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Jiapeng Li,1,2 Yang Liu,2 Jingru Zhang,1,2 Xiaotong Yu,1,2 Xiaoling Wang,1 Libo Zhao11Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, 2Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China Background: The intestinal cytochrome P450 3A (CYP 3A) and P-glycoprotein (P-gp) present a barrier to the oral absorption of saquinavir (SQV). Resveratrol (RESV) has been indicated to have modulatory effects on P-gp and CYP 3A. Therefore, this study was to investigate the effects of RESV on P-gp and CYP 3A activities in vitro and in vivo on oral SQV pharmacokinetics in rats.Methods: In vitro, intestinal microsomes were used to evaluate RESV effect on CYP 3A-mediated metabolism of SQV; MDR1-expressing Madin–Darby canine kidney (MDCKII-MDR1) cells were employed to assess the impact of RESV on P-gp-mediated efflux of SQV. In vivo effects were studied using 10 rats randomly assigned to receive oral SQV (30 mg/kg) with or without RESV (20 mg/kg). Serial blood samples were obtained over the following 24 h. Concentrations of SQV in samples were ascertained using high-performance liquid chromatography-tandem mass spectrometry analysis.Results: RESV (1–100 µM) enhanced residual SQV (% of control) in a dose-dependent manner after incubation with intestinal microsomes. RESV (1–100 µM) reduced the accumulation of SQV in MDCKII-MDR1 cells in a concentration-dependent manner. A double peaking phenomenon was observed in the plasma SQV profiles in rats. The first peak of plasma SQV concentration was increased, but the second peak was reduced by coadministration with RESV. The mean AUC0–∞ of SQV was slightly decreased, with no statistical significance probably due to the high individual variation.Conclusion: RESV can alter the plasma SQV concentration profiles, shorten the Tmax of SQV. RESV might also cause a slight decrease tendency in the SQV bioavailability in rats. Keywords: resveratrol, saquinavir, P-glycoprotein, CYP 3A, pharmacokinetic

Objective: To analyze the value of differential diagnosis of post-reflux swallow-induced peristaltic wave index (PSPWI) between esophageal diseases of gut-brain interaction (E-DGBI) and gastroesophageal reflux disease (GERD). Methods: The patients diagnosed as E-DGBI and GERD in the Department of Gastroenterology, Beijing Tsinghua Changguang Hospital from June 2016 to June 2018 were retrospectively included. The medical records, gastroscopy and 24-hour pH-intraluminal impedance monitoring reports were collected. According to clinical diagnosis, the patients were divided into E-DGBI group and GERD group. PSPWI, acid exposure time (AET), DeMeester score, total reflux times and mean nocturnal baseline impedance (MNBI) were compared between the both group. The receiver operating characteristic curve (ROC) of PSPWI, AET, total reflux times and MNBI was drawn to identify the sensitivity and specificity of E-DGBI and GERD. The cut-off values were calculated with Youden index and the area under the curve (AUC) was compared. Results: A total of 73 patients were included,including 36 males and 37 females, whose age [ M (Q 1 , Q 3 )] was 54.0 (42.6, 63.0) years. There were 39 cases in E-DGBI group and 34 cases in GERD group. The 24-h AET [0.5 (0.1, 1.6) vs 6.0 (3.6, 11.9)], DeMeester score [2.8 (1.1, 5.7) vs 20.4 (14.7, 47.4) score] and total reflux times [32.0 (19.0, 53.0) vs 66.0 (34.3, 96.0) times] were significantly higher in E-DGBI group than those in GERD group (all P <0.001);MNBI in E-DGBI group was higher than that in GERD group[2 375.0 (1 726.0, 2 978.0)Ω vs 1 361.0 (814.0, 2 273.5)Ω, P <0.001]. The PSPWI in E-DGBI group is higher than that in GERD (0.56±0.19 vs 0.25±0.15, P <0.001). According to ROC, with PSPWI>0.46 as the cut-off value, the AUC was 0.895 (95% CI : 0.827-0.963) in differentiating E-DGBI and GERD. The sensitivity was 94.1% and the specificity was 69.2%. There were no significant differences of AUC between PSPWI and AET or total reflux events (all P >0.05). But the AUC of PSPWI was higher than that of MNBI (AUC=0.749,95% CI :0.632-0.866, P =0.031). Conclusion: PSPWI can better distinguish E-DGBI from GERD.

Deoxynivalenol (DON) is a secondary metabolite of Fusarium fungi and belonged to trichothecenes, and it widely presents in various food commodities. Previous studies have highlighted its potent toxicity, adversely affecting the growth, development, and reproductive in both humans and animals. However, the potential impact of DON on porcine oocyte organelles remains elusive. In present study, we delved into the toxic effects of DON on mitochondria, endoplasmic reticulum, Golgi during the porcine oocyte maturation. Our findings revealed that DON exposure significantly impeded granulosa cell diffusion and the expulsion of the first polar body. Additionally, mitochondrial fluorescence intensity and membrane potential underwent notable alterations under DON exposure. Notably, lysosomal fluorescence intensity decreased significantly, suggesting protein degradation and potential autophagy, which was further corroborated by the enhanced fluorescence intensity of LC3. Furthermore, endoplasmic reticulum fluorescence intensity declined, and DON exposure elevated endoplasmic reticulum stress levels, evident from the upregulated expression of GRP78. Concurrently, we observed disruption in the fusiform cortex distribution of the Golgi apparatus, characterized by reduced Golgi apparatus fluorescence intensity and GM130 expression. Collectively, our results indicate that DON exposure profoundly affects the fundamental functions of porcine oocyte organelles during meiosis and maturation., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to design and evaluate the efficacy of pyrrolidone derivatives as potential therapeutic agents against diffuse large B-cell lymphoma (DLBCL), a common and heterogeneous malignancy of the adult lymphohematopoietic system. Given the limitations of current therapies, there is a pressing need to develop new and effective drugs for DLBCL treatment., Methods: A series of pyrrolidone derivatives were synthesized, and their antitumor activities were assessed, particularly against DLBCL cell lines. Structure-activity relationship (SAR) analysis was conducted to identify key structural components essential for activity. The most promising compound, referred to as compound 7, was selected for further mechanistic studies. The expression levels of relevant mRNA and protein were detected by RT-qPCR and Western blotting, and the expression of mitochondrial membrane potential and ROS was detected using flow cytometry for further assessment of cell cycle arrest and apoptosis., Results: The compound 7 exhibited good antitumor activity among the synthesized derivatives, specifically in DLBCL cell lines. SAR analysis highlighted the critical role of α, β-unsaturated ketones in the antitumor efficacy of these compounds. Mechanistically, compound 7 was found to induce significant DNA damage, trigger an inflammatory response, cause mitochondrial dysfunction, and disrupt cell cycle progression, ultimately leading to apoptosis of DLBCL cells., Conclusion: The compound 7 has good antitumor activity and can induce multiple cellular mechanisms leading to cancer cell death. These findings warrant further investigation of the compound 7 as a potential therapeutic agent for DLBCL., (© 2024. Huazhong University of Science and Technology.)

The morphology is a crucial indicator for diagnosing a low-energy, low-brightness particle beam. However, conventional positron beam diagnosis, based on the pixel scanning principle, is limited by physical constraints, such as the resolution of detector pixels. Here, we have presented a novel slow positron diagnosis method using compressive sampling. With a 100 × 100 pixel-sized mask, for example, the positron beam morphology can be significantly reconstructed with a peak signal-to-noise ratio of ∼40 dB, even at half the sampling rate compared to pixel scanning. It explores a promising approach for positron beam diagnosis with an ultra-high resolution and fast sampling rates., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Objective: To investigate the feasibility of 3.0 T glutamate chemical exchange saturation transfer (GluCEST) imaging in evaluating renal redox metabolism in renal ischemia-reperfusion injury (IRI). Methods: Rabbits in the IRI group ( n =56) underwent surgery by clamping the left renal artery for 45 min and then releasing to establish IRI. Rabbits in the sham group ( n =8) underwent the same operation without clamping the left renal artery. GluCEST MRI was performed before and at 1 h, 12 h, 1 day, 3 days, 7 days, and 14 days after the operations, with eight rabbits in the IRI group sacrificed immediately after each scanning and eight in the sham group sacrificed at 14 days after scanning. The left kidneys were removed for histopathological examination and reactive oxygen species (ROS) fluorescence staining. Differences in the magnetic resonance ratio asymmetry (MTR asym ) of the renal cortex and outer medulla among different groups were compared. Correlations between the MTR asym and ROS were analyzed. Results: The MTR asym of the renal cortex in the sham and IRI subgroups were higher than that of the outer medulla ( t =8.16, P <0.001; t =4.78, P =0.002; t =4.94, P =0.002; t =5.76, P =0.001, t =6.68, P <0.001; t =6.40, P <0.001; t =5.16, P =0.001; t =3.30, P =0.013). The MTR asym of the renal cortex and outer medulla in the IRI-1h, IRI-12h, IRI-1d, IRI-3d, IRI-7d, and IRI-14d groups were lower than in the sham and IRI-pre groups (all P <0.05). The MTR asym of the renal cortex and outer medulla in the IRI-1h group were lower than in the IRI-12h, IRI-1d, IRI-3d, IRI-7d, and IRI-14d groups (all P <0.05). The MTR asym of the renal cortex in the IRI-12h group was lower than in the IRI-7d and IRI-14d groups (1.84%±0.09% vs.2.42%±0.19%, 2.41%±0.31%, all P <0.05). The MTR asym of the renal cortex in the IRI-1d group was lower than in the IRI-7d group (1.99%±0.17% vs. 2.42%±0.19%, P =0.008). The MTR asym of the outer medulla in the IRI-12h group was lower than in the IRI-3d, IRI-7d, and IRI-14d groups (1.32%±0.27% vs. 1.79%±0.31%, 1.98%±0.18%, 1.66%±0.40%, respectively, all P <0.05]. The MTR asym of the outer medulla in the IRI-7d group was higher than in the IRI-1d and IRI-14d groups (1.98%±0.18% vs. 1.52%±0.31%, 1.66%±0.40%, all P <0.05). The MTR asym of the renal cortex and outer medulla had a strong negative correlation with the mean fluorescence intensity of ROS ( ρ =-0.889, P <0.001; ρ =-0.784, P <0.001). Conclusion: 3.0 T GluCEST imaging can indirectly reflect the changes of renal redox metabolism in renal IRI.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants)., (© 2024. The Author(s).)

Objective: To review the studies related to keratoconus in China, investigate research hotspots and development trends in this field, and provide reference for future research. Methods: This is a bibliometrics study. The relevant literature written in Chinese was retrieved from the WanFang DATA and the China National Knowledge Infrastructure, English articles were collected from the Web of Science Core Collection database. Searched for journal articles related to keratoconus VOSviewer software, CiteSpace, and Bibliometrix in the R language were employed to create the knowledge map. The analysis encompassed the distribution of published journals, research collaboration networks of countries/regions, institutions, and authors. Additionally, core authors, high-frequency keyword co-occurrence, keyword topic maps, and keyword emergence time ranking were examined. Results: The study ultimately included 1 100 Chinese articles and 668 English articles. Chinese literature and English literature began to increase in 1997 and 2009, respectively, indicating that the field is currently in a developmental stage. The publications involved 244 Chinese journals and 150 English journals, predominantly in the field of ophthalmology. The United States collaborated the most with China, contributing to 123 articles, followed by other countries such as the United Kingdom and Switzerland. Chinese literature and English literature involved 552 and 883 institutions, respectively. The institution with the highest number of Chinese literature publications was the Eye Institute of Shandong First Medical University (63 papers), while Wenzhou Medical University had the highest number of English literature publications (91 papers). Chinese literature involved 2 435 authors, and English literature involved 2 073 authors. The largest collaboration cluster in Chinese literature was formed by the teams of Xie Lixin and Shi Weiyun, while the Gao Hua team formed the largest cluster in English literature. However, collaboration between authors was primarily limited to within each team. A total of 622 and 1 611 keywords were extracted from Chinese and English literature, respectively. The node centrality of the four Chinese keywords, "keratoconus", "cornea", "corneal transplantation" and "myopia" as well as the three English keywords, "keratoconus", "collagen cross-linking" and "penetrating keratoplasty" was greater than 0.1. "Collagen", "riboflavin", "corneal transplantation" and "ultraviolet A" were identified as common core hotspots and important research topics in Chinese and English literature on keratoconus. Keyword emergence analysis indicated that the keywords with the highest intensity of emergence in Chinese and English literature were "myopia" (13.54) and "penetrating keratoplasty" (9.99), respectively. The longest emergence time was observed for "contact lenses" (1995-2006) and "penetrating keratoplasty" (2003-2014). Conclusions: At present, research on keratoconus in China is on the rise, with research hotspots including pathogenesis, various new surgical methods, and improvement in quality of life. The future research trend mainly focuses on early diagnosis and screening methods, artificial intelligence, biomechanical examination, subclinical keratoconus, and small incision lenticule extraction.

Background: Many neuroscience and neurology studies have forced a reconsideration of the traditional motor-related scope of cerebellar function, which has now expanded to include various cognitive functions. Spinocerebellar ataxia type 3 (SCA3; the most common hereditary ataxia) is neuropathologically characterized by cerebellar atrophy and frequently presents with cognitive impairment., Objective: To characterize cognitive impairment in SCA3 and investigate the cerebellum-cognition associations., Methods: This prospective, cross-sectional cohort study recruited 126 SCA3 patients and 41 healthy control individuals (HCs). Participants underwent a brain 3D T1-weighted images as well as neuropsychological tests. Voxel-based morphometry (VBM) and region of interest (ROI) approaches were performed on the 3D T1-weighted images. CERES was used to automatically segment cerebellums. Patients were grouped into cognitively impaired (CI) and cognitively preserved (CP), and clinical and MRI parameters were compared. Multivariable regression models were fitted to examine associations between cerebellar microstructural alterations and cognitive domain impairments., Results: Compared to HCs, SCA3 patients showed cognitive domain impairments in information processing speed, verbal memory, executive function, and visuospatial perception. Between CI and CP subgroups, the CI subgroup was older and had lower education, as well as higher severity scores. VBM and ROI analyses revealed volume loss in cerebellar bilateral lobule VI, right lobule Crus I, and right lobule IV of the CI subgroup, and all these cerebellar lobules were associated with the above cognitive domain impairments., Conclusions: Our findings demonstrate the multiple cognitive domain impairments in SCA3 patients and indicate the responsible cerebellar lobules for the impaired cognitive domain(s)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Colorectal cancer (CRC) is a major malignancy threatening the health of people in China and screening could be effective for preventing the occurrence and reducing the mortality of CRC. We conducted a multicenter, prospective clinical study which recruited 4,245 high-risk CRC individuals defined as having positive risk-adapted scores or fecal immunochemical test (FIT) results, to evaluate the clinical performance of the multitarget fecal immunochemical and stool DNA (FIT-sDNA) test for CRC screening. Each participant was asked to provide a stool sample prior to bowel preparation, and FIT-sDNA test and FIT were performed independently of colonoscopy. We found that 186 (4.4%) were confirmed to have CRC, and 375 (8.8%) had advanced precancerous neoplasia among the high CRC risk individuals. The sensitivity of detecting CRC for FIT-sDNA test was 91.9% (95% CI, 86.8-95.3), compared with 62.4% (95% CI, 54.9-69.3) for FIT ( P  < 0.001). The sensitivity for detecting advanced precancerous neoplasia was 63.5% (95% CI, 58.3-68.3) for FIT-sDNA test, compared with 30.9% (95% CI, 26.3-35.6) for FIT ( P  < 0.001). Multitarget FIT-sDNA test detected more colorectal advanced neoplasia than FIT. Overall, these findings indicated that in areas with limited colonoscopy resources, FIT-sDNA test could be a promising further risk triaging modality to select patients for colonoscopy in CRC screening., Competing Interests: Xiao‐Tian Yu is the Medical Director, Ning Lv is the Chief Technology Officer, and Yi‐You Chen is the Chief Scientist at Hangzhou New Horizon Health Technology Company. The other authors declare no conflicts of interest., (© 2023 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Purpose: KLHDC7B is a member of Kelch family, with a Kelch domain in the C-terminal half, which plays a role in various cellular events, such as cytoskeletal arrangement, protein degradation, gene expression. Although there is increasing evidence supporting KLHDC7B's vital role in tumorigenesis, a systematic analysis of KLHDC7B in cancers remains lacking. Therefore, we intended to investigate the prognostic value for KLHDC7B across 33 cancer types and explore its potential immunological function., Methods: GEO (Gene Expression Omnibus database) and TCGA (The Cancer Genome Atla) database were used to explore the role of KLHDC7B in 33 cancers. TIMER2, GEPIA2 and Kaplan-Meier plotter were utilized to explore the KLHDC7B expression level and prognostic value in different cancers. The pan cancer genetic variation and DNA methylation of KLHDC7B were analyzed by cBioPortal and MEXPRESS. TIMER2 was employed to investigate the correlation between KLHDC7B expression and immune infiltration. The relationship of KLHDC7B expression with TMB (tumor mutational burden) and MSI (microsatellite instability) were evaluated using Spearman correlation analysis. Finally, by GO and KEGG enrichment analysis, the underlying mechanisms of KLHDC7B in tumor pathophysiology were further investigated., Results: KLHDC7B expression level was related to pathological stages, MSI, TMB, immune checkpoint and immune cell infiltration in most cancers. Especially, we found that the KLHDC7B expression was negatively correlated with the immune infiltration of Myeloid derived suppressor cells into TGCT and GBM. Additionally, survival analysis showed that the expression of KLHDC7B was connected with overall survival (OS) in 3 cancers and disease-free survival (DFS) in 5 cancers. Furthermore, the enrichment analysis revealed that the KLHDC7B collecting genes and binding proteins are related to the function of proteins and immune response., Conclusion: KLHDC7B demonstrates strong clinical utility as markers of prognostic and immune response in pan-cancer., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To observe the clinical efficacy of Bushen Anshen acupuncture (acupuncture for tonifying kidney and calming spirit ) in treating perimenopausal insomnia (PMI) of kidney- yin deficiency., Methods: A total of 72 patients with PMI of kidney- yin deficiency were randomized into an observation group (36 cases, 1 case dropped off) and a control group (36 cases, 1 case dropped off). Acupuncture was applied at Baihui (GV 20) and bilateral Shenshu (BL 23), Taixi (KI 3), Anmian (Extra) in the observation group, while sham acupuncture of shallow needling at non-acupoints was applied in the control group. The treatment was required once every other day, 3 times a week for 10 times in the two groups. Before and after treatment, Pittsburgh sleep quality index (PSQI) was used to evaluate the subjective sleep quality, and polysomnography (PSG) was used to monitor the objective sleep quality in the two groups., Results: After treatment, the scores of sleep quality, sleep latency, sleep duration, sleep efficiency, hypnotic, daytime dysfunction and total score of PSQI were decreased compared with those before treatment in the observation group ( P <0.01), the scores of sleep duration, sleep efficiency and total score of PSQI were decreased compared with those before treatment in the control group ( P <0.05); the scores of sleep quality, sleep latency, sleep efficiency, hypnotic and total score of PSQI in the observation group were lower than those in the control group ( P <0.05). After treatment, the sleep time was prolonged, the sleep efficiency was improved, the sleep latency and the awake time after falling asleep were shortened, the arousal awake index was reduced ( P <0.01) when PSG indexes were monitored, and the percentage of non-rapid eye movement sleep period 1 (N1%) was decreased while the percentage of non-rapid eye movement sleep period 3 (N3%) was increased ( P <0.05) compared with those before treatment in the observation group; there was no statistical difference in the PSG indexes compared with those before treatment in the control group ( P >0.05). After treatment, compared with the control group, the sleep time was prolonged, the sleep efficiency was improved, the sleep latency and the awake time after falling asleep were shortened, the arousal awake index and N1% were decreased in the observation group ( P <0.01)., Conclusion: Bushen Anshen acupuncture can effectively improve the subjective and objective sleep quality in PMI patients of kidney- yin deficiency.

Paenibacillus terrae NK3-4 is a plant growth-promoting rhizobacterium. In this study, the effects of NK3-4 on rice growth and gene transcription were determined. The results indicated that a seed soaking treatment and a pre-germination seed treatment using NK3-4 promoted rice growth, especially spraying rice seedlings with NK3-4 increased the root number and root length by 34.2% and 34.1%, respectively. Moreover, NK3-4 induced the differential transcription of genes annotated with gene ontology (GO) terms; the number of up-regulated genes was 4.38-times higher than the number of down-regulated genes. The NK3-4 treatment induced the differential transcription of genes in 1794 GO functional groups, with 1531 functional groups containing up-regulated genes. Specific growth-related genes up-regulated by NK3-4 are involved in biological processes, including responses to auxin, hormone biosynthesis, cellular component biogenesis, root system development, and other functions. Furthermore, stress resistance-related genes were up-regulated, some of which encode WRKYs, NPK1-related protein kinase, NPR1-like 4, CaM-like proteins, MYBs, ERFs, TIFYs, NACs, EL5s, PR1s, PR2, PR8, PODs, and PAD4. Considered together, these findings imply that NK3-4 may promote plant growth and enhance stress resistance by regulating gene expression, making it a potentially useful microbe for regulating rice growth and stress resistance., Competing Interests: The authors declare that they have no competing interests.

Background: In this study, relationships between clinicopathologic characteristics and progression-free survival (PFS) of patients after thymomectomy were analyzed to provide valuable suggestions regarding the treatment of thymoma., Methods: Data from 187 thymoma patients undergoing surgery at Beijing Tongren Hospital between January 1, 2006, and December 31, 2015, were retrospectively reviewed. We explored the risk factors for PFS among sex, age, thymoma-associated MG, completeness of resection, histologic type and TNM stage, and investigated their interrelationship., Results: Among the 187 patients, 18 patients (9.63%) had tumor recurrence/metastasis, and all of whom had in situ recurrence or pleural metastasis, and most of them (10 of 18 patients) had MG symptoms that reappeared or were aggravated. Fifteen patients (8.02%) died, and myasthenic crisis was a leading cause. Based on Cox regression analysis, only age (HR = 3.16; 95% CI: 1.44-6.91; p = 0.004) and the completeness of resection (HR = 9.03; 95% CI: 2.58-31.55; p = 0.001) were independent risk factors for PFS. Furthermore, we found that the completeness of resection was related to the histologic type (p = 0.009) and TNM stage (p < 0.001) by Fisher's exact test., Conclusions: The results of this cohort study remind us that we should pay attention to the reappearance or aggravation of MG after thymoma resection, because it is the leading cause of death and may indicate tumor progression. Furthermore, completeness of resection was related to the histologic type and TNM stage, but it was the independent risk factors of thymoma. Therefore, R0 resection is critical to the prognosis of thymoma., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

D-chiro-inositol (DCI) is an isomer of inositol, abundant in many foods, such as beans and buckwheat, with insulin-sensitizing, anti-inflammatory, and antioxidant effects. DCI has been used to relieve insulin resistance in diabetes and polycystic ovary syndrome in combination with inositol or D-pinitol. Here, we investigated the effect of DCI on aging and stress resistance in C. elegans. We found that DCI could prolong the lifespan of C. elegans by up to 29.6 %. DCI significantly delayed the onset of neurodegenerative diseases in models of C. elegans. DCI decreased the accumulation of Aβ 1 - 42 , alpha-synuclein, and poly-glutamine, the pathological causes of Alzheimer's, Parkinson's, and Huntington's diseases, respectively. DCI significantly increased the stress resistances against pathogens, oxidants and heat shock. Moreover, D-chiro-inositol reduced the content of ROS and malondialdehyde by increasing the total antioxidant capacity and the activity of superoxide dismutase and catalase. Above effects of DCI requires the transcription factors FOXO/DAF-16 and Nrf-2/SKN-1. DCI also increased the expression of downstream genes regulated by FOXO/DAF-16 and Nrf-2/SKN-1. In conclusion, DCI enhanced the antioxidant capacity and healthy lifespan of C. elegans by activating DAF-16, SKN-1, and HSF-1. Our results showed that DCI could be a promising antiaging agent that is worth further research on the mechanism and health supplemental application of DCI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Zoledronic acid (ZOL) is a potent antiresorptive agent that increases bone mineral density (BMD) and reduces fracture risk in postmenopausal osteoporosis (PMOP). The anti-osteoporotic effect of ZOL is determined by annual BMD measurement. In most cases, bone turnover markers function as early indicators of therapeutic response, but they fail to reflect long-term effects. We used untargeted metabolomics to characterize time-dependent metabolic shifts in response to ZOL and to screen potential therapeutic markers. In addition, bone marrow RNA-seq was performed to support plasma metabolic profiling. Sixty rats were assigned to sham-operated group (SHAM, n = 21) and ovariectomy group (OVX, n = 39) and received sham operation or bilateral ovariectomy, respectively. After modeling and verification, rats in the OVX group were further divided into normal saline group (NS, n = 15) and ZOL group (ZA, n = 18). Three doses of 100 μg/kg ZOL were administrated to the ZA group every 2 weeks to simulate 3-year ZOL therapy in PMOP. An equal volume of saline was administered to the SHAM and NS groups. Plasma samples were collected at five time points for metabolic profiling. At the end of the study, selected rats were euthanatized for bone marrow RNA-seq. A total number of 163 compound were identified as differential metabolites between the ZA and NS groups, including mevalonate, a critical molecule in target pathway of ZOL. In addition, prolyl hydroxyproline (PHP), leucyl hydroxyproline (LHP), 4-vinylphenol sulfate (4-VPS) were identified as differential metabolites throughout the study. Moreover, 4-VPS negatively correlated with increased vertebral BMD after ZOL administration as time-series analysis revealed. Bone marrow RNA-seq showed that the PI3K-AKT signaling pathway was significantly associated with ZOL-mediated changes in expression (adjusted-p = 0.018). In conclusion, mevalonate, PHP, LHP, and 4-VPS are candidate therapeutic markers of ZOL. The pharmacological effect of ZOL likely occurs through inhibition of the PI3K-AKT signaling pathway., 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 Li, Wang, Ren, Wei, Hu, Gu, Zhang, Yu and Wang.)

Objective: To observe the clinical effect of acupuncture for delayed sleep-wake phase disorder (DSWPD)., Methods: A total of 84 patients with DSWPD were randomized into an observation group (42 cases, 2 cases dropped off) and a control group (42 cases, 3 cases dropped off). On the basis of sleep hygiene education, acupuncture was applied at Shenmai (BL 62), Zhaohai (KI 6), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, while placebo acupuncture was applied at the same acupoints in the control group. The treatment lasted for 8 weeks, once every other day, 3 times a week in the 1st to 4th weeks; once every 3 days, 2 times a week in the 5th to 8th weeks. Before and after treatment, the actigraphy (ACT) indexes of objective sleep (total time of stay in bed, total sleep time, sleep efficiency, the number of awakenings and the wake time after falling asleep) and plasma cortisol (CORT) level were observed; before and after treatment and in follow-up of 1, 3 months after treatment, the scores of morningness-eveningness questionnaire (MEQ), insomnia severity index (ISI), fatigue severity scale (FSS) and Epworth sleepiness scale (ESS) were observed in the two groups., Results: Compared before treatment, the total sleep time was prolonged, the sleep efficiency was improved, the number of awakenings was reduced, and the wake time after falling asleep was shortened after treatment in the observation group ( P <0.01, P <0.05), and those in the observation group after treatment were superior to the control group ( P <0.01, P <0.05). Compared before treatment, the MEQ scores after treatment in both groups and in the follow-up of 1, 3 months after treatment in the observation group were increased ( P <0.01), and the MEQ score of each time point after treatment in the observation group was higher than the control group ( P <0.01). The scores of ISI, FSS and ESS after treatment, and the scores of ISI、ESS in follow-up of 1, 3 months after treatment in the observation group were decreased compared with those before treatment ( P <0.01, P <0.05), and in the observation group, the scores of ISI, FSS and ESS of each time point after treatment were lower than those in the control group ( P <0.01, P <0.05). After treatment, the plasma CORT level in the observation group was decreased compared with that before treatment and that in the control group ( P <0.01, P <0.05)., Conclusion: Acupuncture can improve the sleep and wake phase of patients with DSWPD, improve sleep quality and daytime function, and its mechanism may be related to the down-regulation of plasma CORT level.

The family of Papilionidae (Lepidoptera: Papilionoidea) is a group of butterflies with high ecological and conservation value. The Hengduan Mountains (HMDs) in Southwest China is an important diversity centre for these butterflies. However, the spatial distribution pattern and the climate vulnerability of Papilionidae butterflies in the HDMs remain unknown to date. The lack of such knowledge has already become an obstacle in formulating effective butterfly conservation strategies. The present research compiled a 59-species dataset with 1938 occurrence points. The Maxent model was applied to analyse the spatial pattern of species richness in subfamilies Parnassiinae and Papilioninae, as well as to predict the response under the influence of climate change. The spatial pattern of both subfamilies in the HDMs has obvious elevation prevalence, with Parnassiinae concentrated in the subalpine to alpine areas (2500-5500 m) in western Sichuan, northwestern Yunnan and eastern Tibet, while Papilioninae is concentrated in the low- to medium-elevation areas (1500-3500 m) in the river valleys of western Yunnan and western Sichuan. Under the influence of climate change, both subfamilies would exhibit northward and upward range shifts. The majority of Parnassiinae species would experience drastic habitat contraction, resulting in lower species richness across the HDMs. In contrast, most Papilioninae species would experience habitat expansion, and the species richness would also increase significantly. The findings of this research should provide new insights and a clue for butterfly diversity and climatic vulnerability in southwestern China. Future conservation efforts should be focused on species with habitat contraction, narrow-ranged distribution and endemicity with both in situ and ex situ measures, especially in protected areas. Commercialised collecting targeting these species must also be regulated by future legislation.

Objectives: To explore the difference in CT values between pulmonary thromboembolism and postmortem clot in postmortem CT pulmonary angiography (CTPA) to further improve the application value of virtual autopsy., Methods: Postmortem CTPA data with the definite cause of death from 2016 to 2019 were collected and divided into pulmonary thromboembolism group ( n =4), postmortem clot group ( n =5), and control group ( n =5). CT values of pulmonary trunk and left and right pulmonary artery contents in each group were measured and analyzed statistically., Results: The average CT value in the pulmonary thromboembolism group and postmortem clot group were (168.4±53.8) Hu and (282.7±78.0) Hu, respectively, which were lower than those of the control group (1 193.0±82.9) Hu ( P <0.05). The average CT value of the postmortem clot group was higher than that of the pulmonary thromboembolism group ( P <0.05)., Conclusions: CT value is reliable and feasible as a relatively objective quantitative index to distinguish pulmonary thromboembolism and postmortem clot in postmortem CTPA. At the same time, it can provide a scientific basis to a certain extent for ruling out pulmonary thromboembolism deaths.

Background: Coronavirus disease 2019 (COVID-19) has progressively impacted our daily lives, resulting in unexpected physical and mental stress on medical staff. This study is designed to investigate the levels of and risk factors for burnout, depression, anxiety, and insomnia among medical staff during the COVID-19 epidemic breakout in Shanghai, China., Methods: This cross-sectional survey was conducted from May 1 to May 31, 2022, among medical staff who were on the frontline during the epidemic breakout in Shanghai from different institutions. The MBI-HSS was used to assess burnout, PHQ-9, GAD-7 and ISI were used to evaluate mental status and insomnia., Results: A total of 543 valid questionnaires were collected. The depersonalization, depression, anxiety, and insomnia scores of medical staff were significantly higher during the pandemic in Shanghai compared with norms, while lack of personal achievement scores were decreased. Working time, work unit, work environment and age are important influencers of burnout, depression and anxiety of medical staff. Long working hours are the most likely causes of burnout and emotional disorders. Medical staff in primary hospitals were most likely to suffer from burnout and emotional disorders, while medical staff in tertiary hospitals had a reduced sense of personal achievement. Young medical staff are prone to negative emotions such as depression and anxiety, while older medical staff have a lower sense of personal accomplishment. Medical staff who were not in the shelter hospitals or designated hospitals were more likely to have problems of emotional exhaustion, depersonalization and anxiety than those who were in the shelter hospitals or designated hospitals. Contracting COVID-19 had no effect on medical staff. Emotional exhaustion and depersonalization were positively correlated with anxiety, depression, and sleep disorders while personal achievement was negatively correlated with these factors., Conclusion: Medical staff in Shanghai had high burnout, depression, anxiety and insomnia levels during the epidemic outbreak in Shanghai. During the COVID-19, medical staff may suffer different psychological problems which should be concerned. Care and supports about burnout, mental health and insomnia need to be taken to promote the mental health of medical staff according to different characteristics of medical staff., Competing Interests: The authors declare that the research was performed in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2023 Tang, Yu, Wu, Zhao, Liang, Gao, Jiang, Chen and Yang.)

Hypertrophic scar is an abnormal fibrous proliferative disease that occurs after deep cutaneous injury, which not only affects aesthetics and function but also has negative psychological effects on the patients. However, the mechanism of hypertrophic scar formation has not been fully elucidated, and its clinical treatment is complex with a high rate of recurrence and no radicle cure. Intervention based on molecular targets will likely be the future direction for the prevention and treatment of hypertrophic scar. In this article, we review the specific roles and mechanisms of drug-targeted interventions in hypertrophic scar formation, including general drugs, cytokines, immunomodulators, herbal extracts, exosomes, and nanomaterials, in the context of advances in both basic and clinical research at home and abroad.

Gastrointestinal diseases are complex diseases that occur in the gastrointestinal tract. Common gastrointestinal diseases include chronic gastritis, peptic ulcers, inflammatory bowel disease, and gastrointestinal tumors. These diseases may manifest a long course, difficult treatment, and repeated attacks. Gastroscopy and mucosal biopsy are the gold standard methods for diagnosing gastric and duodenal diseases, but they are invasive procedures and carry risks due to the necessity of sedation and anesthesia. Recently, several new approaches have been developed, including serological examination and magnetically controlled capsule endoscopy (MGCE). However, serological markers lack lesion information, while MGCE images lack molecular information. This study proposes combining these two technologies in a collaborative noninvasive diagnostic scheme as an alternative to the standard procedures. We introduce an interpretable framework for the clinical diagnosis of gastrointestinal diseases. Based on collected blood samples and MGCE records of patients with gastrointestinal diseases and comparisons with normal individuals, we selected serum metabolite signatures by bioinformatic analysis, captured image embedding signatures by convolutional neural networks, and inferred the location-specific associations between these signatures. Our study successfully identified five key metabolite signatures with functional relevance to gastrointestinal disease. The combined signatures achieved discrimination AUC of 0.88. Meanwhile, the image embedding signatures showed different levels of validation and testing accuracy ranging from 0.7 to 0.9 according to different locations in the gastrointestinal tract as explained by their specific associations with metabolite signatures. Overall, our work provides a new collaborative noninvasive identification pipeline and candidate metabolite biomarkers for image auxiliary diagnosis. This method should be valuable for the noninvasive detection and interpretation of gastrointestinal and other complex diseases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.)

Introduction: Epigenetic-targeted therapy has been increasingly applied in the treatment of cancers. Lysine (K)-specific demethylase 6B (KDM6B) is an epigenetic enzyme involved in the coordinated control between cellular intrinsic regulators and the tissue microenvironment whereas the pan-cancer analysis of KDM6B remains unavailable. Methods: The dual role of KDM6B in 33 cancers was investigated based on the GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) databases. TIMER2 and GEPIA2 were applied to investigate the KDM6B levels in different subtypes or stages of tumors. Besides, the Human Protein Atlas database allowed us to conduct a pan-cancer study of the KDM6B protein levels. GEPIA2 and Kaplan-Meier plotter were used for the prognosis analysis in different cancers. Characterization of genetic modifications of the KDM6B gene was analyzed by the cBioPortal. DNA methylation levels of different KDM6B probes in different TCGA tumors were analyzed by MEXPRESS. TIMER2 was applied to determine the association of the KDM6B expression and immune infiltration and DNA methyltransferases. Spearman correlation analysis was used to assess the association of the KDM6B expression with TMB (tumor mutation burden) and MSI (microsatellite instability). The KEGG (Kyoto encyclopedia of genes and genomes) pathway analysis and GO (Gene ontology) enrichment analysis were used to further investigate the potential mechanism of KDM6B in tumor pathophysiology. Results: KDM6B was downregulated in 11 cancer types and upregulated across five types. In KIRC (kidney renal clear cell carcinoma) and OV (ovarian serous cystadenocarcinoma), the KDM6B level was significantly associated with the pathological stage. A high level of KDM6B was related to poor OS (overall survival) outcomes for THCA (thyroid carcinoma), while a low level was correlated with poor OS and DFS (disease-free survival) prognosis of KIRC. The KDM6B expression level was associated with TMB, MSI, and immune cell infiltration, particularly cancer-associated fibroblasts, across various cancer types with different correlations. Furthermore, the enrichment analysis revealed the relationship between H3K4 and H3K27 methylation and KDM6B function. Conclusion: Dysregulation of the DNA methyltransferase activity and methylation levels of H3K4 and H3K27 may involve in the dual role of KDM6B in tumorigenesis and development. Our study offered a relatively comprehensive understanding of KDM6B's dual role in cancer development and response to immunotherapy., 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 Ding, Yu, He, Chen and Guo.)

Background: Heat stroke is the outcome of excessive heat stress, which results in core temperatures exceeding 40°C accompanied by a series of complications. The brain is particularly vulnerable to damage from heat stress. In our previous studies, both activated microglia and increased neuronal autophagy were found in the cortices of mice with heat stroke. However, whether activated microglia can accelerate neuronal autophagy under heat stress conditions is still unknown. In this study, we aimed to investigate the underlying mechanism that caused neuronal autophagy upregulation in heat stroke from the perspective of exosome-mediated intercellular communication., Methods: In this study, BV2 and N2a cells were used instead of microglia and neurons, respectively. Exosomes were extracted from BV2 culture supernatants by ultracentrifugation and then characterized via transmission electron microscopy, nanoparticle tracking analysis and Western blotting. N2a cells pretreated with/without miR-155 inhibitor were cocultured with microglial exosomes that were treated with/without heat stress or miR-155 overexpression and subsequently subjected to heat stress treatment. Autophagy in N2a cells was assessed by detecting autophagosomes and autophagy-related proteins through transmission electron microscopy, immunofluorescence, and Western blotting. The expression of miR-155 in BV2 and BV2 exosomes and N2a cells was measured using real-time reverse transcription polymerase chain reaction. Target binding analysis was verified via a dual-luciferase reporter assay., Results: N2a autophagy moderately increased in response to heat stress and accelerated by BV2 cells through transferring exosomes to neurons. Furthermore, we found that neuronal autophagy was positively correlated with the content of miR-155 in microglial exosomes. Inhibition of miR-155 partly abolished autophagy in N2a cells, which was increased by coculture with miR-155-upregulated exosomes. Mechanistic analysis confirmed that Rheb is a functional target of miR-155 and that microglial exosomal miR-155 accelerated heat stress-induced neuronal autophagy mainly by regulating the Rheb-mTOR signaling pathway., Conclusion: Increased miR-155 in microglial exosomes after heat stroke can induce neuronal autophagy via their transfer into neurons. miR-155 exerted these effects by targeting Rheb, thus inhibiting the activity of mTOR signaling. Therefore, miR-155 could be a promising target for interventions of neuronal autophagy after heat stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Luo, Luo, He, Shen, Yu, Wang, Tan, Liu and Yang.)

Objectives: To study the correlation between CT imaging features of acceleration and deceleration brain injury and injury degree., Methods: A total of 299 cases with acceleration and deceleration brain injury were collected and divided into acceleration brain injury group and deceleration brain injury group according to the injury mechanism. Subarachnoid hemorrhage (SAH) and Glasgow coma scale (GCS), combined with skull fracture, epidural hematoma (EDH), subdural hematoma (SDH) and brain contusion on the same and opposite sides of the stress point were selected as the screening indexes. χ 2 test was used for primary screening, and binary logistic regression analysis was used for secondary screening. The indexes with the strongest correlation in acceleration and deceleration injury mechanism were selected., Results: χ 2 test showed that skull fracture and EDH on the same side of the stress point; EDH, SDH and brain contusion on the opposite of the stress point; SAH, GCS were correlated with acceleration and deceleration injury ( P <0.05). According to binary logistic regression analysis, the odds ratio (OR) of EDH on the same side of the stress point was 2.697, the OR of brain contusion on the opposite of the stress point was 0.043 and the OR of GCS was 0.238, suggesting there was statistically significant ( P <0.05)., Conclusions: EDH on the same side of the stress point, brain contusion on the opposite of the stress point and GCS can be used as key indicators to distinguish acceleration and deceleration injury mechanism. In addition, skull fracture on the same side of the stress point, EDH and SDH on the opposite of the stress point and SAH were relatively weak indicators in distinguishing acceleration and deceleration injury mechanism.

Objectives: To apply the convolutional neural network (CNN) Inception&#95;v3 model in automatic identification of acceleration and deceleration injury based on CT images of brain, and to explore the application prospect of deep learning technology in forensic brain injury mechanism inference., Methods: CT images from 190 cases with acceleration and deceleration brain injury were selected as the experimental group, and CT images from 130 normal brain cases were used as the control group. The above-mentioned 320 imaging data were divided into training validation dataset and testing dataset according to random sampling method. The model classification performance was evaluated by the accuracy rate, precision rate, recall rate, F 1-value and AUC value., Results: In the training process and validation process, the accuracy rate of the model to classify acceleration injury, deceleration injury and normal brain was 99.00% and 87.21%, which met the requirements. The optimized model was used to test the data of the testing dataset, the result showed that the accuracy rate of the model in the test set was 87.18%, and the precision rate, recall rate, F 1-score and AUC of the model to recognize acceleration injury were 84.38%, 90.00%, 87.10% and 0.98, respectively, to recognize deceleration injury were 86.67%, 72.22%, 78.79% and 0.92, respectively, to recognize normal brain were 88.57%, 89.86%, 89.21% and 0.93, respectively., Conclusions: Inception&#95;v3 model has potential application value in distinguishing acceleration and deceleration injury based on brain CT images, and is expected to become an auxiliary tool to infer the mechanism of head injury.

The increasing cancer morbidity and mortality requires the development of high-efficiency and low-toxicity anticancer approaches. In recent years, photodynamic therapy (PDT) has attracted much attention in cancer therapy due to its non-invasive features and low side effects. Photosensitizer (PS) is one of the key factors of PDT, and its successful delivery largely determines the outcome of PDT. Although a few PS molecules have been approved for clinical use, PDT is still limited by the low stability and poor tumor targeting capacity of PSs. Various nanomaterial systems have shown great potentials in improving PDT, such as metal nanoparticles, graphene-based nanomaterials, liposomes, ROS-sensitive nanocarriers and supramolecular nanomaterials. The small molecular PSs can be loaded in functional nanomaterials to enhance the PS stability and tumor targeted delivery, and some functionalized nanomaterials themselves can be directly used as PSs. Herein, we aim to provide a comprehensive understanding of PDT, and summarize the recent progress of nanomaterials-based PSs and delivery systems in anticancer PDT. In addition, the concerns of nanomaterials-based PDT including low tumor targeting capacity, limited light penetration, hypoxia and nonspecific protein corona formation are discussed. The possible solutions to these concerns are also discussed., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: To explore the research hotspots and development trends of the field of forensic drowning from 1991 to 2020 by bibliometrics methods., Methods: Based on Web of Science, CNKI database, Wanfang Data knowledge service platform, python 3.9.2, CiteSpace 5.8.R3, Gephi 0.9.2, etc. were used to analyze the publishing trends, countries/regions, institutions, authors and topics of the study on drowning., Results: A total of 631 English literature were obtained, including 59 articles from Chinese authors, and 386 Chinese literature were obtained. The Chinese and English journals with the largest number of related literatures were Chinese Journal of Forensic Science (80 articles) and Forensic Science International (106 articles), respectively. Japan published the most articles in English, and China ranked third. Osaka City Univ (Japan, 28 articles) published the most English articles, and Guangzhou Forens Sci Inst (China, 22 articles) ranked second. Among Chinese literature, Guangzhou Forens Sci Inst (32 articles) published the most. The topic analysis of Chinese and English literature showed that diatom examination, virtual autopsy, postmortem biochemical examination, the nature of death, and postmortem submersion interval were the hot spots of current research, but English literature had more studies on new technologies and methods, while Chinese literature was more inclined to practice, application and experience summary., Conclusions: The number of literature in forensic medicine on drowning is relatively stable. The scope of international and domestic collaborations in this field is still limited. The automated examination of diatoms, the establishment of diatom DNA barcodes and virtual autopsy will be the most important research hotspots in the coming period and are expected to achieve breakthroughs in drowning diagnosis, drowning location inference, postmortem submersion interval estimation, etc.

Diabetic foot ulcer (DFU), one of the most serious complications of diabetes mellitus, is associated with a high amputation rate and decreased life quality. The impact of blood serum proteins on the occurrence and development of DFU has attracted a lot of interest. In this study, we aimed to define and compare the serum proteome of patients with DFU and healthy control (HC) to provide new insights into DFU pathogenesis. DFU patients and age- and sex-matched HCs were enrolled in this study (n = 54). We screened alterations in blood serum proteins from DFU patients and HC using a tandem mass tag (TMT) method based on liquid chromatography-mass spectrometry (LC-MS/MS) quantitative proteomics, and the differentially expressed proteins (DEPs) were further validated by parallel reaction monitoring (PRM) and enzyme-linked immunosorbent assay (ELISA). A total of 173 DEPs (100 up-regulated and 73 down-regulated) were identified between the DFU and HC groups ( P < 0.05). Proteomic and bioinformatics analyses indicated that the proteins in the DFU group were mainly related to extracellular matrix (ECM)-receptor interaction and complement and coagulation cascades. The up-regulated DEPs were further verified by PRM and ELISA. LRG1, CD5L, CRP, IGHA1, and LBP were proved upregulated in DFU and these proteins are mainly related to immune response and complement activation. Our findings help to provide a more comprehensive understanding of the pathogenesis of DFU and new insight into potential therapeutic targets.

Aim: To evaluate the macular microvasculature before and after surgery for idiopathic macular hole (MH) and the association of preoperative vascular parameters with postoperative recovery of visual acuity and configuration., Methods: Twenty eyes from 20 patients with idiopathic MH were enrolled. Optical coherence tomography angiography (OCTA) images were obtained before, 2wk, 1, and 3mo after vitrectomy with internal limiting membrane peeling. Preoperative foveal avascular zone (FAZ) area and perimeter and regional vessel density (VD) in both layers were compared according to the 3-month best-corrected visual acuity (BCVA)., Results: The BCVA improved from 0.98±0.59 (logMAR, Snellen 20/200) preoperatively to 0.30±0.25 (Snellen 20/40) at 3mo postoperatively. The preoperative deep VD was smaller and the FAZ perimeter was larger in the 3-month BCVA<20/32 group (all P <0.05). A significant reduction was observed in FAZ parameters and all VDs 2wk postoperatively. Except for deep perifoveal VD, all VDs recovered only to their preoperative values. The postoperative FAZ parameters were lower during follow-up. Decreases in preoperative deep VDs were correlated with worse postoperative BCVA (Pearson's r =-0.667 and -0.619, respectively). A larger FAZ perimeter (Spearman's r =-0.524) and a lower deep perifoveal VD preoperatively (Pearson's r =0.486) were associated with lower healing stage., Conclusion: The status of the deep vasculature may be an indicator of visual acuity in patients with a closed MH. Except for the deep perifoveal region, VD recovers only to preoperative levels., (International Journal of Ophthalmology Press.)

Chinese wild rice (Zizania latifolia; family: Gramineae) is a valuable medicinal homologous grain in East and Southeast Asia. Here, using Nanopore sequencing and Hi-C scaffolding, we generated a 547.38 Mb chromosome-level genome assembly comprising 332 contigs and 164 scaffolds (contig N50 = 4.48 Mb; scaffold N50 = 32.79 Mb). The genome harbors 38,852 genes, with 52.89% of the genome comprising repetitive sequences. Phylogenetic analyses revealed close relation of Z. latifolia to Leersia perrieri and Oryza species, with a divergence time of 19.7-31.0 million years. Collinearity and transcriptome analyses revealed candidate genes related to seed shattering, providing basic information on abscission layer formation and degradation in Z. latifolia. Moreover, two genomic blocks in the Z. latifolia genome showed good synteny with the rice phytocassane biosynthetic gene cluster. The updated genome will support future studies on the genetic improvement of Chinese wild rice and comparative analyses between Z. latifolia and other plants., (© 2022. The Author(s).)

Background: Our study investigated a special series of thymoma with autoimmune hepatitis and myocarditis and tried to reveal the gene expression profiles of this series of thymoma., Methods: From 2011 to 2019, a total of 13 special thymoma patients presented with autoimmune hepatitis and myocarditis, accounting for about 1.26% of thymoma patients undergoing surgery in Beijing TongRen Hospital. Clinical data were retrospectively collected. All samples were harvested during surgical procedures, and analyzed to identify changes in gene expression using the CapitalBio mRNA microarray analysis, the Whole exome sequencing analysis (WES), qPCR and immunohistochemistry (IHC) tools., Results: After surgery, patient symptoms were relieved gradually. Levels of lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate transaminase (AST), and alanine amiotransferase (ALT) increased to some extent within 1 to 3 months after surgery, and fluctuated, and then, gradually decreased close to normal within 6 months after surgery. Enrichment analysis of Kyoto Genome and Genome Encyclopedia (KEGG) pathway was performed and enrichment results were visualized. It indicated that gene expression of 5 signaling pathways, including cell cycle and p53 signaling pathway, were generally abnormal. P53 expression was up-regulated in all tumor tissues. However, IHC and qPCR analysis showed that there was no significant difference in p21 expression between normal and tumor tissue. Results of WES showed that only one driver gene- MDM4 amplified 4 fold in 53.2% thymoma cells. Further qPCR and IHC analysis confirmed the up-regulation of the expression of p53 and mdm4 in 13 thymoma patients with autoimmune hepatitis and myocarditis., Conclusion: Our study reveals the clinical and genetic characteristics of thymoma patients with autoimmune hepatitis and myocarditis. For this special category of thymoma, the up-regulation of p53 and mdm4 plays an important role in the occurrence of thymoma and autoimmune hepatitis/myocarditis., 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 Yu, Yu, Du, Yu, Yang and Jiang.)

Microglial CX3C chemokine receptor 1 (CX3CR1) has been implicated in numerous cellular mechanisms, including signalling pathways that regulate brain homoeostasis and adult hippocampal neurogenesis. Specific environmental conditions can impair hippocampal neurogenesis-related cognition, learning and memory. However, the role of CX3CR1 in the neurogenic alterations resulting from the cross-tolerance protection conferred by heat acclimation (HA) against the effects of electromagnetic field (EMF) exposure is less well understood. Here, we investigated the role of microglial CX3CR1 signalling in adult hippocampal neurogenesis induced by HA in EMF-exposed mice. We found that EMF exposure significantly decreased the number of proliferating and differentiating cells in the dentate gyrus (DG) of the hippocampus, resulting in a reduced neurogenesis rate. Moreover, alterations in the phenotypes of activated microglia and decreased expression levels of CX3CR1, but not sirtuin 1 (SIRT1), were observed in the brains of EMF-exposed mice. Remarkably, HA treatment improved microglial phenotypes, restored the expression of CX3CR1, and ameliorated the decrease in the adult hippocampal neurogenesis rate following EMF exposure. Moreover, pharmacological inhibition of CX3CR1 and SIRT1 failed to restore CX3CR1 expression and ameliorate hippocampal neurogenesis impairment following HA plus EMF stimulation. These results indicate that microglial CX3CR1 is involved in the cross-tolerance protective effect of HA on adult hippocampal neurogenesis upon EMF exposure., (Copyright © 2021. Published by Elsevier Inc.)

The lateral entorhinal cortex (LEC) is an essential component of the brain circuitry supporting long-term memory by serving as an interface between the hippocampus and neocortex. Dysfunction of the LEC affects sensory coding in the hippocampus, leading to a view that the LEC provides the hippocampus with highly processed sensory information. It remains unclear, however, how the LEC modulates neural processing in the neocortical regions. To address this point, we pharmacologically inactivated the LEC of male rats during a temporal associative learning task and examined its impact on local network activity in one of the LEC's efferent targets, the prelimbic region of the medial prefrontal cortex (mPFC). Rats were exposed to two neutral stimuli, one of which was paired with an aversive eyelid shock over a short temporal delay. The LEC inhibition reduced the expression of anticipatory blinking responses to the reinforced stimuli without increasing responses to nonreinforced stimuli. In control rats, both the reinforced and nonreinforced stimuli evoked a short-lived, wide-band increase in the prelimbic network activity. With learning, the initial increase of gamma-band activity started to extend into the interval between the reinforced neutral stimulus and the eyelid shock. LEC inhibition attenuated the learning-induced sustained activity, without affecting the initial transient activity. These results suggest that the integrity of LEC is necessary for the formation of temporal stimulus associations and its neural correlates in the mPFC. Given the minimal effects on the innate network responses to sensory stimuli, the LEC appears not to be the main source of sensory inputs to the mPFC; rather it may provide a framework that shapes the mPFC network response to behaviorally relevant cues., (© 2021 Wiley Periodicals LLC.)

Objective: To construct a preoperative evaluation system for partial nephrectomy using CT three-dimensional visualization technology and to explore its practical value., Methods: The clinical data of the patients who underwent partial nephrectomy for renal tumors in Department of Urology, Peking University First Hospital were collected retrospectively. At the same time, the homogenized standard data of patients who underwent partial nephrectomy for renal tumors were collected in 16 clinical centers in China. The CT three-dimensional visualization system was applied (IPS system, Yorktal) to evaluate tumor anatomy, blood supply, perirenal fat and other information. The parameters were summarized to build a three-dimensional nephrometry system, on the basis of which virtual surgery design and intraoperative navigation were completed., Results: A three-dimensional visualization image was established based on the enhanced CT urography. The nephrometry system included the longest diameter and volume of the tumor, proportion volume of tumor invading the parenchyma, maximum depth of the tumor invading the parenchyma, contact surface area, flatness of the tumor surface, renal segment where the tumor was located, vascular variation, and perirenal fat. The average two-dimensional diameter of the tumor was (2.78±1.43) cm, the average three-dimensional maximum diameter was (3.09±1.35) cm, and the average postoperative pathological size was (3.01±1.38) cm. The maximum tumor diameter in the three-dimensional image was significantly related to the prolonged renal artery clamping time and intra-operative blood loss ( r =0.502, P =0.020; r =0.403, P =0.046). The three-dimensional and pathological tumor volume were (25.7±48.4) cm 3 and (33.0±36.4) cm 3 , respectively ( P =0.229). The tumor volume was significantly related to the intraoperative blood loss ( r =0.660, P < 0.001). The proportion volume of the tumor invading into renal parenchyma was significantly related to the prolongation of renal artery clamping and the occurrence of postoperative complications ( r =0.410, P =0.041; r =0.587, P =0.005). The tumor contact surface area and the presence of vascular variation did not show correlation with the perioperative data and postoperative complications. While the preoperative evaluation was completed, the reconstructed three-dimensional image could be zoomed, rotated, combined display, color adjustment, transparency, and simulated cutting on the Touch Viewer system. The process generally consisted of showing or hiding the tissue, adjusting the transparency of the interested area, rotating and zooming the image to match the position of the surgical patient. Together, these functions met the requirements of preoperative virtual surgery plan and intraoperative auxiliary navigation., Conclusion: Three-dimensional images can provide a more intuitive anatomical structure. The CT three-dimensional visua-lization system clearly displays tumor anatomical parameters, blood supply and perirenal fat. The three-dimensional nephrometry system for renal tumors can help predict the difficulty of partial nephrectomy and perioperative complications. Importing the reconstructed three-dimensional visualization image into the specified program or robot operating system can complete virtual surgery and intraoperative navigation, helping the surgeon to better grasp the surgical process. The indexes included in the nephrometry system and the score weights of each index need to be confirmed and perfected by multi-center study with large samples.

Introduction: Although skin grafts are widely used in reconstruction of large skin defect and complex wounds, many factors lead to suboptimal graft take. Negative-pressure wound therapy (NPWT) reportedly increases the graft take rates when added to skin grafting, but a summary analysis of the data of randomized controlled trials has yet to be performed. We conducted this systematic review and meta-analysis of randomized controlled trials to compare the effectiveness and safety of NPWT and non-NPWT for patients with skin grafts., Methods: We searched PubMed, Embase, Cochrane Library, and CNKI for relevant trials based on predetermined eligibility criteria from database establishment to February 2020. Two reviewers screened citations and extracted data independently. The quality of the included studies was evaluated according to the Cochrane Handbook, whereas statistical heterogeneity was assessed using chi-square tests and I2 statistics. Review Manager 5.3 was used for statistical analysis., Results: Ten randomized controlled trials with 488 patients who underwent NPWT or non-NPWT were included. Compared with non-NPWT, NPWT yielded an improved the percentage of graft take, a reduction in days from grafting to discharge, with lower relative risk of re-operation, and no increased relative risk of adverse event. Further, the subgroup analysis showed an improved the percentage of graft take in negative pressure of 80 mmHg, and no improved the percentage of graft take in negative pressure of 125 mmHg., Conclusion: NPWT is more effective than non-NPWT for the integration of skin grafts, and the negative pressure of 80 mmHg can be recommended. Data on adverse events and negative pressure are, however, limited. A better understanding of complications after NPWT and the ideal negative pressure for the integration of skin grafts is imperative., (Copyright © 2021 Elsevier Ltd and ISBI. All rights reserved.)

Fluorophore-antibody conjugates with high photobleaching resistance, high chemical stability, and Fc-specific attachment is a great advantage for immunofluorescence imaging. Here, an Fc-binding protein (Z-domain) carrying a photo-cross-linker (p-benzoylphenylalanine, Bpa) fused with enhanced green fluorescent protein (EGFP), namely photoactivatable Z Bpa -EGFP recombinant, was directly generated using the aminoacyl-tRNA synthetase/suppressor tRNA technique without any further modification. By employing the photoactivatable Z Bpa -EGFP, an optimal approach was successfully developed which enabled EGFP to site-selectively and covalently attach to native antibody (IgG) with approximately 90% conjugation efficiency. After characterizing the Fc-specific and covalent manner of the EGFP-photoconjugated antibody, its excellent photobleaching resistance for immunofluorescence imaging was demonstrated in a model study by monitoring the toll-like receptor 4 (TLR4) expression in HepG2 cells. The proposed approach here for the preparation of a novel fluorescent antibody is available and reliable, which would play an important role in fluorescence immunoassay, and is expected to be extended to the generation of other biomolecule-photoconjugated antibodies, such as other fluorescent proteins for multiplex immunofluorescence imaging or reporter enzymes for highly sensitive enzyme immunoassays.Graphical abstract.

Objectives: Alzheimer's disease (AD) is a hidden neurological degenerative disease, which main clinical manifestations are cognitive dysfunction, memory impairment and mental disorders. Neuroinflammation is considered as a basic response of the central nervous system. NLRP3 (Nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain containing receptor 3) inflammasome is closely related to the occurrence of neuroinflammation. Activation of the NLRP3 inflammasome results in the release of cytokines, pore formation and ultimately pyroptosis, which has demonstrated one of the critical roles in AD pathogenesis. Inhibition of the activity of NLRP3 is one of the focuses of the research. Therefore, NLRP3 represents an attractive pharmacological target, and discovery compounds with good NLRP3 inhibitory activity are particularly important., Key Findings: Quinones have good neuroprotective effects and prevent AD, which may be related to their regulation of inflammatory response. The molecular docking was used to explore 12 quinones with AD prevention and treatment and NLRP3. Docking results showed that the combination of anthraquinones and NLRP3 were the best, and the top two chemical compounds were Purpurin and Rhein, which are the most promising NLRP3 inhibitors., Summary: These quinones may provide the theoretical basis for finding lead compounds for novel neuroprotective agents., (© 2020 Royal Pharmaceutical Society.)

Background: Although keloids and hypertrophic scars are common benign hyperproliferative growths of dermal fibroblasts, the clinical problems including physical and psychological problems are significant and impairing, with few proven treatments. Intralesional triamcinolone acetonide (TAC) and combination of TAC with 5-fluorouracil (5-FU) are widely used to treat keloids and hypertrophic scars, but their efficacy and safety remain controversial., Methods: We systematically searched MEDLINE, EMBASE, Cochrane Library, and CNKI for relevant trials., Results: The mean scar height and the erythema score in the TAC + 5-FU group were lower than those in the TAC group after treatment (P < 0.05). The effectiveness based on observer assessment after treatment in the TAC + 5-FU group was superior than that in the TAC group (P < 0.05); further, the subgroup analysis showed the TAC + 5-FU group was also superior than the TAC group in the treatment of hypertrophic scars (P = 0.01), and there were no significant differences in the treatment of keloid (P = 0.12). The effectiveness based on patient self-assessment after treatment in the TAC + 5-FU group was also superior than the TAC group (P < 0.05). The overall complication rate in the TAC + 5-FU group was lower than the TAC group (P < 0.05)., Conclusions: Combination of TAC with 5-FU is more effective and safer than TAC alone therapy in the treatment of keloids and hypertrophic scars. Data on keloids alone or hypertrophic scars alone are, however, limited. A better understanding of effective after intralesional combination of TAC with 5-FU in the treatment of keloids alone or hypertrophic scars alone is imperative., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Visible-light-driven photocatalysts have shown tremendous prospects in solving the energy crisis and environmental problems, thanks to their wide spectral response and high quantum efficiency. Several strategies including the expansion of visible light response and the improvement of solar energy utilization and photocatalytic quantum efficiency via more effective separation of photogenerated carriers are the current focuses of research that direct the design and fabrication of viable photocatalysts. Herein, a series of composite photocatalysts assembled from plasmonic Cu nanoparticles (NPs) and Zn3In2S6 (ZIS) solid solutions were synthesized by means of a simple solvothermal method. In comparison with the pristine ZIS semiconductor, Cu NP loaded ZIS solid solutions showed greatly enhanced photocatalytic activity, selectivity and stability towards CO2 reduction under visible irradiation. Of note was that the optimized ZIS-Cu2 exhibited an enhanced CH4 production rate of ca. 292 μL g-1 h-1 and a selectivity of ca. 71.1%, which were among the highest numbers reported hitherto. The localized surface plasmon resonance (LSPR) effect, shown by surface Cu NPs, was believed to play a critical role in the enhanced CO2 photoreduction efficiency. More importantly, the introduction of plasmonic Cu NPs could restrain the recombination of photogenerated electron-hole pairs and promote the migration of photogenerated electrons to better participate in the photocatalytic CO2 reduction in the presence of water vapor. This work thus provides a facile means to design robust and flexible composite photocatalysts for visible-light-driven CO2 photoreduction with high efficiency.

A one-dimensional Cd0.6Zn0.4S nanorod (CZS NR) solid solution with rich sulfur vacancies achieved an excellent photocatalytic hydrogen production activity of 59.3 mmol h-1 g-1 under visible irradiation, which is the highest number observed for CdZnS solid solution nanomaterials to date.

The development of non-invasive, inexpensive, and effective early diagnosis tests for gastric and small-bowel lesions is an urgent requirement. The introduction of magnetically guided capsule endoscopy (MGCE) has aided examination of the small bowel for diagnoses. However, the distribution of the fecal microbiome in abnormal erosions of the stomach and small bowel remains unclear. Herein, alternations in the fecal microbiome in three groups [normal, small-bowel inflammation, and chronic gastritis (CG)] were analyzed by metagenomics and our well-developed method [individual-specific edge-network analysis (iENA)]. In addition to the dominant microbiota identified by the conventional differential analysis, iENA could recognize novel network biomarkers of microbiome communities, such as the genus Bacteroide in CG and small-bowel inflammation. Combined with differential network analysis, the network-hub microbiota within rewired microbiota networks revealed high-ranked iENA microbiota markers, which were disease specific and had particular pathogenic functions. Our findings illuminate the components of the fecal microbiome and the importance of specific bacteria in CG and small-bowel erosions, and could be employed to develop preventive and non-invasive therapeutic strategies., (Copyright © 2020 Chen, Fan, Zhang, Qin, Shen, Yu, Zhang and Zhu.)

Introduction: Insomnia with short sleep duration has a more serious negative impact on patient health. The existing literature suggests that medication therapy is more effective for this phenotype of insomnia compared with cognitive-behavioural therapy. However, the potential side effects of hypnotic medications hinder their clinical application. Acupuncture has been widely used in the treatment of insomnia, but it remains unclear whether it has therapeutic efficacy for insomnia with short sleep duration. The purpose of this trial is to evaluate the efficacy and safety of acupuncture for insomnia with short sleep duration., Methods and Analysis: This study is designed as a randomised, single-centre, single-blinded, placebo acupuncture controlled trial involving 152 participants. Eligible patients will be divided into two groups according to the objective total sleep time: insomnia with normal sleep duration group and insomnia with short sleep duration group. Then, patients in each group will be randomly assigned to two subgroups, the treatment group (acupuncture) and the control group (placebo acupuncture), in a 1:1 ratio with 38 subjects in each subgroup. The primary outcome is the Pittsburgh Sleep Quality Index and the Insomnia Severity Index. Secondary outcomes are actigraphy, the Beck Anxiety Inventory, the Beck Depression Inventory and the Fatigue Severity Scale. All adverse effects will be assessed by the Treatment Emergent Symptom Scale. Outcomes will be evaluated at baseline, post treatment, as well as at 1-week and 1-month follow-up., Ethics and Dissemination: This protocol has been approved by the ethics committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine (no. 2019-17). Written informed consent will be obtained from all participants. The results will be disseminated through peer-reviewed journals for publications., Trial Registration Number: ChiCTR1900023473; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The incidence of breast cancer across the world has been on the rise in recent decades. Because identified risk factors can only explain a relatively small portion of the cases, environmental exposure to organic pollutants is suspected to play a role in breast cancer etiology. Polychlorinated biphenyls (PCBs) are among the most abundant pollutants, and the impact of their exposure on breast cancer risk has been extensively studied in recent decades. However, the results of most epidemiologic studies do not support an association between PCB exposure and breast cancer risk. We hypothesized that the effects of PCBs on breast cancer might have been undervalued for reasons such as insufficient recognition of the confounding effects of several factors and lack of attention on the innate heterogeneity of PCB mixtures or breast cancer. After reviewing the evidence in the existing literature, we concluded that early life exposure, known risk factors of breast cancer, and impact of exposure to other pollutants are the main sources of confounding effects and have potentially masked the associations between PCBs and breast cancer. Because PCBs are mixtures of congeners with varied properties, and because breast cancers of different subtypes are etiologically distinct diseases, the absence of stratified subgroup analysis on individual PCBs and patients with specific biological subtypes and insufficient attention paid to the results of these subgroup analyses may result in an underestimation of the correlations between PCBs and breast cancer. In future studies, these factors must be taken into consideration when exploring the effect of PCB exposure on breast cancer risk., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: To determine the association between dementia and age-related macular degeneration (AMD) using meta-analysis., Methods: We searched in the MEDLINE, EMBASE, Web of Knowledge, PsycInfo and Cochrane database of systematic reviews for studies published from March 1959 to March 2018. We included cross-sectional, case-control and cohort studies that evaluated the association of dementia/Alzheimer's disease (AD) with AMD (as outcome) and the association of AMD with dementia/AD (as outcome). Studies that compared cognitive functions between AMD and controls were also included. The summary outcomes, namely odds ratio (OR), relative risk, mean differences and corresponding 95% CIs, were estimated using random effects models. We performed sensitivity analysis based on study quality and individual study effect to control for potential biases., Results: Among 2159 citation records, we identified 21 studies consisting of 7 876 499 study subjects for meta-analysis. Patients with dementia (p adjusted ≤0.017, OR≥1.24, I 2 ≤9%) or AD (p=0.001, OR unadjusted =2.22, I 2 =50%) were at risk for AMD, particularly for late AMD (p adjusted <0.001, OR=1.37, I 2 =0). AMD was also significantly associated with increased risk of AD/cognitive impairment (p adjusted =0.037, OR=2.42, I 2 =38%). Moreover, patients with AMD had poorer cognitive functions when compared with controls, including Mini-Mental State Examination (p<0.001, I 2 ≤79%) and Trail Making Test A (p<0.001, I 2 =0). Sensitivity analysis and Egger's test indicated our results were less likely biased., Conclusions: A significant association between dementia/AD and AMD calls for greater clinical awareness. The cost-effectiveness of routine screening for the other condition in patients with primary diagnosis of dementia/AD or AMD requires further study., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To observe changes in foveal avascular zone(FAZ) and capillary plexus in idiopathic macular epiretinal membrane (IMEM) in optical coherence tomography angiography (OCTA) and analyze their correlation with the visual acuity. Methods: Cross-sectional study. 42 patients (15 Males and 27 females, age 64.8) from the Eye Hospital of Wenzhou Medical University were included with 51 eyes diagnosed as IMEM (IMEM group), and 23 normal eyes (9 Males and 14 females, control group). All patients received the examination of fissure lamp combined with fundus pre-set lens, best corrected visual acuity (BCVA), OCT angiography (OCTA) and fundus photo. OCTA was performed on 3 mm× 3 mm sections centred on the fovea. The software automatically measured the superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density(VD) and retinal thickness(RT) and FAZ area. The IMEM eyes were compared with the normal eyes and correlation between the parameters of OCTA and BCVA was analyzed in IMEM. Independent-sample t test and MannWhitney test were used for comparison between groups, and Spearman test was used for correlation analysis. Results: LogMAR BCVA in the IMEM group was 0.40(0.15, 0.70), in the control group was 0.10(0.05, 0.22). FAZ area of IMEM group was (0.09±0.05) mm(2), while that of control group was (0.34±0.13)mm(2).Compared with the control group, in IMEM group, the BCVA was worse ( Z= -4.443, P< 0.001), FAZ area was smaller ( t= -9.198, P< 0.001), RT was increased ( P< 0.001), The foveal DCP and SCP vessel density was increased ( t= 4.280, 9.079, P< 0.01), The parafoveal DCP vessel density was decreased ( P< 0.05), The parafoveal SCP vessel density was decreased in superior, inferior and nasal side ( t= -2.759, Z= -3.998, Z= -2.108; P< 0.05). The BCVA was negatively correlated with FAZ area ( r= -0.337, P= 0.017), positively correlated with center macular thickness ( r= 0.324, P= 0.020). The BCVA was no correlated with foveal VD and parafoveal DCP vessel density ( P> 0.05), but correlated with SCP vessel density( P< 0.05). Conclusions: In the IMEM eyes the BCVA was worse, FAZ area was smaller, foveal vessel density was increased and the parafoveal vessel density was decreased compared with the normal eyes. The smaller the FAZ area, the smaller foveal SCP vessel density, the poorer BCVA. There was no correlation between BCVA and DCP vessel density. Changes in VD in IMEM eyes may lead to changes in vision. (Chin J Ophthalmol, 2019, 55:757-762) .

A potential strategy for patients with estrogen receptor (ER)-positive breast cancer is necessary to replace neoadjuvant chemotherapy which has limited benefit. Neoadjuvant endocrine therapy (NAE) has been indicated to be a favorable alternate approach to downstage large or locally advanced breast cancer in ER-positive, human epidermal growth factor receptor 2 (HER2)-negative (ER+/HER2-) patients, especially postmenopausal women. Previous studies have demonstrated the efficacy of various endocrine agents in NAE. Aromatase inhibitors (AIs) have proven superiority over tamoxifen as a suitable choice to optimize treatment efficacy. Fulvestrant was recently reported as an effective agent, similar to AIs. Furthermore, the addition of targeted agents exerts synergistic antiproliferative effects with endocrine agents and rapidly improves response rates in both endocrine sensitive and resistant tumors. The neoadjuvant platform provides a unique opportunity to define the appropriate strategy and address the mechanisms of endocrine resistance. In addition, the predictive value of biomarkers and genomic assays in NAE is under investigation to evaluate individual effects and validate biomarker-based strategies. In this review, we discuss the most relevant evidence on the potential of NAE for ER+ breast cancer. The current understanding also offers new insights into the identification of the optimal settings and valuable predictive tools of NAE to guide clinical treatment decisions and achieve beneficial therapeutic effects.