Investigating the therapeutic effects and mechanisms of Carthamus tinctorius L.-derived nanovesicles in atherosclerosis treatment.

BACKGROUND: Carthamus tinctorius L., a traditional herbal medicine used for atherosclerosis (AS), lacks a clear understanding of its therapeutic mechanisms. This study aimed to investigate the therapeutic effects and mechanisms of Carthamus tinctorius L.-derived nanovesicles (CDNVs) in AS treatment. METHODS: CDNVs were isolated and characterized using improved isolation methods. Transmission electron microscopy, nanoparticle tracking analysis, and protein analysis confirmed their morphology, size, and protein composition. Small RNA sequencing was performed to identify the miRNA profile of CDNVs, and bioinformatics analysis was used to determine their potential biological roles. In vivo biodistribution and toxicity studies were conducted in mice to assess the stability and safety of orally administered CDNVs. The anti-atherosclerotic effects of CDNVs were evaluated in ApoE-/- mice through plaque burden analysis. The protective effects of CDNVs on ox-LDL-treated endothelial cells were assessed through proliferation, apoptosis, reactive oxygen species activation, and monocyte adhesion assays. miRNA and mRNA sequencing of CDNV-treated endothelial cells were performed to explore their regulatory effects and potential target genes. RESULTS: CDNVs were successfully isolated and purified from Carthamus tinctorius L. tissue lysates. They exhibited a saucer-shaped or cup-shaped morphology, with an average particle size of 142.6 ± 0.7 nm, and expressed EV markers CD63 and TSG101. CDNVs contained proteins, small RNAs, and metabolites, including the therapeutic compound HSYA. Small RNA sequencing identified 95 miRNAs, with 10 common miRNAs accounting for 72.63% of the total miRNAs. These miRNAs targeted genes involved in cell adhesion, apoptosis, and cell proliferation, suggesting their relevance in cardiovascular disease. Orally administered CDNVs were stable in the gastrointestinal tract, absorbed into the bloodstream, and accumulated in the liver, lungs, heart, and aorta. They significantly reduced the burden of atherosclerotic plaques in ApoE-/- mice and exhibited superior effects compared to HSYA. In vitro studies demonstrated that CDNVs were taken up by HUVECs, promoted proliferation, attenuated ox-LDL-induced apoptosis and ROS activation, and reduced monocyte adhesion. CDNV treatment resulted in significant changes in miRNA and mRNA expression profiles of HUVECs, with enrichment in inflammation-related genes. CXCL12 was identified as a potential direct target of miR166a-3p. CONCLUSION: CDNVs isolated from Carthamus tinctorius L. tissue lysates represent a promising oral therapeutic option for cardiovascular diseases. The delivery of miRNAs by CDNVs regulates inflammation-related genes, including CXCL12, in HUVECs, suggesting their potential role in modulating endothelial inflammation. These findings provide valuable insights into the therapeutic potential of CDNVs and their miRNAs in cardiovascular disease.

Qing Hua Chang Yin ameliorates chronic colitis in mice by inhibiting PERK-ATF4-CHOP pathway of ER stress and the NF-κB signalling pathway.

CONTEXT: Ulcerative colitis has been clinically treated with Qing Hua Chang Yin (QHCY), a traditional Chinese medicine formula. However, its precise mechanisms in mitigating chronic colitis are largely uncharted. OBJECTIVE: To elucidate the therapeutic efficiency of QHCY on chronic colitis and explore its underlying molecular mechanisms. MATERIALS AND METHODS: A total ion chromatogram fingerprint of QHCY was analysed. Chronic colitis was induced in male C57BL/6 mice using 2% dextran sodium sulphate (DSS) over 49 days. Mice were divided into control, DSS, DSS + QHCY (0.8, 1.6 and 3.2 g/kg/d dose, respectively) and DSS + mesalazine (0.2 g/kg/d) groups (n = 6). Mice were intragastrically administered QHCY or mesalazine for 49 days. The changes of disease activity index (DAI), colon length, colon histomorphology and serum pro-inflammatory factors in mice were observed. RNA sequencing was utilized to identify the differentially expressed transcripts (DETs) in colonic tissues and the associated signalling pathways. The expression of endoplasmic reticulum (ER) stress-related protein and NF-κB signalling pathway-related proteins in colonic tissues was detected by immunohistochemistry staining. RESULTS: Forty-seven compounds were identified in QHCY. Compared with the DSS group, QHCY significantly improved symptoms of chronic colitis like DAI increase, weight loss, colon shortening and histological damage. It notably reduced serum levels of IL-6, IL-1ß and TNF-α. QHCY suppressed the activation of PERK-ATF4-CHOP pathway of ER stress and NF-κB signalling pathways in colonic tissues. DISCUSSION AND CONCLUSIONS: The findings in this study provide novel insights into the potential of QHCY in treating chronic colitis patients.

[Effect of combined application of organic and chemical fertilizers on yield and quality of Epimedium pubescens].

To investigate the effects of different ratios of organic and chemical fertilizers on the yield and quality of Epimedium pubescens,so as to provide a scientific basis for the fertilization of high-yield and high-quality E. pubescens cultivation. In this experiment,a field plot test was conducted,and CK(without fertilizer) was set as the control group,with five treatment groups with different ratios of organic fertilizers and chemical fertilizers set up,namely OF0(100% chemical fertilizers),OF25(25% organic fertilizers),OF50(50% organic fertilizers),OF75(75% organic fertilizers),and OF100(100% organic fertilizers). The effects of different fertilization patterns on the agronomic traits,yield,effective component content,nutrient accumulation,and soil physicochemical properties of E. pubescens were determined,and the yield and quality of the medicinal herb were comprehensively evaluated by using the CRITIC weights method. It was found that the herb yield of each treatment group was significantly increased compared with the CK group,although the yield of the groups with both organic fertilizer and chemical fertilizer was slightly lower than that of OF0. However,there was no significant difference,which indicated that the organic fertilizer combined with chemical fertilizer could ensure the herb yield. With the increase in organic fertilizer ratios,the medicinal components epimedin A,epimedin B,and epimedin C showed a tendency of first increasing and then decreasing,with the highest content in the OF25,while icariin showed a rising trend,with the best in the OF100. However,overall,the total flavonol glycosides ABCI accumulated the most in the OF25. The results of the CRITIC method showed that the top three fertilization treatments in terms of the comprehensive scores of the medicinal herb were OF25,OF50,and OF75. Organic fertilizer combined with chemical fertilizer is conducive to improving the soil's fertilizer holding and supply capacity,and the soil indexes are optimal in OF100. The soil enzyme activity is the highest in OF75. Meanwhile,organic fertilizer combined with chemical fertilizer can help the plant's uptake and accumulation of nutrients,and OF25 shows the most obvious effect.By comprehensively considering the influence of different ratios of organic and chemical fertilizers on the yield,effective component content,nutrient accumulation,and other indexes of E. pubescens,it is recommended that a 25% ratio(7 500 kg·hm~(-2)) of organic fertilizers and chemical fertilizers should be used in E. pubescens production in the first year,so as to promote the E. pubescens industry to increase yield and improve quality.

[Research progress on the mechanism of the impact of maternal childhood trauma on intergenerational transmission]. / æ¯äº²ç«¥å¹´æœŸåˆ›ä¼¤å¯¹ä»£é™ ä¼ é€’å½±å“æœºåˆ¶çš„ç ”ç©¶è¿›å±•.

Childhood trauma refers to trauma experiences encountered during childhood and adolescence. Maternal childhood trauma experiences have a lasting impact on the next generation, affecting their physical and mental well-being. The mechanisms involved include the hypothalamic-pituitary-adrenal axis, inflammatory factors, brain structure and function, gene interactions, and parenting styles. This paper systematically reviews the mechanisms of the impact of maternal childhood trauma on intergenerational transmission, providing insights for the prevention of intergenerational transmission of childhood trauma.

Metastatic clear cell sarcoma of the pancreas: From diagnosis to treatment.

This article presents a comprehensive case report on an uncommon instance of metastatic clear cell sarcoma (CCS) originating from the pancreas. The high mortality rate of pancreatic carcinoma underscores the importance of precise diagnosis and early detection. The authors report a novel case of CCS with pancreatic metastasis, detailing successful surgical intervention through distal pancreatectomy and splenectomy, resulting in favourable outcomes. This study highlights the standard role of surgery in treating advanced CCS and emphasizes preoperative imaging and thorough patient history assessment. This article also underscores the necessity for long-term surveillance due to the potential for recurrence or metastasis. Despite the favourable recovery postsurgery, the absence of subsequent follow-up evaluation prompts consideration of the need for extended monitoring. This article raises questions about the nature of the pancreatic lesion and suggests the possibility of a primary lesion. Further evidence is crucial to establish the correlation between the features related to the development of the patient's primary and metastatic tumours. In conclusion, this study offers valuable insights into metastatic CCS of the pancreas, highlighting the importance of regular postoperative follow-up for improved outcomes through early detection and intervention.

A new species of Amolops (Amphibia, Anura, Ranidae) from Guizhou Province, China.

The Torrent frogs of the genus Amolops are widely distributed in Nepal and northern India eastwards to southern China and southwards to Malaysia. The genus currently contains 84 species. Previous studies indicated underestimated species diversity in the genus. In the context, a new species occurring from the mountains in the northwestern Guizhou Province, China is found and described based on morphological comparisons and molecular phylogenetic analyses, Amolopsdafangensissp. nov. Phylogenetic analyses based on DNA sequences of the mitochondrial 16S rRNA and COI genes supported the new species as an independent lineage. The uncorrected genetic distances between the 16S rRNA and COI genes in the new species and its closest congener were 0.7% and 2.6%, respectively, which are higher than or at the same level as those among many pairs of congeners. Morphologically, the new species can be distinguished from its congeners by a combination of the following characters: body size moderate (SVL 43.2-46.8 mm in males); head length larger than head width slightly; tympanum distinct, oval; vocal sacs absent; vomerine teeth present; dorsolateral folds weak formed by series of glands; nuptial pads present on the base of finger I; heels overlapping when thighs are positioned at right angles to the body; tibiotarsal articulation reaching the level far beyond the tip of the snout when leg stretched forward.

Intra-Articular Delivery of an AAV-Anti-TNF-α Vector Alleviates the Progress of Arthritis in a RA Mouse Model.

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease marked by joint destruction and functional impairment. Tumor necrosis factor (TNF) plays a critical role in RA pathogenesis. Although TNF-targeting drugs are clinically effective, their need for frequent and long-term administration often results in poor patient adherence and suboptimal outcomes. This study developed a gene therapy approach using engineered adeno-associated virus (AAV) vectors to deliver an anti-TNF agent directly into the joint cavity of RA animal models. Animals receiving this therapy demonstrated sustained improvement in clinical scores, inflammatory markers, and joint tissue health. Immunofluorescence staining revealed that AAV vectors could transduce various cell types, including T cells, type A synoviocytes, and dendritic cells. Our results indicate that a single administration of this gene therapy provided long-term efficacy. This suggests that AAV-mediated anti-TNF gene therapy can offer prolonged relief from clinical symptoms and reduce inflammatory damage in a mouse model of RA. This innovative approach presents a promising new therapy with significant clinical prospects to treat patients with RA.

Predicting the Potential Distribution of Hypericum perforatum under Climate Change Scenarios Using a Maximum Entropy Model.

H. perforatum, as one of the Traditional Chinese Medicinal materials, possesses a variety of pharmacological activities and high medicinal value. However, in recent years, the wild resources of H. perforatum have been severely depleted due to global climate change and human activities, and artificial cultivation faces problems such as unstable yield and active ingredient content. This poses a serious obstacle to the development and utilization of its resources. Therefore, this experiment took H. perforatum as the research object and used 894 distribution records of H. perforatum and 36 climatic environmental factors, using the MaxEnt model and GIS technology to explore the main climatic factors affecting the distribution of H. perforatum. Additionally, by utilizing the principles of ecological niche theory, the potential suitable distribution regions of H. perforatum across past, present, and future timelines were predicted, which can ascertain the dynamics of its spatial distribution patterns and the trend of centroid migration. The results indicate that the main environmental factors affecting the geographical distribution of H. perforatum are solar radiation in April (Srad4), solar radiation in September (Srad9), mean temperature of driest quarter (Bio9), solar radiation in November (Srad11), annual mean temperature (Bio1), and annual precipitation (Bio12). Under future climate scenarios, there is a remarkable trend of expansion in the suitable distribution areas of H. perforatum. The centroid migration indicates a trend of migration towards the northwest direction and high-altitude areas. These results can provide a scientific basis for formulating conservation and sustainable use management strategies for H. perforatum resources.

T2-weighted imaging-based radiomic-clinical machine learning model for predicting the differentiation of colorectal adenocarcinoma.

BACKGROUND: The study on predicting the differentiation grade of colorectal cancer (CRC) based on magnetic resonance imaging (MRI) has not been reported yet. Developing a non-invasive model to predict the differentiation grade of CRC is of great value. AIM: To develop and validate machine learning-based models for predicting the differentiation grade of CRC based on T2-weighted images (T2WI). METHODS: We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023. Patients were randomly assigned to a training cohort (n = 220) or a validation cohort (n = 95) at a 7:3 ratio. Lesions were delineated layer by layer on high-resolution T2WI. Least absolute shrinkage and selection operator regression was applied to screen for radiomic features. Radiomics and clinical models were constructed using the multilayer perceptron (MLP) algorithm. These radiomic features and clinically relevant variables (selected based on a significance level of P < 0.05 in the training set) were used to construct radiomics-clinical models. The performance of the three models (clinical, radiomic, and radiomic-clinical model) were evaluated using the area under the curve (AUC), calibration curve and decision curve analysis (DCA). RESULTS: After feature selection, eight radiomic features were retained from the initial 1781 features to construct the radiomic model. Eight different classifiers, including logistic regression, support vector machine, k-nearest neighbours, random forest, extreme trees, extreme gradient boosting, light gradient boosting machine, and MLP, were used to construct the model, with MLP demonstrating the best diagnostic performance. The AUC of the radiomic-clinical model was 0.862 (95%CI: 0.796-0.927) in the training cohort and 0.761 (95%CI: 0.635-0.887) in the validation cohort. The AUC for the radiomic model was 0.796 (95%CI: 0.723-0.869) in the training cohort and 0.735 (95%CI: 0.604-0.866) in the validation cohort. The clinical model achieved an AUC of 0.751 (95%CI: 0.661-0.842) in the training cohort and 0.676 (95%CI: 0.525-0.827) in the validation cohort. All three models demonstrated good accuracy. In the training cohort, the AUC of the radiomic-clinical model was significantly greater than that of the clinical model (P = 0.005) and the radiomic model (P = 0.016). DCA confirmed the clinical practicality of incorporating radiomic features into the diagnostic process. CONCLUSION: In this study, we successfully developed and validated a T2WI-based machine learning model as an auxiliary tool for the preoperative differentiation between well/moderately and poorly differentiated CRC. This novel approach may assist clinicians in personalizing treatment strategies for patients and improving treatment efficacy.

Effects of Liqi Tongbian decoction on gut microbiota, SCFAs production, and 5-HT pathway in STC rats with Qi Stagnation Pattern.

Slow transit constipation (STC) is a common and debilitating condition characterized by delayed colonic transit and difficulty in fecal expulsion, significantly impacting patients' physical and mental wellbeing as well as their overall quality of life. This study investigates the therapeutic potential of Liqi Tongbian Decoction (LTD) in the treatment of STC, especially in cases involving the context of Qi stagnation, through a multifaceted approach involving the modulation of intestinal flora and short-chain fatty acids (SCFAs). We employed a rat model of STC with Qi Stagnation Pattern, established using the "loperamide + tail-clamping provocation method," to explore the effects of LTD on fecal characteristics, intestinal motility, and colonic pathology. Importantly, LTD exhibited the ability to increase the richness, diversity, and homogeneity of intestinal flora while also modulating the composition of microorganisms. It significantly increased the production of SCFAs, especially butyric acid. Moreover, LTD exerted a substantial influence on the synthesis of serotonin (5-HT) by modulating the expression of tryptophan hydroxylase (TPH) and interacting with the 5-HT4 receptor (5-HT4R), resulting in enhanced colonic motility. Correlation analyses revealed a positive correlation between certain bacterial genera, such as Lachnospiraceae_NK4A136 spp. and Clostridiales spp. and the concentrations of butyric acid and 5-HT. These results suggest a mechanistic link between microbiome composition, SCFAs production, and 5-HT synthesis. These findings highlight the potential of LTD to alleviate STC by facilitating a beneficial interplay among intestinal flora, SCFAs production, and 5-HT-mediated colonic motility, providing novel insights into the management of STC with Qi Stagnation Pattern.

C1q/Tumor Necrosis Factor-Related Protein-9 Is a Novel Vasculoprotective Cytokine That Restores High Glucose-Suppressed Endothelial Progenitor Cell Functions by Activating the Endothelial Nitric Oxide Synthase.

BACKGROUND: This study investigated whether gCTRP9 (globular C1q/tumor necrosis factor-related protein-9) could restore high-glucose (HG)-suppressed endothelial progenitor cell (EPC) functions by activating the endothelial nitric oxide synthase (eNOS). METHODS AND RESULTS: EPCs were treated with HG (25 mmol/L) and gCTRP9. Migration, adhesion, and tube formation assays were performed. Adiponectin receptor 1, adiponectin receptor 2, and N-cadherin expression and AMP-activated protein kinase, protein kinase B, and eNOS phosphorylation were measured by Western blotting. eNOS activity was determined using nitrite production measurement. In vivo reendothelialization and EPC homing assays were performed using Evans blue and immunofluorescence in mice. Treatment with gCTRP9 at physiological levels enhanced migration, adhesion, and tube formation of EPCs. gCTRP9 upregulated the phosphorylation of AMP-activated protein kinase, protein kinase B, and eNOS and increased nitrite production in a concentration-dependent manner. Exposure of EPCs to HG-attenuated EPC functions induced cellular senescence and decreased eNOS activity and nitric oxide synthesis; the effects of HG were reversed by gCTRP9. Protein kinase B knockdown inhibited eNOS phosphorylation but did not affect gCTRP9-induced AMP-activated protein kinase phosphorylation. HG impaired N-cadherin expression, but treatment with gCTRP9 restored N-cadherin expression after HG stimulation. gCTRP9 restored HG-impaired EPC functions through both adiponectin receptor 1 and N-cadherin-mediated AMP-activated protein kinase /protein kinase B/eNOS signaling. Nude mice that received EPCs treated with gCTRP9 under HG medium showed a significant enhancement of the reendothelialization capacity compared with those with EPCs incubated under HG conditions. CONCLUSIONS: CTRP9 promotes EPC migration, adhesion, and tube formation and restores these functions under HG conditions through eNOS-mediated signaling mechanisms. Therefore, CTRP9 modulation could eventually be used for vascular healing after injury.

An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species.

Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.

Synthesis of micro-crosslinked adamantane-containing matrix resins designed for deep-UV lithography resists and their application in nanoimprint lithography.

A certain type of photoresist used for deep-UV lithography (DUVL) can also be used for other types of photolithography. Thus, to meet the requirements of two or more lithography technologies simultaneously, it is necessary to design a variety of corresponding functional groups in the molecules of materials and obtain the required properties. Herein, we designed four matrix resins based on acrylate for DUVL, employing alkyl sulfide, adamantane, methyladamantane, and hydroxyl as dangling groups and a microcrosslinking network by adding a small amount of crosslinker. These polymers were used in the thermal nanoimprint lithography (NIL) process, and distinct patterns with a resolution of 100 nm were observed. The acrylate copolymers designed for DUVL in this work can be used as thermal NIL resists and to obtain good patterns. It was found that ethylene dimethacrylate (EDMA) and adamantane endowed the matrix resins with good thermal stability and that PMMHM demonstrated the best patterning performance among the four resins. These polymers can be applied in the manufacturing of high-density integrated circuits, nano-transistors, optoelectronic devices and other components in the future.

The identification of a PTEN-associated gene signature for the prediction of prognosis and planning of therapeutic strategy in endometrial cancer.

Background: Endometrial cancer (EC) is one of the most common malignancies among women. To improve the prognosis and treatment of EC, finding out a phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-associated prognostic signature would be beneficial. Methods: EC clinical data, genetic mutation data, and transcriptome data were downloaded from The Cancer Genome Atlas (TCGA) database. To clarify the specific PTEN-associated signature, cox regression analyses were performed. The clinical value of the selected signature on the overall survival (OS) and the secretoglobin family 2A member 1 (SCGB2A1)-independent analysis, immune and functional analysis were investigated respectively. Results: Five hundred and fourteen EC samples were screened and PTEN mutation occupied 57%. Enrichment analysis indicated that mutant-type PTEN was enriched for pathways related to the upregulated human T-cell leukemia virus-1 (HTLV-1) infection and estrogen signaling pathway. SCGB2A1 was identified by cox regression analysis. Immune analysis exhibited significant immune infiltration with higher expression of T cells, B cells, and macrophage groups. Immune-checkpoint transcripts CD274 molecule (CD274), and cytotoxic T-lymphocyte associated protein 4 (CTLA4), hepatitis A virus cellular receptor 2 (HAVCR2), lymphocyte activation gene 3 (LAG3), programmed cell death 1 (PDCD1), PDCD1 ligand 2 (PDCD1LG2), T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), and sialic acid binding immunoglobulin like lectin 15 (SIGLEC15) were discovered statistically different. In addition, the low-SCGB2A1 group had worse OS than the high-SCGB2A1 group. SCGB2A1 showed significant area under the curve (AUC) values in a time-dependent receiver operating characteristic (ROC) analysis. Prevalence of microsatellite instability (MSI) was detected and SCGB2A1 showed a negative correlation with EC. Immune checkpoint blockade (ICB) response indicated a worse immune response in the low-SCGB2A1 group. The distribution of one-class linear regression (OCLR) scores reflected the negative correlation between messenger RNA expression-based stemness index (mRNAsi) and prognostic gene expression. Furthermore, several SCGB2A1-related signaling pathways in EC were identified. Conclusions: SCGB2A1 is a prognostic immunometabolic signature for patients with EC, which may help improve the prognosis and therapeutic effect.

Retinal photoreceptor cell damage caused by diabetes through down-regulation of glutathione peroxidase 4 and its mechanism / 中华实验眼科杂志

Objective:To investigate the changes of glutathione peroxidase 4 (GPX4) in retinal photoreceptor cells, and the related mechanism correlated with retinal photoreceptor cell damage.Methods:The posterior segment tissues of 8 age-matched male donors were collected from the Body (Organ) Donation Register and Corneal Receiving Station of Tongji Hospital of Wuhan Red Cross from 2018 to 2021, including 4 non-diabetic donors and 4 diabetic donors.The tissues were divided into diabetes group and control group according to their donors.A total of 14 healthy SPF 8-week-old male C57BL/6 mice were selected and randomly divided into diabetes group and control group by the random number method, with 7 mice in each group.The mice in diabetes group were intraperitoneally injected with streptozotocin at a dose of 50 mg/kg for 5 days, and no intervention was given to mice in control group.Mouse photoreceptor cells 661W were divided into advanced glycation end products (AGEs) group and control group.AGEs group was treated with 100 μg/ml AGEs for 24 hours to simulate diabetic injury, and no intervention was given to control group.The outer segment morphology of retinal photoreceptors in human and mouse retinas was observed by hematoxylin-eosin staining.The expressions of glial fibrillary acidic protein (GFAP), rhodopsin and GPX4 in human and mouse retinas were detected by immunofluorescence staining.The expressions of GFAP, rhodopsin and GPX4 in mouse retina and the expression of GPX4 in 661W cells were determined by Western blot.The activity of 661W cells was detected by cell counting kit-8 (CCK8) method.The concentration of malondialdehyde (MDA) in mouse retina and cells was detected by TBA method.The activity of superoxide dismutase (SOD) in mouse retina and cells was detected by hydroxylamine assay.The use of human tissues was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology (No.TJ-C20230301). The animal experiments were conducted with reference to the Standards Guide for the Care and Use of Laboratory Animals of the National Institutes of Health, and the study protocol was approved by the Experimental Animal Ethics Committee of Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology (No.TJH-2016001).Results:Hematoxylin-eosin staining showed that retinal photoreceptor outer segments were deformed or broken in diabetic donors and diabetic mice compared with control groups.GFAP fluorescent signal mainly appeared in the inner retina of human and mice, and the stained cells were spindle or polygonal, which was consistent with the shape of glial cells.The retinal GFAP fluorescent signal of diabetic tissue and mouse groups was stronger than that of respective control groups.Rhodopsin was only expressed in the outer segment layer of photoreceptors with clear boundaries, and GPX4 was expressed in the whole retina with strong signal in the outer segment layer of photoreceptors.The fluorescent signals of rhodopsin and GPX4 in diabetic tissue and mouse groups were weaker than those in respective control groups.The relative expressions of GFAP were significantly higher and the relative expressions of rhodopsin and GPX4 were significantly lower in diabetic tissue and mouse groups than in respective control groups (all at P<0.05). The cell viability of AGEs group was significantly lower than that of control group ( t=13.490, P<0.001). The relative expression of GPX4 protein in AGEs group was 0.42±0.12, which was significantly lower than 1.00±0.04 in control group ( t=9.041, P<0.001). MDA concentration was higher and SOD activity was lower in retinal tissue of diabetic mice and AGEs group than those in respective control groups, and the differences were statistically significant (all at P<0.05). Conclusions:Diabetes can reduce the GPX4 level in retinal photoreceptor cells and cause the imbalance of oxidation-antioxidant system, which may be the mechanism of the damage to retinal photoreceptor cells caused by diabetes.

Research advances on the role of epigenetic modifications in the long-term progression of alcoholic liver disease / 药学学报

There are more than 60 million alcoholic liver disease (ALD) patients in China, which has become a public health problem that cannot be ignored. Moreover, the social problem of "alcohol culture" is still hardly to solve, so that safe and effective prevention and treatment for ALD are in urgent need clinically. Previous studies on ALD have focused on the direct damaging effects of alcohol and its toxic metabolites, while recent studies have shown that the pathogenesis of ALD also include alcohol metabolic reprogramming and endogenous metabolites disorder. Although the endogenous metabolites have no direct toxicity, its long-term effect should not be ignored. These endogenous metabolites could change epigenetic modifications, cause widespread and persistent abnormal gene expression and signal pathway activation abnormally to promote metabolic reprogramming and stamp it as "metabolic memory", which manifest pathological changes and promote ALD, especially liver fibrosis/cirrhosis and liver cancer. Based on this, the article reviews the important epigenetic modifications caused by related metabolites in ALD and their associated effects. The role of traditional Chinese medicine (TCM) and its active ingredients in regulating epigenetics was also analyzed. The results suggest that regulation of epigenetics and alteration of "metabolic memory" may be a novel mechanism of TCM in the prevention and treatment of ALD.

Research Progress of Physiologic Parameters Monitoring Technology for Critical Neonates / 中国医疗器械杂志

Physiological parameter monitoring is essential to medical staff to evaluate, diagnose and treat patients in neonatal intensive care unit (NICU). Monitoring in NICU includes basic vital signal monitoring and functional monitoring. Basic vital signal monitoring (including ECG, respiration, SpO2, blood pressure, temperature) is advanced and focus on study of usability, continuity and anti-interference. Functional monitoring (including respiratory function, circulatory function, cerebral function) still focus on study of monitoring precision and reliability. Meanwhile, video monitoring and artifact intelligence have presented well performance on improving monitoring precision and anti-interference. In this article, the main parameters and relevant measurement technology for monitoring critical neonates were described.

Clinical analysis on diagnosis and treatment of 116 patients with primary duodenal malignant tumor / 中国医师进修杂志

Objective:To explore the diagnosis, surgical methods and therapeutic effect of primary duodenal malignant tumor.Methods:The clinical data of 116 patients with primary duodenal malignant tumor from January 2010 to December 2018 were retrospectively analyzed.Results:Among 116 patients, adenocarcinoma was in 74 cases, interstitial tumor was in 25 cases, carcinoid was in 9 cases, the others was in 8 cases. Before operation, duodenoscopy was performed in 107 cases, and CT examination was performed in 76 cases. There were 57 cases of pancreaticoduodenectomy, 15 cases of duodenal segmental resection, 13 cases of subtotal gastrectomy and duodenal bulbar resection, 13 cases of duodenal partial resection, and 18 cases of palliative short circuit operation. The total incidence of postoperative complication was 31.9% (37/116), including pancreatic fistula in 8 cases (grade B 5 cases, grade C 3 cases), biliary fistula in 6 cases, abdominal infection in 5 cases, pulmonary infection in 4 cases, intestinal fistula in 3 cases, delayed gastric emptying in 3 cases, and hemorrhage in 8 cases. Four cases (3.4%) died during the perioperative period. Single factor Cox regression analysis result showed that the postoperative survival time was related to the tumor differentiation degree, operation method, tumor infiltration degree and lymphatic metastasis ( P<0.05 or <0.01); multi-factor Cox regression analysis results showed that the operation method, tumor infiltration degree and lymphatic metastasis were the independent risk factors for the postoperative survival time of patients with primary duodenal malignant tumor ( P<0.05). The patients were followed up until June 2021, and 9 cases were lost to follow-up. Kaplan-Meier survival curve analysis result showed that the postoperative overall 1-,3- and 5-year survival rates were 82.11%, 57.56% and 33.11%, respectively. Conclusions:Adenocarcinoma is the main primary malignant tumor of duodenum. Duodenoscopy and CT are the main examination methods. Radical resection is the most effective treatment for primary duodenal malignant tumor, and pancreaticoduodenectomy is the first choice. Surgical method, tumor infiltration degree and lymphatic metastasis are the independent risk factors affecting the prognosis of patients.

Review of Physiological Parameters Monitoring Technology in the ICU / 中国医疗器械杂志

Physiological parameters monitoring is essential to direct medical staff to evaluate, diagnose and treat critical patients quantitatively. ECG, blood pressure, SpO2, respiratory rate and body temperature are the basic vital signs of patients in the ICU. The measuring methods are relatively mature at present, and the trend is to be wireless and more accurate and comfortable. Hemodynamics, oxygen metabolism and microcirculation should be taken seriously during the treatment of acute critical patients. The related monitoring technology has made significant progress in recent years, the trend is to reduce the trauma and improve the accuracy and usability. With the development of machine vision and data fusion technology, the identification of patient behavior and deterioration has become hot topics. This review is focused on current parameters monitoring technologies, aims to provide reference for future related research.