Acute kidney injury and cardiogenic shock severity for mortality risk stratification in patients supported with VA ECMO.

AIMS: To assess the stage of acute kidney injury (AKI), as an index of organ perfusion, combined with shock severity, measured by the Society for Cardiovascular Angiography and Interventions (SCAI) shock stage classification, to stratify the risk of mortality in patients diagnosed with cardiogenic shock (CS) and supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). METHODS ANS RESULTS: From January 2018 to December 2020, consecutive adult patients diagnosed with CS and received VA ECMO were retrospectively evaluated. The highest AKI stage within 48 h after ECMO initiation was assessed using the Kidney Disease: Improving Global Outcomes criteria. We included 216 patients with a mean age of 58.8 years and 31.0% were females. 88.4% of patients received ECMO for postcardiotomy, while 11.6% for medical CS. The total in-hospital mortality was 53.2%. AKI occurred in 182 (84.3%) patients receiving ECMO for CS. AKI stage 0, 1, 2, and 3 were present in 15.7%, 17.6%, 18.1%, and 48.6% of patients with in-hospital mortality of 26.5%, 26.3%, 61.5%, and 68.6%, respectively (P < 0.001). The AKI stage (P < 0.001), SCAI shock stage before ECMO (P = 0.008), and NYHA ≥ Class III on admission (P = 0.044) were independent predictors of in-hospital mortality. The area under the receiver operating characteristic curve of 0.754 (95% confidence interval: 0.690 to 0.811) for AKI stage combined with SCAI shock stage was better than those for AKI stage (0.676), SCAI shock stage (0.657), serum lactate level (0.682), SOFA score (0.644), SVAE score (0.582), and VIS score (0.530) prior to ECMO. CONCLUSIONS: In this single-center CS population who received VA ECMO for circulatory support, predominantly postcardiotomy cases, AKI occurred in 84.3% of the patients. AKI stage, as an index of organ perfusion combined with shock severity measured by the SCAI shock classification, demonstrates a good correlation with in-hospital mortality.

Preliminary investigation of nitric oxide release from upconverted nanoparticles excited at 808 nm near-infrared for brain tumors.

Upconverted UCNPs@mSiO2-NH2 nanoparticles were synthesized via thermal decomposition while employing the energy resonance transfer principle and the excellent near-infrared (NIR) light conversion property of up-conversion. The 808 nm NIR-excited photocontrolled nitric oxide (NO) release platform was successfully developed by electrostatically loading photosensitive NO donor Roussin's black salt (RBS) onto UCNPs@mSiO2-NH2, enabling the temporal, spatial, and dosimetric regulation of NO release for biological applications of NO. The release of NO ranged from 0.015⁓0.099 mM under the conditions of 2.0 W NIR excitation power, 20 min of irradiation time, and UCNPs@mSiO2-NH2&RBS concentration of 0.25⁓1.25 mg/mL. Therefore, this NO release platform has an anti-tumor effect. In vitro experiments showed that under the NIR light, at concentrations of 0.3 mg/mL and 0.8 mg/mL of UCNPs@mSiO2-NH2&RBS, the activity of glioma (U87) and chordoma (U-CH1) cells, as measured by CCK8 assay, was reduced to 50 %. Cell flow cytometry and Western Blot experiments showed that NO released from UCNPs@mSiO2-NH2&RBS under NIR light induced apoptosis in brain tumor cells. In vivo experiments employing glioma and chordoma xenograft mouse models revealed significant inhibition of tumor growth in the NIR and UCNPs@mSiO2-NH2&RBS group, with no observed significant side effects in the mice. Therefore, NO released by UCNPs@mSiO2-NH2&RBS under NIR irradiation can be used as a highly effective and safe strategy for brain tumor therapy.

Effect of Nanoporous Molecular Sieves TS-1 on Electrical Properties of Crosslinked Polyethylene Nanocomposites.

Crosslinked polyethylene (XLPE) is an important polyethylene modification material which is widely used in high-voltage direct current (HVDC) transmission systems. Low-density polyethylene (LDPE) was used as a matrix to improve the thermal and electrical properties of XLPE composites through the synergistic effect of a crosslinking agent and nanopore structure molecular sieve, TS-1. It was found that the electrical and thermal properties of the matrices were different due to the crosslinking degree and crosslinking efficiency, and the introduction of TS-1 enhanced the dielectric constants of the two matrices to 2.53 and 2.54, and the direct current (DC) resistivities were increased to 3 × 1012 and 4 × 1012 Ω·m, with the enhancement of the thermal conductivity at different temperatures. As the applied voltage increases, the DC breakdown field strength is enhanced from 318 to 363 kV/mm and 330 to 356 kV/mm. The unique nanopore structure of TS-1 itself can inhibit the injection and accumulation in the internal space of crosslinked polyethylene composites, and the pore size effect of the filler can limit the development of electron impact ionization, inhibit the electron avalanche breakdown, and improve the strength of the external applied electric field (breakdown field) that TS-1/XLPE nanocomposites can withstand. This provides a new method for the preparation of nanocomposite insulating dielectric materials for HVDC transmission systems with better performance.

Morphine timing-dependent modulation of TRPV1 phosphorylation correlates with differential morphine effects on myocardial ischemia/reperfusion injury.

Opioids are used for pain relief in patients suffering from acute myocardial ischemia or infarction. Clinical and laboratory studies demonstrate that morphine treated patients or the experimental animal model suffering acute myocardial ischemia and reperfusion, may worsen myocardial viability. As transient receptor potential vanilloid 1 (TRPV1) plays important roles in pain sensation and cardio-protection, we query whether opioids may exacerbate myocardial viability via interaction with TRPV1 activity in the pain relief. We found the co-expressions of TRPV1 and opioid µ, δ and κ receptors in adult rat cardiomyocytes. Intravenous injection of morphine (0.3 mg/kg) at 20 min after induction of myocardial ischemia, in the rat model of acute myocardial ischemia and reperfusion, induced significant reduction of phosphorylated TRPV1 (p-TRPV1) in the ventricular myocardium and increase in serum cardiac troponin I (cTnI), compared with the ischemia/reperfusion controls (all P < 0.05). The effects of morphine were completely reversed by selective opioid µ, δ and κ receptor antagonists. While significant upregulation of p-TRPV1 (P < 0.05) and improvement of ±dP/dt max (all P < 0.05) were detected in the animals giving the same dose of morphine before induction of myocardial ischemia. The changes in p-TRPV1 correlate with the alterations of cTnI (r = -0.5840, P = 0.0283) and ±dP/dt max (r = 0.8084, P = 0.0005 and r = -0.8133, P = 0.0004, respectively). The findings of this study may indicate that potentiation and attenuation of TRPV1 sensitivity correlate with the improvement of the cardiac performance and the aggravation of myocardial viability, respectively, by giving morphine before and during myocardial ischemia and reperfusion.

Near-Infrared Light-Powered and DNA Nanocage-Confined Catalytic Hairpin Assembly Nanobiosensor with a Nucleic Acid Restriction Behavior and Reinforced Enzymatic Resistance for Robust Imaging Assay in Live Biosystems.

While DNA amplifier-built nanobiosensors featuring a DNA polymerase-free catalytic hairpin assembly (CHA) reaction have shown promise in fluorescence imaging assays within live biosystems, challenges persist due to unsatisfactory precision stemming from premature activation, insufficient sensitivity arising from low reaction kinetics, and poor biostability caused by endonuclease degradation. In this research, we aim to tackle these issues. One aspect involves inserting an analyte-binding unit with a photoinduced cleavage bond to enable a light-powered notion. By utilizing 808 nm near-infrared (NIR) light-excited upconversion luminescence as the ultraviolet source, we achieve entirely a controllable sensing event during the biodelivery phase. Another aspect refers to confining the CHA reaction within the finite space of a DNA self-assembled nanocage. Besides the accelerated kinetics (up to 10-fold enhancement) resulting from the nucleic acid restriction behavior, the DNA nanocage further provides a 3D rigid skeleton to reinforce enzymatic resistance. After selecting a short noncoding microRNA (miRNA-21) as the modeled low-abundance sensing analyte, we have verified that the innovative NIR light-powered and DNA nanocage-confined CHA nanobiosensor possesses remarkably high sensitivity and specificity. More importantly, our sensing system demonstrates a robust imaging capability for this cancer-related universal biomarker in live cells and tumor-bearing mouse bodies, showcasing its potential applications in disease analysis.

Development and validation of an UPLC-MS/MS assay for the simultaneous quantification of seven commonly used antibiotics in human plasma and its application in therapeutic drug monitoring.

OBJECTIVE: To develop and validate an UPLC-MS/MS assay for simultaneous determination of the total concentration of ceftazidime, ciprofloxacin, flucloxacillin, piperacillin, tazobactam, sulfamethoxazole, N-acetyl sulfamethoxazole and trimethoprim, and the protein-unbound concentration of flucloxacillin, in human plasma to be used for research and clinical practice. METHODS: Sample pretreatment included protein precipitation with methanol. For the measurement of protein-unbound flucloxacillin, ultrafiltration was performed at physiological temperature. For all compounds, a stable isotopically labelled internal standard was used. Reliability of the results was assessed by participation in an international quality control programme. RESULTS: The assay was successfully validated according to the EMA guidelines over a concentration range of 0.5-100 mg/L for ceftazidime, 0.05-10 mg/L for ciprofloxacin, 0.4-125 mg/L for flucloxacillin, 0.2-60 mg/L for piperacillin, 0.15-30 mg/L for tazobactam, 1-200 mg/L for sulfamethoxazole and N-acetyl sulfamethoxazole, 0.05-10 mg/L for trimethoprim and 0.10-50 mg/L for unbound flucloxacillin. For measurement of total concentrations, the within- and between-day accuracy ranged from 90.0% to 109%, and 93.4% to 108%, respectively. Within- and between-day precision (variation coefficients, CVs) ranged from 1.70% to 11.2%, and 0.290% to 5.30%, respectively. For unbound flucloxacillin, within-day accuracy ranged from 103% to 106% and between-day accuracy from 102% to 105%. The within- and between-day CVs ranged from 1.92% to 7.11%. Results of the international quality control programme showed that the assay is reliable. CONCLUSIONS: The method provided reliable, precise and accurate measurement of seven commonly prescribed antibiotics, including the unbound concentration of flucloxacillin. This method is now routinely applied in research and clinical practice.

Four new steroidal glycosides from Lilium lancifolium Thunb. and their antitumor activity.

Four new steroidal glycosides (1-4), including two steroidal saponins named lililancifoloside B and C (1-2), one pregnane glycoside named lililancifoloside D (3), and one C22-steroidal lactone glycoside named lililancifoloside E (4), together with five known ones (5-9), were isolated from the bulbs of Lilium lancifolium Thunb. By using spectroscopic analysis, including 1D, 2D NMR, and HR-ESI-MS, the structures of 1-4 were elucidated. All isolates were tested for their cytotoxic potential against the MCF-7, MDA-MB-231, HepG2, and A549 cell lines. Compound 6 distinguished out among them, IC50 values of 3.31, 5.23, 1.78, and 1.49 µM against the four cell lines, respectively. Other compounds such as compound 3, 5, and 9 have also shown specific cytotoxic activity. Next, studies showed that compound 6 might cause HepG2 cells to undergo a cell cycle arrest during the G2/M phase and apoptosis.

Ocular topical application of alpha-glucosyl hesperidin as an active pharmaceutical excipient: in vitro and in vivo experimental evaluation.

Alpha-glucosyl hesperidin (GH) is an aqueous soluble, amphipathic hesperidin derivative with several pharmacological effects, and it is postulated in this manuscript that GH could potentially be utilized as an active pharmaceutical excipient in eyedrops. The ocular safety of GH was evaluated according to in vitro cytotoxicity and in vivo ocular tolerance. The in vivo corneal permeation of coumarin-6 (Cou-6) with or without GH was characterized, and the in vivo inducing corneal wound healing using bisdemethoxycurcumin (BDMC) with or without GH was also evaluated to determine whether GH is an active pharmaceutical excipient in eyedrops. The results demonstrated that as high as 30 mg/ml of GH exhibits high-level in vitro and in vivo safety profiles according to four in vitro and in vivo evaluations. GH improved the corneal permeation of Cou-6 in mice, as well as demonstrated in vitro antioxidant activity. Concerning in vivo activity, a BDMC-GH suspension was shown to be synergistic in promoting corneal wound healing in mice, as well as restoring corneal sensitivity, promoting corneal epithelial wound healing, and restoring the corneal tissue structure without inflammatory cell infiltration. Overall, GH could be a novel and promising active excipient in eyedrops.

A population-based study of Helicobacter pylori: Does asymptomatic infection mean no gastroscopic lesions?

OBJECTIVES: We determined the common clinical characteristics of patients infected with Helicobacter pylori (H. pylori) and investigated the relationship between H. pylori infection, and clinical symptoms, and gastroscopic manifestations. Our focus was specifically on the clinical manifestations in asymptomatic patients. METHODS: We obtained the physical examination data of patients who underwent the 14C urea breath test between January 2018 and December 2020 at our Hospital. Basic demographic data, questionnaire data on clinical symptoms, and clinical examination data of the patients were also collected, and the correlation analysis was performed. RESULTS: A total of 2863 participants were included in the study. The overall H. pylori infection rate was 26.30%. The clinical symptoms between H. pylori-positive patients and H. pylori-negative patients did not differ significantly (P > .05). However, H. pylori-positive patients exhibited more severe gastroscopic manifestations (P < .001). The 14C urea breath test disintegrations per minute (DPM) values in H. pylori-positive patients correlated with their serum pepsinogen and gastrin-17 levels. With an increase in the DPM value, more combinations of clinical symptoms appeared in the patients. Among H. pylori-positive patients, DPM levels in asymptomatic patients were lower than those in symptomatic patients (P < .001). However, gastroscopic manifestations did not vary significantly between asymptomatic and symptomatic patients (P > .05). CONCLUSION: Patients infected with H. pylori showed no specific gastrointestinal symptoms. Patients with asymptomatic infection showed lower DPM levels, but their gastroscopic manifestations were similar to those of patients with symptomatic infection, and their lesions were more severe than H. pylori-negative people.

Low-dose Radiation Therapy for Osteoarthritis / 生物化学与生物物理进展

Osteoarthritis (OA) is a chronic degenerative joint disease and the most common type of arthritis. It involves almost any joint and can lead to chronic pain and disability. In the late 19th century, Roentgen discovered X-rays, and then began to use radiotherapy to treat tumors. In the 1980s, Luckey thought that low-level radiation (LDRT) might be beneficial to biology, and it was gradually applied to the treatment of some diseases. This paper introduces the epidemiology, risk factors, clinical manifestations and treatment methods of OA, points out that the cartilage injury and the important effect of synovial inflammation in the pathogenesis of OA, namely when the homeostasis of articular cartilage are destroyed, synthetic metabolism and catabolism imbalances, cartilage cells damaged their breakdown products consumed by synovial cells. Synovial cells and synovial macrophages secrete proinflammatory cytokines, metalloproteinases and proteolytic enzymes, leading to cartilage matrix degradation and chondrocyte damage, which aggravates synovial inflammation and cartilage damage, forming a vicious cycle. The possible mechanism and clinical research progress of LDRT in alleviating OA are discussed. LDRT can regulate inflammatory response, inhibit the production of pro-inflammatory cytokines, and promote the production of anti-inflammatory cytokines, thereby achieving anti-inflammatory effect. Studies have shown that after irradiation, the expression of inducible nitric oxide synthase (iNOS) was decreased, the release of reactive oxygen species (ROS) and the production of superoxide were inhibited, the anti-inflammatory phenotype of macrophages was differentiated from M1 to M2, the inflammatory CD8+ T cells were transformed into CD4+ T cells, and the number of dendritic cells (DC) was significantly reduced. LDRT inhibit the production of proinflammatory factors in leukocytes, reduce their recruitment and adhesion, and down-regulate the expression levels of cell adhesion molecules such as selectin, intercellular adhesion molecule (ICAM) and vascular endothelial cell adhesion molecule (VCAM). LDRT can regulate endothelial cells, stimulate endothelial cells to produce a large amount of TGF-β1, reduce the adhesion of endothelial cells to peripheral blood mononuclear cells (PBMC), and contribute to the anti-inflammatory effect of LDRT. It also exerted anti-inflammatory effects by regulating mitochondrial growth differentiation factor 15 (GDF15). After low-level radiation, the MMP-13 (matrix metalloproteinases-13) and the ADAMTS5 (recombinant a disintegrin and metalloproteinase with thrombospondin-5) decreased, the Col2a1 (collagen type 2) increased in chondrocytes. In the existing clinical studies, most patients can achieve relief of joint pain and recovery of joint mobility after irradiation, and the patients have good feedback on the efficacy. The adverse reactions (acute reactions and carcinogenic risks) caused by LDRT in the treatment of OA are also discussed. During the treatment of OA, a few patients have symptoms such as redness, dryness or itching at the joint skin, and the symptoms are mild and do not require further treatment. Patients are thus able to tolerate more frequent and longer doses of radiotherapy. In general, LDRT itself has the advantages of non-invasive, less adverse reactions, and shows the effect of pain relief and movement improvement in the treatment of OA. Therefore, LDRT has a broad application prospect in the treatment of OA.

Signaling pathways related to kaempferol active monomers in the treatment of osteoporosis / 中国组织工程研究

BACKGROUND:Recent studies have shown that the occurrence and prevention of osteoporosis often focus on the cellular molecular level,and the mechanism of related signaling pathways is an important way to further understand osteoporosis.At present,traditional Chinese medicine has been proved to play a significant role in alleviating osteoporosis.Kaempferol as an emerging Chinese herbal extract has become the focus of clinical and basic research due to its anti-osteoporosis effectiveness and mechanism of action. OBJECTIVE:To further understand the mechanism underlying the anti-osteoporosis effect of kaempferol active monomer through regulation of related signaling pathways by analyzing and collating domestic and foreign literature. METHODS:"Kaempferol,osteoporosis,osteoblasts,osteoclasts,bone marrow mesenchymal stem cells,signaling pathways"were used as Chinese and English search terms to search CNKI,WanFang,VIP,PubMed,Web of Science and Embase databases for relevant literature published from database inception to February 2023. RESULTS AND CONCLUSION:Kaempferol affects the occurrence and progression of osteoporosis to varying degrees by participating in the regulation of differentiation,proliferation and apoptosis of bone marrow mesenchymal stem cells,osteoblasts and osteoclasts.Kaempferol can prevent and treat osteoporosis by regulating various signaling pathways.Kaempferol can promote the proliferation and differentiation of osteoblasts and inhibit the formation of osteoclasts by interfering with the Wnt/β-catenin signaling pathway to regulate β-catenin protein counting and the formation of β-catenin-TCf/LEF complex.Kaempferol interferes with the RANK/RANKL pathway to maintain the dynamic balance of osteoclasts and bone homeostasis.Kaempferol can promote bone formation by intervening with the PI3K/Akt signaling pathway to upregulate the levels of related osteogenic factors Runx2 and Osterix and promote bone cell calcification.Kaempferol interferes with osteoclast differentiation and inhibits reactive oxygen species activity by regulating the ER/ERK pathway.Kaempferol inhibits the expression of ERK,JNK,p38/MAPK and decreases reactive oxygen species production by interfering with the MAPK pathway,thus protecting osteogenesis.Kaempferol enhances the expression of osteogenic factors,bone morphogenetic protein-2,p-Smad1/5/8,β-catenin and Runx2,inhibits the expression of Peroxisome proliferation-activated receptor,and promotes the differentiation and proliferation of osteoblasts through the BMP/Smad pathway.

The purified extract of steamed Panax ginseng protects cardiomyocyte from ischemic injury via caveolin-1 phosphorylation-mediating calcium influx.

Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca2+ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca2+ ([Ca2+]i) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca2+]i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca2+]i against MI injury in neonatal rat cardiomyocytes and a rat model. Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca2+]i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured. Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca2+ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG. Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca2+]i.

Mega-city construction engineering to residential satisfaction: new insights from Yan' an of China.

Introduction: The contradiction among population, economy and urbanization has gradually intensified, and the Mountain Excavation and City Construction (MECC) project is one of the special solutions. Nevertheless, there are few comparative studies on the project index studies and effect of MECC projects on residential satisfaction. To remedy this deficiency, this study base on the Yan'an new district (YND) reconstruction project, attempting to analyze the specific influencing factors prerelocation and post-relocation from the perspective of residential satisfaction. Methods: After conducting reliability and validity analysis on each dimension, multiple linear regression and paired t-test were used to analyze and compare the questionnaire data. Results: The results show that the residential satisfaction index of the YND is indeed higher than that of the Yan'an old district (YOD). Concurrently, the decisive factors of residential satisfaction are also different. Specifically, the interpersonal communication, supporting facilities, community environment and economic income are significant in the YOD, but only the aspect of supporting facilities is negative significant. The supporting facilities, community environment, economic income and urban development are all positive significant in the YND. The satisfaction factors of middle-aged people in YOD and YND have the most significant differences, and the significance of each dimension is different. Discussion: The research results of this study provide a comparative perspective at the micro-level for evaluating China's urban construction, and it supplies specific directions for future urban development and the improvement of old cities through the new residential satisfaction index.

Light-Driven and Metal-Organic Framework Synergetic Loaded DNA Tetrahedral Amplifier for Exonuclease III-Powered All-in-One Biosensing and Chemotherapy in Live Biosystems.

As a result of inaccurate biosensing and difficult synergetic loading, it is challenging to further impel DNA amplifiers to perform therapeutic application. Herein, we introduce some innovative solutions. First, a smart light-driven biosensing concept based on embedding nucleic acid modules with a simple photocleavage-linker is proposed. In this system, the target identification component is exposed on irradiation with ultraviolet light, thus avoiding an always-on biosensing response during biological delivery. Further, in addition to providing controlled spatiotemporal behavior and precise biosensing information, a metal-organic framework is used for the synergetic loading of doxorubicin in the internal pores, whereafter a rigid DNA tetrahedron-sustained exonuclease III-powered biosensing system is attached to prevent drug leakage and enhance resistance to enzymatic degradation. By selecting a next-generation breast cancer correlative noncoding microRNA biomarker (miRNA-21) as a model low-abundance analyte, a highly sensitive in vitro detection ability even allowing to distinguish single-base mismatching is demonstrated. Moreover, the all-in-one DNA amplifier shows excellent bioimaging competence and good chemotherapy efficacy in live biosystems. These findings will drive research into the use of DNA amplifiers in diagnosis and therapy integrated fields.

[ST266 inhibits neointimal hyperplasia after arterial balloon injury in rats].

Objective    To examine the effect of Human Amnion-Derived Multipotent Progenitor (AMP) cells and their novel ST266 secretome on neointimal hyperplasia after arterial balloon injury in rats.Material and Methods    Sprague-Dawley male rats were randomly divided into four groups (n=7): Control (PBS) group, systemic ST266 group, systemic AMP group and local AMP implant group. Neointimal hyperplasia was induced in the iliac using a 2F Fogarty embolectomy catheter. After surgery, the rats in the ST266 group were treated with 0.1, 0.5, or 1ml ST266 iv daily. In the systemic AMP groups, a single dose (SD) of 0.5 ×106 or 1×106 AMP cells was injected via the inferior vena cava after arterial balloon injury. In local AMP implant groups, 1×106, 5×106, or 20×106 AMP cells were implanted in 300 µl Matrigel (Mtgl) around the iliac artery after balloon injury. The iliac arteries were removed for histologic analysis at 28 days after the surgery. Re-endothelialization index was measured at 10 days after balloon injury.Results    ST266 (1 ml) group had a lower level of the Neointima / Neointima+Media ratio (N / N+M) 0.3±0.1 vs 0.5±0.1, p=0.004) and luminal stenosis (LS) percentage (18.2±1.9 % vs 39.2±5.8 %, p=0.008) compared with the control group. Single-dose AMP (1×106) decreased LS compared to the control group (19.5±5.4 % vs 39.2±5.8 %, p=0.033). Significant reduction in N / N+M were found between implanted AMPs (20×106) and the control group (0.4±0.1 vs 0.5±0.1, p=0.003) and the Mtgl-only group (0.5±0.1, p=0.007). Implanted AMPs (20×106) decreased the LS compared with both the control (39.2±5.8 %, p=0.001) and Mtgl-only group (37.5±8.6 %, p=0.016). ST266 (1 ml) significantly increased the re-endothelialization index compared to the control (0.4±0.1 vs 0.1±0.1, p=0.002).Conclusion    ST266 and AMP cells reduce neointimal formation and increase the re-endothelialization index after arterial balloon injury. ST266 is potentially a novel, therapeutic agent to prevent vascular restenosis in human.

Effects of Stool Sample Preservation Methods on Gut Microbiota Biodiversity: New Original Data and Systematic Review with Meta-Analysis.

Here, we aimed to compare the effects of different preservation methods on outcomes of fecal microbiota. We evaluated the effects of different preservation methods using stool sample preservation experiments for up to 1 year. The stool samples from feces of healthy volunteers were grouped based on whether absolute ethanol was added and whether they were hypothermically preserved. Besides, we performed a systematic review to combine current fecal microbiota preservation evidence. We found that Proteobacteria changed significantly and Veillonellaceae decreased significantly in the 12th month in the room temperature + absolute ethanol group. The four cryopreservation groups have more similarities with fresh sample in the 12 months; however, different cryopreservation methods have different effects on several phyla, families, and genera. A systematic review showed that the Shannon diversity and Simpson index of samples stored in RNAlater for 1 month were not statistically significant compared with those stored immediately at -80°C (P = 0.220 and P = 0.123, respectively). The -80°C refrigerator and liquid nitrogen cryopreservation with 10% glycerine can both maintain stable microbiota of stool samples for long-term preservation. The addition of absolute ethanol to cryopreserved samples had no significant difference in the effect of preserving fecal microbial characteristics. Our study provides empirical insights into preservation details for future studies of the long-term preservation of fecal microbiota. Systematic review and meta-analysis found that the gut microbiota structure, composition, and diversity of samples preserved by storage methods, such as preservation solution, are relatively stable, which were suitable for short-term storage at room temperature. IMPORTANCE The study of gut bacteria has become increasingly popular, and fecal sample preservation methods and times need to be standardized. Here, we detail a 12-month study of fecal sample preservation, and our study provides an empirical reference about experimental details for long-term high-quality storage of fecal samples in the field of gut microbiology research. The results showed that the combination of -80°C/liquid nitrogen deep cryopreservation and 10% glycerol was the most effective method for the preservation of stool samples, which is suitable for long-term storage for at least 12 months. The addition of anhydrous ethanol to the deep cryopreserved samples did not make a significant difference in the preservation of fecal microbiological characteristics. Combined with the results of systematic reviews and meta-analyses, we believe that, when researchers preserve fecal specimens, it is essential to select the proper preservation method and time period in accordance with the goal of the study.

The reason and mechanism of propylene glycol alginate sodium sulfate (PSS) mediated allergic side effect.

Propylene glycol alginate sodium sulfate (PSS) is a heparinoid polysaccharide drug used in clinic for >30 years in China. But its allergy events happened from time to time and should not be ignored. Here, ammonium salt in PSS (PSS-NH4+), PSS fractions with high Mw (PSS-H-Mw) and low mannuronic acid (M) to guluronic acid (G) ratio (PSS-L-M/G) were found to induce allergic response by the structure-activity and impurity-activity relationships in vitro. Furthermore, we confirmed the reason and elucidated the mechanism accounted for allergic side effect of PSS in vivo. It was found that high IgE levels in PSS-NH4+ and PSS-H-Mw groups upregulate the cascade expression of Lyn-Syk-Akt or Erk and second messenger Ca2+, which accelerated mast cells (MCs) degranulation to release histamine, LTB4, TPS, and finally induced lung tissue injury. PSS-L-M/G caused a mild allergic symptom because it only enhanced the expression of p-Lyn and histamine release. In brief, PSS-NH4+ and PSS-H-Mw were main reasons to result in allergic response. Our results suggested that it is very necessary to control the range of Mw and the content of impurities (< 1 % ammonium salt) of PSS to guarantee its safety and effectiveness in clinical treatment.

Clinical Application of Double Ovulation Stimulation in Patients with Diminished Ovarian Reserve and Asynchronous Follicular Development Undergoing Assisted Reproduction Technology.

OBJECTIVE: This study aimed to compare the clinical effects of double ovulation stimulation (DouStim) applied during the follicular and luteal phases with the antagonist protocol in patients with diminished ovarian reserve (DOR) and asynchronous follicular development undergoing assisted reproductive technology (ART). METHODS: The clinical data of patients with DOR and asynchronous follicular development receiving ART from January 2020 to December 2021 were retrospectively analyzed. The patients were divided into two groups according to their ovulation stimulation protocol: DouStim group (n=30) and antagonist group (n=62). Assisted reproduction and clinical pregnancy outcomes were compared between the two groups. RESULTS: In the DouStim group, the number of oocytes retrieved, metaphase II (MII) oocytes, two-pronuclei (2PN), day 3 (D3) embryos, D3 high-quality embryos as well as blastocyst formation, implantation, and human chorionic gonadotropin-positive rates were significantly greater than those in the antagonist group (all P<0.05). No significant differences were found in MII, fertilization, or continued pregnancy rates at the first frozen embryo transfer (FET), in-vitro fertilization (IVF) cancellation, or early medical abortion rates between the groups (all P>0.05). Except for the early medical abortion rate, the DouStim group generally had favorable outcomes. In the DouStim group, the dosage and duration of gonadotropin and the fertilization rate were significantly greater in the first ovulation stimulation induction than in the second ovulation stimulation induction (P<0.05). CONCLUSION: The DouStim protocol efficiently and economically obtained more mature oocytes and high-quality embryos for patients with DOR and asynchronous follicular development.

Biocompatible gliadin-sericin complex colloidal particles used for topical delivery of the antioxidant phloretin.

Oxidative stress caused by environmental exposures results in numerous skin diseases. Phloretin (PHL) is often used to relieve various skin symptoms, however, precipitation or crystallization of PHL in aqueous systems limits its ability to diffuse through the stratum corneum, making it difficult to exert effect at the target. To address this challenge, we herein report a method for the generation of core-shell nanostructure (G-LSS) via the growth of sericin crust around gliadin nanoparticle as a topical nanocarrier of PHL to improve its cutaneous bioavailability. Physicochemical performance, morphology, stability, and antioxidant activity of the nanoparticles were characterized. G-LSS-PHL exhibited uniformed spherical nanostructures with the robust encapsulation on PHL (∼90 %). This strategy protected PHL from UV-induced degradation, facilitating to inhibit erythrocyte hemolysis and quench free radicals in a dose-dependent manner. Transdermal delivery experiments and porcine skin fluorescence imaging indicated that G-LSS facilitated the penetration of PHL across the epidermis layer of skin to reach deep-seated sites, and promoted cumulative turnover of PHL with a 2.0-fold increase. Cell cytotoxicity and uptake assay confirmed that as-prepared nanostructure was nontoxic to HSFs, and promoted cellular absorption of PHL. Therefore, this work opened up new promising avenues for developing robust antioxidant nanostructure for topical applications.

Imaging Features and Risk Factors of Pancreatic Cystic Lesions Complicating Autoimmune Pancreatitis: A Retrospective Study.

OBJECTIVE: This study aimed to explore the imaging features and risk factors of PCLs complicating AIP, and investigate its prognosis through continuous imaging follow-up. PATIENTS AND METHODS: Patients who were diagnosed with AIP from January 2014 to December 2020 in our hospital were recruited. We analyzed the CT and MRI features of PCLs complicating AIP, and investigated its prognosis through imaging follow-up. We also compared subjects with and without PCLs using clinical, laboratory, and imaging data; the related risk factors associated with PCLs were investigated in a multivariate logistic regression analysis. RESULTS: In this group, 16 patients had PCLs and 86 did not. A total of 43 PCLs larger than 5mm were found in 15 patients. Among these PCLs, 35 showed homogeneous signal (density); one, bleeding; three, linear separation; and four, small focal low signal on T2WI. Eight patients with 23 PCLs appeared for the follow-up after steroid treatment. Short-term follow-up showed that 11 PCLs disappeared, nine reduced, one unchanged and two enlarged. Of the 12 PCLs that did not disappear, 10 PCLs disappeared at long-term follow-up, except for two reduced PCLs were not re-examined. Logistic regression analysis showed that drinking history was an independent risk factor, age ≥ 65 years was an independent protective factor for PCLs complicating AIP. CONCLUSION: The imaging features of PCLs complicating AIP are various, which can be single or multiple, most of them are homogeneous, and some lesions may be accompanied by hemorrhage, separation and necrosis. Age ≥ 65 years and avoiding drinking may help to reduce the occurrence of these lesions.