A study on pulmonary function in children with obstructive sleep apnea hypopnea syndrome.

OBJECTIVE: To investigate the pulmonary function of children with obstructive sleep apnea syndrome. METHODS: A total of 328 children aged 3 to 12 years old who were evaluated for a sleep disorder from January 2022 to June 2023 were selected as the observation group, classified into mild, moderate, and severe categories based on the apnea hypopnea index. The number of children with mild, moderate, and severe obstructive sleep apnea is 228, 62, and 28 respectively. Additionally, 126 healthy individuals aged 3 to 13 years old undergoing health examinations during the same period were selected as the control group. All subjects underwent sleep respiratory monitoring, pulmonary function tests, and impulse oscillometry. Comparative analysis was performed on pulmonary function indices (forced vital capacity, maximum ventilation, inspiratory capacity, total lung capacity, and inspiratory reserve volume), and respiratory impedance indices (resonant frequency, total respiratory impedance, viscous resistance at 5 Hz, 20 Hz, and 35 Hz). Pulmonary function indices were also compared among patients in the observation group with mild, moderate, and severe conditions. RESULTS: In the observation group, the FVC pre% of patients decreased by 10.5 ± 5.99 compared to the control group. The MVV of the control group decreased by 28.10 ± 2.22 compared to patients in the observation group. The IC of the control group decreased by 0.68 ± 0.44 compared to patients in the observation group. The TLC of the control group decreased by 1.354 ± 0.51 compared to patients in the observation group. The ERV of the control group decreased by 0.53 ± 0.30 compared to patients in the observation group. Additionally, the Fres, Zrs, R5, R20, and R35 of the observation group were higher than those of the control group by 10.73 ± 0.18, 1.78 ± 0.24, 0.11 ± 0.17, 0.86 ± 0.13, and 0.02 ± 0.21, respectively. In sum, the pulmonary function indices of the observation group were significantly lower than those of the control group, while the respiratory impedance indices were higher (P < 0.05). Within the observation group, the pulmonary function indices of severe patients were lower than those of moderate and mild patients, and moderate patients had lower pulmonary function indices than mild patients (P < 0.05). CONCLUSION: The pulmonary function of children with obstructive sleep apnea syndrome is impaired and varies in severity. There are significant differences in pulmonary function, underscoring the importance of monitoring pulmonary function in these children for clinical assessment and treatment prognosis.

Spinal cord and brain atrophy patterns in neuromyelitis optica spectrum disorder and multiple sclerosis.

BACKGROUND: Spinal cord and brain atrophy are common in neuromyelitis optica spectrum disorder (NMOSD) and relapsing-remitting multiple sclerosis (RRMS) but harbor distinct patterns accounting for disability and cognitive impairment. METHODS: This study included 209 NMOSD and 304 RRMS patients and 436 healthy controls. Non-negative matrix factorization was used to parse differences in spinal cord and brain atrophy at subject level into distinct patterns based on structural MRI. The weights of patterns were obtained using a linear regression model and associated with Expanded Disability Status Scale (EDSS) and cognitive scores. Additionally, patients were divided into cognitive impairment (CI) and cognitive preservation (CP) groups. RESULTS: Three patterns were observed in NMOSD: (1) Spinal Cord-Deep Grey Matter (SC-DGM) pattern was associated with high EDSS scores and decline of visuospatial memory function; (2) Frontal-Temporal pattern was associated with decline of language learning function; and (3) Cerebellum-Brainstem pattern had no observed association. Patients with CI had higher weights of SC-DGM pattern than CP group. Three patterns were observed in RRMS: (1) DGM pattern was associated with high EDSS scores, decreased information processing speed, and decreased language learning and visuospatial memory functions; (2) Frontal-Temporal pattern was associated with overall cognitive decline; and (3) Occipital pattern had no observed association. Patients with CI trended to have higher weights of DGM and Frontal-Temporal patterns than CP group. CONCLUSION: This study estimated the heterogeneity of spinal cord and brain atrophy patterns in NMOSD and RRMS patients at individual level, and evaluated the clinical relevance of these patterns, which may contribute to stratifying participants for targeted therapy.

10 W super-wideband ultra-low-intensity-noise single-frequency fiber laser at 1 µm.

A 10 W super-wideband ultra-low-intensity-noise single-frequency fiber laser (SFFL) at 1 µm is experimentally demonstrated, based on dual gain saturation effects from semiconductors and optical fibers, together with an analog-digital hybrid optoelectronic feedback loop. Three intensity-noise-inhibited units synergistically work, which actualizes a connection of effective bandwidth and enhancement of noise-suppressing amplitude. With the cascade action of the semiconductor optical amplifier and optical fiber amplifier, the laser power is remarkably boosted. Eventually, an SFFL with an output power of 10.8 W and a relative intensity noise (RIN) below -150 dB/Hz at the frequency range over 1 Hz is realized. More meaningfully, within the total frequency range of 10 Hz to 10 GHz exceeding 29 octaves, the RIN is controlled to below -160 dB/Hz, approaching the shot-noise limit (SNL) level. To the best of our knowledge, this is the lowest RIN result of SFFL within such an extensive frequency range, and this is the highest output power of the near-SNL super-wideband SFFL. Furthermore, a linewidth of less than 0.8 kHz, a long-term stable polarization extinction ratio of 20 dB, and an optical signal-to-noise ratio of over 60 dB are obtained simultaneously. This start-of-the-art SFFL has provided a systematic solution for high-power and low-noise light sources, which is competitive for sophisticated applications, such as free-space laser communication, space-based gravitational wave detection, and super-long-distance space coherent velocity measurement and ranging.

RPL35 downregulated by mechanical overloading promotes chondrocyte senescence and osteoarthritis development via Hedgehog-Gli1 signaling.

Objectives: To investigate the potential role of Ribosomal protein L35 (RPL35) in regulating chondrocyte catabolic metabolism and to examine whether osteoarthritis (OA) progression can be delayed by overexpressing RPL35 in a mouse compression loading model. Methods: RNA sequencing analysis was performed on chondrocytes treated with or without 20 % elongation strain loading for 24 h. Experimental OA in mice was induced by destabilization of the medial meniscus and compression loading. Mice were randomly assigned to a sham group, an intra-articular adenovirus-mediated overexpression of the negative group, and an intra-articular adenovirus-mediated overexpression of the RPL35 operated group. The Osteoarthritis Research Society International score was used to evaluate cartilage degeneration. Immunostaining and western blot analyses were conducted to detect relative protein levels. Primary mouse chondrocytes were treated with 20 % elongation strain loading for 24 h to investigate the role of RPL35 in modulating chondrocyte catabolic metabolism and regulating cellular senescence in chondrocytes. Results: The protein expression of RPL35 in mouse chondrocytes was significantly reduced when excessive mechanical loading was applied, while elevated protein levels of RPL35 protected articular chondrocytes from degeneration. In addition, the RPL35 knockdown alone induced chondrocyte senescence, decreased the expression of anabolic markers, and increased the expression of catabolic markers in vitro in part through the hedgehog (Hh) pathway. Conclusions: These findings demonstrated a functional pathway important for OA development and identified intra-articular injection of RPL35 as a potential therapy for OA prevention and treatment. The translational potential of this article: It is necessary to develop new targeted drugs for OA due to the limitations of conventional pharmacotherapy. Our study explores and demonstrates the protective effect of RPL35 against excessive mechanical stress in OA models in vivo and in vitro in animals. These findings might provide novel insights into OA pathogenesis and show its translational potential for OA therapy.

Single-Lung Ventilation in Infants for Surgical Repair of Coarctation of The Aorta Without Cardiopulmonary Bypass.

OBJECTIVE: To investigate the effect of improving the operative field and postoperative atelectasis of single-lung ventilation (SLV) in the surgical repair of coarctation of the aorta (CoA) in infants without the use of cardiopulmonary bypass (CPB). METHODS: This was a retrospective cohort study. The clinical data of 28 infants (aged 1 to 4 months, weighing between 4.2 and 6 kg) who underwent surgical repair of CoA without CPB from January 2019 to May 2022 were analyzed. Fourteen infants received SLV with a bronchial blocker (Group S), and the other 14 infants received routine endotracheal intubation and bilateral lung ventilation (Group R). RESULTS: In comparison to Group R, Group S exhibited improved exposure of the operative field, a lower postoperative atelectasis score (P<0.001), reduced prevalence of hypoxemia (P=0.01), and shorter durations of operation, mechanical ventilation, and ICU stay (P=0.01, P<0.001, P=0.03). There was no difference in preoperative information or perioperative respiratory and circulatory indicators before SLV, 10 minutes after SLV, and 10 minutes after the end of SLV between the two groups (P>0.05). Intraoperative bleeding, intraoperative positive end-expiratory pressure (PEEP), and systolic pressure gradient across the coarctation after operation were also not different between the two groups (P>0.05). CONCLUSION: This study demonstrates that employing SLV with a bronchial blocker is consistent with enhanced operative field, reduced operation duration, lower prevalence of intraoperative hypoxemia, and fewer postoperative complications during the surgical repair of CoA in infants without the use of CPB.

A Porphyrin-Based 3D Metal-Organic Framework Featuring [Cu8Cl6]10+ Cluster Secondary Building Units: Synthesis, Structure Elucidation, Anion Exchange, and Peroxidase-Like Activity.

Herein, we report a rare example of cationic three-dimensional (3D) metal-organic framework (MOF) of [Cu5Cl3(TMPP)]Cl5 ⋅ xSol (denoted as Cu-TMPP; H2TMPP=meso-tetrakis (6-methylpyridin-3-yl) porphyrin; xSol=encapsulated solvates) supported by [Cu8Cl6]10+ cluster secondary building units (SBUs) wherein the eight faces of the Cl--based octahedron are capped by eight Cu2+. Surface-area analysis indicated that Cu-TMPP features a mesoporous structure and its solvate-like Cl- counterions can be exchanged by BF4 -, PF6 -, and NO3 -. The polyvinylpyrrolidone (PVP) coated Cu-TMPP (denoted as Cu-TMPP-PVP) demonstrated good ROS generating ability, producing ⋅OH in the absence of light (peroxidase-like activity) and 1O2 on light irradiation (650 nm; 25 mW cm-2). This work highlights the potential of Cu-TMPP as a functional carrier of anionic guests such as drugs, for the combination therapy of cancer and other diseases.

Irisin attenuates type 1 diabetic cardiomyopathy by anti-ferroptosis via SIRT1-mediated deacetylation of p53.

BACKGROUND: Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia-reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known. METHODS AND RESULTS: T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose. CONCLUSION: This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy.

Clinical spectrum, over 12-year follow-up and experience of SGLT2 inhibitors treatment on patients with glycogen storage disease type Ib: a single-center retrospective study.

BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment. RESULTS: In this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients. CONCLUSION: Empagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested.

Epidemiology and distribution of cruciate ligament injuries in children and adolescents, with an analysis of risk factors for concomitant meniscal tear.

Introduction: To investigate the epidemiological features and prevalence of cruciate ligament injuries (CLI) in children and adolescents, and to examine the potential risk factors associated with concomitant meniscal tear (MT) among this population. Methods: The demographic data and injury details of children and adolescents with CLI from Southeast China were analyzed to describe their distribution characteristics, alongside an analysis of the prevalence of MTs, the most frequent complication. In addition, binary logistic analysis was employed to ascertain the risk factors linked to MT in individuals suffering from CLI. Results: A total of 203 patients with CLI (n = 206) met the inclusion criteria, with a male-to-female ratio of 2.3:1. Notably, a higher proportion of females were aged ≤16 years old compared to males, who predominated in patients aged >16 years (P = 0.001). Among children and adolescents, anterior cruciate ligament (ACL) injuries were the primary type of CLI, accounting for 88.18% (179/203) of all cases. The majority of cases (132/203, 65.02%) were sustained during sports activities, and sprains were the predominant mechanism of injury (176/203, 86.7%). Additionally, the most common associated injury was an MT (157/203, 77.34%). The posterior horn is the most frequently affected site for both medial MT (62.93% out of 73 cases) and lateral MT (70.19% out of 73 cases). Moreover, vertical tears constituted the majority of medial MTs (59.48% out of 116 cases). Furthermore, patients with a higher BMI faced an increased risk of associated MT in comparison to non-overweight patients (88% vs. 73.86%; P = 0.038). Each increase in BMI unit was linked with a 14% higher probability of associated MT occurrence in children and adolescents with CLI (OR = 1.140; P = 0.036). Discussion: ACL injuries are a common form of knee ligament injury among children and adolescents, especially those over the age of 16, and are often the result of a sprain. Meniscal posterior horn injury is the most commonly associated injury of youth with CLI. Additionally, overweight or obese people with CLI are at a greater risk of developing MT.

Rapamycin facilitates the tendon-bone interface healing in an aging rat model of chronic rotator cuff injury.

BACKGROUND: Tendon-bone interface (TBI) healing in chronic rotator cuff injury (CRCI) in older individuals is a common clinical challenge due to cellular senescence, as well as decreased tissue repair and regeneration. Many studies have demonstrated the anti-aging, improved tissue repair, and bone regeneration properties of rapamycin (RPM) in multiple age-related diseases. This study aimed to explore the effects of RPM on TBI healing after CRCI in an aging rat model. METHODS: A CRCI model was established in 60 Sprague-Dawley rats (24 months old). Rats were then randomly allocated into the control, 0.1 µg RPM, and 1 µg RPM groups. At 4 and 8 weeks post-reconstructive surgery, the supraspinatus tendon-humerus complexes were harvested for biomechanical, microimaging, histological, and immunohistochemical evaluations. RESULTS: Biomechanical testing results demonstrated that the failure load, ultimate strength, and stiffness of the two RPM groups were significantly higher than those of the control group at 4 and 8 weeks postoperatively. Microradiographically, both RPM groups had significantly higher values of bone mineral density and the ratio of trabecular bone volume to total volume than controls at each time point. Moreover, the RPM groups had higher histological scores and showed better regenerated TBI, characterized by better organizational tissue, more fibrocartilage cells, and more bone formation. Immunohistochemical evaluations showed that RUNX2-, SOX9-, and SCX-positive cells were significantly more in the two RPM groups than in the controls at each time point. CONCLUSIONS: RPM may effectively enhance CRCI healing after reconstruction by facilitating osteogenesis, tenogenesis, and fibrocartilage reformation at the TBI, as well as improving biomechanical properties.

Ketogenic diet combined with intermittent fasting: an option for type 2 diabetes remission?

With increasing attention to diabetes remission, various special dietary patterns have been found to be effective in achieving diabetes remission. The effect of a single dietary pattern on lowering blood glucose is clear, but studies on the synergistic effects of different dietary patterns are limited. This article describes the types of intermittent fasting and ketogenic diets, potential mechanisms, contraindications of combination diets, recommendations for combination diets, and their health outcomes. This paper aims to illustrate the evidence for intermittent fasting combined with a ketogenic diet on outcomes of diabetes remission and effect on blood glucose control. Knowledge of these findings can help doctors and patients determine dietary patterns for achieving diabetes remission and understanding their application.

Positive benefit-risk ratio of Psoraleae Fructus: Comprehensive safety assessment and osteogenic effects in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (PF), the dried fruit of Psoralea corylifolia L., is a commonly used traditional medicine that has contributed to the treatment of orthopedic diseases for thousands of years in China. However, recent PF-related liver injury reports have drawn widespread attention regarding its potential hepatotoxicity risks. AIM OF THE STUDY: This study was aimed to evaluate the long-term efficacy and chronic toxicity of PF using a 26-week administration experiment on rats in order to simulate the clinical usage situation. MATERIALS AND METHODS: The PF aqueous extract was consecutively administrated to rats daily at dosages of 0.7, 2.0, and 5.6 g/kg (equivalent to 1-8 times the clinical doses for humans) for as long as 26 weeks. Samples were collected after 13, 26, and 32 weeks (withdrawal for 6 weeks) since the first administration. The chronic toxicity of PF was evaluated by conventional toxicological methods, and the efficacy of PF was evaluated by osteogenic effects in the natural growth process. RESULTS: In our experiments, only the H group (5.6 g/kg) for 26-week PF treatment demonstrated liver or kidney injury, which the injuries were reversible after 6 weeks of withdrawal. Notably, the PF treatment beyond 13 weeks showed significant benefits for bone growth and development in rats, with a higher benefit-risk ratio in female rats. CONCLUSIONS: PF displayed a promising benefit-risk ratio in the treatment and prevention of osteoporosis, a disease that lacks effective medicine so far. This is the first study to elucidate the benefit-risk balance associated with clinical dosage and long-term use of PF, thereby providing valuable insights for rational clinical use and risk control of PF.

Prediction of Human Pharmacokinetics of E0703, a Novel Radioprotective Agent, Using Physiologically Based Pharmacokinetic Modeling and an Interspecies Extrapolation Approach.

E0703, a new steroidal compound optimized from estradiol, significantly increased cell proliferation and the survival rate of KM mice and beagles after ionizing radiation. In this study, we characterize its preclinical pharmacokinetics (PK) and predict its human PK using a physiologically based pharmacokinetic (PBPK) model. The preclinical PK of E0703 was studied in mice and Rhesus monkeys. Asian human clearance (CL) values for E0703 were predicted from various allometric methods. The human PK profiles of E0703 (30 mg) were predicted by the PBPK model in Gastro Plus software 9.8 (SimulationsPlus, Lancaster, CA, USA). Furthermore, tissue distribution and the human PK profiles of different administration dosages and forms were predicted. The 0.002 L/h of CL and 0.005 L of Vss in mice were calculated and optimized from observed PK data. The plasma exposure of E0703 was availably predicted by the CL using the simple allometry (SA) method. The plasma concentration-time profiles of other dosages (20 and 40 mg) and two oral administrations (30 mg) were well-fitted to the observed values. In addition, the PK profile of target organs for E0703 exhibited a higher peak concentration (Cmax) and AUC than plasma. The developed E0703-PBPK model, which is precisely applicable to multiple species, benefits from further clinical development to predict PK in humans.

Controlled-release hydrogel loaded with magnesium-based nanoflowers synergize immunomodulation and cartilage regeneration in tendon-bone healing.

Tendon-bone interface injuries pose a significant challenge in tissue regeneration, necessitating innovative approaches. Hydrogels with integrated supportive features and controlled release of therapeutic agents have emerged as promising candidates for the treatment of such injuries. In this study, we aimed to develop a temperature-sensitive composite hydrogel capable of providing sustained release of magnesium ions (Mg2+). We synthesized magnesium-Procyanidin coordinated metal polyphenol nanoparticles (Mg-PC) through a self-assembly process and integrated them into a two-component hydrogel. The hydrogel was composed of dopamine-modified hyaluronic acid (Dop-HA) and F127. To ensure controlled release and mitigate the "burst release" effect of Mg2+, we covalently crosslinked the Mg-PC nanoparticles through coordination bonds with the catechol moiety within the hydrogel. This crosslinking strategy extended the release window of Mg2+ concentrations for up to 56 days. The resulting hydrogel (Mg-PC@Dop-HA/F127) exhibited favorable properties, including injectability, thermosensitivity and shape adaptability, making it suitable for injection and adaptation to irregularly shaped supraspinatus implantation sites. Furthermore, the hydrogel sustained the release of Mg2+ and Procyanidins, which attracted mesenchymal stem and progenitor cells, alleviated inflammation, and promoted macrophage polarization towards the M2 phenotype. Additionally, it enhanced collagen synthesis and mineralization, facilitating the repair of the tendon-bone interface. By incorporating multilevel metal phenolic networks (MPN) to control ion release, these hybridized hydrogels can be customized for various biomedical applications.

Cast versus Kirschner wire fixation in type II paediatric phalangeal neck fractures.

PURPOSE: To compare the outcomes of type II pediatric phalangeal neck fractures (PPNFs) treated with closed reduction and cast immobilization (CRCI) versus closed reduction percutaneous pinning (CRPP), and evaluated the clinical efficacy of conservative versus surgical treatment of type II PPNFs via meta-analysis. METHODS: Patients aged ≤ 14 years with type II PPNFs were divided into conservative (CRCI) and operative (CRPP) groups. Radiographs measured angulation and translation; hand function was assessed with total active range of motion (TAM) and Quick-DASH. Complication rates were also compared between the groups. A meta-analysis of conservative versus operative treatment confirmed the clinical results. Statistical analysis was performed using SPSS 26.0 and R studio 3.0 with two-tailed, chi-squared, and Mann-Whitney U or t-tests, P < 0.05. Meta-analysis used fixed or random effects models, calculating mean differences and odds ratios for outcomes, and assessing heterogeneity with I2 and Q tests. RESULTS: Final angulation (3.4° ± 3.7° and 4.9° ± 5.4° vs. 3.6° ± 3.7° and 4.2° ± 4.3°) and displacement (6.3% ± 5.8% and 5.7% ± 4.7% vs. 5.8% ± 5.5% and 3.2% ± 4.2%) in the coronal and sagittal planes were not different statistically between the conservative and surgical groups (P > 0.05), but improved significantly compared to preoperative values (P < 0.05). Although Quick-DASH scores were comparable in both groups (P = 0.105), conservatively treated patients had a significantly better TAM at the last follow-up visit (P = 0.005). The complication rates were 24.2% and 41.7% in the surgical and conservatively treated groups respectively (P = 0.162). However, the latter primarily experienced imaging-related complications, whereas the former experienced functional complications (P = 0.046). Our meta-analysis (n = 181 patients) also showed comparable functional (P = 0.49) and radiographic (P = 0.59) outcomes and complication rates (P = 0.21) between the surgical (94 patients) and conservative (87 patients) groups. CONCLUSIONS: Conservative and surgical treatments are both reliable and safe approaches for managing type II PPNF in children. However, conservatively treated patients generally experience similar radiographic outcomes, lower complication rates, and better functional outcomes than surgically treated ones.

Metabolic control of adaptive ß-cell proliferation by the protein deacetylase SIRT2.

Selective and controlled expansion of endogenous ß-cells has been pursued as a potential therapy for diabetes. Ideally, such therapies would preserve feedback control of ß-cell proliferation to avoid excessive ß-cell expansion and an increased risk of hypoglycemia. Here, we identified a regulator of ß-cell proliferation whose inactivation results in controlled ß-cell expansion: the protein deacetylase Sirtuin 2 (SIRT2). Sirt2 deletion in ß-cells of mice increased ß-cell proliferation during hyperglycemia with little effect in homeostatic conditions, indicating preservation of feedback control of ß-cell mass. SIRT2 restrains proliferation of human islet ß-cells cultured in glucose concentrations above the glycemic set point, demonstrating conserved SIRT2 function. Analysis of acetylated proteins in islets treated with a SIRT2 inhibitor revealed that SIRT2 deacetylates enzymes involved in oxidative phosphorylation, dampening the adaptive increase in oxygen consumption during hyperglycemia. At the transcriptomic level, Sirt2 inactivation has context-dependent effects on ß-cells, with Sirt2 controlling how ß-cells interpret hyperglycemia as a stress. Finally, we provide proof-of-principle that systemic administration of a GLP1-coupled Sirt2-targeting antisense oligonucleotide achieves ß-cell selective Sirt2 inactivation and stimulates ß-cell proliferation under hyperglycemic conditions. Overall, these studies identify a therapeutic strategy for increasing ß-cell mass in diabetes without circumventing feedback control of ß-cell proliferation.

Are radiomic spleen features useful for assessing the response to infliximab in patients with Crohn's disease? A multicentre study.

OBJECTIVES: To develop and validate a radiomics nomogram for assessing the response of patients with Crohn's disease (CD) to infliximab. METHODS: Radiomics features of the spleen were extracted from computed tomography enterography (CTE) images of each patient's arterial phase. The feature selection process was performed using the least absolute shrinkage and selection operator (LASSO) algorithm, and a radiomics score (Rad-score) was calculated based on the radiomics signature formula. Subsequently, the radiomic model and the clinical risk factor model were separately established based on the Rad-score and clinically significant features, respectively. The performance of both models was evaluated using receiver operating characteristic (ROC) curves, decision curve analysis (DCA) curves, and clinical impact curves (CICs). RESULTS: Among the 175 CD patients, 105 exhibited a clinical response, and 60 exhibited clinical remission after receiving infliximab (IFX) treatment. Our radiomic model, comprising 20 relevant features, demonstrated excellent predictive performance. The radiomic nomogram for predicting clinical response showed good calibration and discrimination in the training cohort (AUC=0.909, 95% CI=0.840-0.978), the validation cohort (AUC=0.954, 95% CI=0.889-1) and the external cohort (AUC=0.902, 95% CI=0.83-0.974). Accordingly, the nomogram was also suitable for predicting clinical remission. Decision curve analysis and clinical impact curves highlighted the clinical utility of our nomogram. CONCLUSIONS: Our radiomics nomogram is a non-invasive predictive tool constructed from radiomic features of the spleen. It also demonstrated good predictive accuracy in evaluating CD patients' response to infliximab treatment. Multicentre validation provided high-level evidence for its clinical application.

Dual antiplatelet therapy after intravenous thrombolysis for patients with minor ischemic stroke：A meta-analysis.

OBJECTIVE: Intravenous thrombolysis (IVT) has been shown to effectively decrease both the disability rate and mortality associated with acute ischemic stroke, however, there is also a risk of vascular re-occlusion. Antiplatelet therapy can mitigate this risk. Nevertheless, there are no relevant guidelines recommending whether the administration of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel can be performed following thrombolysis. The aim of this study was to conduct a meta-analysis utilizing multiple studies in order to assess the effectiveness and safety of DAPT after IVT in cases of acute mild ischemic stroke (AMIS). METHODS: A comprehensive search on English literature published was performed on databases including PubMed, Embase, Web of Science, and Cochrane up until September 1, 2023. All cases were ischemic stroke patients who underwent IVT within a 4.5-hour timeframe and had a National Institutes of Health Stroke Scale (NIHSS) score of ≤5 (or 3) upon admission. The primary efficacy endpoint is the 90-day Modified Rankin Scale (mRS) Score (MRS score 0-1), while the primary safety endpoint encompassed the occurrence of symptomatic intracranial hemorrhage (SICH) and 90-day mortality. The study's secondary objective is the recurrence of any type of stroke (hemorrhagic and ischemic) within a 90-day period. The included studies underwent an evaluation of bias risk using the Newcastle Ottawa scale. Risk ratios (RRs) and CIs were calculated using a random effects model, and the findings and heterogeneity among the included studies were visually presented on a forest plot. (There was a protocol registration (PROSPERO):). RESULTS: Out of the 1081 studies that were obtained, only 3 met the criteria and were included in the meta-analysis (657 patients in total). The findings indicate that, there was a significant difference in the mRS of 0-1 between single antiplatelet therapy (SAPT) with only aspirin or clopidogrel and DAPT with aspirin and clopidogrel ((RR,1.11[95%CI,0.99-1.24];P=0.07;I2=55%), and no significant difference in stroke recurrence after 90 days or 1 year ((RR,0.94[95%CI,0.41-2.16];P=0.89;I2=30%); Regarding safety evaluation, the results showed no significant difference in the SICH (RR,0.65[95%CI,0.11-3.97];P=0.64;I2=0%) and the incidence of mortality (RR,0.97[95%CI,0.19-4.96];P=0.97;I2=0%) between the two groups. CONCLUSIONS: For patients with acute mild ischemic stroke (AMIS), in conjunction with DAPT after IVT can improve the 90-day prognosis, without increasing the risk of intracranial hemorrhage and 90-day mortality. However, it cannot reduce the risk of stroke recurrence.

Frequency-stabilized improvement of saturated absorption spectroscopy based on laser linewidth-control strategy.

Single-frequency fiber lasers (SFFLs), 1083 nm, have been extensively applied in 4He optical pumping magnetometers (OPMs) for magnetic field detection. However, the sensitivity and accuracy of OPMs are constrained by the frequency stability of SFFLs. Focusing on this concern, the frequency-stabilized performance of the 1083 nm SFFLs is successfully improved by externally tailoring the laser linewidth to match the spectral width of the error signal in saturated absorption spectroscopy. Thereinto, a high-intensity error signal of saturated absorption is generated as a large number of 4He atoms with a wide range of velocities interacting with the 1083 nm laser. Consequently, the root mean square value of the fluctuating frequency after locking is effectively decreased from 24.6 to 13.6 kHz, which achieves a performance improvement of 44.7%. Such a strategy can provide a technical underpinning for effectuating an absolute frequency stabilization with higher precision based on atomic and molecular absorption spectroscopy techniques.