PDZK1 protects against mechanical overload-induced chondrocyte senescence and osteoarthritis by targeting mitochondrial function.

Mechanical overloading and aging are two essential factors for osteoarthritis (OA) development. Mitochondria have been identified as a mechano-transducer situated between extracellular mechanical signals and chondrocyte biology, but their roles and the associated mechanisms in mechanical stress-associated chondrocyte senescence and OA have not been elucidated. Herein, we found that PDZ domain containing 1 (PDZK1), one of the PDZ proteins, which belongs to the Na+/H+ Exchanger (NHE) regulatory factor family, is a key factor in biomechanically induced mitochondrial dysfunction and chondrocyte senescence during OA progression. PDZK1 is reduced by mechanical overload, and is diminished in the articular cartilage of OA patients, aged mice and OA mice. Pdzk1 knockout in chondrocytes exacerbates mechanical overload-induced cartilage degeneration, whereas intraarticular injection of adeno-associated virus-expressing PDZK1 had a therapeutic effect. Moreover, PDZK1 loss impaired chondrocyte mitochondrial function with accumulated damaged mitochondria, decreased mitochondrion DNA (mtDNA) content and increased reactive oxygen species (ROS) production. PDZK1 supplementation or mitoubiquinone (MitoQ) application alleviated chondrocyte senescence and cartilage degeneration and significantly protected chondrocyte mitochondrial functions. MRNA sequencing in articular cartilage from Pdzk1 knockout mice and controls showed that PDZK1 deficiency in chondrocytes interfered with mitochondrial function through inhibiting Hmgcs2 by increasing its ubiquitination. Our results suggested that PDZK1 deficiency plays a crucial role in mediating excessive mechanical load-induced chondrocyte senescence and is associated with mitochondrial dysfunction. PDZK1 overexpression or preservation of mitochondrial functions by MitoQ might present a new therapeutic approach for mechanical overload-induced OA.

[FeIIICl(TMPPH2)][FeIIICl4]2: A Stand-Alone Molecular Nanomedicine That Induces High Cytotoxicity by Ferroptosis.

Developing clinically meaningful nanomedicines for cancer therapy requires the drugs to be effective, safe, simple, cheap, and easy to store. In the present work, we report that a simple cationic Fe(III)-rich salt of [FeIIICl(TMPPH2)][FeIIICl4]2 (Fe-TMPP) exhibits a superior anticancer performance on a broad spectrum of cancer cell lines, including breast, colorectal cancer, liver, pancreatic, prostate, and gastric cancers, with half maximal inhibitory concentration (IC50) values in the range of 0.098-3.97 µM (0.066-2.68 µg mL-1), comparable to the best-reported medicines. Fe-TMPP can form stand-alone nanoparticles in water without the need for extra surface modification or organic-solvent-assisted antisolvent precipitation. Critically, Fe-TMPP is TME-responsive (TME = tumor microenvironment), and can only elicit its function in the TME with overexpressed H2O2, converting H2O2 to the cytotoxic •OH to oxidize the phospholipid of the cancer cell membrane, causing ferroptosis, a programmed cell death process of cancer cells.

Radiomics analysis based on CT for predicting lymph node metastasis and prognosis in duodenal papillary carcinoma.

OBJECTIVES: Radiomics has been demonstrated to be strongly associated with TNM stage and patient prognosis. We aimed to develop a model for predicting lymph node metastasis (LNM) and survival. METHODS: For radiomics texture selection, 3D Slicer 5.0.3 software and the least absolute shrinkage and selection operator (LASSO) algorithm were used. Subsequently, the radiomics model, computed tomography (CT) image, and clinical risk model were compared. The performance of the three models was evaluated using receiver operating characteristic (ROC) curves, decision curve analysis (DCA), calibration plots, and clinical impact curves (CICs). RESULTS: For the LNM prediction model, 224 patients with LNM information were used to construct a model that was applied to predict LNM. According to the CT data and clinical characteristics, we constructed a radiomics model, CT imaging model and clinical model. The radiomics model for evaluating LNM status showed excellent calibration and discrimination in the training cohort (AUC = 0.926, 95% CI = 0.869-0.982) and the validation cohort (AUC = 0.872, 95% CI = 0.802-0.941). DeLong's test demonstrated that the difference among the three models was significant. Similarly, DCA and CIC showed that the radiomics model has better clinical utility than the CT imaging model and clinical model. Our model also exhibited good performance in predicting survival-in line with the findings of the model built with clinical risk factors. CONCLUSIONS: CT radiomics models exhibited better predictive performance for LNM than models built based on clinical risk characteristics and CT imaging and had comparative clinical utility for predicting patient prognosis. CRITICAL RELEVANCE STATEMENT: The radiomics model showed excellent performance and discrimination for predicting LNM and survival of duodenal papillary carcinoma (DPC). KEY POINTS: LNM status determines the most appropriate treatment for DPC. Our radiomics model for evaluating the LNM status of DPC performed excellently. The radiomics model had high sensitivity and specificity for predicting survival, exhibiting great clinical value.

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.

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.

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.

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.

Rapamycin facilitates healing of the tendon-bone interface 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 antiaging, 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 postreconstructive 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 2 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 2 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.

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.

Are Radiomic Spleen Features Useful for Assessing the Response to Infliximab in Patients With Crohn's Disease? A Multicenter Study.

INTRODUCTION: 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 images of each patient's arterial phase. The feature selection process was performed using the least absolute shrinkage and selection operator algorithm, and a radiomics 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 radiomics score and clinically significant features, respectively. The performance of both models was evaluated using receiver operating characteristic curves, decision curve analysis curves, and clinical impact curves. RESULTS: Among the 175 patients with CD, 105 exhibited a clinical response, and 60 exhibited clinical remission after receiving infliximab 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 (area under the curve [AUC] 0.909, 95% confidence interval [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. DISCUSSION: Our radiomics nomogram is a noninvasive predictive tool constructed from radiomic features of the spleen. It also demonstrated good predictive accuracy in evaluating CD patients' response to infliximab treatment. Multicenter validation provided high-level evidence for its clinical application.

Machine learning-based radiomics to distinguish pulmonary nodules between lung adenocarcinoma and tuberculosis.

BACKGROUND: Radiomics is increasingly utilized to distinguish pulmonary nodules between lung adenocarcinoma (LUAD) and tuberculosis (TB). However, it remains unclear whether different segmentation criteria, such as the inclusion or exclusion of the cavity region within nodules, affect the results. METHODS: A total of 525 patients from two medical centers were retrospectively enrolled. The radiomics features were extracted according to two regions of interest (ROI) segmentation criteria. Multiple logistic regression models were trained to predict the pathology: (1) The clinical model relied on clinical-radiological semantic features; (2) The radiomics models (radiomics+ and radiomics-) utilized radiomics features from different ROIs (including or excluding cavities); (3) the composite models (composite+ and composite-) incorporated both above. RESULTS: In the testing set, the radiomics+/- models and the composite+/- models still possessed efficient prediction performance (AUC ≥ 0.94), while the AUC of the clinical model was 0.881. In the validation set, the AUC of the clinical model was only 0.717, while that of the radiomics+/- models and the composite+/- models ranged from 0.801 to 0.825. The prediction performance of all the radiomics+/- and composite+/- models were significantly superior to that of the clinical model (p < 0.05). Whether the ROI segmentation included or excluded the cavity had no significant effect on these models (radiomics+ vs. radiomics-, composite+ model vs. composite-) (p > 0.05). CONCLUSIONS: The present study established a machine learning-based radiomics strategy for differentiating LUAD from TB lesions. The ROI segmentation including or excluding the cavity region may exert no significant effect on the predictive ability.

Chemokine CCL2 promotes cardiac regeneration and repair in myocardial infarction mice via activation of the JNK/STAT3 axis.

Stimulation of adult cardiomyocyte proliferation is a promising strategy for treating myocardial infarction (MI). Earlier studies have shown increased CCL2 levels in plasma and cardiac tissue both in MI patients and mouse models. In present study we investigated the role of CCL2 in cardiac regeneration and the underlying mechanisms. MI was induced in adult mice by permanent ligation of the left anterior descending artery, we showed that the serum and cardiac CCL2 levels were significantly increased in MI mice. Intramyocardial injection of recombinant CCL2 (rCCL2, 1 µg) immediately after the surgery significantly promoted cardiomyocyte proliferation, improved survival rate and cardiac function, and diminished scar sizes in post-MI mice. Alongside these beneficial effects, we observed an increased angiogenesis and decreased cardiomyocyte apoptosis in post-MI mice. Conversely, treatment with a selective CCL2 synthesis inhibitor Bindarit (30 µM) suppressed both CCL2 expression and cardiomyocyte proliferation in P1 neonatal rat ventricle myocytes (NRVMs). We demonstrated in NRVMs that the CCL2 stimulated cardiomyocyte proliferation through STAT3 signaling: treatment with rCCL2 (100 ng/mL) significantly increased the phosphorylation levels of STAT3, whereas a STAT3 phosphorylation inhibitor Stattic (30 µM) suppressed rCCL2-induced cardiomyocyte proliferation. In conclusion, this study suggests that CCL2 promotes cardiac regeneration via activation of STAT3 signaling, underscoring its potential as a therapeutic agent for managing MI and associated heart failure.

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

ABSTRACT 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.

Treatment of Work Type II Congenital First Branchial Cleft Anomalies: A Summary of 35 Cases.

Objective: This study aims to summarize the data and treatment of 35 children with Work type II congenital first branchial cleft anomalies (CFBCAs) to provide significant insights into the correlation between these anomalies and the facial nerve. Methods: A total of 35 children diagnosed with Work type II CFBCAs who received treatment at the Department of Otolaryngology-Head and Neck Surgery at Shenzhen Children's Hospital from August 2017 to March 2023 were analyzed retrospectively. Pearson chi-square tests and Fisher's exact tests were used to examine the relationship between clinical characteristics and the location of the lesion, which included the superficial and deep surfaces as well as the area between the branches of the facial nerve. Results: All 35 children underwent open incision and complete resection of fistulae. During the surgery, the lesions were found to be in the superficial facial nerve in 12 (34.3%) cases, between branches in 5 (14.3%) cases, and in the deep facial nerve in 18 (51.4%) cases. In those patients, lesions in females, with a lower edge of the lesion located below the angle of the mandible and the presence of a tympanic membranous attachment, are more likely to be located deep to the facial nerve or between its branches. The difference is statistically significant (P = .007, .032, .015). Conclusion: The treatment principle of Work type II CFBCAs consists of achieving a quiescent stage of inflammation, followed by a complete resection of the lesion on the premise of preserving facial nerve function. Certain clinical features of this disease can predict the relationship between the lesion and the facial nerve. The lesions in females, with a lower edge of the lesion located below the angle of the mandible, non-cystic type of Olsen, and the presence of tympanic membranous attachment, tend to be located deep to the facial nerve or between its branches.

The effects of rate pressure product at admission on cardiopulmonary function during hospitalization in patients with acute myocardial infarction.

OBJECTIVE: This study aimed to analyze the correlation between the rate pressure product (RPP) and cardiopulmonary function during hospitalization in patients with acute myocardial infarction (AMI). METHODS: A total of 362 patients with AMI were selected for the study, and the median admission RPP was used as the cutoff point to divide the patients into a low-RPP group (n = 181) and a high-RPP group (n = 181). The relationship between the RPP at admission and the cardiopulmonary function during hospitalization was analyzed. RESULTS: The patients in the high-RPP group had a higher body mass index (BMI) (p = 0.014), a higher prevalence of combined hypertension and diabetes mellitus (p < 0.001), a lower incidence of smoking (p = 0.044), and a higher incidence of oscillatory ventilation (6.1% vs. 1.7%, p = 0.029). The differences in RPP at rest, during warm-up, and within 1 and 4 minutes of recovery were statistically significant between the two groups (p < 0.01 on each occasion), while the differences in anaerobic threshold (AT) and watt max (Max) were not statistically significant (p > 0.05 for both). The patients in the low-RPP group had higher oxygen uptake (VO2 [AT]: 14.9 ± 3.4 vs. 14.2 ± 3.6, p = 0.048) and (VO2peak [Max]:18.2 ± 3.8 vs. 17.3 ± 3.8, p = 0.020). The RPP at admission was negatively correlated with VO2 (AT) and VO2peak (p < 0.05) using the regression Equation VO2peak = 33.682 + (-0.012 * RPP at admission/100) + (-0.105 * Age) + (-0.350 * BMI), while there was no correlation between the RPP at admission and VO2 (AT) (p = 0.149). CONCLUSION: The RPP at admission was negatively correlated with cardiopulmonary function during hospitalization in patients with AMI. Patients with a high RPP were more likely to have a combination of obesity, hypertension, diabetes mellitus, and reduced oxygen uptake during exercise, while a high RPP at admission appeared to affect their cardiovascular response indicators during exercise.

Clinical characteristics and acute complication of COVID-19 patients with diabetes: a multicenter, retrospective study in Southern China.

Aims: This study aims to describe the clinical characteristics, laboratory data and complications of hospitalized COVID-19 patients with type 2 diabetes mellitus (T2DM) since epidemic prevention and control optimization was adjusted in December 2022 in China. Methods: This retrospective multicenter study included 298 patients with confirmed type 2 diabetes mellitus with or without COVID-19. We collected data from the first wave of the pandemic in The Fifth Affiliated Hospital of Guangzhou Medical University, Loudi Central Hospital and The First People's Hospital of Xiangtan from December 1, 2022 to February 1, 2023. We extracted baseline data, clinical symptoms, acute complications, laboratory findings, treatment and outcome data of each patient from electronic medical records. Results: For among 298 hospitalized patients with type 2 diabetes, 136 (45.6%) were COVID-19 uninfected, and 162 (54.4%) were COVID-19 infected. We found that the incidence of cough, fatigue, fever, muscle soreness, sore throat, shortness of breath, hyposmia, hypogeusia and polyphagia (all p<0.01) were significantly higher in the exposure group. They showed higher levels of ketone (p=0.04), creatinine (p<0.01), blood potassium (p=0.01) and more diabetic ketoacidosis (p<0.01). Patients with COVID-19 less use of metformin (p<0.01), thiazolidinediones (p<0.01) and SGLT2 (p<0.01) compared with patients without COVID-19. Conclusion: COVID-19 patients with diabetes showed more severe respiratory and constitutional symptoms and an increased proportion of hyposmia and hypogeusia. Moreover, COVID-19 patients with diabetes have a higher incidence of acute complications, are more prone to worsening renal function, and are more cautious about the use of antidiabetic drugs.

Prediction model for lymph node metastasis in superficial colorectal cancer: a better choice than computed tomography.

BACKGROUND: Risk evaluation of lymph node metastasis (LNM) in superficial colorectal cancer resected by endoscopic surgery is critical for determining subsequent therapeutic strategies, but the role of existing clinical methods, including computed tomography, remains limited. METHODS: Features of the nomogram were determined by logistic regression analysis, and the performance was validated by calibration plots, ROC curves and DCA curves in both the training set and the validation set. RESULTS: A total of 608 consecutive superficial CRC cases were randomly divided into 426 training and 182 validation cases. Univariate and multivariate logistic regression analyses revealed that age < 50, tumour budding, lymphatic invasion and lower HDL levels were risk factors for LNM. Stepwise regression and the Hosmer‒Lemeshow goodness of fit test showed that the nomogram had good performance and discrimination, which was validated by ROC curves and calibration plots. Internal and external validation demonstrated that the nomogram had a higher C-index (training group, 0.749, validation group, 0.693). DCA and clinical impact curves graphically show that the use of the nomogram to predict LNM had remarkable predictive power. Finally, in comparison with CT diagnosis, the nomogram also visually showed higher superiority, as demonstrated by ROC, DCA and clinical impact curves. CONCLUSION: Using common clinicopathologic factors, a noninvasive nomogram for individualized prediction of LNM after endoscopic surgery was conveniently established. Nomograms have great superiority in the risk stratification of LNM compared with traditional CT imaging.

Expression pattern analysis of m6A regulators reveals IGF2BP3 as a key modulator in osteoarthritis synovial macrophages.

BACKGROUND: Disruption of N6 methyl adenosine (m6A) modulation hampers gene expression and cellular functions, leading to various illnesses. However, the role of m6A modification in osteoarthritis (OA) synovitis remains unclear. This study aimed to explore the expression patterns of m6A regulators in OA synovial cell clusters and identify key m6A regulators that mediate synovial macrophage phenotypes. METHODS: The expression patterns of m6A regulators in the OA synovium were illustrated by analyzing bulk RNA-seq data. Next, we built an OA LASSO-Cox regression prediction model to identify the core m6A regulators. Potential target genes of these m6A regulators were identified by analyzing data from the RM2target database. A molecular functional network based on core m6A regulators and their target genes was constructed using the STRING database. Single-cell RNA-seq data were collected to verify the effects of m6A regulators on synovial cell clusters. Conjoint analyses of bulk and single-cell RNA-seq data were performed to validate the correlation between m6A regulators, synovial clusters, and disease conditions. After IGF2BP3 was screened as a potential modulator in OA macrophages, the IGF2BP3 expression level was tested in OA synovium and macrophages, and its functions were further tested by overexpression and knockdown in vitro. RESULTS: OA synovium showed aberrant expression patterns of m6A regulators. Based on these regulators, we constructed a well-fitting OA prediction model comprising six factors (FTO, YTHDC1, METTL5, IGF2BP3, ZC3H13, and HNRNPC). The functional network indicated that these factors were closely associated with OA synovial phenotypic alterations. Among these regulators, the m6A reader IGF2BP3 was identified as a potential macrophage mediator. Finally, IGF2BP3 upregulation was verified in the OA synovium, which promoted macrophage M1 polarization and inflammation. CONCLUSIONS: Our findings revealed the functions of m6A regulators in OA synovium and highlighted the association between IGF2BP3 and enhanced M1 polarization and inflammation in OA macrophages, providing novel molecular targets for OA diagnosis and treatment.

CT features of primary pleural gritty meningioma: A case report and review of the literature.

Primary ectopic meningiomas, although widely reported in multiple sites of the body, are particularly rare in the pleura. Here, we report a 35-year-old asymptomatic woman who was found to have a large mass in the right pleural area on physical examination chest radiography. Chest CT scan showed a large irregular mass from the right second anterior costal pleura to the right supradiaphragm, in which calcified plaques of varying sizes were widely and heterogeneously distributed. The mass was connected to the pleura (anterior rib pleura, mediastinal pleura, diaphragmatic pleura) in a wide base, with oblique "Z" changes in the coronal view. After the contrast agent injection, the mass exhibited mild enhancement on both arterial and venous phase scans. Furthermore, a linear enhancement that was indicative of "pleural tail sign" changes in the pleura adjacent to the mass was observed. The disease was preoperatively misdiagnosed as malignant pleural mesothelioma, and the postoperative pathological diagnosis was right pleural meningioma (gritty type). Therefore, we carefully analyzed its imaging features and differential diagnosis by consulting relevant literature.