Assessment of metabolomic variations among individuals returning to plain areas after exposure to high altitudes: a metabolomic analysis of human plasma samples with high-altitude de-acclimatization syndrome.

Background: High altitude de-acclimatization (HADA) is gradually becoming a public health concern as millions of individuals of different occupations migrate to high-altitude areas for work due to economic growth in plateau areas. HADA affects people who return to lower elevations after exposure to high altitudes. It causes significant physiological and functional changes that can negatively impact health and even endanger life. However, uncertainties persist about the detailed mechanisms underlying HADA. Methods: We established a population cohort of individuals with HADA and assessed variations in metabolite composition. Plasm samples of four groups, including subjects staying at plain (P) and high altitude (H) as well as subjects suffering from HADA syndrome with almost no reaction (r3) and mild-to-moderate reaction (R3) after returning to plain from high altitude, were collected and analyzed by Liquid Chromatography-Mass Spectrometry metabolomic. Multivariate statistical analyses were used to explore significant differences and potential clinical prospect of metabolites. Result: Although significantly different on current HADAS diagnostic symptom score, there were no differences in 17 usual clinical indices between r3 and R3. Further multivariate analyses showed isolated clustering distribution of the metabolites among the four groups, suggesting significant differences in their metabolic characteristics. Through K-means clustering analysis, we identified 235 metabolites that exhibited patterns of abundance change consistent with phenotype of HADA syndrome. Pathway enrichment analysis indicated a high influence of polyunsaturated fatty acids under high-altitude conditions. We compared the metabolites between R3 and r3 and found 107 metabolites with differential abundance involved in lipid metabolism and oxidation, suggesting their potential role in the regulation of oxidative stress homeostasis. Among them, four metabolites might play a key role in the occurrence of HADA, including 11-beta-hydroxyandrosterone-3-glucuronide, 5-methoxyindoleacetate, 9,10-epoxyoctadecenoic acid, and PysoPC (20:5). Conclusion: We observed the dynamic variation in the metabolic process of HADA. Levels of four metabolites, which might be provoking HADA mediated through lipid metabolism and oxidation, were expected to be explore prospective indices for HADA. Additionally, metabolomics was more efficient in identifying environmental risk factors than clinical examination when dramatic metabolic disturbances underlying the difference in symptoms were detected, providing new insights into the molecular mechanisms of HADAS.

Applications of phase-separating multi-bilayers in protein-membrane domain interactions.

Synthetic model membranes are important tools to elucidate lipid domain and protein interactions due to predefined lipid compositions and characterizable biophysical properties. Here, we introduce a model membrane with multiple lipid bilayers (multi-bilayers) stacked on a mica substrate that is prepared through a spin-coating technique. The spin-coated multi-bilayers are useful in the study of phase separated membranes with a high cholesterol content, mobile lipids, microscopic and reversible phase separation, and easy conjugation with proteins, which make them a good model to study interactions between proteins and membrane domains.

Take-out food enhances the risk of MPs ingestion and obesity, altering the gut microbiome in young adults.

Young people are consuming large amounts of microplastics (MPs) due to the booming development of the take-out industry. To investigate the association between MPs exposure and obesity, 121 volunteers were divided into high MPs exposure (HME) and low MPs exposure (LME) according to the frequency of take-out food consumption. Fecal samples were collected for MPs detection using Raman spectra analysis, and identification of the gut microbiota was based on 16 S rDNA/ITS, while metabolite analysis was performed by LC-MS/MS. High levels of MPs and body mass index (BMI) were observed in the HME group (P < 0.05). Both the multiple linear regression (MLR) model and the binary logistic regression (BLR) (OR: 1.264, 95 % CI: 1.108-1.441, P < 0.001) analysis showed a positive correlation between MPs content and BMI. Microbial community analysis revealed that Veillonella, Alistipes and Dothideomycotes (pathogenic fungi) increased in HME participants, whereas Faecalibacterium and Coprococcus decreased. Meanwhile, analysis of stool metabolites showed that vancomycin resistance, selenocompound metabolism and drug metabolism pathways were enhanced in HME participants. These findings indicate that frequent consumption of take-out food may elevate the intake of microplastics, consequently modifying the gut microbiota and metabolites of young adults, and could represent a potential risk factor for obesity.

Beat-to-Beat Blood Pressure Variability Within 24 Hours of Ischemic Stroke Onset: A Potential Predictor of Functional Prognosis.

BACKGROUND: Beat-to-beat blood pressure variability (BPV) is based on each heartbeat and represents a dynamic equilibrium process modulated by artery and cardiac involvement of pressure-receptive reflexes. To date, there remains a lack of prospective studies illustrating the clinical value of beat-to-beat BPV within 24 hours of acute ischemic stroke onset. METHODS AND RESULTS: This study prospectively monitored beat-to-beat blood pressure and heart rate in patients with acute ischemic stroke within 24 hours of onset using a noninvasive plethysmograph and calculated beat-to-beat BPV, heart rate variability, and the cross-correlation baroreflex sensitivity. A modified Rankin Scale score of ≥2 at 90 days was defined as an unfavorable prognosis. Multivariate logistic regression was performed, and the nomogram model was developed by adding the beat-to-beat BPV to the traditional model for predicting prognosis. Beat-to-beat BPV increased significantly in the unfavorable outcome group (P<0.05) compared with that in the favorable outcome group, whereas no difference was observed in beat-to-beat heart rate variability and cross-correlation baroreflex sensitivity between both groups (P>0.05). Furthermore, beat-to-beat BPV within 24 hours of acute ischemic stroke onset was independently associated with unfavorable outcome at 90 days (P<0.005). The addition of beat-to-beat BPV to the traditional model for predicting prognosis enhanced the area under the receiver operating characteristic curve from 0.816 to 0.830. CONCLUSIONS: Increased beat-to-beat BPV within 24 hours of acute ischemic stroke onset was independently associated with a poor prognosis at 90 days and may be a potential predictor for discriminating unfavorable prognosis.

Effects of the Fasting-Postprandial State on Arterial Spin Labeling MRI-Based Cerebral Perfusion Quantification in Alzheimer's Disease.

BACKGROUND: The fasting-postprandial state remains an underrecognized confounding factor for quantifying cerebral blood flow (CBF) in the cognitive assessment and differential diagnosis of Alzheimer's disease (AD). PURPOSE: To investigate the effects of fasting-postprandial state on arterial spin labeling (ASL)-based CBF in AD patients. STUDY TYPE: Prospective. SUBJECTS: Ninety-two subjects (mean age = 62.5 ± 6.4 years; females 29.3%), including 30 with AD, 32 with mild cognitive impairment (MCI), and 30 healthy controls (HCs). Differential diagnostic models were developed with a 4:1 training to testing set ratio. FIELD STRENGTH/SEQUENCE: 3-T, T1-weighted imaging using gradient echo and pseudocontinuous ASL imaging using turbo spin echo. ASSESSMENT: Two ASL scans were acquired to quantify fasting state and postprandial state regional CBFs based on an automated anatomical labeling atlas. Two-way ANOVA was used to assess the effects of fasting/postprandial state and disease state (AD, MCI, and HC) on regional CBF. Pearson's correlation analysis was conducted between regional CBF and cognitive scores (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). The diagnostic performances of the fasting state, postprandial state, and mixed state (random mixing of the fasting and postprandial state CBF) in differential diagnosis of AD were conducted using support vector machine and logistic regression models. STATISTICAL TESTS: Two-way ANOVA, Pearson's correlation, and area under the curve (AUC) of diagnostic model were performed. P values <0.05 indicated statistical significance. RESULTS: Fasting-state CBF was correlated with cognitive scores in more brain regions (17 vs. 4 [MMSE] and 15 vs. 9 [MoCA]) and had higher absolute correlation coefficients than postprandial-state CBF. In the differential diagnosis of AD patients from MCI patients and HCs, fasting-state CBF outperformed mixed-state CBF, which itself outperformed postprandial-state CBF. DATA CONCLUSION: Compared with postprandial CBF, fasting-state CBF performed better in terms of cognitive score correlations and in differentiating AD patients from MCI patients and HCs. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Heart Rate Variability in Patients with Spontaneous Intracerebral Hemorrhage and its Relationship with Clinical Outcomes.

BACKGROUND: Although abnormal heart rate variability (HRV) is frequently observed in patients with spontaneous intracerebral hemorrhage (ICH), its time course and presentation of different indices remain unclear, and few studies have focused on its association with clinical outcomes. METHODS: We prospectively recruited consecutive patients with spontaneous ICH between June 2014 and June 2021. HRV was evaluated twice during hospitalization (within 7 days and 10-14 days after stroke). Time and frequency domain indices were calculated. A modified Rankin Scale score ≥ 3 at 3 months was defined as a poor outcome. RESULTS: Finally, 122 patients with ICH and 122 age- and sex-matched volunteers were included. Compared with controls, time domain and absolute frequency domain HRV parameters (total power, low frequency [LF], and high frequency [HF]) in the ICH group were significantly decreased within 7 days and 10-14 days. For relative values, normalized LF (LF%) and LF/HF were significantly higher, whereas normalized HF (HF%) was significantly lower, in the patient group than in the control group. Furthermore, LF% and HF% measured at 10-14 days were independently associated with 3-month outcomes. CONCLUSIONS: HRV values were impaired significantly within 14 days after ICH. Furthermore, HRV indices measured 10-14 days after ICH were independently associated with 3-month outcomes.

Membrane lipids couple synaptotagmin to SNARE-mediated granule fusion in insulin-secreting cells.

Insulin secretion depends on the Ca2+-regulated fusion of granules with the plasma membrane. A recent model of Ca2+-triggered exocytosis in secretory cells proposes that lipids in the plasma membrane couple the calcium sensor Syt1 to the membrane fusion machinery (Kiessling et al., 2018). Specifically, Ca2+-mediated binding of Syt1's C2 domains to the cell membrane shifts the membrane-anchored SNARE syntaxin-1a to a more fusogenic conformation, straightening its juxtamembrane linker. To test this model in live cells and extend it to insulin secretion, we enriched INS1 cells with a panel of lipids with different acyl chain compositions. Fluorescence lifetime measurements demonstrate that cells with more disordered membranes show an increase in fusion efficiency, and vice versa. Experiments with granules purified from INS1 cells and recombinant SNARE proteins reconstituted in supported membranes confirmed that lipid acyl chain composition determines SNARE conformation and that lipid disordering correlates with increased fusion. Addition of Syt1's C2AB domains significantly decreased lipid order in target membranes and increased SNARE-mediated fusion probability. Strikingly, Syt's action on both fusion and lipid order could be partially bypassed by artificially increasing unsaturated phosphatidylserines in the target membrane. Thus, plasma membrane lipids actively participate in coupling Ca2+/synaptotagmin-sensing to the SNARE fusion machinery in cells.

Chain Mediation Analysis of the Effects of Nutrition and Cognition on the Association of Apolipoprotein E ɛ4 with Neuropsychiatric Symptoms in Alzheimer's Disease.

BACKGROUND: Apolipoprotein E (APOE) is the most recognized risk gene for cognitive decline and clinical progression of late-onset Alzheimer's disease (AD); nonetheless, its association with neuropsychiatric symptoms (NPSs) remains inconclusive. OBJECTIVE: To investigate the association of APOE ɛ4 with NPSs and explore nutritional status and cognition as joint mediators of this association. METHODS: Between June 2021 and October 2022, patients with amnestic mild cognitive impairment (aMCI) or AD were recruited from the Chinese Imaging, Biomarkers, and Lifestyle Study. NPSs were assessed using the Neuropsychiatric Inventory, while global cognition and nutritional status were evaluated using the Mini-Mental State Examination (MMSE) and Mini-Nutritional Assessment (MNA), respectively. Simple mediation and multiple chain mediation models were developed to examine the mediating effects of the MNA and MMSE scores on the relationship between APOE ɛ4 and specific neuropsychiatric symptom. RESULTS: Among 310 patients, 229 (73.87%) had NPSs, and 110 (35.48%) carried APOE ɛ4. Patients with APOE ɛ4 were more likely to have hallucinations (p = 0.014), apathy (p = 0.008), and aberrant motor activity (p = 0.018). MNA and MMSE scores mediated the association between APOE ɛ4 and hallucinations (17.97% and 37.13%, respectively), APOE ɛ4 and apathy (30.73% and 57.72%, respectively), and APOE ɛ4 and aberrant motor activity (17.82% and 34.24%), respectively. Chain-mediating effects of MNA and MMSE scores on the association of APOE ɛ4 with hallucinations, apathy, and aberrant motor activity after adjusting for confounding factors were 6.84%, 11.54%, and 6.19%, respectively. CONCLUSION: Nutritional status and cognition jointly mediate the association between APOE ɛ4 and neuropsychiatric symptoms in patients with aMCI or AD.

[Effects of Different Control Measures on Cadmium and Lead Accumulation and Quality in Lettuce].

To explore the safe utilization technology of farmland polluted by the heavy metals cadmium (Cd) and lead (Pb) and to realize the safe production of agricultural products, a pot experiment was conducted to investigate the effects of two soil passivators and five foliar inhibitors on Cd and Cd-accumulation and quality of lettuce with low Pb and Cd accumulation (KCW). The results showed that different control measures had different effects on the soil pH value of lettuce, and the application of 45 g·m-2biochar-based passivator had the most significant difference in improving the soil pH value, which was increased by 0.8 units compared with that in CK. By using 72 g·m-2 of humic acid passivator yielded notable difference in reducing the soil pH value of lettuce. A reduction of 0.25 units was achieved compared with that in CK. Among all the control measures, the application of 45 g·m-2 biocharcoal-based passivation agent had the best effect on reducing soil available Cd content, which was significantly reduced by 53% compared with that in CK, and the application of 135 g·m-2biocharcoal-based passivation agent had the best effect on reducing soil available Pb content, which was significantly reduced by 64% compared with that in CK. Spraying 0.8% FAK-Zn foliar inhibitor not only had the best control effect on reducing Cd and Pb contents in the edible parts of lettuce, which were significantly reduced by 77% and 60%, respectively, compared with that in CK, but it also significantly reduced Cd and Pb enrichment coefficients and transport coefficients from the root to the edible parts of the lettuce. Different control measures had different effects on the nutritional quality of lettuce, and 0.4% FAK-Zn foliar inhibitor had the best effect on soluble protein. The 0.6% FAK-Zn had the best effect on soluble sugar, and the 0.4% FAK-Zn inhibitor had the best effect on vitamin C content. The application of biocarbon-based passivator could effectively repair lettuce soil polluted by Cd and Pb, whereas the application of FAK-Zn leaf surface inhibitor could effectively inhibit the accumulation, absorption, and transfer of Cd and Pb in lettuce; improve the nutritional quality of lettuce; provide a theoretical basis for safe production of vegetables polluted by heavy metals; and promote the recycling of resources and environment.

Three New Benzophenone Derivatives from Selaginella tamariscina.

Six compounds including three new benzophenones, selagibenzophenones D-F (1-3), two known selaginellins (4-5) and one known flavonoid (6), were isolated from Selaginella tamariscina. The structures of new compounds were established by 1D-, 2D-NMR and HR-ESI-MS spectral analyses. Compound 1 represents the second example of diarylbenzophenone from natural sources. Compound 2 possesses an unusual biphenyl-bisbenzophenone structure. Their cytotoxicity against human hepatocellular carcinoma HepG2 and SMCC-7721 cells and inhibitory activities on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells were evaluated. Compound 2 showed moderate inhibitory activity against HepG2 and SMCC-7721 cells, and compounds 4 and 5 showed moderate inhibitory activity to HepG2 cells. Compounds 2 and 5 also exhibited inhibitory activities on lipopolysaccharide-induced nitric oxide (NO) production.

Synergistic Reduction of Arsenic Uptake and Alleviation of Leaf Arsenic Toxicity in Maize (Zea mays L.) by Arbuscular Mycorrhizal Fungi (AMF) and Exogenous Iron through Antioxidant Activity.

Arbuscular mycorrhizal fungi (AMF) play key roles in enhancing plant tolerance to heavy metals, and iron (Fe) compounds can reduce the bioavailability of arsenic (As) in soil, thereby alleviating As toxicity. However, there have been limited studies of the synergistic antioxidant mechanisms of AMF (Funneliformis mosseae) and Fe compounds in the alleviation of As toxicity on leaves of maize (Zea mays L.) with low and moderate As contamination. In this study, a pot experiment was conducted with different concentrations of As (0, 25, 50 mgꞏkg-1) and Fe (0, 50 mgꞏkg-1) and AMF treatments. Results showed that under low and moderate As concentrations (As25 and As50), the co-inoculation of AMF and Fe compound significantly increased the biomass of maize stems and roots, phosphorus (P) concentration, and P-to-As uptake ratio. Moreover, the co-inoculation of AMF and Fe compound addition significantly reduced the As concentration in stem and root, malondialdehyde (MDA) content in leaf, and soluble protein and non-protein thiol (NPT) contents in leaf of maize under As25 and As50 treatments. In addition, co-inoculation with AMF and Fe compound addition significantly increased the activities of catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) in the leaves of maize under As25 treatment. Correlation analysis showed that stem biomass and leaf MDA content were very significantly negatively correlated with stem As content, respectively. In conclusion, the results indicated that the co-inoculation of AMF and Fe compound addition can inhibit As uptake and promote P uptake by maize under low and moderate As contamination, thereby mitigating the lipid peroxidation on maize leaves and reducing As toxicity by enhancing the activities of antioxidant enzymes under low As contamination. These findings provide a theoretical basis for the application of AMF and Fe compounds in the restoration of cropland soil contaminated with low and moderate As.

Coupling of protein condensates to ordered lipid domains determines functional membrane organization.

During T cell activation, the transmembrane adaptor protein LAT (linker for activation of T cells) forms biomolecular condensates with Grb2 and Sos1, facilitating signaling. LAT has also been associated with cholesterol-rich condensed lipid domains; However, the potential coupling between protein condensation and lipid phase separation and its role in organizing T cell signaling were unknown. Here, we report that LAT/Grb2/Sos1 condensates reconstituted on model membranes can induce and template lipid domains, indicating strong coupling between lipid- and protein-based phase separation. Correspondingly, activation of T cells induces cytoplasmic protein condensates that associate with and stabilize raft-like membrane domains. Inversely, lipid domains nucleate and stabilize LAT protein condensates in both reconstituted and living systems. This coupling of lipid and protein assembly is functionally important, as uncoupling of lipid domains from cytoplasmic protein condensates abrogates T cell activation. Thus, thermodynamic coupling between protein condensates and ordered lipid domains regulates the functional organization of living membranes.

Rab3 mediates a pathway for endocytic sorting and plasma membrane recycling of ordered microdomains.

The composition of the plasma membrane (PM) must be tightly controlled despite constant, rapid endocytosis, which requires active, selective recycling of endocytosed membrane components. For many proteins, the mechanisms, pathways, and determinants of this PM recycling remain unknown. We report that association with ordered, lipid-driven membrane microdomains (known as rafts) is sufficient for PM localization of a subset of transmembrane proteins and that abrogation of raft association disrupts their trafficking and leads to degradation in lysosomes. Using orthogonal, genetically encoded probes with tunable raft partitioning, we screened for the trafficking machinery required for efficient recycling of engineered microdomain-associated cargo from endosomes to the PM. Using this screen, we identified the Rab3 family as an important mediator of PM localization of microdomain-associated proteins. Disruption of Rab3 reduced PM localization of raft probes and led to their accumulation in Rab7-positive endosomes, suggesting inefficient recycling. Abrogation of Rab3 function also mislocalized the endogenous raft-associated protein Linker for Activation of T cells (LAT), leading to its intracellular accumulation and reduced T cell activation. These findings reveal a key role for lipid-driven microdomains in endocytic traffic and suggest Rab3 as a mediator of microdomain recycling and PM composition.

Abdominal paracentesis drainage improves outcome of acute pancreatitis complicated with intra-abdominal hypertension in early phase.

BACKGROUND: Intra-abdominal hypertension (IAH) is an important risk factor for organ dysfunction, and it occurs in the early phase of severe acute pancreatitis (SAP). We have reported a novel step-up approach and shown the benefit of performing abdominal paracentesis drainage (APD) ahead of percutaneous catheter drainage (PCD) when treating Patients with SAP with fluid collections. This study aimed to evaluate the efficacy of APD in Patients with SAP complicated with IAH in the early phase. METHODS: In the present study, 206 AP patients complicated with IAH in the early phase were enrolled in hospital between June 2017 and December 2020. The patients were divided into two groups: 109 underwent APD (APD group) and 97 were managed without APD (non-APD group). We retrospectively compared the outcomes of the APD and non-APD groups for IAH treatment. The parameters including mortality, infection, organ failure, inflammatory factors, indications for further interventions, and drainage-related complications were observed. RESULTS: The demographic data and severity scores of the two groups were comparable. The mortality rate was lower in the APD group (3.7%) than in the non-APD group (8.2%). Compared with the non-APD group, the intra-abdominal pressure and laboratory parameters of the APD group decreased more rapidly, and the mean number of failed organs was lower. However, there was no significant difference in incidence of infections between the two groups. CONCLUSIONS: Application of APD is beneficial to AP patients. It significantly attenuated inflammation injury, avoided further interventions, and reduced multiple organ failure.

Development of dynamical network biomarkers for regulation in Epstein-Barr virus positive peripheral T cell lymphoma unspecified type.

Background: This study was performed to identify key regulatory network biomarkers including transcription factors (TFs), miRNAs and lncRNAs that may affect the oncogenesis of EBV positive PTCL-U. Methods: GSE34143 dataset was downloaded and analyzed to identify differentially expressed genes (DEGs) between EBV positive PTCL-U and normal samples. Gene ontology and pathway enrichment analyses were performed to illustrate the potential function of the DEGs. Then, key regulators including TFs, miRNAs and lncRNAs involved in EBV positive PTCL-U were identified by constructing TF-mRNA, lncRNA-miRNA-mRNA, and EBV encoded miRNA-mRNA regulatory networks. Results: A total of 96 DEGs were identified between EBV positive PTCL-U and normal tissues, which were related to immune responses, B cell receptor signaling pathway, chemokine activity. Pathway analysis indicated that the DEGs were mainly enriched in cytokine-cytokine receptor interaction and chemokine signaling pathway. Based on the TF network, hub TFs were identified regulate the target DEGs. Afterwards, a ceRNA network was constructed, in which miR-181(a/b/c/d) and lncRNA LINC01744 were found. According to the EBV-related miRNA regulatory network, CXCL10 and CXCL11 were found to be regulated by EBV-miR-BART1-3p and EBV-miR-BHRF1-3, respectively. By integrating the three networks, some key regulators were found and may serve as potential network biomarkers in the regulation of EBV positive PTCL-U. Conclusion: The network-based approach of the present study identified potential biomarkers including transcription factors, miRNAs, lncRNAs and EBV-related miRNAs involved in EBV positive PTCL-U, assisting us in understanding the molecular mechanisms that underlie the carcinogenesis and progression of EBV positive PTCL-U.

Effective treatment of high-voltage pulsed radiofrequency combined with oxygen-ozone injection in acute zoster neuralgia.

INTRODUCTION: Postherpetic neuralgia (PHN) is the most common and severe complication of acute herpes zoster. Early treatment of herpes zoster neuralgia is of great significance to reduce the incidence of PHN. This retrospective study evaluated the efficacy and safety of the combination of high-voltage pulsed radiofrequency (PRF) and oxygen-ozone(O2-O3) injection in patients with acute zoster neuralgia (AZN) who failed to respond to conservative treatment. METHODS: One-hundred patients diagnosed with AZN were classified into two groups (high-voltage PRF group [HP group, n = 50] and high-voltage PRF combined with O2-O3 injection group [HPO group, n = 50]) based on different treatment methods. Therapeutic effectiveness was assessed using a numerical rating scale (NRS) and the Pittsburgh Sleep Quality Index (PSQI). The dosages of gabapentin and tramadol (mg/d) before treatment and after 1 week and 1, 3, and 6 months of treatment were measured. The incidence of clinically meaningful PHN after treatment was also recorded. RESULTS: Pain intensity and sleep quality in both groups at all time points improved after treatment compared to before treatment (P < 0.05). After 1 week and 1 month of treatment, NRS and PSQI scores in both groups decreased, but the differences were not statistically significant (P > 0.05). NRS, PSQI scores, and the dosages of gabapentin and tramadol decreased more significantly in the HPO group than those in the HP group after 3 months (P < 0.05). The incidence of PHN was significantly lower in the HPO group than in the HP group (P < 0.05). There were no significant differences in adverse events between the groups. CONCLUSIONS: High-voltage PRF is a safe and effective method for treating AZN. The combination of high-voltage PRF and O2-O3 injection is superior to high-voltage PRF alone for treating late-stage AZN. This approach could be recommended as an alternative treatment for patients with refractory AZN and could significantly reduce the risk of PHN.

Dose caffeinated energy drink is a consideration issue for endurance performance.

Caffeinated energy drinks are commonly taken to improve exercise performance, but there are few studies on the influence of different doses on an athlete's performance. We conducted a double-blind, randomized, counter-balanced, and crossover research study to examine the effects of low caffeinated energy drink (Low ED) or high caffeinated energy drink (High ED) supplement on the performance, haematological response, and oxidative stress in triathletes. Twelve male participants underwent three testing sessions separated by weekly intervals, consisting of sprint triathlon training (0.75 km swim, 20 km cycle, and 5 km run). Before and during the trials, participants were randomly provided with either placebo (PLA) group, Low ED group, or High ED group. Exercise performance in the High ED group decreased significantly compared with the PLA and Low ED groups (p < 0.05). However, participants in the Low ED group also experienced an improved performance (p = 0.054). Analysis of variance revealed no differences among the three groups in cortisol and testosterone levels, or the Borg Rating of Perceived Exertion score (p > 0.5). Furthermore, superoxide dismutase (SOD) was reduced with exercise and were lowest in the High ED group. However, compared with PLA, a significant decrease of thiobarbituric acid reactive substances (TBARS) was observed in Low ED and High ED groups (p < 0.05). This indicates that caffeinated energy drink consumption may improve performance and reduce oxidative stress in sprint triathlon athletes. However, individual differences should be considered when supplementing with caffeinated energy drinks to decrease side effects.

Analysis of non-retinopathy of prematurity (ROP)-related fundus hemorrhage in preterm infants in China.

Objective: To determine the incidence of fundus hemorrhage (FH) not associated with retinopathy of prematurity (ROP) during ocular screening and report their clinical features, risk factors, therapies, and prognosis in a large population of premature newborns. Methods: The medical records of all preterm newborns admitted to the Department of Ophthalmology, Peking University People's Hospital, Beijing, from January 1, 2016 through August 31, 2021 were retrospectively reviewed. Fundus examinations were carried out by experienced retinal experts. Examination under anesthesia was carried out in newborns with abnormal fundus including vitreous hemorrhage (VH) or retinal hemorrhage (RH) >2 disks' diameter by a Retcam 2 system. A lens-preserving vitrectomy was performed in infants requiring a vitrectomy. A comprehensive medical history was also recorded and analyzed. Results: During the 5-year period, a total of 7,260 preterm babies were screened. There were 82 (1.13%) newborns and 104 (0.72) eyes with FH, including VH or RH.Twelve (14.63%) newborns (16 eyes, 15.38%) had VH; 56 (68.29%) (74 eyes, 71.15%) had flame-shaped, superficial hemorrhages; six (7.31%) (6 eyes, 5.77%) had small, round, deep hemorrhages (<2 disk diameters in size); and eight (9.76%) (8 eyes, 7.69%) had large, round hemorrhages (>2 disk diameters). In all, there were 10 (12.20%) cases of intracranial hemorrhage. The mode of delivery was not found to be a significant factor in the occurrence of birth-related retinal hemorrhage (P = 0.22).Six newborns (eyes) with large, round retinal hemorrhage at the posterior pole while the macular was not impacted and 11 cases (15 eyes) with vitreous hemorrhage were required to receive close follow-up with average follow-up time of 105 days. A lens-sparing vitreous surgery was conducted in three patients without any complications. Conclusion: Preterm newborns with FH that are not caused by ROP are more likely to have superficial, peripheral hemorrhages. Vaginal delivery compression and forceps may be associated with hemorrhage. A lens-preserving vitrectomy is required and considered safe for dense FH involving the refractive media.

Effects of electroacupuncture with dexmedetomidine on myocardial ischemia/reperfusion injury in rats.

BACKGROUND: To investigate the protective effect of electroacupuncture combined with dexmedetomidine (EA + Dex) on oxidative stress injury in myocardial ischemia/reperfusion (I/R) rats. METHODS: A total of 50 male Sprague-Dawley (SD) rats were randomly divided into 5 groups: sham operation (sham group); I/R group; dexmedetomidine group (Dex group); electroacupuncture group (EA group); and EA + Dex group. The myocardial I/R model was established. The EA group received EA at the Neiguan acupoint [pericardium 6 (PC6)] every day for 1 week before modeling. Rats in the EA + Dex group received EA at PC6 every day for 1 week before modeling, and intraperitoneal injection of Dex was performed 15 minutes before modeling. Dex was injected intraperitoneally in the Dex group 15 minutes before modeling. The rats were sacrificed 1 hour after reperfusion, and myocardial tissue was obtained to measure the myocardial infarction area. The myocardial tissue pathologic changes were shown by hematoxylin and eosin (HE) staining, and the superoxide dismutase (SOD), malondialdehyde (MDA), adenosine triphosphate (ATP), and reactive oxygen species (ROS) content in serum was determined. RESULTS: Compared with the sham group, the myocardial infarction area was significantly increased (P<0.01), SOD and ATP content was significantly decreased (P<0.01), and MDA and ROS content was significantly increased (P<0.01) in the I/R group; this change was significantly reduced in the Dex, EA, and EA + Dex groups (P<0.01). The indicators in the EA + Dex group were better than those in the EA and Dex groups (P<0.05). There was no significant change in the above indices in the Dex group compared with the EA group (P>0.05). CONCLUSIONS: EA + Dex pretreatment improved the damage of myocardial I/R by increasing SOD and ATP content and reducing the generation of MDA and ROS in an oxygen-free radical system.

Mitochondrion, lysosome, and endoplasmic reticulum: Which is the best target for phototherapy?

Photodynamic therapy (PDT) is a robust cancer treatment modality, and the precise spatiotemporal control of its subcellular action site is crucial for its effectiveness. However, accurate comparison of the efficacy of different organelle-targeted PDT approaches is challenging since it is difficult to find a single system that can achieve separate targeting of different organelles with separable time windows and similar binding amounts. Herein, we conjugated chlorin e6 (Ce6) with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-5000] (ammonium salt) (DSPE-PEG5000-NH2) to afford DSPE-PEG-Ce6, which could migrate from mitochondrion to lysosome and ultimately to endoplasmic reticulum (ER) after cellular internalization. Benefiting from the dynamic subcellular distribution of DSPE-PEG-Ce6 with tunable organelle-binding amounts, we accurately determined the PDT efficacy order of the molecule, i.e., mitochondrion > ER > lysosome. This work proposes an ideal model system for accurately evaluating the specific organelle-targeted PDT efficacy and may promote the future development of effective PDT strategies.