Miracle-dz/UniFAR-FTUs huggingface dataset:
Diabetes Is Associated with Musculoskeletal Pain, Osteoarthritis, Osteoporosis, and Rheumatoid Arthritis

Aim To investigate the associations between diabetes and musculoskeletal pain, osteoarthritis, osteoporosis, and rheumatoid arthritis. Methods Self-reported data were provided by the nationwide Danish National Health Survey 2013. Inclusion criteria were age ≥ 40 years and known diabetes status. The exposure variable was diabetes, and the outcome variables included musculoskeletal pain during the last 14 days in three body sites (back/lower back, limbs, and shoulder/neck), osteoarthritis, osteoporosis, and rheumatoid arthritis. Logistic regression analyses adjusted for age, gender, BMI, education, marital status, and physical activity were performed. Results 9,238 participants with diabetes were 65.6 ± 11.0 (mean ± SD) years old; 55.6% were males. 99,980 participants without diabetes were 59.2 ± 11.8 years old; 46.7% were males. Diabetes was associated with back/lower back pain (OR 1.2 (CI 95% 1.1-1.2), p < 0.001), pain in the limbs (1.4 (1.3-1.4), p < 0.001), shoulder/neck pain (1.2 (1.1-1.3), p < 0.001), osteoarthritis (1.3 (1.2-1.4), p < 0.001), osteoporosis (1.2 (1.1-1.4), p = 0.010), and rheumatoid arthritis (1.6 (1.4-1.7), p < 0.001). In participants with diabetes, physical activity was associated with reduced pain (e.g., back/lower back pain (0.7 (0.6-0.7), p < 0.001)). Conclusion Diabetes was associated with elevated odds of having musculoskeletal pain. Diabetes was also associated with elevated odds of having osteoarthritis, osteoporosis, and rheumatoid arthritis. The most frequent disease in individuals with diabetes was osteoarthritis. The reported pain may have negative impacts on the level of physical activity. Health-care professionals should remember to inform patients with diabetes that musculoskeletal pain, osteoarthritis, osteoporosis, and rheumatoid arthritis are not contraindications to exercise training.
Upregulation of VEGF and PEDF in Placentas of Women with Lower Extremity Venous Insufficiency during Pregnancy and Its Implication in Villous Calcification

Pregnancy is a period in a woman's life in which changes can occur that affect different physiological processes. Common conditions during this period include vascular changes, such as lower extremity venous insufficiency (VI). This is an observational, analytical, and prospective cohort study in which 114 pregnant women were analyzed, of which 62 were clinically diagnosed with VI. In parallel, 52 control patients without VI (HC) were studied. The aim of this study was to observe changes in angiogenesis and inflammation markers as well as the presence of calcium deposits. The expression of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and pigment epithelium-derived factor (PEDF) was analyzed by immunohistochemistry and RT-qPCR. The presence of calcium deposits was revealed using the von Kossa method. In the placentas of mothers with VI, gene expression of VEGF (34.575 [32.380–36.720] VI vs 32.965 [30.580–36.320] HC) and PEDF (25.417 [24.459–27.675] VI vs 24.400 [23.102–30.223] HC) significantly increased, as was protein expression in the placental villi. An increase in calcium deposits was observed in the placentas of women with VI (72.58% VI/53.84% HC). This study revealed the existence of cellular damage in the placental villi of mothers with VI with tissue implications such as increased calcification.
The Cerebellum Posterior Lobe Associates with the Exophthalmos of Primary Hyperthyroidism: A Resting-State fMRI Study

Background Exophthalmos occurs in patients with primary hyperthyroidism. There were few studies about the changes of brain functional networks of patients with exophthalmos of primary hyperthyroidism (EOPH). However, differences in spontaneous brain activity in patients with EOPH remain unclear. Objective This study explored alterations in the brain functional networks of patients with EOPH using a voxel-wise degree centrality (DC) method. Methods A total of 20 patients with EOPH (8 men and 12 women) were enrolled. In addition, 20 patients with primary hyperthyroidism without exophthalmos, matched in age, sex, and education status, were enrolled as a control group. The Hospital Anxiety and Depression Scale was used to assess the anxiety and depression status of participants. All participants were examined using resting-state functional MRI. Changes in spontaneous brain activity were investigated using the DC method. To distinguish between the DC values of the patients with EOPH and those of the control group, we analyzed the receiver operating characteristic (ROC) curve. The interrelationships between the DC values and clinical variables in the patients with EOPH were evaluated using Pearson's correlation coefficient. Results Patients with EOPH exhibited notably lower DC values in the cerebellum posterior lobe than the control group. In addition, there were negative correlations between the anxiety scores (AS) and the depression scores (DS) and DC values of the cerebellum posterior lobe. The ROC curve analysis of the cerebellum posterior lobe demonstrated that the area under the curve method had a high diagnostic accuracy. Conclusions Our study was the first, to our knowledge, to explore changes in the brains of patients with EOPH using the DC method. The DC value was significantly different in the cerebellum posterior lobe in patients with EOPH, indicating that the cerebellum posterior lobe is associated with EOPH.
Hypoxia-Induced ROS Contribute to Myoblast Pyroptosis during Obstructive Sleep Apnea via the NF-κB/HIF-1α Signaling Pathway

Tissue hypoxia caused by upper airway collapse is a main cause of excessive oxidative stress and systemic inflammation in obstructive sleep apnea (OSA) patients. Increased reactive oxygen species (ROS) and inflammatory responses affect cell survival and ultimately contribute to tissue injury. In the present study, we proposed that the induction of ROS by hypoxia, as an intrinsic stress, activates myoblast pyroptosis in OSA. We found increased cell death and abnormal expression of pyroptosis markers in the skeletal muscle of OSA mice. In vitro studies showed hypoxia-induced pyroptotic death of C2C12 myoblasts, as evidenced by the activation of caspase-1 and gasdermin D (GSDMD). Hypoxia induced ROS overproduction and accumulation in myoblasts. More importantly, applying N-acetylcysteine (NAC), an ROS scavenger, rescued cell swelling, downregulated the inflammatory response, and prevented pyroptotic death in hypoxia-cultured myoblasts. Hypoxia stimulation promoted NF-κB P65 phosphorylation and HIF-1α nuclear translocation. Moreover, hypoxia increased the nuclear level of cleaved caspase-1 and GSDMD. NAC inhibited hypoxia-induced variations in the HIF-1α and NF-κB signaling pathway. Taken together, our results determined that hypoxia-induced ROS contribute to myoblast pyroptosis. Therefore, our findings suggest that ROS may be a potential therapeutic target for ameliorating hypoxia-induced cell death and tissue injury, especially in OSA and hypoxia-related diseases.
Arrhythmias and Sudden Cardiac Death in Beta-Thalassemia Major Patients: Noninvasive Diagnostic Tools and Early Markers

Beta-thalassemias are a group of inherited, autosomal recessive diseases, characterized by reduced or absent synthesis of beta-globin chains of the hemoglobin tetramer, resulting in variable phenotypes, ranging from clinically asymptomatic individuals to severe anemia. Three main forms have been described: heterozygotes, homozygotes β+, and homozygotes β°. Beta-thalassemia major (β-TM), the most serious form, is characterized by an absent synthesis of globin chains that are essential for hemoglobin formation, causing chronic hemolytic anemia. Cardiac complications represent a leading cause of mortality in β-TM patients, although an important and progressive increase of life expectancy has been demonstrated after the introduction of chelating therapies. Iron overload is the primary factor of cardiac damage resulting in thalassemic cardiomyopathy, in which diastolic dysfunction usually happens before systolic impairment and overt heart failure (HF). Although iron-induced cardiomyopathy is slowly progressive and it usually takes several decades for clinical and laboratory features of cardiac dysfunction to manifest, arrhythmias or sudden death may be present without signs of cardiac disease and only if myocardial siderosis is present. Careful analysis of electrocardiograms and other diagnostic tools may help in early identification of high-risk β-TM patients for arrhythmias and sudden cardiac death.
Favorable Response to CD34+ Cell Therapy Is Associated with a Decrease of Galectin-3 Levels in Patients with Chronic Heart Failure

Background Galectin-3 plasma levels (gal-3) were shown to correlate with the scar burden in chronic heart failure (CHF) setting. As scar burden predicts response to stem cell therapy, we sought to explore a correlation between gal-3 and response to CD34+ cell transplantation in patients with CHF. Methods We performed a post hoc analysis of patients, enrolled in 2 prospective trials investigating the clinical effects of CD34+ cell therapy in patients with ischemic cardiomyopathy (ICMP) and nonischemic dilated cardiomyopathy (DCMP). CD34+ cells were mobilized by G-CSF, collected via apheresis, and injected transendocardially using NOGA system. Patients were followed for 3 months and demographic, echocardiographic, and biochemical parameters and gal-3 were analyzed at baseline and at follow-up. Response to cell therapy was defined as an LVEF increase of ≥5%. Results 61 patients were included in the analysis. The mean age of patients was 52 years and 83% were male. DCMP and ICMP were present in 69% and 31% of patients, respectively. The average serum creatinine was 86 ± 23 μmol/L, NT-proBNP 1132 (IQR 350-2279) pg/mL, and LVEF 30 ± 6%. Gal-3 at baseline and at 3 months did not differ significantly (13.4 ± 5.5 ng/mL vs. 13.1 ± 5.8 ng/mL; p = 0.72), and there were no differences in baseline gal-3 with respect to heart failure etiology (15.1 ± 7.2 ng/mL in ICMP vs. 12.7 ± 4.3 ng/mL in DCMP; p = 0.12). Comparing responders (N = 49) to nonresponders (N = 18), we found no differences in baseline gal-3 (13.6 ± 5.7 ng/mL vs. 13.2 ± 4.9 ng/mL; p = 0.80). However, responders had significantly lower gal-3 at 3-month follow-up (12.1 ± 4.0 ng/mL vs. 15.7 ± 8.4 ng/mL; p < 0.05). Also, responders demonstrated a significant decrease in gal-3 over 3 months, while in nonresponders, an increase in gal-3 occurred (−1.5 ± 5.4 ng/mL vs. +2.7 ± 4.3 ng/mL; p = 0.01). Conclusions In patients with chronic heart failure undergoing CD34+ cell therapy, a decrease in galectin-3 plasma levels is associated with beneficial response to this treatment modality. Further prospective data is warranted to confirm our findings and to deepen our understanding of the role of gal-3 in the field of stem cell therapy.
Ginsenoside Rg3 Attenuates Angiotensin II-Mediated Renal Injury in Rats and Mice by Upregulating Angiotensin-Converting Enzyme 2 in the Renal Tissue

Angiotensin II- (Ang II-) mediated renal injury represents a major pathogenetic mechanism in most chronic kidney diseases. Our previous research demonstrated that ginsenoside Rg3 (Rg3) attenuates Ang II elevation in the myocardium in spontaneously hypertensive rats (SHR). It is possible that Rg3 has similar effects in the renal tissue. In this research, we first demonstrated that Rg3 could attenuate Ang II increase in the kidney of SHR and reduce hypertensive nephropathy progression. Then, we found that Rg3 attenuated Ang II increase by upregulating angiotensin-converting enzyme 2 (ACE2) in the renal tissue. We confirmed this finding in an exogenous Ang II-infused mice model of renal injury, and two models showed consistent results. In conclusion, Rg3 attenuates Ang II-mediated renal injury in rats and mice by upregulating ACE2 in the renal tissue. This research is the first to demonstrate that Rg3 increases tissue ACE2 levels in vivo.
Leiomyosarcoma of the Rectum as a Radiation-Induced Second Malignancy after Cervical Cancer Treatment: Case Report with Review of the Literature

Background Incidence of cervical cancer among women of reproductive age still remains significantly high. In regard to prognostic features and risk factors, the standard treatment for most types of cervical cancer represents a combination of surgical treatment and radiation therapy, such as external beam radiation therapy and brachytherapy. Despite significant advances of long-term oncological outcomes, radiation-induced secondary malignancies among cervical cancer survivors are still an issue. Current case report describes an incredibly rare case of radiation-induced leiomyosarcoma of the rectum, which occurred 32 years after cervical cancer treatment. Case Presentation A 62-year-old female had a past medical history of FIGO stage IIB cervical cancer (squamous cell carcinoma pT2bN0M0). In 1987, she underwent radical hysterectomy with bilateral iliac lymph node dissection, followed by adjuvant radiation therapy—70 Gy external beam pelvic irradiation followed by 30.5 Gy of brachytherapy. Thirty-two years later, she presented with signs of rectal bleeding. Regarding past medical history, radiologic, endoscopic, and pathologic data, the patient was initially diagnosed with a malignant nonepithelial lower rectal tumor of the unknown origin and staged as mrT3a mrN0 cM0. Total mesorectal excision with complete mesocolic excision and central vascular ligation (CME/CVL) carried by an open approach was carried out. In an attempt to identify the tissue of origin, an immunohistochemistry assay had been performed. Tumor cells showed a high rate of mitotic activity with a 45% rate of Ki-67 expression, positive reaction for desmin, and SMA in all samples. Negative reaction for CD117 and S100 was observed. As a conclusion, the immunophenotype was identified as a grade 3 leiomyosarcoma (ISD-code 8890/3). Conclusions We suggest that up to date, radical surgery with curative intent, as it was performed in our study, is the most evidence-based treatment option for patients with radiation-induced sarcomas of the rectum.
Systematic Review with Meta-Analysis: The Effects of Probiotics in Nonalcoholic Fatty Liver Disease

Background and Aims Probiotics was considered as a potential therapy for nonalcoholic fatty liver disease (NAFLD) without approval and comprehensive assessment in recent years, which call for a meta-analysis. Methods We performed electronic and manual searches including English and Chinese databases published before April 2019, with the use of mesh term and free text of “nonalcoholic fatty liver disease” and “probiotics. ” Clinical trials evaluating the efficacy of probiotic therapy in NAFLD patients were included according to the eligibility criteria. With the use of random effects models, clinical outcomes were presented as weighted mean difference (WMD) with 95% confidence interval (CI), while heterogeneity and meta-regression were also assessed. Results 28 clinical trials enrolling 1555 criterion proven NAFLD patients with the use of probiotics from 4 to 28 weeks were included. Overall, probiotic therapy had beneficial effects on body mass index (WMD: -1.46, 95% CI: [-2.44, -0.48]), alanine aminotransferase (WMD: -13.40, 95% CI: [-17.03, -9.77]), aspartate transaminase (WMD: -13.54, 95% CI: [-17.86, -9.22]), gamma-glutamyl transpeptidase (WMD: -9.88, 95% CI: [-17.77, -1.99]), insulin (WMD: -1.32, 95% CI: [-2.43, -0.21]), homeostasis model assessment-insulin resistance (WMD: -0.42, 95% CI: [-0.73, -0.12]), and total cholesterol (WMD: -15.38, 95% CI: [-26.50, -4.25]), but not in fasting blood sugar, lipid profiles, or tumor necrosis factor-alpha. Conclusion The systematic review and meta-analysis support that probiotics are superior to placebo in NAFLD patients and could be utilized as a common complementary therapeutic approach.
Serum Levels of Epithelial-Derived Cytokines as Interleukin-25 and Thymic Stromal Lymphopoietin after a Single Dose of Mepolizumab in Patients with Severe Non-Allergic Eosinophilic Asthma: A Short Report

The bronchial epithelium has continuous contact with environmental agents initiating and maintaining airway type 2 inflammation in asthma. However, there is a lack of data on whether reduced airway eosinophilic inflammation can affect the production of epithelial-derived mediators, such as interleukin-25 (IL-25) and thymic stromal lymphopoietin (TSLP). The aim of this study was to investigate the changes in serum levels of IL-25 and TSLP after a single dose of mepolizumab, a humanized monoclonal antibody to interleukin-5 (IL-5), in patients with severe non-allergic eosinophilic asthma (SNEA). We examined 9 SNEA patients before and four weeks after administration of 100 mg mepolizumab subcutaneously. The fractional exhaled nitric oxide (FeNO) level was analysed using an electrochemical assay (NIOX VERO®, Circassia, UK). Serum IL-25 and TSLP levels were measured by ELISA. Four weeks after the single dose of mepolizumab, blood eosinophil count significantly decreased from 0.55 ± 0.20 × 109/l to 0.14 ± 0.04 × 109/l (p = 0.01) and FEV1 increased from 2.1 ± 0.5 l (65.4 ± 8.8% of predicted) to 2.6 ± 0.4 l (76.4 ± 9.1% of predicted) (p = 0.04), while FeNO level has not changed (32.3 ± 8.4 vs 42.9 ± 12.6 ppb). Serum IL-25 level significantly decreased from 48.0 ± 17.2 pg/mL to 34.8 ± 17.1 pg/mL (p = 0.02) with same tendency in TSLP level: from 359.8 ± 71.3 pg/mL to 275.6 ± 47.8 pg/mL (p = 0.02). It has also been noticed a significant relation between changes in the blood eosinophil count and serum IL-25 level (r = 0.81, p = 0.008), as well as between changes in serum IL-25 and TSLP levels (r = 0.93, p = 0.004) after a single dose of mepolizumab. Thus, anti-IL-5 treatment with mepolizumab might diminish the production of bronchial epithelial-derived cytokines IL-25 and TSLP in patients with SNEA which is potentially related to reduced eosinophilic inflammation. This trial is registered in ClinicalTrial.gov with identifier NCT03388359.
Green Tea Prevents NAFLD by Modulation of miR-34a and miR-194 Expression in a High-Fat Diet Mouse Model

Background/Aims Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. It is currently the most common chronic liver disease with complex pathogenesis and challenging treatment. Here, we investigated the hepatoprotective role of green tea (GT) and determined the involvement of miRNAs and its mechanism of action. Methods Male C57Bl/6 mice were fed with a high-fat diet for 4 weeks. After this period, the animals received gavage with GT (500 mg/kg body weight) over 12 weeks (5 days/week). HepG2 cell lines were transfected with miR-34a or miR-194 mimetics and inhibitors to validate the in vivo results or were treated with TNF-α to evaluate miRNA regulation. Results GT supplementation protects against NAFLD development by altering lipid metabolism, increasing gene expression involved in triglycerides and fatty acid catabolism, and decreasing uptake and lipid accumulation. This phenotype was accompanied by miR-34a downregulation and an increase in their mRNA targets Sirt1, Pparα, and Insig2. GT upregulated hepatic miR-194 by inhibiting TNF-α action leading to a decrease in miR-194 target genes Hmgcs/Apoa5. Conclusion Our study identified for the first time that the beneficial effects of GT in the liver can be due to the modulation of miRNAs, opening new perspectives for the treatment of NAFLD focusing on epigenetic regulation of miR-34a and miR-194 as green tea targets.
A Pilot Study of Echinocandin Combination with Trimethoprim/Sulfamethoxazole and Clindamycin for the Treatment of AIDS Patients with Pneumocystis Pneumonia

Background and Objectives Pneumocystis pneumonia (PCP) is a common opportunistic infection in acquired immune deficiency syndrome (AIDS) patients that continues to result in a high mortality rate. To develop a better treatment strategy and improve PCP prognosis, a cohort study was conducted to evaluate the therapeutic potential of echinocandin treatment for AIDS patients with PCP (AIDS-PCP). Methods The AIDS-PCP patients were analyzed in our retrospective cohort study that were hospitalized in The First Affiliated Hospital of Zhejiang University during 2013–2018. The antifungal effects of echinocandins were evaluated in two subgroups that were classified by oxygenation as a proxy for the disease state: PaO2/FiO2 > 200 mmHg and PaO2/FiO2 ≤ 200 mmHg. Intergroup comparisons and survival curves were used to evaluate the effectiveness of the two AIDS-PCP treatment regimens. Results During the follow-up, 182 AIDS-PCP patients were diagnosed and analyzed in the study. After excluding 55 patients with other superinfections and five patients that were treated with HAART, the remaining 122 patients were enrolled in the study. The group treated with echinocandins combined with trimethoprim-sulfamethoxazole (TMP-SMZ) and clindamycin exhibited a lower mortality rate (9.62%, 5/52) than did the group with TMP-SMZ and clindamycin treatment (20%, 14/70). For AIDS-PCP patients in the PaO2/FiO2 > 200 mmHg subgroup, treatment with echinocandins combined with TMP-SMZ and clindamycin significantly reduced their mortality rate (4.44% (2/45) vs. 18.18% (10/55), P = 0.035). Conclusion The results of this study indicate that treatment with echinocandins in combination with the standard TMP-SMZ and clindamycin regimen can improve the prognosis and reduce the mortality rate in patients with mild to moderate AIDS-PCP disease.
Bioinformatic Profiling Identifies a Fatty Acid Metabolism-Related Gene Risk Signature for Malignancy, Prognosis, and Immune Phenotype of Glioma

Cancer cells commonly have metabolic abnormalities. Aside from altered glucose and amino acid metabolism, cancers cells often share the attribute of fatty acid metabolic alterations. However, fatty acid metabolism related-gene set has not been systematically investigated in gliomas. Here, we provide a bioinformatic profiling of the fatty acid catabolic metabolism-related gene risk signature for the malignancy, prognosis and immune phenotype of glioma. In this study, a cohort of 325 patients with whole genome RNA-seq expression data from the Chinese Glioma Genome Atlas (CGGA) dataset was used as training set, while another cohort of 667 patients from The Cancer Genome Atlas (TCGA) dataset was used as validating set. After confirmed that fatty acid catabolic metabolism-related gene set could distinguish clinicopathological features of gliomas, we used LASSO regression analysis to develop a fatty-acid metabolism-related gene risk signature for glioma. This 8-gene risk signature was found to be a good predictor of clinical and molecular features involved in the malignancy of gliomas. We also identified that this 8-gene risk signature had high prognostic values in patients with gliomas. Correlation analysis showed that our risk signature was closely associated with the immune cells involved in the microenvironment of glioma. Furthermore, the fatty acid catabolic metabolism-related gene risk signature was also found to be significantly correlated with immune checkpoint members B7-H3 and Tim-3. In summary, we have identified a fatty acid metabolism-related gene risk signature for malignancy, prognosis, and immune phenotype of glioma; and our study might contribute to better understanding of metabolic pathways and further developing of novel therapeutic approaches for gliomas.