Neuropeptide substance P attenuates colitis by suppressing inflammation and ferroptosis via the cGAS-STING signaling pathway.

Neuropeptide substance P (SP) belongs to a family of bioactive peptides and regulates many human diseases. This study aims to investigate the role and underlying mechanisms of SP in colitis. Here, activated SP-positive neurons and increased SP expression were observed in dextran sodium sulfate (DSS)-induced colitis lesions in mice. Administration of exogenous SP efficiently ameliorated the clinical symptoms, impaired intestinal barrier function, and inflammatory response. Mechanistically, SP protected mitochondria from damage caused by DSS or TNF-α exposure, preventing mitochondrial DNA (mtDNA) leakage into the cytoplasm, thereby inhibiting the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. SP can also directly prevent STING phosphorylation through the neurokinin-1 receptor (NK1R), thereby inhibiting the activation of the TBK1-IRF3 signaling pathway. Further studies revealed that SP alleviated the DSS or TNF-α-induced ferroptosis process, which was associated with repressing the cGAS-STING signaling pathway. Notably, we identified that the NK1R inhibition reversed the effects of SP on inflammation and ferroptosis via the cGAS-STING pathway. Collectively, we unveil that SP attenuates inflammation and ferroptosis via suppressing the mtDNA-cGAS-STING or directly acting on the STING pathway, contributing to improving colitis in an NK1R-dependent manner. These findings provide a novel mechanism of SP regulating ulcerative colitis (UC) disease.

The relationship between mean corpuscular hemoglobin concentration and mortality in hypertensive individuals: A population-based cohort study.

INTRODUCTION: Hematology is an essential field for investigating the prognostic outcomes of cardiovascular diseases (CVDs). Recent research has suggested that mean corpuscular hemoglobin concentration (MCHC) is associated with a poor prognosis in several CVDs. There is no evidence of a correlation between MCHC and hypertension. Therefore, our study aimed to analyze the association of MCHC with all-cause and cardiovascular mortality in hypertensive patients. METHODS: We used cohort data from U.S. adults who participated in the National Health and Nutrition Examination Survey from 1999-2014. COX regression was applied to analyze the relationship between MCHC and all-cause and cardiovascular mortality. In addition, three models were adjusted to reduce confounding factors. We reanalyzed the data after propensity score matching (PSM) to inspect the stability of the results. Stratified analysis was additionally adopted to investigate the results of each subgroup. RESULTS: Our research included 15,154 individuals. During a mean follow-up period of 129 months, 30.6% of the hypertensive population succumbed to mortality. Based on previous studies, we categorized patients with MCHC ≤33mg/dl as the hypochromia group and those with >33mg/dl as the non-hypochromia group. After PSM, the hypochromia group had higher all-cause mortality (adjusted hazard ratio [HR]:1.26, 95% confidence interval [95%CI]:1.11-1.43) and cardiovascular mortality (adjusted HR:1.42, 95%CI:1.12-1.80) than the non-hypochromia group. The results of the COX regression remain stable after matching. Stratified analyses before PSM revealed an interaction of anemia in the relationship between MCHC and mortality, whereas there was no significant interaction after matching. CONCLUSION: In hypertensive individuals, low MCHC was correlated with a poor prognosis. Further studies on MCHC are necessary to analyze the potential mechanisms of its poor prognosis in hypertensive populations.

Deficiency of leucine-rich repeat kinase 2 aggravates thioacetamide-induced acute liver failure and hepatic encephalopathy in mice.

BACKGROUND: Hepatic encephalopathy (HE) is closely associated with inflammatory responses. However, as a crucial regulator of the immune and inflammatory responses, the role of leucine-rich repeat kinase 2 (LRRK2) in the pathogenesis of HE remains unraveled. Herein, we investigated this issue in thioacetamide (TAA)-induced HE following acute liver failure (ALF). METHODS: TAA-induced HE mouse models of LRRK2 wild type (WT), LRRK2 G2019S mutation (Lrrk2G2019S) and LRRK2 knockout (Lrrk2-/-) were established. A battery of neurobehavioral experiments was conducted. The biochemical indexes and pro-inflammatory cytokines were detected. The prefrontal cortex (PFC), striatum (STR), hippocampus (HIP), and liver were examined by pathology and electron microscopy. The changes of autophagy-lysosomal pathway and activity of critical Rab GTPases were analyzed. RESULTS: The Lrrk2-/--HE model reported a significantly lower survival rate than the other two models (24% vs. 48%, respectively, p < 0.05), with no difference found between the WT-HE and Lrrk2G2019S-HE groups. Compared with the other groups, after the TAA injection, the Lrrk2-/- group displayed a significant increase in ammonium and pro-inflammatory cytokines, aggravated hepatic inflammation/necrosis, decreased autophagy, and abnormal phosphorylation of lysosomal Rab10. All three models reported microglial activation, neuronal loss, disordered vesicle transmission, and damaged myelin structure. The Lrrk2-/--HE mice presented no severer neuronal injury than the other genotypes. CONCLUSIONS: LRRK2 deficiency may exacerbate TAA-induced ALF and HE in mice, in which inflammatory response is evident in the brain and aggravated in the liver. These novel findings indicate a need of sufficient clinical awareness of the adverse effects of LRRK2 inhibitors on the liver.

Pharmacokinetics and tissue distribution of Yigong San in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM), Yigong San (YGS) is mainly used to treat dyspepsia caused by deficiency of spleen and stomach qi. Although the chemical composition and bioactivity of YGS has been well studied, the main in vivo compounds and their distribution in tissues still need to be made clearer. AIM OF THE STUDY: To elucidate the pharmacokinetic profiles and tissue distribution of eight main compounds of YGS in rats, and provide a reference for clinical application and new drug development. MATERIALS AND METHODS: UPLC-Q-Exactive-Orbitrap-MS was used to qualitatively characterize the parent compounds and their metabolites in the plasma of rats after oral administration of YGS. A sensitive, reliable, and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method using UPLC-AB Sciex QTRAP 5500 MS was established to quantitatively determine eight main compounds of YGS in rat plasma and tissues, including liquiritin, isoliquiritin, hesperidin, ginsenosides Rb1, Re and Rg1, atractylenolides I and II. RESULTS: The mean area under the concentration-time curve (AUC) values of ginsenoside Rb1, hesperidin, and liquiritin at low, medium, and high doses were greater than 150 ng h/mL. The elimination half-life (t1/2) values of ginsenoside Rb1, atractylenolides I and II (low and medium doses) were longer than 10 h. Peak time (Tmax) values of all compounds were shorter than 10 h. Except for atractylenolides, the maximum concentration (Cmax) values of the compounds were greater than 10 ng/mL. The eight compounds were detected in the heart, brain, liver, spleen and kidney at 0.25 h after oral administration. Liquiritin and isoliquiritin had higher exposure in the liver and heart. Hesperidin and ginsenosides Rb1, Re, and Rg1 are mainly distributed in the spleen and kidney. Atractylenolides I and II are mainly distributed in spleen, liver and kidney. CONCLUSION: All main compounds of YGS, i.e., liquiritin, isoliquiritin, hesperidin, ginsenosides Rb1, Re, and Rg1, and atractylenolides I and II are absorbed into plasma and widely distributed in various tissues. Among them, hesperidin, ginsenoside Rb1, and atractylenolide I are main in vivo compounds. They are mainly distributed in spleen, liver and kidney. The results of this study provide a basis for further in-depth development and application of YGS.

The early change in pH values after out-of-hospital cardiac arrest is not associated with neurological outcome at hospital discharge.

Background: The association between pH values and outcome for patients after out-of-hospital cardiac arrest (OHCA) was not fully elucidated; besides, the relationship of change in pH values and neurological outcome was unknown. The aim was to explore the association of pH values as well as change in pH values and neurological outcome for OHCA cardiac patients. Methods: The adult patients with non-traumatic out-of-hospital cardiac arrest, shock-refractory ventricular fibrillation or pulseless ventricular tachycardia, and at least two arterial blood gases analysis recorded after admission were included. The change in pH values is calculated as the difference between the second and first pH value, and divided by time interval got the rate of change in pH values. The primary outcome was modified Rankin Score (mRS), dichotomized to good (mRS 0-3) and poor (mRS 4-6) outcomes at hospital discharge. The independent relationship of the first pH value, second pH value, and changes in pH values with neurological outcome was investigated with multivariable logistic regression models, respectively. Results: A total of 1388 adult patients were included for analysis, of which 514 (37%) had good neurological outcome. The median first pH value and second pH value after admission were 7.21 (interquartile range [IQR] 7.09-7.29) and 7.28 (IQR 7.20-7.36), respectively. The median absolute, relative change, and rate of changes in pH values were 0.08 (IQR 0.01-0.16), 1.10% (IQR 0.11-2.22%), and 0.02 (IQR 0-0.06) per hour, respectively. After adjusting for confounders, the higher first pH value (odds ratio [OR] 3.81, confidence interval [CI] 1.60-9.24, P = 0.003) and higher second pH value (OR 9.54, CI 3.45-26.87, P < 0.001) after admission were associated with good neurological outcome, respectively. The absolute (OR 1.58, CI 0.58-4.30, P = 0.368) and relative (OR 1.03, CI 0.96-1.11, P = 0.399) change as well as the rate of change (OR 0.98, CI 0.33-2.71, P = 974) in pH values were not associated with neurological outcome. Conclusions: For OHCA patients, abnormality in pH values was very common, with a more acidic pH value indicating poor neurological outcome. However, the change in pH values was not associated with outcomes.

Trim27 aggravates airway inflammation and oxidative stress in asthmatic mice via potentiating the NLRP3 inflammasome.

Asthma is a prevalent chronic respiratory disease, yet understanding its ecology and pathogenesis remains a challenge. Trim27, a ubiquitination ligase belonging to the TRIM (tripartite motif-containing) family, has been implicated in regulating multiple pathophysiological processes such as inflammation, oxidative stress, apoptosis, and cell proliferation. However, the role of Trim27 in asthma has not been investigated. Our study found that Trim27 expression significantly increases in the airway epithelium of asthmatic mice. Knockdown of Trim27 expression effectively relieved ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) and lung tissue histopathological changes. Moreover, Trim27 knockdown exhibited a significant reduction in airway inflammation and oxidative stress in asthmatic mice, and in vitro analysis confirmed the favorable effect of Trim27 deletion on inflammation and oxidative stress in mouse airway epithelial cells. Furthermore, our study revealed that deletion of Trim27 in MLE12 cells significantly decreased NLRP3 inflammasome activation, as evidenced by reduced expression of NLRP3, ASC, and pro-IL-1ß mRNA. This downregulation was reversed when Trim27, but not its mutant lacking ubiquitination ligase activity, was replenished in these cells. Consistent with these findings, protein levels of NLRP3, pro-caspase-1, pro-IL-1ß, cleaved-caspase-1, and cleaved-IL-1ß were higher in Trim27-replenished cells compared to cells expressing Trim27C/A. Functionally, the downregulation of IL-1ß and IL-18 levels induced by Trim27 deletion was rescued by replenishing Trim27. Overall, our findings provide evidence that Trim27 contributes to airway inflammation and oxidative stress in asthmatic mice via NLRP3 inflammasome activation, providing crucial insights into potential therapeutic interventions targeting Trim27 as a way to treat asthma.

How does technological innovation affect the fiscal decentralization of local governments? Evidence from China.

Technological innovation is a pivotal driver of high-quality economic development, and China's distinctive fiscal decentralization model stands out as a crucial institutional factor behind the country's economic growth miracle. Despite its significant academic and practical implications, there is a noticeable scarcity of literature on examining government fiscal decentralization through the lens of technological innovation. This paper addresses fundamental research questions regarding the relationship between technological innovation and fiscal decentralization. Leveraging balanced panel data from 30 provinces in China spanning 2005 to 2020, our findings indicate that technological innovation positively impacts the fiscal decentralization of local governments. Specifically, for each standard deviation increase in technological innovation, there is a corresponding 0.1508 standard deviation in fiscal decentralization. The mechanism driving this relationship lies in technological innovation's ability to enhance enterprise profit levels, increasing tax and non-tax revenues for local governments. Importantly, when non-tax revenue at the central government level surpasses tax revenue, the resulting augmentation in local government revenue contributes to an elevated level of fiscal decentralization. In conclusion, this paper offers valuable insights into the government's endeavors to promote scientific and technological innovation while enhancing local fiscal decentralization. These insights contribute to an improved quality of economic development.

Cross-Linking CdSO4-Type Nets with Hexafluorosilicate Anions to Form an Ultramicroporous Material for Efficient C2H2/CO2 and C2H2/C2H4 Separation.

A 44.610.8 topology hybrid ultramicroporous material (HUM), {[Cu1.5F(SiF6)(L)2.5]·G}n, (L = 4,4'-bisimidazolylbiphenyl, G = guest molecules), 1, formed by cross-linking interpenetrated 3D four-connected CdSO4-type nets with hexafluorosilicate anions is synthesized and evaluated in the context of gas sorption and separation herein. 1 is the first HUM functionalized with two different types of fluorinated sites (SiF6 2- and F- anions) lining along the pore surface. The optimal pore size (≈5 Å) combining mixed and high-density electronegative fluorinated sites enable 1 to preferentially adsorb C2H2 over CO2 and C2H4 by hydrogen bonding interactions with a high C2H2 isosteric heat of adsorption (Qst) of ≈42.3 kJ mol-1 at zero loading. The pronounced discriminatory sorption behaviors lead to excellent separation performance for C2H2/CO2 and C2H2/C2H4 that surpasses many well-known sorbents. Dynamic breakthrough experiments are conducted to confirm the practical separation capability of 1, which reveal an impressive separation factor of 6.1 for equimolar C2H2/CO2 mixture. Furthermore, molecular simulation and density functional theory (DFT) calculations validate the strong binding of C2H2 stems from the chelating fix of C2H2 between SiF6 2- anion and coordinated F- anion.

Mild-Temperature Supercritical Water Confined in Hydrophobic Metal-Organic Frameworks.

Fluids under extreme confinement show characteristics significantly different from those of their bulk counterpart. This work focuses on water confined within the complex cavities of highly hydrophobic metal-organic frameworks (MOFs) at high pressures. A combination of high-pressure intrusion-extrusion experiments with molecular dynamic simulations and synchrotron data reveals that supercritical transition for MOF-confined water takes place at a much lower temperature than in bulk water, ∼250 K below the reference values. This large shifting of the critical temperature (Tc) is attributed to the very large density of confined water vapor in the peculiar geometry and chemistry of the cavities of Cu2tebpz (tebpz = 3,3',5,5'-tetraethyl-4,4'-bipyrazolate) hydrophobic MOF. This is the first time the shift of Tc is investigated for water confined within highly hydrophobic nanoporous materials, which explains why such a large reduction of the critical temperature was never reported before, neither experimentally nor computationally.

Oral vitamin A supplements to prevent acute upper respiratory tract infections in children up to seven years of age.

BACKGROUND: According to global prevalence analysis studies, acute upper respiratory tract infections (URTIs) are the most common acute infectious disease in children, especially in preschool children. Acute URTIs lead to an economic burden on families and society. Vitamin A refers to the fat-soluble compound all-trans-retinol and also represents retinol and its active metabolites. Vitamin A interacts with both the innate immune system and the adaptive immune system and improves the host's defences against infections. Correlation studies show that serum retinol deficiency was associated with a higher risk of respiratory tract infections. Therefore, vitamin A supplementation may be important in preventing acute URTIs. OBJECTIVES: To assess the effectiveness and safety of vitamin A supplements for preventing acute upper respiratory tract infections in children up to seven years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the Chinese Biomedical Literature Database, and two trial registration platforms to 8 June 2023. We also checked the reference lists of all primary studies and reviewed relevant systematic reviews and trials for additional references. We imposed no language or publication restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs), which evaluated the role of vitamin A supplementation in the prevention of acute URTIs in children up to seven years of age. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six studies (27,351 participants). Four studies were RCTs and two were cluster-RCTs. The included studies were all conducted in lower-middle-income countries (two in India, two in South Africa, one in Ecuador, and one in Haiti). Three studies included healthy children who had no vitamin A deficiency, one study included children born to HIV-infected women, one study included low-birthweight neonates, and one study included children in areas with a high local prevalence of malnutrition and xerophthalmia. In two studies, vitamin E was a co-treatment administered in addition to vitamin A. We judged the included studies to be at either a high or unclear risk of bias for random sequence generation, incomplete outcome data, and blinding. Primary outcomes Six studies reported the incidence of acute URTIs during the study period. Five studies reported the number of acute URTIs over a period of time, but there was population heterogeneity and the results were presented in different forms, therefore only three studies were meta-analysed. We are uncertain of the effect of vitamin A supplementation on the number of acute URTIs over two weeks (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.92 to 1.09; I2 = 44%; 3 studies, 22,668 participants; low-certainty evidence). Two studies reported the proportion of participants with an acute URTI. We are uncertain of the effect of vitamin A supplementation on the proportion of participants with an acute URTI (2 studies, 15,535 participants; low-certainty evidence). Only one study (116 participants) reported adverse events. No infant in either the placebo or vitamin A group was found to have feeding difficulties (failure to feed or vomiting), a bulging fontanelle, or neurological signs before or after vitamin A administration (very low-certainty evidence). Secondary outcomes Two studies (296 participants) reported the severity of subjective symptoms, presented by the mean duration of acute URTI. Vitamin A may have little to no effect on the mean duration of acute URTI (very low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for the use of vitamin A supplementation to prevent acute URTI is uncertain, because population, dose and duration of interventions, and outcomes vary between studies. From generally very low- to low-certainty evidence, we found that there may be no benefit in the use of vitamin A supplementation to prevent acute URTI in children up to seven years of age. More RCTs are needed to strengthen the current evidence. Future research should report over longer time frames using validated tools and consistent reporting, and ensure adequate power calculations, to allow for easier synthesis of data. Finally, it is important to assess vitamin A supplementation for preschool children with vitamin A deficiency.

Potential Association of Gut Microbial Metabolism and Circulating mRNA Based on Multiomics Sequencing Analysis in Fetal Growth Restriction.

Objective: Fetal growth restriction (FGR) is a significant contributor to negative pregnancy and postnatal developmental outcomes. Currently, the exact pathological mechanism of FGR remains unknown. This study aims to utilize multiomics sequencing technology to investigate potential relationships among mRNA, gut microbiota, and metabolism in order to establish a theoretical foundation for diagnosing and understanding the molecular mechanisms underlying FGR. Methods: In this study, 11 healthy pregnant women and nine pregnant women with FGR were divided into Control group and FGR group based on the health status. Umbilical cord blood, maternal serum, feces, and placental tissue samples were collected during delivery. RNA sequencing, 16S rRNA sequencing, and metabolomics methods were applied to analyze changes in umbilical cord blood circulating mRNA, fecal microbiota, and metabolites. RT-qPCR, ELISA, or western blot were used to detect the expression of top 5 differential circulating mRNA in neonatal cord blood, maternal serum, or placental tissue samples. Correlation between differential circulating mRNA, microbiota, and metabolites was analyzed by the Spearman coefficient. Results: The top 5 mRNA genes in FGR were altered with the downregulation of TRIM34, DEFA3, DEFA1B, DEFA1, and QPC, and the upregulation of CHPT1, SMOX, FAM83A, GDF15, and NAPG in newborn umbilical cord blood, maternal serum, and placental tissue. The abundance of Bacteroides, Akkermansia, Eubacterium_coprostanoligenes_group, Phascolarctobacterium, Parasutterella, Odoribacter, Lachnospiraceae_UCG_010, and Dielma were significantly enriched in the FGR group. Metabolites such as aspartic acid, methionine, alanine, L-tryptophan, 3-methyl-2-oxovalerate, and ketoleucine showed notable functional alterations. Spearman correlation analysis indicated that metabolites like methionine and alanine, microbiota (Tyzzerella), and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) might play a role as mediators in the communication between the gut and circulatory system interaction in FGR. Conclusion: Metabolites (METHIONINE, alanine) as well as microbiota (Tyzzerella) and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) were possible mediators that communicated the interaction between the gut and circulatory systems in FGR.

Are spending more time outdoors able to prevent and control myopia in children and adolescents? A meta-analysis.

INTRODUCTION: Spending more time outdoors was treated as a safe and cost-effective method to prevent and control myopia. While prior research has established an inverse association between outdoor time and the risk of myopia onset, the effect of increasing outdoor time in delaying the progression of myopia remains a subject of debate. The present meta-analysis aimed to assess the relationship between outdoor time and the myopia onset, and further examine whether there is a dose-response relationship between outdoor time and the risk of myopia onset. Meanwhile, perform whether the outdoor time is related to delaying the progression of myopia. METHODS: Studies were retrieved from PubMed, Web of Science, Embase, Medline, and the Cochrane Database, spanning from their inception to February 2023. 3 cohort studies and 5 prospective intervention studies were included, with a total of 12,922 participants aged 6 to 16 years. RESULTS: Comparing the highest with the lowest exposure levels of time spent outdoors, the highest outdoor time was strongly associated with a reduced risk of myopia onset (OR: 0.53; 95% CI: 0.34, 0.82). A non-linear dose-response relationship was found between outdoor time and myopia onset risk. Compared to 3.5 hours of outdoor time per week, an increase to 7, 16.3, and 27 hours per week corresponded with a respective reduction in the risk of myopia onset by 20%, 53%, and 69%. Among children and adolescents who were not myopic, spending more time outdoors significantly slowed down the speed of change in spherical equivalent refractive (SER) (WMD=0.10D, 95%CI: 0.07, 0.14) and axial length (AL) (WMD=-0.05mm, 95%CI: -0.06, -0.03). Among children and adolescents who were already myopic, spending more time outdoors did not slow myopia progression. CONCLUSIONS: Overall, spending more time outdoors can prevent the onset of myopia, but it doesn't seem to slow its progression. Further studies are needed to better understand these trends.

Prognostic implication of consolidation-to-tumor ratio in early lung adenocarcinoma: a retrospective cross-sectional study.

Background: The threshold value of consolidation-to-tumor ratio (CTR) for distinguishing between ground-glass opacity (GGO)-predominant and solid-predominant ground-glass nodules (GGNs) needs to be clarified, as the lack of clarity has caused the prognostic implications to remain ambiguous. This study aimed to determine the threshold value of CTR for distinguishing between GGO-predominant GGNs and solid-predominant GGNs and elucidate the prognostic implications of the solid-predominant GGNs categorized by CTR on c-stage IA lung adenocarcinoma. Methods: Between January 2016 and October 2018, 764 c-stage IA lung adenocarcinoma cases were assembled from the First Affiliated Hospital of Chongqing Medical University. Of the 764 lesions, 515 (67.4%) were nodules with a GGO component, and 249 (32.6%) were solid nodules (SNs) on thin-section computed tomography (CT). We evaluated the correlation of the 3-dimensional (3D) consolidation component volume ratio with CTR based on the coefficient of determination, r. After receiver operating characteristic (ROC) analysis of 515 GGNs, we defined the nodule with CTR >0.750 as solid-predominant GGN and the nodule with CTR ≤0.750 as GGO-predominant GGN. Subsequently, the prognosis of 439 patients who had follow-up registration was evaluated. Survival curves were calculated using the Kaplan-Meier method, and the log-rank test was employed to compare survival rates among different groups. Cox proportional hazard regression models were applied to evaluate the independent risk factors for recurrence-free survival (RFS). Results: Among 764 patients, 515 (67.4%) were nodules with a GGO component, and 249 (32.6%) were SNs on thin-section CT. For 515 GGNs, the 3D consolidation component volume ratio correlated well with CTR (r=0.888). CTR tended to be slightly larger than the 3D consolidation component volume ratio. A 3D consolidation component volume ratio >50% was best predicted by CTR >0.750, followed by CTR >0.549. CTR >0.750 and CTR >0.549 predicted 3D consolidation component volume ratio >50% with 85% and 99.2% sensitivity and 91.6% and 57.2% specificity, respectively. The 5-year RFS and overall survival (OS) of patients with 0.750< CTR <1 were worse than those of patients with 0≤ CTR ≤0.750 (P<0.001 and P<0.001, respectively) but better than those of patients with CTR =1 (P=0.002 and P=0.03, respectively). Carcinoembryonic antigen (CEA) >2.1 [hazard ratio (HR) =12.516, 95% confidence interval (CI): 1.729-90.598], CTR >0.750 (HR =13.934, 95% CI: 3.341-58.123), larger consolidation component size with diameter more than 20 mm (HR =1.855, 95% CI: 1.242-2.770), poorly differentiated (HR =1.622, 95% CI: 1.056-2.491), lymph node metastasis (HR =2.473, 95% CI: 1.601-3.821), and sublobar resection (HR =2.596, 95% CI: 1.701-3.962) could predict the poor prognosis. Patients with 0≤ CTR ≤0.750 receiving sublobar resection had prognoses comparable to those receiving lobar resection, whether the tumor size ≤2 cm or consolidation component size ≤3 cm. Lobar resection was superior to sublobar resection for non-small cell lung cancer (NSCLC) ≤2 cm with CTR >0.750. Conclusions: Compared to CTR =0.5, the 2-dimensional (2D) CTR =0.750 found using the 3D consolidation component volume ratio as the gold standard better differentiated between solid-predominant GGNs and GGO-predominant GGNs. CTR >0.750 was an independent risk factor associated with the poor prognosis of patients with c-stage IA lung adenocarcinoma. Sublobar resection should be cautiously adopted in GGNs with 0.750< CTR ≤1.

Early enteral nutrition with exclusive donor milk instead of formula milk affects the time of full enteral feeding for very low birth weight infants.

This study investigated the effects of exclusive donor milk or formula in the first 7 days after birth, on the time to full enteral feeding, growth, and morbidity of adverse events related to premature infants. This was a retrospective study carried out from July 2014 to December 2019 at the Department of Neonatology of Shanghai Children's Hospital. All infants with a birth weight < 1,500 g and a gestational age ≤ 32 who received exclusive donor milk or formula in the first 7 days after birth were included in this study. The time to full enteral feeding (defined as 150 mL/kg) in the donor milk group was significantly shorter than in the formula group (18 vs. 22 days, p = 0.01). Donated breast milk was also associated with a lower incidence of NEC (4.4 vs. 7%, p < 0.01), ROP (3.8 vs. 13.2%, p < 0.01), and culture-confirmed sepsis (11 vs. 22.6%, p < 0.01). Using donated breast milk instead of current formula milk for early enteral nutrition can shorten the time to full enteral feeding and reduce the incidence of NEC, ROP, and sepsis.

Evaluating the Effectiveness of Radiofrequency Therapy and Manual Pelvic Fascial Release in Treating Myofascial Pelvic Pain.

INTRODUCTION AND HYPOTHESIS: Myofascial pelvic pain (MFPP), characterized by sensitive trigger points in the pelvic floor muscles, leads to chronic pain and affects various aspects of life. Despite the availability of different treatment modalities, there is limited comparative research on their effectiveness. This study compares radiofrequency (RF) therapy and myofascial manual therapy (MMT) in treating MFPP. We aimed to evaluate pelvic floor muscle strength changes, clinical symptoms, and patient comfort during treatment. METHODS: The study involved 176 participants, divided equally into RF and MMT groups. We assessed pelvic floor pain using the Visual Analogue Scale (VAS), muscle strength using the Modified Oxford Scale (MOS) and surface electromyography (sEMG), clinical symptom improvement through questionnaires, and patient discomfort during treatment. RESULTS: Both RF and MMT groups significantly reduced pelvic floor and paraurethral muscle pain (VAS scores, p < 0.001). RF treatment significantly decreased vaginal laxity in its group (p < 0.001), with no notable change in the MMT group (p = 0.818). RF therapy also resulted in greater patient comfort than MMT (p < 0.001). Although both treatments improved clinical symptoms, there was no significant difference between the two (p = 0.692). MOS scores and pelvic floor sEMG values showed no significant differences between the groups before and after treatment (p > 0.05). CONCLUSIONS: Both RF and MMT effectively alleviate pelvic floor pain and improve clinical symptoms in MFPP patients. RF therapy, however, offers additional benefits in reducing vaginal laxity and enhancing treatment comfort.

Cardioprotective effects of curcumin against Diabetic Cardiomyopathies: A systematic review and meta-analysis of preclinical studies.

BACKGROUND: As a common complication of diabetes, diabetic cardiomyopathy (DCM) often leads to further damage to the heart muscle. Curcumin has been proven to have a variety of cardioprotective effects, however, the protective effect against DCM has not been systematically reviewed. PURPOSE: In this study, we aimed to analyze the preclinical (animal model) evidence of curcumin's therapeutic effects in DCM. METHODS: Eight databases and two registry systems were searched from the time of library construction to 1 November 2023. We performed rigorous data extraction and quality assessment. The included studies' methodological quality was appraised using the SYRCLE RoB tool, statistical analyses were carried out using RevMan 5.4 software, and Funnel plots and Egger's test were performed using Stata 17.0 software to assess publication bias. RESULTS: This study included 32 trials with a total of 681 animals. Meta-analysis showed that curcumin significantly improved cardiac function indices (LVEF, LVFS, and LVSd) (p < 0.01), decreased markers of myocardial injury, HW/BW ratio, and randomized blood glucose compared to the control group, in addition to showing beneficial effects on mechanistic indices of myocardial oxidation, inflammation, apoptosis, and autophagy (p < 0.05). CONCLUSIONS: Curcumin may exert cardioprotective effects in DCM through its antioxidant, anti-inflammatory, autophagy-enhancing, and anti-apoptotic effects. Its protective effect is proportional to the dose, and the efficacy may be further increased at a concentration of more than 200 mg/kg, and further validation is needed.

Role of small nucleolar RNAs in alternative splicing of the doublesex gene in the silkworm, Bombyx mori.

More and more evidence shows that small noncoding RNAs (ncRNAs) play diverse roles in development, stress response and other cellular processes, but functional study of intermediate-size ncRNAs is still rare. Here, the expression profile of 16 intermediate-size ncRNAs in ovary and testis of silkworm Bombyx mori were analyzed. Twelve ncRNAs, including 5 small nucleolar RNAs (snoRNAs) and 7 unclassified ncRNAs, accumulated more in the testis than in the ovary of silkworm, especially Bm-163, Bm-51 and Bm-68. Four ncRNAs (including three orphan snoRNAs and one unclassified ncRNA) had higher expression level in the ovary than in the testis, especially Bm-86. Overexpression of the testis-enriched snoRNA Bm-68 in the female led to the accumulation of male-specific isoform of doublesex (BmdsxM) and increased the expression ratio of BmdsxM: BmdsxF. While overexpression of ovary-enriched snoRNA Bm-86 in the male decreased the expression ratio of BmdsxM: BmdsxF, indicating the roles of the two snoRNAs played in the alternative splicing of Bmdsx of silkworm, which will provide new clues for the functional study of snoRNAs in insects.

Establishment and Verification of an Artificial Intelligence Prediction Model for Children With Sepsis.

BACKGROUND: Early identification of high-risk groups of children with sepsis is beneficial to reduce sepsis mortality. This article used artificial intelligence (AI) technology to predict the risk of death effectively and quickly in children with sepsis in the pediatric intensive care unit (PICU). STUDY DESIGN: This retrospective observational study was conducted in the PICUs of the First Affiliated Hospital of Sun Yat-sen University from December 2016 to June 2019 and Shenzhen Children's Hospital from January 2019 to July 2020. The children were divided into a death group and a survival group. Different machine language (ML) models were used to predict the risk of death in children with sepsis. RESULTS: A total of 671 children with sepsis were enrolled. The accuracy (ACC) of the artificial neural network model was better than that of support vector machine, logical regression analysis, Bayesian, K nearest neighbor method and decision tree models, with a training set ACC of 0.99 and a test set ACC of 0.96. CONCLUSIONS: The AI model can be used to predict the risk of death due to sepsis in children in the PICU, and the artificial neural network model is better than other AI models in predicting mortality risk.