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The nearby radio galaxy M87 is a very high-energy (VHE) gamma-ray emitter established by observations with ground-based gamma-ray detectors. Here we report the long-term monitoring of M87 from 2021 to 2024 with the Large High Altitude Air Shower Observatory (LHAASO). M87 has been detected by LHAASO with a statistical significance ∼ 9 σ . The observed energy spectrum extends to 20 TeV, with a possible hardening at ∼20 TeV and then a clear softening at higher energies. Assuming that the intrinsic spectrum is described by a single power law up to 20 TeV, a tight upper bound on the extragalactic background light intensity is obtained. A strong VHE flare lasting 8 days, with a rise time of ${\tau }_{r}^{\mathrm{rise}}=1.05\pm 0.49$ days and decay time of ${\tau }_{d}^{\mathrm{decay}}=2.17\pm 0.58$ days, was found in early 2022. A possible GeV flare is seen also in Fermi Large Area Telescope data during the VHE flare period. The variability time as short as 1 day seen in the LHAASO data suggests a compact emission region with a size of ∼3 × 10 ^15 δ cm ( δ being the Doppler factor of the emitting region), corresponding to a few Schwarzschild radii of the central supermassive black hole in M87. The continuous monitoring of the source reveals a duty cycle of ∼1% for VHE flares with a flux above 10 ^−11 erg cm ^−2 s ^−1 .

The first source catalog of the Large High Altitude Air Shower Observatory (LHAASO) reported the detection of a very high energy gamma-ray source, 1LHAASO J1219+2915. This Letter presents a further detailed study of the spectral and temporal behavior of this pointlike source. The best-fit position of the TeV source (R.A. = 185.°05 ± 0.°04, decl. = 29.°25 ± 0.°03) is compatible with NGC 4278 within ∼0.°03. Variation analysis shows an indication of variability on a timescale of a few months in the TeV band, which is consistent with low-frequency observations. Based on these observations, we report the detection of TeV γ -ray emissions from this low-luminosity active galactic nucleus. The observation by LHAASO's Water Cherenkov Detector Array during the active period has a significance level of 8.8 σ with a best-fit photon spectral index Γ = 2.56 ± 0.14 and a flux f _1–10 TeV = (7.0 ± 1.1 _sta ± 0.35 _syst ) × 10 ^−13 photons cm ^−2 s ^−1 , or approximately 5% of the Crab Nebula. The discovery of VHE gamma-ray emission from NGC 4278 indicates that compact, weak radio jets can efficiently accelerate particles and emit TeV photons.

Rotating radio transients (RRATs) are neutron stars that emit sporadic radio bursts. We detected 1955 single pulses from RRAT J1913+1330 using the 19 beam receiver of the Five-hundred-meter Aperture Spherical radio Telescope. These pulses were detected in 19 distinct clusters, with 49.4% of them occurring with a waiting time of one rotation period. The energy distribution of these individual pulses exhibited a wide range, spanning 3 orders of magnitude, reminiscent of repeating fast radio bursts (FRBs). Furthermore, we observed abrupt variations in pulse profile, width, peak flux, and fluence between adjacent sequential pulses. These findings suggest that this RRAT could be interpreted as a pulsar with extreme pulse-to-pulse modulation. The presence of sequential pulse trains during active phases, along with significant pulse variations in profile, fluence, flux, and width, should be intrinsic to a subset of RRATs. Our results indicate that J1913+1330 represents a peculiar source that shares certain properties with populations of nulling pulsars, giant pulses, and FRBs from different perspectives. The dramatic pulse-to-pulse variation observed in J1913+1330 could be attributed to unstable pair creation above the polar cap region and the variation of the site where streaming pairs emit coherently. Exploring a larger sample of RRATs exhibiting similar properties to J1913+1330 has the potential to significantly advance our understanding of pulsars, RRATs, and FRBs.

We present the first catalog of very-high-energy and ultra-high-energy gamma-ray sources detected by the Large High Altitude Air Shower Observatory. The catalog was compiled using 508 days of data collected by the Water Cherenkov Detector Array from 2021 March to 2022 September and 933 days of data recorded by the Kilometer Squared Array from 2020 January to 2022 September. This catalog represents the main result from the most sensitive large coverage gamma-ray survey of the sky above 1 TeV, covering decl. from −20° to 80°. In total, the catalog contains 90 sources with an extended size smaller than 2° and a significance of detection at >5 σ . Based on our source association criteria, 32 new TeV sources are proposed in this study. Among the 90 sources, 43 sources are detected with ultra-high energy ( E > 100 TeV) emission at >4 σ significance level. We provide the position, extension, and spectral characteristics of all the sources in this catalog.

Recent James Webb Space Telescope data analyses have shown that massive red galaxies existed at redshifts z ≳ 6, a discovery that is difficult to understand in the context of standard cosmology (ΛCDM). Here, we analyze these observations more deeply, by fitting a stellar population model to the optical and near-infrared photometric data. These fits include a main stellar population in addition to a residual younger population and with the same extinction for both (a lower extinction for the younger population is unphysical). Extra stellar populations or the inclusion of an active galactic nucleus component do not significantly improve the fits. These galaxies are being viewed at very high redshifts, with an average 〈 z 〉 ≈ 8.2, when the ΛCDM Universe was only ≈600 Myr old. This result conflicts with the inferred ages of these galaxies, however, which were on average between 0.9 and 2.4 Gyr old within a 95% confidence level. Given the sequence of star formation and galaxy assembly in the standard model, these galaxies should instead be even younger than 290 Myr on average, for which our analysis assigns a probability of only

Objective: To explore the mechanism by which Yigong San (YGS) improves learning and memory abilities of APP/PS1 transgenic mice in light of cerebral fluid metabolism regulation., Methods: Three-month-old male APP/PS1 transgenic mice and wild-type C57BL/6 mice were both randomized into control group, model group, donepezil (1.67 mg/kg) group, and YGS (7.5 g/kg) group and received the corresponding treatments via gavage once daily for one month. After the treatments, the mice were assessed for learning and memory functions using Morris water maze test and examined for hippocampal and cortical pathologies and amyloid plaques using HE, immunohistochemical and thioflavin S staining; ELISA and Evans blue method were used for detecting Aβ 1-40 and Aβ 1-42 levels in the brain tissue and serum and assessing blood-brain barrier (BBB) integrity. Immunofluorescence colocalization was used to investigate AQP4 polarization on astrocytes. Western blotting was performed to detect the expressions of VE-cadherin, ZO-1, occludin, β-amyloid precursor protein (APP), BACE1, insulin-degrading enzyme (IDE), LRP1, RAGE, and AQP4 proteins., Results: Compared with the control mice, APP/PS1 mice showed significant impairment of learning and memory abilities, increased degeneration or necrosis of hippocampal and cortical neurons, pathological scores, Aβ-positive plaques, elevated Aβ 1-40 and Aβ 1-42 levels in the brain tissue and serum, increased BBB permeability, upregulated RAGE expression, lowered expressions of VE-cadherin, LRP1, ZO-1, occludin, and AQP4 proteins, and reduced AQP4- expressing GFAP-positive cells. YGS treatment significantly improved the performance of the transgenic mice in Morris water maze test, reduced hippocampal and cortical pathologies and Aβ-positive plaques, and ameliorated the abnormal changes in Aβ 1-40 and Aβ 1-42 levels, BBB permeability, protein expressions of RAGE, VE-cadherin, LRP1, ZO-1, occludin and AQP4, and the number of AQP4-expressing GFAP-positive cells., Conclusion: YGS improves learning and memory changes in APP/PS1 mice by ameliorating neuronal damage and Aβ pathology in the brain and regulating brain fluid metabolism.

Introduction: Xerostomia is a subjective sensation of dry mouth affecting millions of people worldwide. Current management has limitations, often causing side effects. This study aims to investigate whether electrical stimulation of the lingual nerve could offer effective relief for xerostomia sufferers., Methods: Eligible participants were randomly assigned (1:1) to either the experimental or sham group, receiving electrical stimulation of the lingual nerve ( n = 24) or sham stimulation ( n = 23) for 12 wk. The primary outcome is the changes in xerostomia score using a 100-mm visual analog scale throughout the therapy. Participants assessed their dryness and assigned corresponding scores, with lower scores indicating more severe dry mouth. Secondary outcomes included remission rate in dry mouth frequency, changes in stimulated/unstimulated salivary flow rate (SSFR/USFR), and changes in Oral Health Impact Profile-14 (OHIP-14) questionnaire scores, where higher scores indicate greater impact on oral quality of life., Results: At week 12, the electrical stimulation group showed greater improvement in xerostomia score compared to the sham group, with a mean between-group difference of 13.8 (95% confidence interval [CI], 10.0-17.6). The therapeutic effect of electrical stimulation was also confirmed by secondary outcomes. The remission rate of dry mouth was higher at 12 wk in the electrical stimulation group (61.9% [95% CI, 40.9%-79.3%] vs. 28.6% [95% CI, 13.8%-50.0%]). Participants in the electrical stimulation group also experienced a greater increase in USFR, with a mean difference of 14.5 (6.1-23.0) μL/min. Moreover, they exhibited significant improvement in OHIP-14 score after 12 wk of therapy, with a mean between-group difference of -10.0 (-13.9 to -6.2). No significant difference was observed between the 2 groups for SSFR ( P = 0.702)., Conclusions: Electric stimulation offers promise as a noninvasive, nonpharmacological strategy for the management of xerostomia. Further research is needed to understand its long-term effectiveness, optimal parameters, and underlying mechanisms., Knowledge Transfer Statement: The study confirmed that electrical stimulation of the lingual nerve is a promising noninvasive and nonpharmacological modality for relief of xerostomia., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To investigate the changes of the distribution and drug resistance profile of bacteria from ICU children with lower respiratory tract infection (LRTI) in Suzhou City, Jiangsu Province from 2017 to 2022. Methods: From January 2017 to December 2022, a cross-sectional observational study on the bacterial spectrum analysis among intensive care unit (ICU) children with LRTI was conducted in Children's Hospital of Soochow University. The bacteria was cultivated by culture methods from sputum samples, and identified by MALDI-TOF mass spectrometry. Drug sensitivity tests were performed by the VITEK2 Compact fully automated analysis system and the paper slide method. The χ 2 test or Fisher's exact probability was used to analyze the changes of the distribution of sputum culture-positive bacteria and drug resistance in ICU children. Results: The overall detection rate of sputum culture was 42.06% (1 182/2 810). Staphylococcus aureus (25.63%,303/1 182), Acinetobacter baumannii (13.62%,161/1 182) and Haemaphilus influenzae (13.28%,157/1 182) were the top three. Proportions of Acinetobacter baumannii (17.90% vs. 11.02%, χ ²=11.17, P =0.001), especially carbapenem-resistant Acinetobacter baumannii (43.70% vs. 23.50%, χ² =15.21, P <0.001) increased significantly from 2020 to 2022. However, the proportions of Haemophilus influenzae (8.50% vs. 16.19%, χ ²=14.27, P <0.001), Streptococcus pneumoniae (8.50% vs. 15.92%, χ ²=13.42, P <0.001) and extended-spectrum-lactamase producing Escherichia coli (8.89% vs. 18.00%, χ ²=5.45, P =0.025) decreased. Drug resistant results showed that Acinetobacter baumannii was obviously more resistant to imipenem ( χ² =4.43, P =0.035) and levofloxacin ( χ ²=12.53, P <0.001), while more sensitive to minocycline ( χ ²=8.34, P =0.004). Escherichia coli showed a significant increase in resistance to piperacillin tazobactam ( χ ²=8.29, P =0.008) and cefoperazone sulbactam ( χ ²=5.07, P =0.024) from 2020 to 2022; Klebsiella pneumoniae consistently maintained a resistance rate of more than 60% to first and second-generation cephalosporins, and remain susceptible to quinolones and carbapenems. Staphylococcus aureus remained highly susceptible to levofloxacin (drug resistance rate: 2.31%,7/303) and sulfamethoxazole/trimethoprim (drug resistance rate: 4.95%,15/303) from 2020 to 2022. Conclusion: Higher detection and resistance rates of Acinetobacter baumannii from sputum culture in ICU children from 2020 to 2022 were explored. Resistance of Escherichia coli to β-lactamase inhibitor combinations was more serious. Regular monitoring the changes of the etiology of respiratory tract infections in ICU Children is particularly important for the prevention and treatment of multidrug-resistant bacterial infections.

Objective: To investigate the trimester-specific associations between maternal total physical activity level vs moderate-to-vigorous exercise and fetal growth disorders., Methods: We analyzed 2062 mother-neonate pairs participating in the longitudinal China Medical University Birth Cohort Study. The Pregnancy Physical Activity Questionnaire was used to assess the physical activity level of women during the three trimesters. A higher level of total physical activity was defined as meeting or exceeding the cohort-specific 75 th percentile, and a higher level of exercise was defined according to the Physical Activity Guidelines for Americans. Fetal growth disorder was defined as small-for-gestational age (SGA) or large-for-gestational age (LGA) at birth., Results: Of the neonates included in this study, 7.1% were SGA and 15.5% were LGA. A higher level of total physical activity during the first trimester (adjusted relative risk (aRR), 0.62 (95% CI, 0.42-0.91)) and second trimester (aRR, 0.62 (95% CI, 0.41-0.95)) was associated with a lower risk of SGA, and a higher level of total physical activity during the third trimester was associated with a lower risk of LGA (aRR, 0.73 (95% CI, 0.54-0.97)). When analyzing physical activity by subtype, a higher level of occupational physical activity during the first and second trimesters was associated negatively with SGA risk, and higher levels of occupational and low-intensity physical activity during the first trimester were associated negatively with LGA risk. No significant association was found between maternal adherence to the Physical Activity Guidelines for Americans and risk of fetal growth disorders., Conclusions: A higher total physical activity level during the first and second trimesters was associated with a decreased risk of SGA, whereas a higher total physical activity level in the third trimester was associated with a decreased risk of LGA. Pregnant women should be advised to increase their total physical activity levels instead of focusing on engaging in only moderate-to-vigorous exercise. © 2024 International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To investigate the clinicopathological, immunohistochemical and molecular genetic characteristics of TFE3-rearranged perivascular epithelioid cell tumor (PEComa). Methods: Eight cases of PEComa with TFE3 rearrangement diagnosed in the First Affiliated Hospital of Air Force Medical University from January 2014 to July 2022 were collected. Three were consultation cases and 5 were collected from our hospital; 7 cases were resection specimens and 1 case was a needle biopsy specimen. Routine histolopathological analysis, immunohistochemical staining, fluorescence in situ hybridization (FISH) and the next-generation sequencing were performed. Clinical data were collected and the prognosis was assessed. Results: The 8 patients consisted of 5 females and 3 males with a median age of 45 years (ranged from 25 to 65 years). The tumor location included 1 uterus, 1 liver, 1 urachus, 2 kidneys, 1 abdominal cavity, 1 colon, and 1 retroperitoneum (3 subsequent recurrences in the abdominal cavity, pelvis and ovary, and abdominal cavity, respectively). Morphologically, the tumor cells were uniform and epithelioid with translucent or eosinophilic cytoplasm. They were arranged in nests or sheets, most of which were separated by thin-walled blood vessels. There were no papillary structures, and no overt smooth muscle or fat components. Atypical features were seen in 3 cases, with bizarre nuclei and tumor giant cells. Large areas of necrosis were visible, and mitosis was common (up to 28/50 HPF). Melanin deposition was present in 3 cases. Immunohistochemical staining showed diffuse and strong positivity for TFE3 in 8/8 cases and for HMB45 in 6/8 cases; focal positivity for Cathepsin K and Melan-A in 6/8 cases and for SMA in 2/8 of cases. All cases were negative for CKpan, PAX8 and Desmin. TFE3 gene break-apart was detected by FISH in all 8 cases, 4 of which underwent next-generation sequencing, and it revealed that 2 cases presented with SFPQ::TFE3 fusion, 1 case with ASPSCR1::TFE3 fusion, and 1 case with no chimeric fusion. Seven cases were followed up for 4-94 months. All cases were alive; 4 cases were disease-free, 2 cases showed recurrence, and 1 case had metastasis at initial diagnosis. Conclusions: TFE3-rearranged PEComa has unique histomorphological, immunohistochemical and molecular characteristics. The biological behavior is aggressive, which could lead to recurrence and metastasis, and warrants close clinical follow-up.

Objective: To investigate the effect of Yigong San (YGS) on learning and memory abilities of rats with lipopolysaccharide (LPS)‑induced cognitive decline and explore its possible mechanism in light of intestinal microbiota., Methods: Forty SD rats were randomly divided into control group, model group, donepezil (1.3 mg/kg) group, and high-dose (5.25 g/kg) and low-dose (2.63 g/kg) YGS treatment groups. After 24 days of treatment with the corresponding drugs or water by gavage, the rats in the latter 4 groups received an intraperitoneal injection of LPS (0.5 mg/kg) to establish models of Alzheimer's disease (AD). Water maze test and HE staining were used to evaluate the changes in learning and memory abilities and pathomorphology of the hippocampus. The changes in gut microbial species of the rats were analyzed with 16S rRNA sequencing, and the levels of IL-6, TNF- α , and IL-1β in the brain tissue and serum were detected using ELISA., Results: Compared with the AD model group, the YGS-treated rats showed significantly shortened escape latency on day 5 after modeling, reduced neuronal degeneration and necrosis in the hippocampus, lowered pathological score of cell damage, and decreased levels IL-6, TNF- α and IL-1β in the brain tissue and serum. The YGS-treated rats showed also obvious reduction of Alpha diversity indicators (ACE and Chao1) of intestinal microbiota with significantly increased abundance of Prevotellaceae species at the family level and decreased abundance of Desulfovibrionaceae , which were involved in such metabolic signaling pathways as cell community prokaryotes, membrane transport, and energy metabolism., Conclusion: YGS improves learning and memory abilities and hippocampal pathomorphology in AD rat models possibly by regulating the abundance of intestinal microbial species such as Prevotellaceae to affect the metabolic pathways for signal transduction, cofactors, and vitamin metabolism.

Constipation during pregnancy can induce serious complications, including miscarriage and preterm labour, while the evidence of probiotics in improving constipation during pregnancy was little. In this study, 29 healthy pregnant women and 65 constipated pregnant women were enrolled to assess the effectiveness of probiotics on constipation during pregnancy. Our results showed that the probiotics were effective in improving the Constipation Severity Scale (CSS) and Bristol Stool Scale (BSS) scores, including increasing defecation frequency, decreasing defecation time, and improving fecal characteristics. 16S rRNA sequencing revealed that the probiotics effectively restored the diversity of intestinal microbiota. At the phylum level, Firmicutes (13.27% vs 57.20%) and Actinobacteria (3.77% vs 12.80%) were increased, while Bacteroidetes (77.82% vs 20.24%) was decreased. At the level of the genus, Faecalibacterium (2.03% vs 10.33%), Bifidobacterium (1.21% vs 8.56%), and Phascolarctobacterium (0.05% vs 2.88%), the beneficial bacteria were increased, while the Bacteroides (29.23% vs 12.28%) and Prevotella (24.32% vs 4.92%) were decreased. In conclusion, these results indicated that probiotics can effectively relieve the constipation symptoms by improving the diversity of intestinal microbiota, regulating the disturbance of microflorae, and restoring the balance of microflorae to exert a stronger moderating effect than diet and lifestyle modification. Our results provided clinical data and a theoretical basis for the exploitation of probiotics in treating constipation during pregnancy. Chinese Clinical Trial Registry: ChiCTR2100052069.

Precision measurements by the Alpha Magnetic Spectrometer (AMS) on the International Space Station of the deuteron (D) flux are presented. The measurements are based on 21×10^{6} D nuclei in the rigidity range from 1.9 to 21 GV collected from May 2011 to April 2021. We observe that over the entire rigidity range the D flux exhibits nearly identical time variations with the p, ^{3}He, and ^{4}He fluxes. Above 4.5 GV, the D/^{4}He flux ratio is time independent and its rigidity dependence is well described by a single power law ∝R^{Δ} with Δ&#95;{D/^{4}He}=-0.108±0.005. This is in contrast with the ^{3}He/^{4}He flux ratio for which we find Δ&#95;{^{3}He/^{4}He}=-0.289±0.003. Above ∼13  GV we find a nearly identical rigidity dependence of the D and p fluxes with a D/p flux ratio of 0.027±0.001. These unexpected observations indicate that cosmic deuterons have a sizable primarylike component. With a method independent of cosmic ray propagation, we obtain the primary component of the D flux equal to 9.4±0.5% of the ^{4}He flux and the secondary component of the D flux equal to 58±5% of the ^{3}He flux.

Objective: To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice. Methods: Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate's parents used the JCard to measure jaundice at the neonate's cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson's correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis. Results: Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r =0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0 μmol/L. The TcB value of 205.2 μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P> 0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P <0.05). Conclusions: JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Lifestyle intervention encompassing nutrition and physical activity are effective strategies to prevent progressive lipid deposition in the liver. This study aimed to explore the effect of dietary change, and/or high-intensity interval training (HIIT) on hepatic lipid accumulation in high fat diet (HFD)-induced obese rats. We divided lean rats into lean control (LC) or HIIT groups (LH), and obese rats into obese normal chow diet (ND) control (ONC) or HIIT groups (ONH) and obese HFD control (OHC) or HIIT groups (OHH). We found that dietary or HIIT intervention significantly decreased body weight and the risk of dyslipidemia, prevented hepatic lipid accumulation. HIIT significantly improved mitochondrial fatty acid oxidation through upregulating mitochondrial enzyme activities, mitochondrial function and AMPK/PPARalpha/CPT1alpha pathway, as well as inhibiting hepatic de novo lipogenesis in obese HFD rats. These findings indicate that dietary alone or HIIT intervention powerfully improve intrahepatic storage of fat in diet induced obese rats. Keywords: Obesity, Exercise, Diet, Mitochondrial function, Lipid deposition.

Objective: To investigate the effects of different ventilation strategies on intraocular pressure (IOP) and intracranial pressure in patients undergoing spinal surgery in the prone position under general anesthesia., Methods: Seventy-two patients undergoing prone spinal surgery under general anesthesia between November, 2022 and June, 2023 were equally randomized into two groups to receive routine ventilation (with Vt of 8mL/kg, Fr of 12-15/min, and etCO 2 maintained at 35-40 mmHg) or small tidal volume hyperventilation (Vt of 6 mL/kg, Fr of18-20/min, and etCO 2 maintained at 30-35 mmHg) during the surgery. IOP of both eyes (measured with a handheld tonometer), optic nerve sheath diameter (ONSD; measured at 3 mm behind the eyeball with bedside real-time ultrasound), circulatory and respiratory parameters of the patients were recorded before anesthesia (T 0 ), immediately after anesthesia induction (T 1 ), immediately after prone positioning (T 2 ), at 2 h during operation (T 3 ), immediately after supine positioning after surgery (T 4 ) and 30 min after the operation (T 5 )., Results: Compared with those at T 1 , IOP and ONSD in both groups increased significantly at T 3 and T 4 ( P < 0.05). IOP was significantly lower in hyperventilation group than in routine ventilation group at T 3 and T 4 ( P < 0.05), and ONSD was significantly lower in hyperventilation group at T 4 ( P < 0.05). IOP was positively correlated with the length of operative time ( r =0.779, P < 0.001) and inversely with intraoperative etCO 2 at T 3 ( r =-0.248, P < 0.001) and T 4 ( r =-0.251, P < 0.001).ONSD was correlated only with operation time ( r =0.561, P < 0.05) and not with IOP ( r =0.178, P >0.05 at T 3 ; r =0.165, P >0.05 at T 4 )., Conclusion: Small tidal volume hyperventilation can relieve the increase of IOP and ONSD during prone spinal surgery under general anesthesia.

Background: Heart failure with preserved ejection fraction (HFpEF) is the most common cardiac complication in patients with coronary microvascular dysfunction (CMD), yet its underlying pathways remain unclear. Aortic pulse-wave velocity (aPWV) is an indicator of large artery stiffness and a predictor for cardiovascular disease. However, aPWV in CMD and HFpEF is not well characterized and may provide understanding of disease progression., Methods: Among participants without obstructive coronary artery disease, we evaluated 51 women with suspected CMD and 20 women and men with evidence of HFpEF. All participants underwent aPWV measurement (SphygmoCor, Atcor Medical) with higher aPWV indicating greater vascular stiffness. Cardiac magnetic resonance imaging (CMRI) assessed left ventricular (LV) ejection fraction, CMD via myocardial perfusion reserve index (MPRI), and ventricular remodeling via LV mass-volume ratio. . Statistical analysis was performed using Wilcoxon rank sum tests, Pearson correlations and linear regression analysis., Results: Compared to the suspected CMD group, the HFpEF participants were older (65 ± 12 vs 56 ± 11 yrs., p  = 0.002) had higher BMI (31.0 ± 4.3 vs 27.8 ± 6.7 kg/m 2 , p  = 0.013), higher aPWV (10.5 ± 2.0 vs 8.0 ± 1.6 m/s, p  = 0.05) and lower MPRI (1.5 ± 0.3 vs1.8 ± 0.3, p  = 0.02), but not remodeling. In a model adjusted for cardiovascular risk factors, the HFpEF group had a lower LVEF (estimate -4.78, p  = 0.0437) than the suspected CMD group., Conclusions: HFpEF participants exhibit greater arterial stiffness and lower myocardial perfusion reserve, with lower LVEF albeit not remodeling, compared to suspected CMD participants. These findings suggest arterial stiffness may contribute to progression from CMD to HFpEF. Prospective work is needed and ongoing., Competing Interests: Dr. Bairey Merz has disclosures from iRhythm and SHL Telemedicine. Dr. Pepine: Research Grant from Gilead Sciences, Inc., Pfizer, Park-Davis, Sanofi-Aventis, Fujisawa HealthCare Inc., Baxter, Brigham & Women's Hospital, AstraZeneca, NIH/NHLBI, Amorcyte/Neostem, Cytori, InfraReDx, NHLBI/NCRR CTSA grant 1UL1RR029890, AHA. Consultant/Advisory Board: NIH Study Section of Cardiovascular Sciences Small Business Activities 2RG1 CVS-K-10, Lilly/Cleveland Clinic DSMB Member for a Phase 2 Efficacy and Safety Study of Ly2484595, Medtelligence, NHLBI Study Section for Progenitor Cell Biology Consortium, NHLBI DSMB Chair for Freedom Trial. Dr. Handberg receives research grants from Aastrom Biosciences, Amorcyte, Biocardia, Brigham and Women's Hospital, Capricor, Cytori Therapeutics, Department of Defense, Direct Flow Medical, Duke Clinical Research Institute, East Carolina University, Everyfit Inc., Medtronic, Merck & Co., Mesoblast, National Institutes of Health (NIH), NIH through University of Rochester, NIH through Brigham and Women's Health, NIH through University of Texas, PCORI, and Sanofi Aventis; Research grant and educational grant from Gilead Sciences; Unrestricted educational grants for the Vascular Biology Working Group from Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Ionis, and Relypsa; and Consultant fees from Bristol-Myers Squibb Company. Dr. C. Noel Bairey Merz, serve as Board of Director for iRhythm, fees paid through CSMC from Abbott Diagnostics and SHL Telemedicine. Dr. Janet Wei served on an advisory board for Abbott Vascular. All other authors have no disclosures to disclose., (© 2024 The Authors.)

Objectives: The aim of the study is to assess obstetric and fetal outcomes of Jehovah's Witnesses (JWs) mothers in an inner city teaching hospital, as well as to examine the acceptance rates of various blood fractions and blood transfusion alternatives., Methods: Case series to evaluate the maternal and fetal outcomes of JWs over a nine period between 2013 and 2021., Results: There were 146 pregnancies extracted from our database, of which 10 were early pregnancy losses. Data from 136 deliveries > 24 weeks' gestation were assessed, with a mean maternal age and gestational age of 30.26 (± 5.4) years and 38.7 (± 5.3) weeks, respectively. 57% had normal vaginal deliveries, 8% had instrumental births and 35% had caesarean births. Mean estimated blood loss at caesarean was 575 (± 305.6) mls, while the overall mean estimated loss was 427.8 (± 299.8) mls. Cell salvage was performed in all caesarean sections but autologous transfusion was only necessary for 26%. Consultant presence was documented in 62% of caesarean births. The mean birthweight and 5-min Apgar scores were 3.31 (± 0.05) kg and 9.1 (± 0.09), respectively. There were no maternal deaths or admissions to the adult intensive care unit and the most serious complication was a uterine rupture following a trial of scar, after which the baby required cooling for hypoxic ischaemic encephalopathy., Conclusions: Pregnant JWs received obstetric care led by senior clinicians, with optimisation of haematinics, minimizing of blood loss at delivery and access to technology such as cell salvage., (© 2023. Crown.)

Background: Aging is considered a key risk factor for Alzheimer's disease (AD). This study aimed to identify and validate potential aging-related genes associated with AD using bioinformatics analysis., Methods: Datasets GSE36980 and GSE5281 were selected to screen differentially expressed genes (DEGs), and the immune cell correlation analysis and GSEA analysis of DEGs were performed. The intersection with senescence genes was taken as differentially expressed senescence-related genes (DESRGs), and the GSE44770 dataset was used for further validation. The potential biological functions and signaling pathways were determined by GO and KEGG, and the hub genes were identified by 12 algorithms in Cytohubba. The expression of 10 hub genes in different brain regions was determined and single-cell sequencing analysis was performed, and diagnostic genes were further screened by gene expression and receiver operating characteristic (ROC) curve. Finally, a miRNA-gene network of diagnostic genes was constructed and targeted drug prediction was performed., Results: A total of 2137 DEGs were screened from the GSE36980 and GSE5281 datasets, and 278 SRGs were identified from the CellAge database. The overlapping DEGs and SRGs constituted 29 DESRGs, including 14 senescence suppressor genes and 15 senescence inducible genes. The top 10 hub genes, including MDH1, CKB, PSMD14, SMARCA4, PEBP1, DDB2, ITPKB, ATF7IP, YAP1, and EWSR1 were screened. Furthermore, four diagnostic genes were identified: PMSD14, PEBP1, ITPKB, and ATF7IP. The ROC analysis showed that the respective area under the curves (AUCs) of PMSD14, PEBP1, ITPKB, and ATF7IP were 0.732, 0.701, 0.747, and 0.703 in the GSE36980 dataset and 0.870, 0.817, 0.902, and 0.834 in the GSE5281 dataset. In the GSE44770 dataset, PMSD14 (AUC, 0.838) and ITPKB (AUC, 0.952) had very high diagnostic values in the early stage of AD. Finally, based on these diagnostic genes, we found that the drug Abemaciclib is a targeted drug for the treatment of age-related AD. Flutamide can aggravate aging-related AD., Conclusion: The results of this study suggest that cellular SRGs might play an important role in AD. PMSD14, PEBP1, ITPKB, and ATF7IP have the potential as specific biomarkers for the early diagnosis of AD., Competing Interests: The authors declare no conflict of interest.