Association of dietary carbohydrate intake with bone mineral density, osteoporosis and fractures among adults without diabetes: Evidence from National Health and Nutrition Examination Survey.

Background: The impact of dietary carbohydrate intake on bone health remains a subject of controversy, potentially influenced by individuals with diabetic osteoporosis who exhibit normal or elevated bone mineral density (BMD). The cross-sectional study was conducted to explore the association between carbohydrate intake and BMD, osteoporosis and fractures among adults without diabetes, based on the National health and nutrition examination survey (NHANES). Methods: Participants were from the NHANES 2005-2010, excluding individuals with diabetes and those with incomplete data. The association between carbohydrate intake and BMD was analyzed using Spearman correlation, linear regression analysis and subgroup analysis, respectively. The association between carbohydrate intake and osteoporosis/fractures was analyzed using weighted logistic regression analysis. Results: A total of 7275 adult participants were included and their dietary carbohydrate intake was inversely associated with BMD in the total femur [ß = -0.20 95%CI (-0.30, -0.10); p < 0.001], femoral neck [ß = -0.10 95%CI (-0.20, -0.00); p = 0.002], and lumbar spine [ß = -0.10 95%CI (-0.20, -0.00); p = 0.004]. Stratified analysis indicated that individuals aged 65 and over, women, and non-Hispanic whites were more likely to have lower BMD. Furthermore, a higher intake of dietary carbohydrates was associated with an increased risk of osteoporosis [OR = 1.001 95%CI (1.001, 1.001); p < 0.001] and fractures at the hip [OR = 1.005 95%CI (1.005, 1.005); p < 0.001], wrist [OR = 1.001 95%CI (1.001, 1.001), p < 0.001], and spine [OR = 1.003 95%CI(1.003, 1.003); p < 0.001]. Conclusions: A higher carbohydrate diet is associated with lower BMD and a higher risk of osteoporosis and fractures among adults without diabetes, and a higher carbohydrate consumption show a stronger effect in individuals aged 65 and over, women, and non-Hispanic whites.

Advances in Polysaccharide-Based Microneedle Systems for the Treatment of Ocular Diseases.

The eye, a complex organ isolated from the systemic circulation, presents significant drug delivery challenges owing to its protective mechanisms, such as the blood-retinal barrier and corneal impermeability. Conventional drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and compliance. Polysaccharide-based microneedles (PSMNs) have emerged as a transformative solution for ophthalmic drug delivery. However, a comprehensive review of PSMNs in ophthalmology has not been published to date. In this review, we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug delivery. We provide a thorough analysis of PSMNs, summarizing the design principles, fabrication processes, and challenges addressed during fabrication, including improving patient comfort and compliance. We also describe recent advances and the performance of various PSMNs in both research and clinical scenarios. Finally, we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.

RNA-binding protein GIGYF2 orchestrates hepatic insulin resistance through STAU1/PTEN-mediated disruption of the PI3K/AKT signaling cascade.

BACKGROUND: Obesity is well-established as a significant contributor to the development of insulin resistance (IR) and diabetes, partially due to elevated plasma saturated free fatty acids like palmitic acid (PA). Grb10-interacting GYF Protein 2 (GIGYF2), an RNA-binding protein, is widely expressed in various tissues including the liver, and has been implicated in diabetes-induced cognitive impairment. Whereas, its role in obesity-related IR remains uninvestigated. METHODS: In this study, we employed palmitic acid (PA) exposure to establish an in vitro IR model in the human liver cancer cell line HepG2 with high-dose chronic PA treatment. The cells were stained with fluorescent dye 2-NBDG to evaluate cell glucose uptake. The mRNA expression levels of genes were determined by real-time qRT-PCR (RT-qPCR). Western blotting was employed to examine the protein expression levels. The RNA immunoprecipitation (RIP) was used to investigate the binding between protein and mRNA. Lentivirus-mediated gene knockdown and overexpression were employed for gene manipulation. In mice, an IR model induced by a high-fat diet (HFD) was established to validate the role and action mechanisms of GIGYF2 in the modulation of HFD-induced IR in vivo. RESULTS: In hepatocytes, high levels of PA exposure strongly trigger the occurrence of hepatic IR evidenced by reduced glucose uptake and elevated extracellular glucose content, which is remarkably accompanied by up-regulation of GIGYF2. Silencing GIGYF2 ameliorated PA-induced IR and enhanced glucose uptake. Conversely, GIGYF2 overexpression promoted IR, PTEN upregulation, and AKT inactivation. Additionally, PA-induced hepatic IR caused a notable increase in STAU1, which was prevented by depleting GIGYF2. Notably, silencing STAU1 prevented GIGYF2-induced PTEN upregulation, PI3K/AKT pathway inactivation, and IR. STAU1 was found to stabilize PTEN mRNA by binding to its 3'UTR. In liver cells, tocopherol treatment inhibits GIGYF2 expression and mitigates PA-induced IR. In the in vivo mice model, GIGYF2 knockdown and tocopherol administration alleviate high-fat diet (HFD)-induced glucose intolerance and IR, along with the suppression of STAU1/PTEN and restoration of PI3K/AKT signaling. CONCLUSIONS: Our study discloses that GIGYF2 mediates obesity-related IR by disrupting the PI3K/AKT signaling axis through the up-regulation of STAU1/PTEN. Targeting GIGYF2 may offer a potential strategy for treating obesity-related metabolic diseases, including type 2 diabetes.

Pain, obesity, adenosine salvage disruption, and smoking behavior mediate the effect of gut microbiota on sleep disorders: results from network Mendelian randomization and 16S rDNA sequencing.

Objectives: The objective of this study is to investigate the indirect causalities between gut microbiota and sleep disorders. Methods: In stage 1, we utilized 196 gut microbiota as the exposure factor and conducted a two-sample univariable Mendelian randomization (MR) analysis on five sleep disorders: insomnia, excessive daytime sleepiness (EDS), sleep-wake rhythm disorders (SWRD), obstructive sleep apnea (OSA), and isolated REM sleep behavior disorder (iRBD). In stage 2, we validated the MR findings by comparing fecal microbiota abundance between patients and healthy controls through 16S rDNA sequencing. In stage 3, we explored the indirect pathways by which the microbiota affects sleep, using 205 gut microbiota metabolic pathways and 9 common risk factors for sleep disorders as candidate mediators in a network MR analysis. Results: In stage 1, the univariable MR analysis identified 14 microbiota potentially influencing five different sleep disorders. In stage 2, the results from our observational study validated four of these associations. In stage 3, the network MR analysis revealed that the Negativicutes class and Selenomonadales order might worsen insomnia by increasing pain [mediation: 12.43% (95% CI: 0.47, 24.39%)]. Oxalobacter could raise EDS by disrupting adenosine reuptake [25.39% (1.84, 48.95%)]. Allisonella may elevate OSA risk via obesity promotion [36.88% (17.23, 56.54%)], while the Eubacterium xylanophilum group may lower OSA risk by decreasing smoking behavior [7.70% (0.66, 14.74%)]. Conclusion: Triangulation of evidence from the MR and observational study revealed indirect causal relationships between the microbiota and sleep disorders, offering fresh perspectives on how gut microbiota modulate sleep.

A DoS attack detection method based on adversarial neural network.

In order to analyze the influence of deep learning model on detecting denial-of-service (DoS) attacks, this article first examines the concepts and attack strategies of DoS assaults before looking into the present detection methodologies for DoS attacks. A distributed DoS attack detection system based on deep learning is established in response to the investigation's limitations. This system can quickly and accurately identify the traffic of distributed DoS attacks in the network that needs to be detected and then promptly send an alarm signal to the system. Then, a model called the Improved Conditional Wasserstein Generative Adversarial Network with Inverter (ICWGANInverter) is proposed in response to the characteristics of incomplete network traffic in DoS attacks. This model automatically learns the advanced abstract information of the original data and then employs the method of reconstruction error to identify the best classification label. It is then tested on the intrusion detection dataset NSL-KDD. The findings demonstrate that the mean square error of continuous feature reconstruction in the sub-datasets KDDTest+ and KDDTest-21 steadily increases as the noise factor increases. All of the receiver operating characteristic (ROC) curves are shown at the top of the diagonal, and the overall area under the ROC curve (AUC) values of the macro-average and micro-average are above 0.8, which demonstrates that the ICWGANInverter model has excellent detection performance in both single category attack detection and overall attack detection. This model has a greater detection accuracy than other models, reaching 87.79%. This demonstrates that the approach suggested in this article offers higher benefits for detecting DoS attacks.

A chemical reaction entity recognition method based on a natural language data augmentation strategy.

Impressive applications of artificial intelligence in the field of chemical reaction prediction heavily depend on abundant reliable datasets. The automated extraction of reaction procedures to build structured chemical databases is of growing importance. Here, we propose a novel model named DACRER for large-scale reaction extraction, in which transfer learning and a data augmentation strategy were employed. This model was evaluated for chemical datasets and shows good performance in identifying and processing chemical texts.

An exploration of the solution of direct methanol fuel cell cost effectiveness.

The work in this paper incorporated printed circuit board (PCB) technology into micro-direct methanol fuel cells (µDMFCs) and conjectured and verified the performance degradation factors of PCB current collectors in µDMFCs by testing different designed configuration µDMFCs. The experiment results showed that all kinds of PCB coating can benefit from the porous stainless-steel plates covering to a great extent. At the end of 48 h discharging, µDMFCs with porous stainless-steel plates between MEA and PCB coating achieved higher performance than those of the direct contacting series. It can be inferred from various types of experimental data that because of stainless-steel porous plate isolating, the impact of corrosion on the surface of the PCB electrode plate was reduced to a certain extent. The corrosion of the electrode plate was slowed down in the µDMFC discharging as a result of the passivation behavior on the iron surface and a decrease in corrosion current. Consequently, the attenuation of the PCB performance was delayed. The conclusion of this work explores a practical direction to enhance the cost-effectiveness of fuel cells, promoting the large-scale application of DMFCs in the future.

[Incidence of comorbid ED with LUTS and its risk factors in patients with BPH].

OBJECTIVE: To investigate the incidence of comorbid ED with lower urinary tract symptoms (LUTS) and its risk factors in BPH patients. METHODS: Based on inclusion and exclusion criteria, we selected BPH patients visiting the outpatient department of the Second Xiangya Hospital of Central South University from January 2020 to January 2023. We collected the general and clinical data from the patients, including age, height, body weight, abdominal circumference, hip circumference, blood pressure, blood routine, liver function, kidney function, blood lipids and fasting blood glucose, obtained their IPSS, quality of life (QOL) scores, and IIEF-5 scores by questionnaire investigation, and performed data processing and analysis with the SPSS 22.0 software. RESULTS: The incidence rate of comorbid ED with LUTS in the BPH patients rose with the increase of age, 36.46% in the 45－49-year group, 43.72% in the 50－54-year group, 53.66% in the 55－59-year group, 69.23% in the 60－64-year group, and 78.74% in the 65－70-year group. The lipid accumulation product (LAP), visceral adiposity index (VAI), triglycerides and glucose (TyG), hepatic steatosis index (HSI), body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) were correlated positively with IPSS scores and negatively with IIEF-5 scores, while LDL-C and total cholesterol (TC) negatively with IPSS scores and positively with IIEF-5 scores. CONCLUSION: The incidence of comorbid ED with LUTS in BPH patients increases with age. The risk factors for this comorbidity include hypertension, dyslipidemia, diabetes, BMI, and lifestyle, and the risk of the condition can be effectively assessed by LAP, VAI, TYG, HSI, BMI, WHtR, WHR, TG and HDL-C.

Hounsfield units in assessing bone mineral density in ankylosing spondylitis patients with cervical fracture-dislocation.

BACKGROUND: Cervical spine fracture-dislocations in patients with ankylosing spondylitis (AS) are mostly unstable and require surgery. However, osteoporosis, one of the comorbidities for AS, could lead to detrimental prognoses. There are few accurate assessments of bone mineral density in AS patients. AIM: To analyze Hounsfield units (HUs) for assessing bone mineral density in AS patients with cervical fracture-dislocation. METHODS: The HUs from C2 to C7 of 51 patients obtained from computed tomography (CT) scans and three-dimensional reconstruction of the cervical spine were independently assessed by two trained spinal surgeons and statistically analyzed. Inter-reader reliability and agreement were assessed by interclass correlation coefficient. RESULTS: The HUs decreased gradually from C2 to C7. The mean values of the left and right levels were significantly higher than those in the middle. Among the 51 patients, 25 patients (49.02%) may be diagnosed with osteoporosis, and 16 patients (31.37%) may be diagnosed with osteopenia. CONCLUSION: The HUs obtained by cervical spine CT are feasible for assessing bone mineral density with excellent agreement in AS patients with cervical fracture-dislocation.

Optimization of culture conditions for endophytic bacteria in mangrove plants and isolation and identification of bacteriocin.

Introduction: The antibacterial protein PAG14 was extracted from a metabolite of Bacillus G14 isolated from mangrove plants. Methods: In this study, Pseudomonas aeruginosa, Pasteurell multocide, Enterobacter aerogenes, and Enterococcus faecalis were used as indicator bacteria to screen endophytes that exhibited antibacterial activity. The endophyte culture conditions were optimized to enhance productivity. Subsequently, the culture supernatant was salted using ammonium sulfate, followed by purification using dextran gel chromatography and ion exchange column techniques. Finally, the structures of antibacterial proteins were identified using mass spectrometry. Results and Discussion: The optimal culture conditions for Bacillus G14 were 2% mannitol, 0.5% fish peptone, 0.05% KH2PO4 + 0.05% K2HPO4 + 0.025% MnSO4·H2O. The antibacterial substances exhibited stability within the temperature range of 30-40°C and pH range of 5.0-7.0, while displaying sensitivity toward enzymes. The antibacterial activity decreased as the duration of UV irradiation increased. The antibacterial protein PAG14, isolated from the culture broth of Bacillus G14 through purification using dextran gel and ion-exchange columns, was identified as a class III bacteriocin using LC-MS/MS, similar to Lysozyme C. These findings serve as a theoretical foundation for the investigation and application of bacteriocins in food products.

FLAT: Fusing layer representations for more efficient transfer learning in NLP.

Parameter efficient transfer learning (PETL) methods provide an efficient alternative for fine-tuning. However, typical PETL methods inject the same structures to all Pre-trained Language Model (PLM) layers and only use the final hidden states for downstream tasks, regardless of the knowledge diversity across PLM layers. Additionally, the backpropagation path of existing PETL methods still passes through the frozen PLM during training, which is computational and memory inefficient. In this paper, we propose FLAT, a generic PETL method that explicitly and individually combines knowledge across all PLM layers based on the tokens to perform a better transferring. FLAT considers the backbone PLM as a feature extractor and combines the features in a side-network, hence the backpropagation does not involve the PLM, which results in much less memory requirement than previous methods. The results on the GLUE benchmark show that FLAT outperforms other tuning techniques in the low-resource scenarios and achieves on-par performance in the high-resource scenarios with only 0.53% trainable parameters per task and 3.2× less GPU memory usagewith BERTbase. Besides, further ablation study is conducted to reveal that the proposed fusion layer effectively combines knowledge from PLM and helps the classifier to exploit the PLM knowledge to downstream tasks. We will release our code for better reproducibility.

Electrochemical Dehydrogenative [3 + 2]/[5 + 2] Annulation of N-Arylacrylamides with γ,σ-Unsaturated Malonates via Direct C(sp3)-H/C(sp2)-H Functionalization.

Herein, we introduce an electrochemical dehydrogenative [3 + 2]/[5 + 2] annulation of easily available N-arylacrylamides with γ,σ-unsaturated malonates through C(sp3)-H/C(sp2)-H functionalization. The employment of inexpensive ferrocene as the redox catalyst allows access to diverse benzo[b]azepin-2-ones in moderate to excellent yields without stoichiometric oxidants. This protocol features broad substrate scope and excellent selectivity, and mechanistic studies indicated that the reaction proceeded through the oxidation of a C(sp3)-H bond to generate an alkyl radical, radical addition across the C═C bond, [3 + 2]/[5 + 2] annulations, and C(sp2)-H functionalization cascades.

[Amplitude-integrated electroencephalography monitoring results of hospitalized neonates in plateau areas]. / æŒ¯å¹ æ•´åˆè„‘ç”µå›¾åœ¨é«˜åŽŸåœ°åŒºä½é™¢æ–°ç”Ÿå„¿ä¸­çš„ç›‘æµ‹ç»“æžœåˆ†æž.

OBJECTIVES: To investigate the amplitude-integrated electroencephalography (aEEG) monitoring results of hospitalized neonates in plateau areas. METHODS: A retrospective analysis was conducted on 5 945 neonates who were admitted to the Department of Neonatology, Kunming Children's Hospital, and received aEEG monitoring from January 2020 to December 2022. According to the aEEG monitoring results, they were divided into a normal aEEG group and an abnormal aEEG group. The incidence rate of aEEG abnormalities was analyzed in neonates with various systemic diseases, as well as the manifestations of aEEG abnormalities and the consistency between aEEG abnormalities and clinical abnormalities. RESULTS: Among the 5 945 neonates, the aEEG abnormality rate was 19.28% (1 146/5 945), with an abnormality rate of 29.58% (906/3 063) in critically ill neonates and 8.33% (240/2 882) in non-critically ill neonates (P<0.05). The children with inherited metabolic diseases showed the highest aEEG abnormality rate of 60.77% (79/130), followed by those with central nervous system disorders [42.22% (76/180)] and preterm infants [35.53% (108/304)]. Compared with the normal aEEG group, the abnormal aEEG group had significantly lower age and gestational age, as well as a significantly lower birth weight of preterm infants (P<0.05). Among the 1 146 neonates with aEEG abnormalities, the main types of aEEG abnormalities were sleep cycle disorders in 597 neonates (52.09%), background activity abnormalities in 294 neonates (25.65%), and epileptiform activity in 255 neonates (22.25%), and there were 902 neonates (78.71%) with abnormal clinical manifestations. The sensitivity and specificity of aEEG monitoring for brain function abnormalities were 33.51% and 92.50%, respectively. CONCLUSIONS: In plateau areas, there is a relatively high rate of aEEG abnormalities among hospitalized neonates, particularly in critically ill neonates and those with smaller gestational ages and younger ages, suggesting a high risk of brain injury. Therefore, routine aEEG monitoring for the hospitalized neonates can help with the early detection of brain function abnormalities, the decision-making in treatment, and the formulation of brain protection strategies.

Calcium-mediated DAD in membrane potentials and triggered activity in atrial myocytes of ETV1f / fMyHCCre /+ mice.

The E-twenty-six variant 1 (ETV1)-dependent transcriptome plays an important role in atrial electrical and structural remodelling and the occurrence of atrial fibrillation (AF), but the underlying mechanism of ETV1 in AF is unclear. In this study, cardiomyocyte-specific ETV1 knockout (ETV1f/fMyHCCre/+, ETV1-CKO) mice were constructed to observe the susceptibility to AF and the underlying mechanism in AF associated with ETV1-CKO mice. AF susceptibility was examined by intraesophageal burst pacing, induction of AF was increased obviously in ETV1-CKO mice than WT mice. Electrophysiology experiments indicated shortened APD50 and APD90, increased incidence of DADs, decreased density of ICa,L in ETV1-CKO mice. There was no difference in VINACT,1/2 and VACT,1/2, but a significantly longer duration of the recovery time after inactivation in the ETV1-CKO mice. The recording of intracellular Ca2+ showed that there was significantly increased in the frequency of calcium spark, Ca2+ transient amplitude, and proportion of SCaEs in ETV1-CKO mice. Reduction of Cav1.2 rather than NCX1 and SERCA2a, increase RyR2, p-RyR2 and CaMKII was reflected in ETV1-CKO group. This study demonstrates that the increase in calcium spark and SCaEs corresponding to Ca2+ transient amplitude may trigger DAD in membrane potential in ETV1-CKO mice, thereby increasing the risk of AF.

SFRP4 contributes to insulin resistance-induced polycystic ovary syndrome by triggering ovarian granulosa cell hyperandrogenism and apoptosis through the nuclear ß-catenin/IL-6 signaling axis.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic ovulation dysfunction and overproduction of androgens. Women with PCOS are commonly accompanied by insulin resistance (IR), which can impair insulin sensitivity and elevate blood glucose levels. IR promotes ovarian cysts, ovulatory dysfunction, and menstrual irregularities in women patients, leading to the pathogenesis of PCOS. Secreted frizzled-related protein 4 (SFRP4), a secreted glycoprotein, exhibits significantly elevated expression levels in obese individuals with IR and PCOS. Whereas, whether it plays a role in regulating IR-induced PCOS still has yet to be understood. In this study, we respectively established in vitro IR-induced hyperandrogenism in human ovarian granular cells and in vivo IR-induced PCOS models in mice to investigate the action mechanisms of SFRP4 in modulating IR-induced PCOS. Here, we revealed that SFRP4 expression levels in both mRNA and protein were remarkably upregulated in the IR-induced hyperandrogenism with elevated testosterone in the human ovarian granulosa cell line KGN. Under normal conditions without hyperandrogenism, overexpressing SFRP4 triggered the remarkable elevation of testosterone along with the increased nuclear translocation of ß-catenin, cell apoptosis and proinflammatory cytokine IL-6. Furthermore, we found that phytopharmaceutical disruption of SFRP4 by genistein ameliorated IR-induced increase in testosterone in ovarian granular cells, and IR-induced PCOS in high-fat diet obese mice. Our study reveals that SFRP4 contributes to IR-induced PCOS by triggering ovarian granulosa cell hyperandrogenism and apoptosis through the nuclear ß-catenin/IL-6 signaling axis. Elucidating the role of SFRP4 in PCOS may provide a novel therapeutic strategy for IR-related PCOS therapy.

Chemical Isotope Labeling and Dual-Filtering Strategy for Comprehensive Profiling of Urinary Glucuronide Conjugates.

Glucuronidation, a crucial process in phase II metabolism, plays a vital role in the detoxification and elimination of endogenous substances and xenobiotics. A comprehensive and confident profiling of glucuronate-conjugated metabolites is imperative to understanding their roles in physiological and pathological processes. In this study, a chemical isotope labeling and dual-filtering strategy was developed for global profiling of glucuronide metabolites in biological samples. N,N-Dimethyl ethylenediamine (DMED-d0) and its deuterated counterpart DMED-d6 were used to label carboxylic acids through an amidation reaction. First, carboxyl-containing compounds were extracted based on a characteristic mass difference (Δm/z, 6.037 Da) observed in MS between light- and heavy-labeled metabolites (filter I). Subsequently, within the pool of carboxyl-containing compounds, glucuronides were identified using two pairs of diagnostic ions (m/z 247.1294/253.1665 and 229.1188/235.1559 for DMED-d0/DMED-d6-labeled glucuronides) originating from the fragmentation of the derivatized glucuronic acid group in MS/MS (filter II). Compared with non-derivatization, DEMD labeling significantly enhanced the detection sensitivity of glucuronides, as evidenced by a 3- to 55-fold decrease in limits of detection for representative standards. The strategy was applied to profiling glucuronide metabolites in urine samples from colorectal cancer (CRC) patients. A total of 685 features were screened as potential glucuronides, among which 181 were annotated, mainly including glucuronides derived from lipids, organic oxygen, and phenylpropanoids. Enzymatic biosynthesis was employed to accurately identify unknown glucuronides without standards, demonstrating the reliability of the dual-filtering strategy. Our strategy exhibits great potential for profiling the glucuronide metabolome with high coverage and confidence to reveal changes in CRC and other diseases.

The relationship between ultrasound and physical examination in the assessment of enthesitis in SpA patients: results from the DEUS multicentre study: The role of ultrasound and physical examination in assessing enthesitis in SpA patients.

OBJECTIVES: i) To explore the agreement between the OMERACT ultrasound lesions of enthesitis and physical examination in assessing enthesitis in spondyloarthritis (SpA) patients; ii) To investigate the prevalence and clinical relevance of subclinical enthesitis in this population. METHODS: Twenty rheumatology centres participated in this cross-sectional study. SpA patients, including axial SpA (axSpA) and psoriatic arthritis (PsA) patients, underwent both ultrasound scan and physical examination of large lower limb entheses. The OMERACT ultrasound lesions of enthesitis were considered, along with a recently proposed definition for 'active enthesitis' by our group. Subclinical enthesitis was defined as the presence of 'active enthesitis' in ≥1 enthesis in SpA patients without clinical enthesitis (i.e., number of positive entheses on physical examination and Leeds Enthesitis Index score =0). RESULTS: 4130 entheses in 413 SpA patients (224 axSpA/189 PsA) were evaluated through ultrasound and physical examination. Agreement between ultrasound and physical examination ranged from moderate (i.e., enthesophytes) to almost perfect (i.e., power Doppler and 'active enthesitis'). Patellar tendon entheses demonstrated the highest agreement, whereas Achilles tendon insertion showed the lowest. Among 158/413 (38.3%) SpA patients with clinical enthesitis, 108 (68.4%) exhibited no 'active enthesitis' on ultrasound. Conversely, of those 255 without clinical enthesitis, 39 (15.3%) showed subclinical enthesitis. Subclinical enthesitis was strongly associated with local structural damage. However, no differences were observed regarding the demographic and clinical profiles of SpA patients with and without subclinical enthesitis. CONCLUSIONS: Our study underscores the need for a comprehensive tool integrating ultrasound and physical examination for assessing enthesitis in SpA patients.

Clinical effect of operative vs nonoperative treatment on humeral shaft fractures: Systematic review and meta-analysis of clinical trials.

BACKGROUND: Whether operation is superior to non-operation for humeral shaft fracture remains debatable. We hypothesized that operation could decrease the nonunion and reintervention rates and increase the functional outcomes. AIM: To compare the clinical efficacy between operative and nonoperative approaches for humeral shaft fractures. METHODS: We searched the PubMed, Web of Science, ScienceDirect, and Cochrane databases from 1990 to December 2023 for clinical trials and cohort studies comparing the effects of operative and conservative methods on humeral shaft fractures. Two investigators independently extracted data from the eligible studies, and the other two assessed the methodological quality of each study. The quality of the included studies was assessed using the Cochrane risk bias or Newcastle-Ottawa Scale. The nonunion, reintervention and the overall complications and functional scores were pooled and analyzed using Review Manager software (version 5.3). RESULTS: A total of four randomized control trials and 13 cohort studies were included, with 1285 and 1346 patients in the operative and nonoperative groups, respectively. Patients in the operative group were treated with a plate or nail, whereas those in the conservative group were managed with splint or functional bracing. Four studies were assessed as having a high risk of bias, and the other 13 were of a low risk of bias according to the Newcastle-Ottawa Scale or Cochrane risk bias tool. The operative group had a significantly decreased rate of nonunion [odds ratio (OR) 0.30; 95%CI: 0.23 to 0.40), reintervention (OR: 0.33; 95%CI: 0.24 to 0.47), and overall complications (OR: 0.62; 95%CI: 0.49 to 0.78)]. The pooled effect of the Disabilities of Arm, Shoulder, and Hand score showed a significant difference at 3 [mean difference (MD) -8.26; 95%CI: -13.60 to -2.92], 6 (MD: -6.72; 95%CI: -11.34 to -2.10), and 12 months (MD: -2.55; 95%CI: -4.36 to -0.74). The pooled effect of Visual Analog Scale scores and the Constant-Murley score did not significantly differ between the two groups. CONCLUSION: This systematic review and meta-analysis revealed a trend of rapid functional recovery and decreased rates of nonunion and reintervention after operation for humeral shaft fracture compared to conservative treatment.

PFN1 Knockdown Aggravates Mitophagy to Retard Lung Adenocarcinoma Initiation and M2 Macrophage Polarization.

Tumor-associated macrophages (TAM) are considered as crucial influencing factors of lung adenocarcinoma (LUAD) carcinogenesis and metastasis. Profilin 1 (PFN1) has been proposed as a potent driver of migration and drug resistance in LUAD. The focus of this work was to figure out the functional mechanism of PFN1 in macrophage polarization in LUAD. PFN1 expression and its significance in patients' survival were detected by ENCORI and Kaplan-Meier Plotter. RT-qPCR and western blotting examined PFN1 expression in LUAD cells. CCK-8 assay and colony formation assay detected cell proliferation. Flow cytometry detected cell apoptosis. Relevant assay kit tested caspase3 concentration. Western blotting analyzed the expression of proliferation- and apoptosis-related proteins. RT-qPCR and immunofluorescence staining measured M1 and M2 macrophages markers. Mitophagy was assessed by MitoTracker Red staining, immunofluorescence staining, and western blotting. PFN1 expression was increased in LUAD tissues and cells and correlated with the poor survival rate of LUAD patients. Deficiency of PFN1 hindered the proliferation, whereas facilitated the apoptosis of LUAD cells. Additionally, PFN1 interference impaired M2 macrophage polarization. Moreover, PFN1 knockdown exacerbated the mitophagy in LUAD cells and mitophagy inhibitor mitochondrial division inhibitor 1 (Mdivi-1) notably reversed the effects of PFN1 down-regulation on the proliferation, apoptosis as well as macrophage polarization in LUAD cells. To sum up, activation of mitophagy initiated by PFN1 depletion might obstruct the occurrence and M2 macrophage polarization in LUAD.

Gastroesophageal reflux disease increases the risk of rheumatoid arthritis: a bidirectional two-sample Mendelian randomization study.

Rheumatoid arthritis (RA) is a common autoimmune disease, and some observational studies have indicated an association between Gastroesophageal Reflux Disease (GERD) and RA. However, the causal relationship between the two remains uncertain. We used Mendelian randomization (MR) to assess the causal relationship between GERD and RA. Two-sample Mendelian randomization analysis was performed using pooled data from large-scale genome-wide association studies. In addition, we performed multivariate MR analyses to exclude confounding factors between GERD and RA, including smoking quantity, drinking frequency, BMI, depression, and education attainment. The MR results for GERD on RA suggested a causal effect of the genetic susceptibility of GERD on RA (discovery dataset, IVW, odds ratio [OR] = 1.41, 95% confidence interval [CI] 1.22-1.63, p = 2.81 × 10-6; validation dataset, IVW, OR = 1.38, 95% CI 1.23-1.55, P = 1.76 × 10-8). Multivariate MR analysis also supports this result. But the results of the reverse MR analysis did not reveal compelling evidence that RA can increase the risk of developing GERD. Our bidirectional Two-Sample Mendelian randomization analysis and multivariate MR analysis provide support for the causal effect of GERD on RA. This discovery could offer new insights for the prevention and treatment of RA.