and side effects. Local administration as enema can increase the local GCs concentrations and reduce systemic exposure to high oral doses by directly delivering GCs to the inflammation site in the distal colorectum. However, UC patients are often accompanied by diarrhea, leading to the short colonic residence time of GCs and failure to exert their function fully.Purpose: A kind of mucoadhesive nanoparticles (NPs) loading different dexamethasone derivatives (DDs) were developed, which could attach to the positively charged inflammatory colonic mucosa through electrostatic adsorption after administered by enema, thereby improving the local concentration and achieving effective targeted therapy for UC.Methods: Two DDs, dexamethasone hemisuccinate and dexamethasone phosphate, were synthesized. In NPs preparation, The core PEI-DDs NPs were built by the electrostatic adsorption of DDs and the cationic polymer polyethyleneimine (PEI). Then, the natural polyanionic polysaccharide sodium alginate (SA) was electronically coated around NPs to construct the final SA-PEI-DDs NPs, followed by the in vitro stability and release tests, in vitro and in vivo colonic mucosal adhesion tests. In the in vivo anti-UC test, the experimental colitis mice were induced by 2,4,6-trinitrobenzenesulfonic acid. The body weight and disease activity index changes were measured, and the myeloperoxidase activity, pro-inflammatory cytokines concentration, and hematoxylin and eosin staining were also investigated to evaluate the therapeutic effect of NPs.Results: The structures of two DDs were demonstrated by 1H-NMR and MS. Both NPs were negatively charged and achieved high loading efficiency of DDs, while their particle sizes were significantly different. NPs showed good stability and sustained release properties in the simulated colonic environment. Moreover, the negative charge on the of NPs surface made them easier to adhere to the positively charged inflammatory colonic mucosa, thereby enhancing the enrichment and retention of DDS in the colitis site. Furthermore, the NPs exhibited better therapeutic effects than free Dex on the experimental colitis mice induced by TNBS through the enema rectal.Conclusion: These results indicated the mucoadhesive NPs as a kind of novel nano-enema showed great potential to achieve efficient treatment on UC.Keywords: ulcerative colitis, glucocorticoids, mucoadhesive, polyethyleneimine, sodium alginate

Yu C, Sun J, Leng X, Yang J. Cancer Manag Res. 2019;11:611–624. At the authors request, the Editor and Publisher of Cancer Management and Research are retracting the published article. The authors have informed the journal that they are unable to verify the reported findings and cannot provide the original data for their study. To maintain the integrity of the scholarly record the authors requested to retract the article and the Editor agreed with this decision. The authors apologize to the journal’s readers for any inconvenience. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Jun Wu,1 Xuefeng Leng,1 Zhengbo Pan,2 Linfei Xu,2 Haitao Zhang2 1Department of Urology, Naval 971 Hospital of Chinese People’s Liberation Army, Qingdao City, Shandong Province, People’s Republic of China; 2Department of Urology, Municipal Hospital Affiliated to Taizhou University, Taizhou City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Haitao ZhangDepartment of Urology, Municipal Hospital Affiliated to Taizhou University, Taizhou City, Zhejiang Province, People’s Republic of ChinaEmail zhanghaitao_123@yeah.netBackground: Growing findings have demonstrated that interferon regulatory transcription factor (IRF) family members are linked to the progression of various cancers. However, the roles of IRFs in clear cell renal cell carcinoma (ccRCC) remain undefined. Herein, we conducted a comprehensive analysis using the bioinformatics method to evaluate the expression patterns, clinical significance, and regulation of IRFs-related mechanisms in patients with ccRCC.Methods: Data from the Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGA), and Gene Expression Omnibus (GEO) databases were used for investigation comprehensively. Specifically, we carried out a series of analyses to identify the candidate IRF and to explore its potential action mechanisms using the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. What is more, we emphatically investigate the association of candidate IRF with tumor immunity in ccRCC through the CIBERSORT algorithm, TIMER and GEPIA databases.Results: Herein, IRF3 was identified as candidate IRF, which was highly expressed in ccRCC, and its overexpression was significantly associated with worse clinical outcomes and adverse overall survival. Uni- and multi-variate Cox regression analysis demonstrated that IRF3 overexpression was an independent predictor of worse prognosis. Functional enrichment analysis showed that IRF3 might participate in several cancer-related biological processes and signaling pathways, thereby promoting the progression of ccRCC. Additionally, we found that IRF3 was remarkably associated with tumor-infiltrating immune cells (TIICs) and various immune-related genes.Conclusion: Herein, we identified IRF3 from the IRF gene family members, which could serve as promising prognostic marker and therapeutic target in ccRCC.Keywords: kidney renal clear cell carcinoma, bioinformatics, interferon regulatory transcription factor, prognosis

Chen Yu, Junxi Sun, Xiaogang Leng, Jianxiu Yang Department of Anus & Intestine Surgery, Weifang People’s Hospital, Weifang, Shandong, China Background: Long noncoding RNAs (lncRNAs) have been identified as a novel class of regulators implicated in diverse biological processes in human cancers. Currently, evidence have shown that SNHG6, a cancer-associated lncRNA, exerts critical functions in gastric cancer and hepatocellular carcinoma; however, its role in colorectal cancer (CRC) remains unclear.Methods: The expression of SNHG6 was determined by quantitative real-time PCR in CRC tissues and cells. SNHG6 was downregulated by using RNAi technology. Cell proliferation was examined by MTT and clone formation assays. Cell migration and invasion were determined by wound healing and transwell assays. Fluorescence in situ hybridization assays were performed to examine subcellular localization of SNHG6 in CRC cells. Fluorescence reporter and Western blot assays were used to explore the potential mechanisms of SNHG6 in CRC progression.Results: In this study, we found that SNHG6 was significantly upregulated in CRC tissues and cell lines, compared with normal tissues and normal colorectal epithelial cell line NCM460, respectively. High expression of SNHG6 was positively correlated with tumor size, advanced TNM stage, and distant metastasis. Survival analyses revealed that SHNG6 was significantly associated with poor clinical outcomes and could serve as an independent prognostic factor. Loss-of-function studies demonstrated that SNHG6 knockdown inhibited CRC cell proliferation, induced G0/G1 arrest, promoted apoptosis, suppressed CRC cell migration and invasion, and restrained tumor growth. Mechanistic investigations showed that SNHG6 acted as a competing endogenous RNA for miR-181a-5p and attenuated the inhibitory effect of miR-181a-5p on E2F5.Conclusion: Taken together, these results demonstrated that SNHG6 plays a crucial role in CRC progression via miR-181a-5p/E2F5 axis. Therefore, SNHG6 may serve as a prognostic and therapeutic biomarker in CRC. Keywords: SNHG6, colorectal cancer, miR-181a-5p, E2F5, proliferation

Xia Dong, Lanxia Liu, Dunwan Zhu, Hailing Zhang, Xigang Leng Laboratory of Bioengineering, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin, People’s Republic of China Abstract: Carbon nanotube (CNT)-based drug delivery vehicles might find great potential in cancer therapy via the combination of chemotherapy with photothermal therapy due to the strong optical absorbance of CNTs in the near-infrared region. However, the application of CNTs in cancer therapy was considerably constrained by their lack of solubility in aqueous medium, as well as the cytotoxicity caused by their hydrophobic surface. Intracellular delivery efficiency is another factor determining the application potential of CNTs in cancer therapy. In the present study, low-molecular-weight chitosan conjugated with transactivator of transcription (TAT) peptide was used for noncovalent functionalization of multiwalled carbon nanotubes (MWCNTs), aiming at providing a more efficient drug delivery vehicle for cancer therapy. The TAT–chitosan-conjugated MWCNTs (MWCNTs-TC) were further investigated for their water solubility, cytotoxicity, cell-penetrating capability, and accumulation in tumor. It was found that MWCNTs-TC were essentially nontoxic with satisfying water solubility, and they were more efficient in terms of cancer-targeted intracellular transport both in vitro and in vivo as compared with chitosan-modified MWCNTs (MWCNTs-CS), suggesting the great application potential of MWCNTs-TC in cancer therapy. Keywords: carbon nanotube, TAT, chitosan, drug delivery

To investigate the gas-liquid two-phase flow characteristics in an emergency rescue drainage pump, the MUSIG model was adopted to analyze the effect of the gas phase on the internal flow characteristics of the pump. The results show that the gas phase predominantly accumulated in the impeller region, with significant tendencies for large diameter bubbles to fragment into smaller diameter bubbles. The bubbles of the impeller blades converged towards the middle zone of the blade near the hub, forming an air pocket that obstructed the flow passage through the impeller. Such findings ultimately resulted in a loss of pump performance. Moreover, as the diameter of inlet bubble increased, there was a greater tendency for the gas phase to converge into a concentration distribution, leading to unfavorable flow conditions in the pump. This phenomenon ultimately led to a decline in pump performance and may have resulted in the loss of water conveyance functionality. Meanwhile, the O method was used to investigate the vortex flow within the drainage pump under different gas contents. As the inlet gas volume fraction increased, the vortex area expanded and the vortex tended to fragment into multiple smaller pieces, resulting in the formation of more complex structures. [ABSTRACT FROM AUTHOR]

Saline alkali soil is used as spare arable soil, and its improvement is necessary for its development and utilization. There are many research studies on improving saline-alkali soil by using organic wastes produced by various industries, but there are few studies on using wastes produced by traditional Chinese medicine enterprises for saline alkali soil improvement. The purpose of this study was to explore the improvement effect of using Ganoderma lucidum residue (GLR) organic fertiliser on saline alkali soil and determine the application amount of GLR organic fertiliser with the best improvement effect. The results showed that the pH, EC and cation leaching loss of the leaching solution of the soil treated with GLR organic fertiliser were significantly higher than those of the unmodified soil. After leaching, the pH, EC, and base ions of the soil were significantly lower than those of unmodified saline alkali soil. The coefficient score of PCA was significantly higher than that of the unmodified saline alkali soil. When the ratio of organic fertilizer to saline-alkali soil was 1:3 and 1:5, the comprehensive evaluation level of the improvement effect was the highest, which could effectively reduce the soil saline-alkali index and promote the leaching of salt in saline-alkali soil. [ABSTRACT FROM AUTHOR]

To reveal the interaction mechanism between lithium (Li) and silicon/graphene (Si/Gra) interface at the atomic scale, it was calculated that the energy band structure, density of states, charge transfer, radial distribution function and Li diffusion coefficient based on the first principles. The results indicated that the volume expansion of Si was effectively limited by the Si/Gra interface during Li insertion. There appeared the interface effect of Si/Gra on the combination of Li and Si atoms, according to the longer Li‐C (2.9 Å) and the larger electron cloud near the Li atom at the Si/Gra interface. The better diffusion channel for Li atoms was constructed at the Si/Gra interface, due to the lower diffusion energy barrier (0.42–0.44 eV) and higher diffusion coefficient (DLi = 0.784 × 10−4 cm2/s) for Li+ diffusion. [ABSTRACT FROM AUTHOR]

Myocardial ischemia-reperfusion injury (MIRI) is one of the leading causes of death from cardiovascular disease in humans, especially in individuals exposed to cold environments. Long non-coding RNAs (lncRNAs) regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.

ObjectiveThe choice of neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC) is controversial. This study aims to provide a basis for clinical treatment selection by establishing a predictive model for the efficacy of neoadjuvant immunochemotherapy (NICT).MethodsA retrospective analysis of 30 patients was conducted, divided into Response and Non-response groups based on whether they achieved major pathological remission (MPR). Differences in genes and immune microenvironment between the two groups were analyzed through next-generation sequencing (NGS) and multiplex immunofluorescence (mIF). Variables most closely related to therapeutic efficacy were selected through LASSO regression and ROC curves to establish a predictive model. An additional 48 patients were prospectively collected as a validation set to verify the model’s effectiveness.ResultsNGS suggested seven differential genes (ATM, ATR, BIVM-ERCC5, MAP3K1, PRG, RBM10, and TSHR) between the two groups (P < 0.05). mIF indicated significant differences in the quantity and location of CD3+, PD-L1+, CD3+PD-L1+, CD4+PD-1+, CD4+LAG-3+, CD8+LAG-3+, LAG-3+ between the two groups before treatment (P < 0.05). Dynamic mIF analysis also indicated that CD3+, CD8+, and CD20+ all increased after treatment in both groups, with a more significant increase in CD8+ and CD20+ in the Response group (P < 0.05), and a more significant decrease in PD-L1+ (P < 0.05). The three variables most closely related to therapeutic efficacy were selected through LASSO regression and ROC curves: Tumor area PD-L1+ (AUC= 0.881), CD3+PD-L1+ (AUC= 0.833), and CD3+ (AUC= 0.826), and a predictive model was established. The model showed high performance in both the training set (AUC= 0.938) and the validation set (AUC= 0.832). Compared to the traditional CPS scoring criteria, the model showed significant improvements in accuracy (83.3% vs 70.8%), sensitivity (0.625 vs 0.312), and specificity (0.937 vs 0.906).ConclusionNICT treatment may exert anti-tumor effects by enriching immune cells and activating exhausted T cells. Tumor area CD3+, PD-L1+, and CD3+PD-L1+ are closely related to therapeutic efficacy. The model containing these three variables can accurately predict treatment outcomes, providing a reliable basis for the selection of neoadjuvant treatment plans.