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Abstract Background Low-density lipoprotein cholesterol (LDL-C) is acknowledged as an independent risk factor (IRF) for atherosclerotic cardiovascular disease. Nevertheless, studies on the impact of LDL-C on microvasculature are still scarce. The retina, abundant in microvasculature, can now be examined for microvascular alterations through the novel, non-invasive, and quantitative optical coherence tomography angiography (OCTA) technique. Methods In this cross-sectional study, 243 patients from the geriatric department were recruited (between December 2022 and December 2023). Individuals were classified into four groups based on their LDL-C levels: Group 1 (≤ 1.8 mmol/L), Group 2 (> 1.8 mmol/L to ≤ 2.6 mmol/L), Group 3 (> 2.6 mmol/L to ≤ 3.4 mmol/L), and Group 4 (> 3.4 mmol/L). The OCTA results including retinal vessel density (VD), foveal avascular zone (FAZ) area, macula thickness, and retinal nerve fiber layer (RNFL) thickness were contrasted across these groups. T-tests, analysis of variance, Welch’s tests, or rank-sum tests were employed for statistical comparisons. In cases where significant differences between groups were found, post-hoc multiple comparisons or rank-sum tests were performed for pairwise group comparisons. Spearman’s correlation coefficient was employed to perform bivariate correlation analysis to evaluate the relationship between LDL-C levels and various OCTA measurements. Multivariable regression analysis was used to evaluate the association between LDL-C levels and various OCTA measurements. Linear regression analysis or mixed-effects linear models were applied. Results It was discovered that individuals with LDL-C levels exceeding 2.6 mmol/L (Groups 3 and 4) exhibited reduced VD in the retina, encompassing both the optic disc and macular regions, compared to those with LDL-C levels at or below 2.6 mmol/L (Groups 1 and 2). A negative correlation among LDL-C levels and retinal VD was identified, with r values spanning from − 0.228 to -0.385. Further regression analysis presented β values between − 0.954 and − 2.378. Additionally, no notable disparities were detected among the groups regarding FAZ area, macular thickness, and RNFL thickness. Conclusions The outcomes of this study suggest that elevated LDL-C levels constitute an IRF for decreased VD across the entire retina. Trial registration NCT05644548, December 1, 2022.

Abstract Objective The influence of robot-assisted radical prostatectomy (RARP) in obese (OB) and non-obese (NOB) prostate cancer patients remains a topic of debate. The objective of this study was to juxtapose the perioperative, functional, and oncologic outcomes of RARP in OB and NOB cohorts. Materials and methods We systematically searched the databases such as PubMed, Embase, Web of Science, and the Cochrane Library database to identify relevant studies published in English up to September 2023. Review Manager was used to compare various parameters. The study was registered with PROSPERO (CRD42023473136). Sixteen comparative trials were included for 8434 obese patients compared with 55,266 non-obese patients. Results The OB group had a longer operative time (WMD 17.8 min, 95% CI 9.7,25.8; p

Objective To evaluate the associations between serum level of trimethylamine oxide （TMAO） and vascular calcification and explore the risk factors of vascular calcification in patients with chronic kidney disease （CKD）. Methods A total of 118 CKD3-5 patients were assigned into two experimental groups of calcification and non-calcification according to whether or not there was calcification of abdominal aorta. And 60 healthy people with matching age and gender were selected as control group. Serum level of TMAO was determined by enzyme-linked immunosorbent assay （ELISA）. The clinical data of two groups were compared. Results TMAO（6.49 ± 0.76）μmol/L，serum phosphorus (1.73±0.62)μmol/L，calcium-phosphorus product(3.66±1.30)，parathyroid hormone （PTH）[232.90（96.90，521.60）ng/L]，alkaline phosphatase （ALP） [72.00（55.75，113.50）U/L]，serum creatinine （Scr）[684.50（511.25，921.00）μmol/L] and C-reactive protein （CRP）[5.00（1.28，21.88）mg/L] were higher in experimental group than those in control group （P＜0.05）. Serum calcium（Scr）(2.13±0.24)μmol/L，25-hydroxyvitamin D[23.67（16.84，30.06）μg/L]，albumin （Alb）(37.35±5.97)g/L and estimated glomerular filtration rate （eGFR）[6.02（4.70，8.50）mL·min-1·（1.73m2）-1] were lower in control group （P＜0.05）. TMAO(6.01±0.90)μmol/L，age(47.81±13.51)year，proportion of hemodialysis，serum calcium (2.07±0.21)μmol/L and CRP[4.70（0.80，19.44）mg/L] were higher in calcification group than that in non-calcification group （P＜0.05）. No statistically significant inter-group difference existed in gender，basic diseases （hypertension & diabetes mellitus），blood phosphorus，calcium-phosphorus product，PTH，ALP，Alb，total cholesterol （TC），triglyceride （TG），25 hydroxyvitamin D，Scr and eGFR （P＞0.05）. Vascular calcification was correlated positively with age （r = 0.446，P＜0.001），TMAO （r = 0.614，P＜0.001），serum calcium （r = 0.192，P = 0.038），CRP （r = 0.208，P = 0.024） and hemodialysis （r = 0.238，P = 0.009）. Logistic analysis revealed that age （OR = 1.069，95%CI: 1.025-1.115，P = 0.002） and TMAO （OR = 19.295，95%CI: 5.785-64.663，P＜0.001） were the independent risk factors for vascular calcification. ROC curve indicated that area under curve （AUC） of TMAO and serum calcium were 0.855 and 0.611 respectively for diagnosing vascular calcification. AUC of combination was 0.868 with a sensitivity of 85.2% and a specificity of 71.9%. Conclusion Serum level of TMAO is correlated with vascular calcification in CKD patients. And TMAO is expected to become an adjunct to diagnosing vascular calcification. Due to a low specificity，it should be combined with other risk factors for assessing vascular calcification. The common risk factors for vascular calcification include age，TMAO，serum calcium，CRP and hemodialysis. And age and serum level of TMAO are independent risk factors for vascular calcification in CKD patients.

Abstract N-oxides play a pivotal role in natural products and emerging drug design, while also serving as valuable ligand scaffolds in organometallic chemistry. Among heteroatom oxidations, the conversion of amines to N-oxides is a critical and challenging facet. We present here a highly enantioselective N-oxidation methodology for both cyclic and acyclic amines. The method employs an ion-pair catalyst comprising a chiral bisguanidinium [BG]2+ cation and an achiral oxodiperoxomolybdosulfate anion [(µ-SO4)2Mo2O2(µ-O2)2(O2)2]2-. Notably, the bisguanidinium cation undergoes modification through silyl group incorporation and is elucidated by X-ray crystallography. Our findings underscore the crucial role of the side chain in the determination of the chiral pocket size, allowing for the oxidation of diverse tertiary amines with enantioselectivities. Comprehensive mechanistic investigations are conducted to explain the catalytic system’s efficacy in achieving dynamic kinetic resolution (DKR) with high efficiency.

AIM: To prevent neovascularization in diabetic retinopathy (DR) patients and partially control disease progression. METHODS: Hypoxia-related differentially expressed genes (DEGs) were identified from the GSE60436 and GSE102485 datasets, followed by gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Potential candidate drugs were screened using the CMap database. Subsequently, a protein-protein interaction (PPI) network was constructed to identify hypoxia-related hub genes. A nomogram was generated using the rms R package, and the correlation of hub genes was analyzed using the Hmisc R package. The clinical significance of hub genes was validated by comparing their expression levels between disease and normal groups and constructing receiver operating characteristic curve (ROC) curves. Finally, a hypoxia-related miRNA-transcription factor (TF)-Hub gene network was constructed using the NetworkAnalyst online tool. RESULTS: Totally 48 hypoxia-related DEGs and screened 10 potential candidate drugs with interaction relationships to upregulated hypoxia-related genes were identified, such as ruxolitinib, meprylcaine, and deferiprone. In addition, 8 hub genes were also identified: glycogen phosphorylase muscle associated (PYGM), glyceraldehyde-3-phosphate dehydrogenase spermatogenic (GAPDHS), enolase 3 (ENO3), aldolase fructose-bisphosphate C (ALDOC), phosphoglucomutase 2 (PGM2), enolase 2 (ENO2), phosphoglycerate mutase 2 (PGAM2), and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). Based on hub gene predictions, the miRNA-TF-Hub gene network revealed complex interactions between 163 miRNAs, 77 TFs, and hub genes. The results of ROC showed that the except for GAPDHS, the area under curve (AUC) values of the other 7 hub genes were greater than 0.758, indicating their favorable diagnostic performance. CONCLUSION: PYGM, GAPDHS, ENO3, ALDOC, PGM2, ENO2, PGAM2, and PFKFB3 are hub genes in DR, and hypoxia-related hub genes exhibited favorable diagnostic performance.

Abstract Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I–III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p

To further explore the metabolism of Lycium barbarum polysaccharides, the cell wall microstructure of Lycium barbarum fruits in different growth periods was observed by transmission electron microscopy, and the cell wall polysaccharide content and its degrading enzyme activity were extracted by chemical method. The changes of polysaccharide components in cell wall of Lycium barbarum fruits in different growth periods were analyzed by microcopolymer Raman spectroscopy. The correlation between the content of polysaccharide in cell wall and the activity of degrading enzyme was analyzed. The results showed that the changes of cell wall structure mainly occurred during 28~35 d, with the cell wall becoming significantly thinner, pectin degrading, and the cell wall structure gradually collapsing. Cell wall material (CWM) content increased first and then decreased, and water-soluble pectin (WSP) content increased significantly (P

Abstract Background Central nervous system involvement in chronic lymphocytic leukemia rarely occurs, and there is no standard therapy for central nervous system involvement in chronic lymphocytic leukemia. This article aims to analyze the diagnosis and treatment of central nervous system involvement in chronic lymphocytic leukemia. Case presentation It reports two cases of central nervous system involvement in chronic lymphocytic leukemia describing the clinical course, therapy, and prognosis. Case 1 is a 67-year-old Asian male patient, he experienced complications with central nervous system involvement after developing resistance to ibrutinib, bendamustine, and rituximab (BR) chemotherapies. The central nervous system lesion was controlled with high-dose methotrexate combined with pomalidomide, but Richter transformation occurred several months later. Case 2 is a 62-year-old Asian female patient, she had central nervous system involvement at initial diagnosis, and bone marrow and central nervous system lesions were controlled by ibrutinib therapy. Conclusion Central nervous system involvement in chronic lymphocytic leukemia is rare and can be diagnosed on the basis of clinical features, cerebrospinal fluid testing, and radiographic evaluation. Ibrutinib, pomalidomide, and other drugs that can cross the blood–brain barrier may be effective for treating central nervous system involvement in chronic lymphocytic leukemia.

Abstract Background According to traditional Chinese medicine (TCM), drugs supplementing the vital energy, Qi, can eliminate tumors by restoring host immunity. The objective of this study is to investigate the underlying immune mechanisms of anti‐tumor activity associated with Qi‐supplementing herbs, specifically the paired use of Huangqi and Danggui. Methods Analysis of compatibility regularity was conducted to screen the combination of Qi‐supplementing TCMs. Using the MTT assay and a transplanted tumor mice model, the anti‐tumor effects of combination TCMs were investigated in vitro and in vivo. High content analysis and flow cytometry were then used to evaluate cellular immunity, followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms. Finally, the anti‐tumor activity and the mechanism of the active ingredients were verified by molecular experiments. Results There is an optimal combination of Huangqi and Danggui that, administered as an aqueous extract, can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo. Based on network pharmacology analysis, PIK3R1 is the core target for the anti‐tumor immunity activity of combined Huangqi and Danggui. Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract (quercetin, jaranol, isorhamnetin, kaempferol, calycosin, and suchilactone) that bind to PIK3R1. Jaranol is the most important component against breast cancer. The suchilactone/jaranol combination and, especially, the suchilactone/kaempferol combination are key for immunity enhancement and the anti‐tumor effects of the extract. Conclusions The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.

Abstract The eukaryotic asparagine (N)-linked glycan is pre-assembled as a fourteen-sugar oligosaccharide on a lipid carrier in the endoplasmic reticulum (ER). Seven sugars are first added to dolichol pyrophosphate (PP-Dol) on the cytoplasmic face of the ER, generating Man5GlcNAc2-PP-Dol (M5GN2-PP-Dol). M5GN2-PP-Dol is then flipped across the bilayer into the lumen by an ER translocator. Genetic studies identified Rft1 as the M5GN2-PP-Dol flippase in vivo but are at odds with biochemical data suggesting Rft1 is dispensable for flipping in vitro. Thus, the question of whether Rft1 plays a direct or an indirect role during M5GN2-PP-Dol translocation has been controversial for over two decades. We describe a completely reconstituted in vitro assay for M5GN2-PP-Dol translocation and demonstrate that purified Rft1 catalyzes the translocation of M5GN2-PP-Dol across the lipid bilayer. These data, combined with in vitro results demonstrating substrate selectivity and rft1∆ phenotypes, confirm the molecular identity of Rft1 as the M5GN2-PP-Dol ER flippase.

Background: Different risk factors are responsible for the occurrence of coronary artery disease (CAD). Among these, the main factors are dyslipidemia, dysglycaemia, and endothelial inflammation. The aim of the study was to analyze the levels of lipids, glucose, and cytokine in patients with different coronary heart diseases. Methods: A total of 2147 patients diagnosed with coronary atherosclerosis, stable angina, unstable angina, acute non-ST-segment elevation infarction (NSTEMI) and acute ST-segment-elevation myocardial infarction (STEMI) at the Cardiovascular Center of Beijing Tongren Hospital from February 2022 to April 2023. The data were gathered from the medical record system.Nonparametric Wilcoxon test was used for statistical analysis of continuous variables, and chi-square test was used for statistical analysis of categorical variables among multiple groups. Results: Compared with coronary atherosclerosis group, acute myocardial infarction group showed a significant increase in IL-6 level (p

Abstract Despite significant progress in therapy, there remains a lack of substantial evidence regarding the molecular factors that lead to renal fibrosis. Neuraminidase 4 (NEU4), an enzyme that removes sialic acids from glycoconjugates, has an unclear role in chronic progressive fibrosis. Here, this study finds that NEU4 expression is markedly upregulated in mouse fibrotic kidneys induced by folic acid or unilateral ureter obstruction, and this elevation is observed in patients with renal fibrosis. NEU4 knockdown specifically in the kidney attenuates the epithelial‐to‐mesenchymal transition, reduces the production of pro‐fibrotic cytokines, and decreases cellular senescence in male mice. Conversely, NEU4 overexpression exacerbates the progression of renal fibrosis. Mechanistically, NEU4254‐388aa interacts with Yes‐associated protein (YAP) at WW2 domain (231‐263aa), promoting its nucleus translocation and activation of target genes, thereby contributing to renal fibrosis. 3,5,6,7,8,3ʹ,4ʹ‐Heptamethoxyflavone, a natural compound, is identified as a novel NEU4 inhibitor, effectively protecting mice from renal fibrosis in a NEU4‐dependent manner. Collectively, the findings suggest that NEU4 may represent a promising therapeutic target for kidney fibrosis.

Ischemic heart disease refers to the imbalance between the supply and demand of myocardial blood; it has various causes and results in a class of clinical diseases characterized by myocardial ischemia (MI). In recent years, the incidence of cardiovascular disease has become higher and higher, and the number of patients with ischemic heart disease has also increased year by year. Traditional treatment methods include drug therapy and surgical treatment, both of which have limitations. The former maybe develop risks of drug resistance and has more significant side effects, while the latter may damage blood vessels and risk infection. At this stage, a new cell-free treatment method needs to be explored. Many research results have shown that exosomes from different cell sources can protect the ischemic myocardium via intercellular action methods, such as promoting angiogenesis, inhibiting myocardial fibrosis, apoptosis and pyroptosis, and providing a new basis for the treatment of MI. In this review, we briefly introduce the formation and consequences of myocardial ischemia and the biology of exosomes, and then focus on the role and mechanism of exosomes from different sources in MI. We also discuss the role and mechanism of exosomes pretreated with Chinese and Western medicines on myocardial ischemia. We also discuss the potential of exosomes as diagnostic markers and therapeutic drug for MI.

BackgroundAcupuncture is a promising non-pharmaceutical complementary therapy in treating prolonged Disorders of consciousness (pDOC), but solid evidence to support its effectiveness and safety is still lacking. Thus, the purpose of this study is to investigate the efficacy and safety of acupuncture-assisted therapy for pDOC patients.MethodsA single-center, prospective, randomized, conventional-controlled, assessor-and-statistician-blinded trial has been designed and is being conducted at West China Hospital of Sichuan University. A total of 110 participants will be randomly assigned to the experimental group and the control group in a 1:1 allocation ratio and evaluated using Coma Recovery Scale-Revised (CRS-R) at 8 a.m., 12 p.m., and 4 p.m. on 2 consecutive days before enrollment to determine the consciousness level. The experimental group will receive acupuncture combined with conventional treatment, while the control group will receive only conventional treatment during the trial observation period. The treatment duration of both groups will be 20 days. Among them, the frequency of acupuncture-assisted therapy is once a day, with 10 consecutive sessions followed by a day’s rest for a total of 24 days. Data will be collected separately during baseline and after the final treatment. For data analysis, both Full Analysis Set (FAS) and Per Protocol Set (PPS) principles will be performed together by applying SPSS 27.0 software. The primary outcome measures are the changes of CRS-R before and after treatment, while the secondary outcome measures are the changes of Full Outline of Unresponsiveness Scale (FOUR), the changes of Nociception Coma Scale-Revised (NCS-R), the changes of Disability Rating Scale (DRS), the changes of Mismatch Negativity (MMN) and P300 before and after treatment, respectively.DiscussionThis trial aims to rationally assess the consciousness level from multiple 2 perspectives through subjective evaluation and objective detection by selecting several standardized clinical scales combined with Event-Related Potential (ERP) detection technology. In this way, we will be able to reduce the subjectivity of consciousness assessment and objectively evaluate the clinical efficacy of acupuncture-assisted therapy for pDOC. The study, if proven to be effective and safe enough, will provide a favorable evidence to guide medical decision-making choices and future researches.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2300076180.

BackgroundCOVID-19 began in December 2019, rapidly spreading worldwide. China implemented a dynamic zero-COVID strategy and strict control measures after the outbreak. However, Guangzhou city ended closed-off management by the end of November 2022, leading to exposure to SARS-CoV-2. Despite most hospitalized patients being infected or co-infected with SARS-CoV-2, some remained uninfected. We report two cases of bacterial pneumonia with elevated globulin levels not infected with SARS-CoV-2, aiming to identify protection factors of SARS-CoV-2 infection and provide a scientific basis for SARS-CoV-2 prevention.Case presentationCase 1, a 92-year-old male, admitted on October 21, 2022, developed worsening cough and sputum after aspiration, diagnosed with bacterial pneumonia with Pseudomonas aeruginosa, Escherichia coli (CRE) and carbapenem-resistant Acinetobacter baumannii (CRAB) infections. He was treated with imipenem anti-infective therapy and mechanical ventilation, then switched to a combination of meropenem, voriconazole and amikacin anti-infective therapy due to recurrent infections and septic shock, and died of sepsis on 8 January 2023. Case 2 is an 82-year-old male admitted on 30 September 2022, with recurrent cough, sputum, and shortness of breath, diagnosed with bacterial pneumonia with carbapenem-resistant Klebsiella pneumoniae (CRKP) and Mycobacterium pneumoniae infections. He was treated with ventilator-assisted ventilation, meropenem, amikacin, tigecycline and mucomycin nebulization and discharged with improvement on 26 October. He was readmitted on 21 November 2022 and diagnosed with bacterial pneumonia. He was treated with cefoperazone sulbactam, amikacin, meropenem and fluconazole and discharged on 31 December. Neither patient was infected with SARS-CoV-2 during hospitalization. Notably, their globulin levels were elevated before SARS-CoV-2 exposure, gradually decreasing afterward.ConclusionsPatients with bacterial pneumonia with high globulin levels likely have large amounts of immunoglobulin, and that immunoglobulin cross-reactivity causes this protein to be involved in clearing SARS-CoV-2 and preventing infection. Therefore, bacterial pneumonia patients with high globulin levels included in this study were not infected with SARS-CoV-2. After exposure to SARS-CoV-2, the amount of globulin in the patient’s body was reduced because it was used to clear SARS-CoV-2. The results of this study are expected to provide a theoretical basis for the study of the mechanism of prevention and treatment of SARS-CoV-2 infection.