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Background The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD. Methods A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors. Results The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle. Conclusion Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.

Abstract Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion and/or insulin action. Increasing evidence suggests that inflammation played an important role in the pathogenesis of T2DM. Prospective studies on the link between immunoglobulins concentrations and the risk of T2DM in adults are limited. We developed a cohort study including 7,093 adults without T2DM history. The incidence of T2DM was 16.45 per 1,000 person-years. Compared with the lowest quartiles, the hazard ratios (95% confidence intervals) of T2DM for the highest quartiles of IgG, IgE, IgM and IgA were 0.64 (0.48–0.85), 0.94 (0.72–1.23), 0.68 (0.50–0.92) and 1.62 (1.24–2.11) (P for trend was

Objective: Filamin B (FLNB) encodes an actin-binding protein that is known to function as a novel RNA-binding protein involved in cell movement and signal transduction and plays a pivotal role in bone growth. This study aimed to investigate possible FLNB function in the skeletal system by characterizing the effecs of FLNB knockdown in mouse preosteoblast cells. Methods: Stable FLNB MC3T3-E1 knockdown cells were constructed for RNA-seq and alternative splicing event (ASE) analysis of genes involved in osteoblast differentiation and function that may be regulated by FLNB. Standard transwell, MTT, ALP, qPCR, Western blot, and alizarin red staining assays were used to assess functional changes of FLNB-knockdown MC3T3-E1 cells. Results: Analysis of differentially expressed genes (DEGs) in FLNB knockdown cells revealed enrichment for genes related to osteoblast proliferation, differentiation and migration, such as ITGA10, Cebpβ, Grem1, etc. Alternative splicing (AS) analysis showed changes in the predominant mRNA isoforms of skeletal development-related genes, especially Tpx2 and Evc. Functional asslysis indicated that proliferation, migration, and differentiation were all inhibited upon FLNB knockdown in MC3T3-E1 cells compared to that in vector control cells. Conclusions: FLNB participates in regulating the transcription and AS of genes required for osteoblast development and function, consequently affecting growth and development in MC3T3-E1 cells.

Abstract Background Internal and external fixation are common surgical procedures for treating fractures. However, the impact of different surgical approaches (including internal and external fixations) on patients’ psychological status and Quality of Life (QoL) is rarely examined. Herein, we aimed to investigate the effects of internal and external fixation on anxiety, depression, insomnia, and overall mental and physical health in Distal Radius Fractures (DRF) patients. Methods We performed a retrospective study on 96 fracture patients who underwent internal fixation (57 patients) or external fixation (39 patients). The Visual Analog Scale (VAS), the Hospital Anxiety and Depression Scale (HADS), the Athens Insomnia Scale (AIS), and the Medical Outcomes Study Short Form 36 (SF-36) questionnaire were used to assess the patients’ pain, anxiety, depression, sleep, and QoL before surgery and at seven days, one month, and three months post-surgery. Results The VAS scores were significantly lower in the Internal Fixation Group (IFG) than in the External Fixation Group (EFG) on the seventh day and one month postoperatively (P 0.05), the EFG showed significantly higher HADS-A, HADS-D, and AIS scores than the IFG at seven days and one and three months postoperatively (P 0.05). However, both groups showed positive changes in PCS and MCS scores at postoperative day seven and one and three months postoperatively, with the IFG having significantly higher average PCS and MCS scores compared to the EFG (P

Introduction: Chronic osteomyelitis is a complex clinical condition that is associated with a high recurrence rate. Traditional surgical interventions often face challenges in achieving a balance between thorough debridement and managing resultant bone defects. Radiomics is an emerging technique that extracts quantitative features from medical images to reveal pathological information imperceptible to the naked eye. This study aims to investigate the potential of radiomics in optimizing osteomyelitis diagnosis and surgical treatment.Methods: Magnetic resonance imaging (MRI) scans of 93 suspected osteomyelitis patients were analyzed. Radiomics features were extracted from the original lesion region of interest (ROI) and an expanded ROI delineated by enlarging the original by 5 mm. Feature selection was performed and support vector machine (SVM) models were developed using the two ROI datasets. To assess the diagnostic efficacy of the established models, we conducted receiver operating characteristic (ROC) curve analysis, employing histopathological results as the reference standard. The model’s performance was evaluated by calculating the area under the curve (AUC), sensitivity, specificity, and accuracy. Discrepancies in the ROC between the two models were evaluated using the DeLong method. All statistical analyses were carried out using Python, and a significance threshold of p < 0.05 was employed to determine statistical significance.Results and Discussion: A total of 1,037 radiomics features were extracted from each ROI. The expanded ROI model achieved significantly higher accuracy (0.894 vs. 0.821), sensitivity (0.947 vs. 0.857), specificity (0.842 vs. 0.785) and AUC (0.920 vs. 0.859) than the original ROI model. Key discriminative features included shape metrics and wavelet-filtered texture features. Radiomics analysis of MRI exhibits promising clinical translational potential in enhancing the diagnosis of chronic osteomyelitis by accurately delineating lesions and identifying surgical margins. The inclusion of an expanded ROI that encompasses perilesional tissue significantly improves diagnostic performance compared to solely focusing on the lesions. This study provides clinicians with a more precise and effective tool for diagnosis and surgical decision-making, ultimately leading to improved outcomes in this patient population.

BackgroundCystic echinococcosis, caused by the larval stage of Echinococcus granulosus, remains a global health challenge. Mesenchymal stem cells (MSCs) are renowned for their regenerative and immunomodulatory properties. Given the parasite’s mode of establishment, we postulate that MSCs likely play a pivotal role in the interaction between the parasite and the host. This study aims to explore the response of MSCs to antigens derived from Echinococcus granulosus, the etiological agent of hydatid disease, with the hypothesis that exposure to these antigens may alter MSC function and impact the host’s immune response to the parasite.MethodsMSCs were isolated from mouse bone marrow and co-cultured with ESPs, HCF, or pLL antigens. We conducted high-throughput sequencing to examine changes in the MSCs’ mRNA expression profile. Additionally, cell cycle, migration, and secretory functions were assessed using various assays, including CCK8, flow cytometry, real-time PCR, Western blot, and ELISA.ResultsOur analysis revealed that hydatid antigens significantly modulate the mRNA expression of genes related to cytokine and chemokine activity, impacting MSC proliferation, migration, and cytokine secretion. Specifically, there was a downregulation of chemokines (MCP-1, CXCL1) and pro-inflammatory cytokines (IL-6, NOS2/NO), alongside an upregulation of anti-inflammatory mediators (COX2/PGE2). Furthermore, all antigens reduced MSC migration, and significant alterations in cellular metabolism-related pathways were observed.ConclusionHydatid disease antigens induce a distinct immunomodulatory response in MSCs, characterized by a shift towards an anti-inflammatory phenotype and reduced cell migration. These changes may contribute to the parasite’s ability to evade host defenses and persist within the host, highlighting the complex interplay between MSCs and hydatid disease antigens. This study provides valuable insights into the pathophysiology of hydatid disease and may inform the development of novel therapeutic strategies.

Abstract Background Human hydatid disease typically occurs in organs such as the liver and kidney. Primary solitary intramuscular hydatid disease, however, is rare. Case Presentation We report a case of a giant muscle hydatid in the lower extremity, with neurological symptoms as the first manifestation. The symptoms specifically manifested as intermittent pain in the right lower extremity and numbness in the sole of the right foot. However, there were no obvious abnormalities detected in electromyography and lumbar MRI. Subsequent ultrasonography and calf MRI showed that the patient had cystic lesions in the calf. The patient was initially diagnosed with a muscle hydatid cyst. Treatment involved complete surgical excision of the lesion, and the diagnosis of a hydatid cyst was confirmed through macroscopic and microscopic histopathological examination after the mass was excised. The patient was given oral albendazole, and no recurrence was observed during the 12 months of follow-up. Conclusions This case underscores the need to consider hydatid disease when diagnosing soft tissue masses in muscles, particularly in endemic areas. Patients may initially present with atypical symptoms like peripheral nerve issues.

BackgroundHydatid disease is caused by Echinococcus parasites and can affect various tissues and organs in the body. The disease is characterized by the presence of hydatid cysts, which contain specific antigens that interact with the host’s immune system. Mesenchymal stem cells (MSCs) are pluripotent stem cells that can regulate immunity through the secretion of extracellular vesicles (EVs) containing microRNAs (miRNAs).MethodsIn this study, hydatid antigens were isolated from sheep livers and mice peritoneal cavities. MSCs derived from mouse bone marrow were treated with different hydatid antigens, and EVs were isolated and characterized from the conditioned medium of MSCs. Small RNA library construction, miRNA target prediction, and differential expression analysis were conducted to identify differentially expressed miRNAs. Functional enrichment and network construction were performed to explore the biological functions of the target genes. Real-time PCR and Western blotting were used for miRNA and gene expression verification, while ELISA assays quantified TNF, IL-1, IL-6, IL-4, and IL-10 levels in cell supernatants.ResultsThe study successfully isolated hydatid antigens and characterized MSC-derived EVs, demonstrating the impact of antigen concentration on MSC viability. Key differentially expressed miRNAs, such as miR-146a and miR-9-5p, were identified, with functional analyses revealing significant pathways like Endocytosis and MAPK signaling associated with these miRNAs’ target genes. The miRNA-HUB gene regulatory network identified crucial miRNAs and HUB genes, such as Traf1 and Tnf, indicating roles in immune modulation and osteogenic differentiation. Protein–protein interaction (PPI) network analysis highlighted central HUB genes like Akt1 and Bcl2. ALP activity assays confirmed the influence of antigens on osteogenic differentiation, with reduced ALP activity observed. Expression analysis validated altered miRNA and chemokine expression post-antigen stimulation, with ELISA analysis showing a significant reduction in CXCL1 expression in response to antigen exposure.ConclusionThis study provides insights into the role of MSC-derived EVs in regulating parasite immunity. The findings suggest that hydatid antigens can modulate the expression of miRNAs in MSC-derived EVs, leading to changes in chemokine expression and osteogenic capacity. These findings contribute to a better understanding of the immunomodulatory mechanisms involved in hydatid disease and provide potential therapeutic targets for the development of new treatment strategies.

Abstract Background The purpose of this study was to report the outcomes of single-level bone transport with a unilateral external fixator for treatment of proximal, intermediate and distal tibial bone defects caused by fracture-related infection (FRI) and compare their complications. Methods The clinical records and consecutive X-ray photographs of patients with tibial bone defects treated by single-level bone transport using a unilateral external fixator (Orthofix Limb Reconstruction System) were analyzed retrospectively, from January 2012 to December 2018. Patients were divided into the proximal group (P, n = 19), intermediate group (I, n = 25), and distal group (D, n = 18) according to the location of the tibial bone defect. The Association for the Study and Application of the Method of Ilizarov (ASAMI) standard was applied to assess the bone and functional outcomes and postoperative complications evaluated by the Paley classification. Results A total of 62 participants were included in this study, with a median age of 36 ± 7.14 years. Sixty patients with tibial bone defects caused by FRI were successfully treated by single-level bone transport using a unilateral external fixator, with a mean bone union time (BUT) of 7.3 ± 1.71 months. According to the ASAMI criteria, there were statistical differences in bone and function results between the three groups (P vs. I vs. D, P

Abstract Background Several previous studies have shown that dietary patterns are associated with the incidence of depressive symptoms. However, the results have been inconsistent. This study aimed to prospectively investigate the association between dietary patterns and the risk of depressive symptoms in two large cohort studies. Methods The Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort study included a total of 7,094 participants living in Tianjin, China from 2013 to 2019, and the UK Biobank cohort study includes 96,810 participants who were recruited from 22 assessment centers across the UK taken between 2006 and 2010. All participants were free of a history of cardiovascular disease (CVD), cancer, and depressive symptoms at baseline. Dietary patterns at baseline were identified with factor analysis based on responses to a validated food frequency questionnaire in TCLSIH or Oxford WebQ in UK Biobank. Depressive symptoms were evaluated using the Chinese version of the Zung Self-Rating Depression Scale (SDS) in TCLSIH or hospital inpatient records in UK Biobank. Cox proportional hazards regression models were used to estimate the association between dietary patterns and depressive symptoms. Results A total of 989, and 1,303 participants developed depressive symptoms during 17,410 and 709,931 person-years of follow-up. After adjusting for several potential confounders, the multivariable HRs (95% CIs) of the depressive symptoms were 0.71 (0.57, 0.88) for traditional Chinese dietary pattern, 1.29 (1.07, 1.55) for processed animal offal included animal food dietary pattern, and 1.22 (1.02, 1.46) for sugar rich dietary pattern in TCLSIH (all Q4 vs Q1). In the UK Biobank, the HRs (95% CIs) of depressive symptoms were 1.39 (1.16, 1.68) for processed food dietary pattern (Q4 vs Q1), 0.90 (0.77, 1.00) for healthy dietary pattern (Q3 vs Q1), and 0.89 (0.75, 1.05) for meat dietary pattern (Q4 vs Q1) in the final adjusted model. Conclusion Dietary patterns rich in processed foods were associated with a higher risk of depressive symptoms, and following a traditional Chinese dietary pattern or healthy dietary pattern was associated with a lower risk of depressive symptoms, whereas meat dietary pattern was not associated.

Background: Mushrooms are a good source of many nutrients which are potentially beneficial for chronic diseases. We speculated that due to its abundant nutrients edible mushrooms might have a beneficial effect on the prevention of subclinical thyroid dysfunction (SCTD). Therefore, we designed a large-scale cohort study to examine whether mushrooms consumption is a protective factor for SCTD in adults. Methods: This prospective cohort study investigated 6631 participants (mean age: (45.0 ± 10.2) years; 55.1 % men). Edible mushrooms consumption was measured at baseline using a validated food frequency questionnaire. SCTD was defined as abnormal serum thyroid-stimulating hormone levels and normal free thyroxine. Cox proportional hazards regression models were used to examine the association of edible mushrooms consumption with incident SCTD. Results: During follow-up period, a total of 262 new cases of SCTD were identified, the incidence rate of subclinical hypothyroidism was 8.9/1000 person-years and subclinical hyperthyroidism was 7.2/1000 person-years. After adjusting potential confounding factors, the multivariable hazard ratios (95 % confidence intervals) for subclinical hypothyroidism were 1.00 (reference) for almost never, 0.53 (0.29, 0.97) for 1–3 times/week and 0.30 (0.10, 0.87) for ≥ 4 times/week (P for trend = 0.02). It also showed edible mushrooms consumption was inversely associated with subclinical hypothyroidism in obese individuals but not non-obese individuals, the final hazard ratios (95 % confidence intervals) were 0.14 (0.03, 0.73) (P for trend < 0.01). Conclusions: his population-based prospective cohort study has firstly demonstrated that higher edible mushrooms consumption was significantly associated with lower incidence of subclinical hypothyroidism among general adult population, especially in obese individuals.

ObjectiveThis study aimed to investigate and analyze the clinical application value of thoracoscopic segmentectomy and lobectomy in patients with invasive pulmonary adenocarcinoma.Methods286 patients with invasive pulmonary adenocarcinoma who underwent segmentectomy or lobectomy at the First Hospital of Jiaxing City from January 2018 to June 2020 were retrospectively analyzed. Patients were divided into a thoracoscopic segmentectomy group(n=97) and a lobectomy group (n=189). Patients were compared after obtaining 1:1 propensity score-matched cohorts. Outcome indicators included surgery-related indicators, immune-inflammation-related indicators, postoperative complications, recurrence, and metastasis.ResultsAfter 1:1 propensity score matching, 93 patients were included in each group. We found that the volume of intraoperative blood loss in the segmentectomy group was significantly less than in the lobectomy group (P=0.014). The duration of postoperative drainage (P = 0.005) and hospitalization (P=0.002) in the segmentectomy group were significantly shorter than in the lobectomy group. In terms of immunoinflammatory response, compared with the lobectomy group, white blood cells, neutrophils, SII, and NLR in the segmentectomy group were significantly lower than in the lobectomy group (P< 0.05). The recurrence-free survival (RFS) rates in the segmentectomy and lobectomy were 80.5% and 88.2% at 1 year and 35.1% and 52.6% at 3 years, respectively, and the difference was statistically significant (P 0.05). Multivariate COX regression analysis showed that CAR was an independent risk factor for RFS in patients undergoing invasive adenocarcinoma surgery.ConclusionCompared with lobectomy, thoracoscopic segmentectomy can effectively reduce the postoperative inflammatory response in patients with early invasive lung adenocarcinoma and promote patient recovery. Although segmentectomy is associated with a higher recurrence rate in the short term for patients with early invasive lung adenocarcinoma, the associated survival rate is similar to the lobectomy group. Segmentectomy should be considered in the treatment of early invasive lung adenocarcinoma. Meanwhile, postoperative CAR represents an independent risk factor for early postoperative recurrence in patients with IAC.

Abstract Background Existing approaches for treating elbow fractures include lateral, medial, anterior and posterior approaches, though the anterior approach is often not chosen by surgeons to avoid damage to important nerves and blood vessels. However, the anterior approach has unique advantages. The purpose of this study was to report outcomes of 38 patients with coronal plane elbow fractures treated through the anterior approach. Methods We retrospectively analyzed 38 cases of coronal plane elbow fracture treated through an anterior approach at our institution between March 2015 and July 2019. The length of the surgical incision, operation time, and postoperative complications were recorded. The range of flexion, extension, and rotation of the affected elbow and the healthy elbow were collected at follow-up. Functional outcomes were evaluated using the Mayo Elbow Function Score (MEPS). Results All 38 patients were followed up for a mean of 21.26 months (range 12–36 months). Intraoperatively, the mean surgical incision length was 8 ± 2 cm and the mean operative time was 123 ± 59 min. At the final follow-up, solid osseous union was confirmed for all coronal plane elbow fractures. The mean elbow flexion arc was 129 ± 7°, and the extension arc was 9 ± 6°. The mean pronation arc was 83 ± 3°, and the supination arc was 80 ± 3°. The mean MEPS was 90 ± 8 points, with 18 excellent cases and 20 cases of excellent and good results, respectively. In 31 cases, there was no significant difference in elbow extension, flexion, or pronation between the single-fracture and healthy elbows (P > 0.05), though the arc of supination was slightly worse than that of the healthy elbow (P

BackgroundTendon adhesions after hand tendon repair are one of the most difficult complications of hand surgery and can cause severe disability. This study aimed to assess the risk factors associated with tendon adhesions after hand tendon repair to provide a theoretical foundation for the early prevention of tendon adhesions in patients with tendon injuries. Moreover, this study intends to increase doctors' awareness of the issue and serves as a reference for developing new prevention and treatment strategies.MethodsWe retrospectively analyzed 1,031 hand trauma cases that underwent repair after finger tendon injury in our department between June 2009 and June 2019. Tendon adhesions, tendon injury zones, and other relevant information were collected, summarized, and analyzed. The significance of data was determined using a t-test or Pearson's chi-square test, and odds ratios (OR) were calculated using logistic regression tests to describe factors associated with post-tendon repair adhesions.ResultsA total of 1,031 patients were enrolled in this study. There were 817 males and 214 females with an average age of 34.98 (2–82) years. The injured side included 530 left and 501 right hands. Postoperative finger tendon adhesions occurred in 118 cases (11.45%), including 98 males and 20 females, 57 left and 61 right hands. The risk factors for the total sample in the descending order were degloving injury, no functional exercise, zone II flexor tendon injury, time from injury to surgery >12 h, combined vascular injury, and multiple tendon injuries. The flexor tendon sample shared the same risk factors as the total sample. Risk factors for the extensor tendon sample were degloving injury, no functional exercise.ConclusionsClinicians should pay close attention to patients with tendon trauma in hand having the following risk factors: degloving injury, zone II flexor tendon injury, lack of functional exercise, time from injury to surgery >12 h, combined vascular injury, and multiple tendon injuries. Due to the high risk of post-repair adhesions in patients with the conditions mentioned above, individualized treatment measures should be designed for the risk factors, and postoperative functional exercise of the hand is required.

Abstract Background The most commonly used approach for distal radius fractures is the traditional Henry approach. However, it requires an intraoperative incision of the pronator quadratus (PQ) muscle, which results in a series of complications if the repair of the PQ fails. Aim The objective of this study was to investigate the efficacy of sparing the pronator quadratus for volar plating of the distal radius fractures. Methods Seventy-six patients who suffered from distal radius fractures of types 23-B, 23-C1, and 23-C2 as per the AO Foundation and Orthopaedic Trauma Association (AO/OTA) classification were treated with volar locking plate fixation using either the PQ muscle incision and repair (group A, n = 39) or the PQ muscle preservation approach (group B, n = 37). Intraoperative index, postoperative efficacy and complications of patients were recorded and evaluated. Results All patients were followed up for more than one year after surgery. All fractures achieved union. There were significant differences in mean operative time, mean intraoperative blood loss, and mean fracture healing time between the two groups. Still, there were no significant differences in limb function scores between the two groups at the 12-month postoperative follow-up. Outcomes assessed at 1 week, 1 month, and 3 months after surgery demonstrated significant differences in the mean range of motion and pain-related visual analog scale (VAS) between the two groups. As the range of motion and grip strength increased, the VAS scores decreased, and there was no significant difference between the two groups at 12 months postoperatively. Although tendon irritation and delayed carpal tunnel syndrome were more common in group A than in group B (7.6% vs. 0% and 5.1% vs. 0%, respectively), the differences were not statistically significant. Conclusion The modified Henry approach with sparing pronator quadratus muscle has no significant advantage in the range of wrist motion and upper limb function in the late stage. Nevertheless, the intraoperative placement of the plate under the pronator quadratus muscle can shorten the operation time, reduce intraoperative bleeding, reduce early postoperative pain, promote early activity, and improve the patient's quality of life. It is recommended that the pronator be preserved at the time of surgery.

Abstract Background Humeral nonunion with significant bone loss or shortening is uncommon and poses a complex clinical problem. We present a case of humeral nonunion with a large segmental bone defect treated with the distraction osteogenesis technique and remedy the radial nerve palsy produced during distraction osteogenesis by forearm tendon transfers. The reconstruction of upper limb function was achieved with satisfactory results. This case provides a referenceable alternative method for repairing large segmental bone defects due to complex nonunion of the upper extremity, as well as a remedy in the unfortunate event of radial nerve palsy, providing a reference and lessons learned for the treatment of similar cases and the management of possible complications. Case presentation A 31-year-old male patient experienced 9 years of hypertrophic nonunion due to an unreliable internal fixation. The radiographs showed the absence of bone bridging between the two fragments, loosening of the screws, and extensive osteolysis around the internal screws. The patient was treated with distraction osteogenesis. At the end of the distraction period, the patient unfortunately developed right radial nerve paresis, which was salvaged by forearm tendon transplantation, and finally reconstructed hand function and achieved bone union of the humerus. Conclusion Distraction osteogenesis, although not a panacea for all humeral nonunions with significant segmental bone loss, does offer a viable salvage procedure in this unusual and often complex clinical problem. When irreversible radial nerve palsy occurs during distraction, forearm tendon transfers can have a good clinical effect.

Background: In the clinical treatment of large bone defects, distraction osteogenesis can be used. However, some patients may suffer from poor bone regeneration, or even delayed healing or non-union. Problems with the aggregation and proliferation of primary osteoblasts, or problems with the differentiation of primary osteoblasts will lead to poor bone regeneration. Therefore, supplementing exogenous primary osteoblasts and growth factors when using distraction osteogenesis may be a treatment plan with great potential.Methods: Bone marrow mesenchymal stem cells (BMSCs) were extracted from rats and cultured. Subsequently, Recombinant Rat Platelet-derived Growth Factor BB (rrPDGF-BB) was used to induce bone marrow mesenchymal stem cells. At the same time, male adult rats were selected to make the right femoral distraction osteogenesis model. During the mineralization period, phosphate buffer salt solution (control group), non-induction bone marrow mesenchymal stem cells (group 1) and recombinant rat platelet-derived growth factor BB intervened bone marrow mesenchymal stem cells (group 2) were injected into the distraction areas of each group. Then, the experimental results were evaluated with imaging and histology. Statistical analysis of the data showed that the difference was statistically significant if p < 0.05.Results: After intervention with recombinant rat platelet-derived growth factor BB on bone marrow mesenchymal stem cells, the cell morphology changed into a thin strip. After the cells were injected in the mineralization period, the samples showed that the callus in group 2 had greater hardness and the color close to the normal bone tissue; X-ray examination showed that there were more new callus in the distraction space of group 2; Micro-CT examination showed that there were more new bone tissues in group 2; Micro-CT data at week eight showed that the tissue volume, bone volume, percent bone volume, bone trabecular thickness, bone trabecular number and bone mineral density in group 2 were the largest, and the bone trabecular separation in group 2 was the smallest. There was a statistical difference between the groups (p < 0.05); HE staining confirmed that group 2 formed more blood vessels and chondrocytes earlier than the control group. At 8 weeks, the bone marrow cavity of group 2 was obvious, and some of them had been fused.Conclusion: The study confirmed that injecting bone marrow mesenchymal stem cellsBB into the distraction space of rats can promote the formation of new bone in the distraction area and promote the healing of distraction osteogenesis.

BackgroundProspective studies on the association between Helicobacter pylori (H. pylori) infection and subclinical hyperthyroidism are limited. We, therefore, designed a large-scale cohort study to explore the association between H. pylori infection and the risk of subclinical hyperthyroidism in women.MethodsThis prospective cohort study investigated 2,713 participants. H. pylori infection was diagnosed with the carbon 13 breath test. Subclinical hyperthyroidism was defined as serum thyroid-stimulating hormone levels are low or undetectable but free thyroxine and tri-iodothyronine concentrations are normal. Propensity score matching (PSM) analyses and Cox proportional hazards regression models were used to estimate the association between H. pylori infection and subclinical hyperthyroidism.ResultsA total of 1,025 PS-matched pairs of H. pylori infection women were generated after PSM. During 6 years of follow-up, the incidence rate of subclinical hyperthyroidism was 7.35/1,000 person-years. After adjusting potential confounding factors (including iodine intake in food and three main dietary patterns score), the multivariable hazard ratio (HR; 95% confidence intervals) of subclinical hyperthyroidism by H. pylori infection was 2.49 (1.36, 4.56). Stratified analyses suggested a potential effect modification by age, the multivariable HR (95% confidence intervals) was 2.85 (1.45, 5.61) in participants aged ≥ 40 years and 0.70 (0.08, 6.00) in participants aged < 40 years (P for interaction = 0.048).ConclusionOur prospective study first indicates that H. pylori infection is significantly associated with the risk of subclinical hyperthyroidism independent of dietary factors among Chinese women, especially in middle-aged and older individuals.Clinical Trial Registration:https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031137, identifier UMIN000027174.

BackgroundEpidemiological evidence for the relationship between riboflavin intake and bone health is inconsistent, and this relationship has not been examined in Chinese population. This study aimed to investigate the relationship between dietary intake of riboflavin and prevalence of osteoporosis in a Chinese adult population.MethodsA total of 5,607 participants (mean age, 61.2 years; males, 34.4%) were included in this cross-sectional study. We calculated the riboflavin intake by using the food frequency questionnaire (FFQ) in combination with Chinese food composition database. Bone mineral density (BMD) was detected by an ultrasound bone densitometer. Multivariable logistic regression models were used to evaluate the relationship between dietary riboflavin intake and prevalence of osteoporosis.ResultsIn this population, the dietary intake of riboflavin ranged from 0.13 to 1.99 mg/d, and the proportion of abnormal BMD was 36.6%. The prevalence of osteoporosis decreased gradually with increasing quartiles of riboflavin intake, before and after adjustment for a range of confounding factors. In the final model, the multivariate-adjusted ORs (95% CI) across the quartiles of riboflavin intake were 1.00 (reference), 0.84 (0.54, 1.31), 0.59 (0.34, 1.04), and 0.47 (0.22, 0.96), respectively (P for trend < 0.05). In sex-disaggregated analysis, similar results to the total population were observed in women, while no significant results were found in men.ConclusionThe dietary riboflavin intake was negatively associated with the prevalence of osteoporosis. However, the association was significant in women but not in men. Our findings indicated that women are more sensitive to riboflavin intake in maintaining a normal BMD.

BackgroundEmerging evidence suggests sarcopenia, which is involved in the serum vitamin D deficiency and development of abnormal muscle metabolism, is predominately centered in the general older population. In the present study, we aimed to explore the relationship between the level of serum vitamin D and irisin concentrations in the older adults with sarcopenia.MethodsA cross-sectional study was conducted which included 422 sarcopenia participants (146 males and 276 females). Sarcopenia was assessed according to the recommended diagnostic criteria of the Asia Working Group for Sarcopenia (AWGS). The levels of serum 25-hydroxyvitamin D (25(OH)D), 25-hydroxyvitamin D2 (25(OH)D2) and 25-hydroxyvitamin D3 (25(OH)D3) were determined by LC-MS/MS. Irisin levels were measured by enzyme-linked immunosorbent assay (ELISA). The relationship between serum concentration of vitamin D and irisin were determined using multiple linear regression analysis.ResultsAfter adjustment for potential confounding factors, a significant and positive relationship between changes in irisin across 25(OH)D, and 25(OH)D3 was observed (standard regression coefficients of 0.150 and 0.151, respectively, P < 0.05). However, no significant relationship was observed between serum vitamin D concentrations and irisin levels in males.ConclusionsThis study demonstrated that a higher level of serum vitamin D is independently related to the increment of irisin in sarcopenia females, not in males. These investigations need to be verified in other large-scale prospective studies.

Background: Honey has been shown to have multiple positive effects on human health. However, data on the associations of honey consumption with prehypertension are scarce. The aim of this study was to investigate whether honey consumption is associated with prehypertension in a Chinese population. Method: A cross-sectional study was conducted in 4,561 individuals aged ≥40 years. A validated 100-item semi-quantitative food frequency questionnaire was used to assess honey consumption. Blood pressure was measured at least twice by trained nurses. Multiple logistic regression models were used to explore the associations between honey consumption and prehypertension. Results: After adjustment for potential confounders, the odds ratios and 95% confidence intervals of prehypertension across increasing frequency of honey consumption were 1.00 (reference) for almost never, 1.17 (0.96, 1.41) for ≤6 times/week, and 1.25 (0.86, 1.84) for ≥7 times/week in men (P for trend = 0.09); 1.00 (reference) for almost never, 0.76 (0.62, 0.92) for ≤6 times/week, and 0.84 (0.63, 1.12) for ≥7 times/week in women (P for trend = 0.055), respectively. Conclusion: Our results showed that light-to-moderate intake of honey was associated with lower prevalence of prehypertension in women, but not men. Future studies are required to confirm these associations.

Abstract Background Early-life hormonal and nutritional factors can greatly influence the risk of non-alcoholic fatty liver disease (NAFLD). Adult height is a simple marker for these factors. This study aimed to investigate the association between adult height and NAFLD. Methods We performed a prospective cohort study of 35,994 participants aged 25 years or over with measured height at baseline. NAFLD was diagnosed by abdominal ultrasound and self-reported history of alcohol intake. Multivariable Cox proportional hazards regression models were conducted to assess the gender-specific association between height and the risk of NAFLD. Results During a follow-up period of 5.5 years, 6245 of 35,994 subjects developed NAFLD. The adjusted hazard ratios (95% confidence interval) of NAFLD for increasing quintiles of height were 1.00 (reference), 0.82 (0.73, 0.92), 0.84 (0.73, 0.97), 0.72 (0.61, 0.85) and 0.63 (0.50, 0.79) (P for trend

Abstract Background The health benefits of dietary fibre (DF) intake on non-alcoholic fatty liver disease (NAFLD) are controversial. Thus, this large cross-sectional study aimed to determine the associations between DF intake and the prevalence of newly-diagnosed NAFLD in a large general population. Methods A total of 23,529 participants were enrolled in the analyses. Newly-diagnosed NAFLD was diagnosed according to liver ultrasonography and history of alcohol intake. DF intake was assessed using a validated self-administered food frequency questionnaire. Logistic regression analysis was applied to estimate the associations between DF intake and NAFLD. Results In total, 18.81% (n = 4426) of the participants were newly diagnosed with NAFLD. Compared with the participants in the lowest quartile of DF intake, the ORs (95% CI) for the participants in the highest quartile were 0.81 (0.67, 0.97), 0.78 (0.62, 0.99), and 0.85 (0.62, 1.17) for all participants, men, and women, respectively. Compared with the participants in the lowest quartile of insoluble DF intake, the ORs (95% CI) for the participants in the highest quartile were 0.70 (0.58, 0.85), 0.60 (0.47, 0.76), and 0.95 (0.68, 1.32) in all participants, men, and women, respectively. No association was observed between soluble DF intake and NAFLD. DF from whole grain, soy foods, vegetables, and nuts but not fruits were negatively associated with NAFLD. Conclusions A higher intake of insoluble DF is associated with lower prevalence of newly-diagnosed NAFLD in men. Moreover, intake DF from whole grain, soy foods, vegetables, and nuts, but not fruits have favorable effect on the prevalence of newly diagnosed NAFLD. Further cohort studies and randomized controlled trials are needed to validate this finding.

Background: The relationship between dietary patterns and atherosclerosis is inconclusive. Usually, diets vary greatly among different regions due to cultural differences and lifestyles. Few studies to date based on a Chinese population have investigated the relationship between dietary patterns and the formation of atherosclerosis in carotid arteries. We aimed to investigate whether dietary patterns were related to carotid atherosclerosis among an adult population in Tianjin, China.Methods: This cross-sectional study included a total of 2,346 participants aged 50 years or older (mean: 59.7 ± 6.29 years). Dietary intakes were assessed using a validated 81-item semiquantitative food frequency questionnaire, and factor analysis was used to identify dietary patterns. Carotid atherosclerosis was defined as a common carotid artery intima-media thickness ≥1.0 mm or plaques, or a carotid bifurcation intima-media thickness ≥1.2 mm. Multiple logistic regression models were used to explore the relationship between dietary patterns and carotid atherosclerosis.Results: Three factors were determined: “health” dietary pattern (factor 1), “traditional Tianjin” dietary pattern (factor 2), and “sweets” dietary pattern (factor 3). The multivariable-adjusted odds ratios (95% CI) of carotid atherosclerosis for the increasing quartiles of the sweets dietary pattern scores in women were as follows: 1.00 (reference), 1.33 (0.91, 1.97), 1.21 (0.82, 1.79), 1.64 (1.08, 2.51) (p for trend

Purpose: This study aimed to determine the longitudinal association between hand grip strength (HGS) and the development of non-alcoholic fatty liver disease (NAFLD) in adults.Design: A cohort study.Methods: This study was conducted in a general Chinese population (n = 14,154) from 2013–2018. NAFLD was diagnosed by liver ultrasonography during evaluating alcohol consumption. The associations between the HGS and NAFLD were assessed using a multivariable Cox proportional hazards regression model.Results: During the study period with a mean follow-up duration of 3.20 years, 2,452 participants developed NAFLD. The risk of NAFLD decreased progressively with increasing HGS in both men and women (P for trend

Abstract Background Previous studies have reported that tea extract supplementation has potential benefits on the risk factors of non-alcoholic fatty liver disease (NAFLD); however, no study has investigated the direct effect of daily tea consumption on the prevalence of NAFLD in the general population. This cross-sectional study aimed to evaluate the associations between tea consumption and the prevalence of newly diagnosed NAFLD among Chinese adults. Methods The present cross-sectional study was based on the Tianjin Chronic Low-grade Systemic Inflammation and Health Cohort Study. In total, 19,350 participants were enrolled in the analyses. Tea consumption was assessed via a self-administered food frequency questionnaire. NAFLD was diagnosed via liver ultrasonography and no history of heavy alcohol intake. Logistic regression analysis was used to estimate the associations between tea consumption and the prevalence of NAFLD. Results Consumption of green tea, oolong tea, and black tea were positively associated with the prevalence of newly diagnosed NAFLD before adjustments. Compared with the participants who never drink tea, the odds ratios (95% confidence interval) of newly diagnosed NAFLD in the highest categories (≥ 1 cup/day) of green tea, oolong tea, black tea, and jasmine tea were 1.48 (1.33, 1.65), 1.50 (1.33, 1.68), and 1.28 (1.13, 1.46), and 1.36 (1.20, 1.54) before adjustments, respectively. However, no significant association was found between tea consumption and the prevalence of NAFLD after adjusting for socio-demographic, behavioural, anthropometric, dietary, and clinical confounding factors. Conclusion There is no significant association between daily tea drinking and newly-diagnosed NAFLD in general Chinese adults.

Abstract Objective Metabolic syndrome (MS) is a group of risk factors which includes hypertension, hyperglycemia, abnormal cholesterol levels, and obesity. Red blood cell distribution width (RDW) is a parameter that reflects the heterogeneity of erythrocyte volume. But the relationship between MS and RDW is intricate and remains poorly understood. We hypothesized that high RDW was associated with MS via inflammation. Our study aimed to investigate the association between RDW and MS in Chinese elderly large cohort. If RDW had a strong correlation with MS, RDW could become a predictor of MS? Methods We recruited 10,887 ostensibly healthy participants aged from 60 to 93 (5795 male, 5092 female). Associations between RDW and other variables were assessed by Pearson correlation. Crude and adjusted odds ratio for MS with 95% confidence intervals was calculated by binary logistic regression models. Results In elderly Chinese, RDW was significantly higher in males than in females. The prevalence of both men and women decreased with the rise of RDW. For both sexes, RDW demonstrated positive correlations with age, systolic blood pressure (0.070 in males,0.058 in females), high density lipoprotein(0.027in males,0.064 in females), negative correlations with triglycerides (− 0.120 in males,-0.074 in females) and fasting glucose (− 0.048 in males,-0.016 in females). Notably, we detected the associated reduced risks at the the third and fourth quartile of RDW in males. In women, there was no statistical significance. Conclusion We found the adjusted odds ratios of MS was lower at the third and fourth quartile of RDW in males.

In this paper, a hybrid SEIAM model for infectious disease with a continuous age structure is established, where combined dynamic effects of media coverage and multi-staged infected progression on threshold dynamics are discussed. Sufficient conditions for uniform persistence of the solution are studied by using the basic reproduction number. By constructing appropriate Lyapunov functions, the global stability analysis of endemic equilibrium is investigated based on Lyapunov–LaSalle’s stability theorem. In order to minimize costs incurred due to applied controls and infectious disease burden, an optimal cost-effective control strategy associated with disease treatment and media coverage is discussed. Numerical simulations are carried out to show consistency with theoretical analysis.

Background: Previous animal and clinical studies have reported beneficial effects of garlic preparations on carotid intima-media thickness (cIMT). However, no epidemiological study has yet investigated the association between dietary raw garlic consumption and cIMT in the general population. The objective of this study was investigating the association between dietary raw garlic consumption and thickened cIMT in Chinese adults.Methods: This cross-sectional study used data from the Tianjin Chronic Low-grade Systemic Inflammation and Health Cohort Study. A total of 4,329 general adults from 2015 to 2017 were included in this study. Frequency of consumption of raw garlic was summarized as four categories for analysis: < 1 time/week, 1 time/week, 2-3 times/week, ≥4 times/week with a validated food frequency questionnaire. The thickened cIMT was defined as common carotid artery IMT ≥ 1.0 mm or a carotid bifurcation IMT ≥ 1.2 mm by ultrasonography. Multivariable logistic regression analysis was used to examine the association between frequency of raw garlic consumption and thickened cIMT.Results: The prevalence of thickened cIMT is 22.9% among these participants. The adjusted odds ratios (95% confidence intervals) associated with the different frequencies were 1.00 (reference) for < 1 time/week, 0.74 (0.59, 0.94) for 1 time/week, 0.71 (0.55, 0.92) for 2–3 times/week, and 0.94 (0.71, 1.25) for ≥ 4 times/week.Conclusions: Light-to-moderate raw garlic consumption was inversely associated with thickened cIMT, whereas greater raw garlic consumption (i.e., ≥4 times/week) was not associated with thickened cIMT. Future longitudinal studies should be conducted to test these findings.

Background and Aims: Previous studies have explored the associations between nutrition (food groups, nutrients, and dietary patterns) and the prevalence of non-alcoholic fatty liver disease. However, it remains unclear whether how foods are consumed together is associated with non-alcoholic fatty liver disease. The present study aims to construct dietary networks from network science and to explore the associations between complex dietary networks and non-alcoholic fatty liver disease.Methods: The present case–control study generated 2,043 multivariate matched controls for 2,043 newly diagnosed non-alcoholic fatty liver disease cases. Mutual information, which represents both linear and non-linear dependencies among food groups, was used to construct the network topologies.Results: The dietary topologies in the studied case and control groups were different despite the fact that only few food groups show differences in absolute intake. The dietary structure of the case group focused on two major components with more cohesion among food groups, while contrarily the control group had one major component with higher diversity of food groups. The dietary topology of the case group showed equality in connections among beneficial and detrimental food groups, whereas the control group focused more on healthier food choices.Conclusions: This study suggests how foods are consumed, besides the absolute intake, could be an important determinant of the occurrence of non-alcoholic fatty liver disease. A diverse diet that focuses on whole grain, tubers, and vegetables could yield beneficial effects regarding non-alcoholic fatty liver disease. Network science could offer a complementary tool in nutritional epidemiology.

Tooth loss is a prevailing condition in China due to the high prevalence of oral diseases. Since previous studies explored the association between tooth loss and handgrip strength showed incongruous results, the aim of this study was to investigate the association between tooth loss and handgrip strength in Tianjin, China. Cross-sectional data in the present study used baseline data of Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) Cohort Study during 2013-2016. Eligible adults (n = 26275) were classified into four groups depending on the number of missing teeth (excluding third molars): 0, 1-2, 3-5 and ≥6. Handgrip strength was measured using a handheld type dynamometer. Analysis of covariance was used to examine the relationships between tooth loss and handgrip strength and handgrip strength per body weight according to gender. After adjustment for potential confounders, the relationships existed between increasing categories of tooth loss and handgrip strength, as well as handgrip strength per weight. The data of stratified analysis showed that there was a trending association between decreased handgrip strength and fewer retained teeth both in males and females less than 60 years of age (P for trend

Abstract Objective Dyslipidemia can cause some chronic diseases. Bilirubin is reported to have anti-inflammatory and anti-oxidant properties. We aimed to explore the relationship between triglyceride and total bilirubin (TB) in a large Chinese cohort. Methods A total of 80,298 healthy Chinese (48,971 male, 31,327 female) enrolled in this cross-sectional study. Clinical data were collected from participants. Database was divided according to sex and age. The relationship between triglyceride and TB was analyzed by quartiles of TB. Levels of triglyceride were compared in different TB subgroups by one-way analysis of variance and independent sample’s t-test. Crude and adjusted odds ratios of triglyceride for TB with 95% confidence intervals were analyzed by binary logistic regression models. Results Overall, men showed higher levels of TB and triglyceride than women. In people older than 60 years, women had higher triglyceride levels than men. Linear logistic regression analyses showed a negative relationship between triglyceride and TB in both genders. Men showed significantly higher overall incidence of high triglyceride than women. Men less than 60 years old showed a higher incidence of high triglyceride. For women older than 60 years, the incidence of high triglyceride was higher. However, high TB showed no protective effects on both genders from high TG in the binary logistic regression models. TB showed a detrimental effect on high TG in model 2 which included TB as a covariate. But that effect disappeared after other confounding factors were included. Conclusions Our findings showed no association between TB and triglyceride in Chinese.

Prehypertension is a public health epidemic associated with various adverse outcomes, but can be reversed by timely intervention. However, little attention has been paid to prehypertension. Complement C3 is a central hub of complement-related immune system. We examined the association between C3 and prehypertension in an adult population for the first time, aiming to investigate whether pro-inflammatory immune response is involved in the prehypertensive state. About 7820 Tianjin residents without hypertension were categorized into sex-specific quintiles based on their serum concentration of complement C3. Adjusted logistic regression models were used separately by gender to assess the association between C3 quintiles and the prevalence of prehypertension. After multiple adjustment, the odds ratios (95% confidence interval) for prehypertension across increasing quintiles of C3 were 1.00 (reference), 1.02 (0.84, 1.25), 1.15 (0.94, 1.42), 1.25 (1.01, 1.54), and 1.71 (1.35, 2.17) (p for trend < 0.0001) among men and were 1.00 (reference), 1.17 (0.92, 1.49), 1.13 (0.88, 1.44), 1.15 (0.89, 1.48), and 1.40 (1.07, 1.84) (p for trend = 0.03) among women. The findings suggested that elevated serum C3 levels are associated with prehypertension. Reducing inflammation may be a potential therapeutic strategy for prehypertension and hypertension that is worthy of further studies and discussion.

Depressive symptoms have become the most important global public health issue. Iron plays an important role in brain function, cognition, and behavior, and its impacts on depressive symptoms may be multifactorial with both positive and negative effects. Previous observational studies focusing on the association between iron status and depressive symptoms showed inconsistent results. Ferritin is a ubiquitous intracellular protein that can store and release iron and is widely used as a clinical biomarker to evaluate iron status. We performed a cross-sectional study to examine the relationship between serum ferritin and depressive symptoms among 3,839 subjects who were from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIHealth) cohort. Depressive symptoms were assessed using the Chinese version of 20-item self-rating Depression Scale (SDS) with 4 cutoffs (40, 45, 48 and 50) to indicate elevated depressive symptoms (40 was the primary cut-off). The prevalence of depressive symptoms was 36.5%, 17.6%, 11.0% and 7.0% for SDS ≥40, ≥45, ≥48 and ≥50, respectively. With the primary cut-off point of 40, multiple potential confounding factors were adjusted and the odds ratios (95% confidence interval) of having elevated depressive symptoms by quartiles of serum ferritin concentrations were 1.00 (reference), 1.10 (0.91, 1.34), 0.81 (0.66, 1.01) and 1.02 (0.81, 1.28) for the first, second, third and fourth quartile, respectively (P for trend = 0.76). Similar relations were observed with the use of other cut-offs as a definition of depressive symptoms. In conclusion, there is no significant relationship between serum ferritin concentrations and depressive symptoms among Chinese adults.

Activation of the innate immune system plays a key role in the development of fatty liver disease (FLD). The complement system is a major humoral component of the innate immune response and complement C3 plays a central role, implying that C3 may be a powerful predictor or therapeutic target for FLD. However, few studies have assessed the association between C3 and FLD in a large population. Here we use a cross-sectional study to investigate the link between serum C3 levels and FLD. Participants were recruited from Tianjin Medical University's General Hospital-Health Management Centre. Serum C3 was measured using immunoturbidimetry method and FLD was diagnosed by liver ultrasonography. Multiple logistic regression analysis was used to examine the association between quartiles of C3 and FLD prevalence. The overall prevalence of nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) were 37.3% and 10.1%, respectively. After adjusting for covariates, the odds ratio of having NAFLD or AFLD (only in males) in the fourth quartile of C3 compared with the first quartile was 4.13 times greater (95% confidence interval, 2.97-5.77) (trend P values < 0.0001) and 2.09 times greater (95% confidence interval, 1.08-4.18) (trend P values = 0.02). This is the first study to demonstrate that serum C3 levels are independently associated with a higher prevalence of NAFLD and AFLD (only in males) in an adult population. Further studies are needed to establish a causal link and determine the precise role of C3 in FLD.

Persistent low-grade inflammation is thought to underlie the pathogenesis of many chronic diseases, such as cardiovascular diseases and metabolic syndrome. Autoimmunity is correlated with increased levels of chronic low-grade inflammation, and immunoglobulin M (IgM) is reactive to autoantigens and believed to be important for autoimmunity. Triglyceride (TG) is fatty acid carrier and initiator of oxidative stress, and it has been hypothesized that TG stimulates B cells to secrete IgM. However, few studies have investigated the relationship between TG and IgM in human populations. We designed a cross-sectional and prospective cohort study to evaluate how serum TG levels are related to IgM concentration. Participants were recruited from Tianjin Medical University General Hospital-Health Management Centre. Both a baseline cross-sectional (n = 10,808) and a prospective assessment (n = 2,615) were performed. Analysis of covariance was used in the cross-sectional analysis. After multiple adjustments for confounding factors, serum IgM level in the highest quartile of TG in males was significantly higher than levels in lower quartiles (P

Persistent low-grade systemic inflammation has been increasingly recognized as a common pathological process, and an important contributing factor to cardiovascular diseases and its risk factor, metabolic syndrome. Immunoglobulin M is reactive to multiple autoantigens and is inferred to be important for autoimmunity, implying that immunoglobulin M may be a potential risk factor for metabolic syndrome. However, few epidemiological studies are available which are related to this potential link. Therefore, we designed a cross-sectional study of 9,379 subjects to evaluate the relationship between immunoglobulin M and metabolic syndrome in an adult population. Subjects who received health examinations were recruited from the Tianjin Medical University General Hospital-Health Management Center in Tianjin, China. Immunoglobulin M was determined with an immunonephelometric technique. Metabolic syndrome was defined according to the criteria of the American Heart Association scientific statements of 2009. Multiple logistic regression analysis was used to examine the relationships between the quartiles of immunoglobulin M and the prevalence of metabolic syndrome. After adjustment for covariates, the odds ratio of having metabolic syndrome in the fourth quartile compared with the first quartile of immunoglobulin M was 1.19 times for males (95% confidence interval, 1.002-1.41) and 1.39 times for females (95% confidence interval, 1.07-1.80). Immunoglobulin M levels also showed positive relationships with the ratio of elevated triglycerides and reduced high-density lipoprotein cholesterol in males. The study is the first to show that immunoglobulin M is independently related to metabolic syndrome and its individual components (elevated triglycerides and reduced high-density lipoprotein cholesterol) in males, whereas immunoglobulin M is independently related to metabolic syndrome in females but not to its individual components. Further studies are needed to explore the causality and the exact role of immunoglobulin M in metabolic syndrome.

OBJECTIVE: Bilirubin is considered an important antioxidant, anti-inflammatory factor and immunomodulator. The current investigation aimed to explore the association between bilirubin and white blood cell (WBC) count in a large Chinese cohort. METHODS: A total of 61091 participants (29259 males, 31832 females) were recruited from a Chinese tertiary hospital. Data were sorted by sex, and the association between bilirubin and WBC count was analyzed after dividing bilirubin levels into quartiles. RESULTS: Most parameters (including age, body mass index, systolic blood pressure, diastolic blood pressure, alanine aminotransferase, total bilirubin, blood urea nitrogen, creatinine, uric acid, triglycerides and WBC count) were significantly higher in men than in women. Bilirubin displayed significant negative relationships with most other measured variables. Linear logistic regression analysis further indicated their negative relationships. Females showed a significantly higher frequency of leucopenia than males. Significant associations of leucopenia with high bilirubin quartiles were shown in binary logistic regression models for both sexes, with a much closer association in men than in women. For instance, for men with bilirubin levels in quartile 4, the adjusted likelihood of leucopenia was 1.600-times higher than that of men with values in quartile 1. For women with bilirubin levels in quartile 4, the adjusted likelihood of leucopenia was 1.135-times higher than that of women with values in quartile 1. CONCLUSION: Bilirubin is negatively related to WBC count. Significant associations exist between leucopenia and high bilirubin quartiles, and these associations are more obvious in men than in women.

Abstract Background Targeted protein degradation of neosubstrates plays a crucial role in hematological cancer treatment involving immunomodulatory imide drugs (IMiDs) therapy. Nevertheless, the persistence of inevitable drug resistance and hematological toxicities represents a significant obstacle to their clinical effectiveness. Methods Phenotypic profiling of a small molecule compounds library in multiple hematological cancer cell lines was conducted to screen for hit degraders. Molecular dynamic-based rational design and cell-based functional assays were conducted to develop more potent degraders. Multiple myeloma (MM) tumor xenograft models were employed to investigate the antitumor efficacy of the degraders as single or combined agents with standard of care agents. Unbiased proteomics was employed to identify multiple therapeutically relevant neosubstrates targeted by the degraders. MM patient-derived cell lines (PDCs) and a panel of solid cancer cell lines were utilized to investigate the effects of candidate degrader on different stage of MM cells and solid malignancies. Unbiased proteomics of IMiDs-resistant MM cells, cell-based functional assays and RT-PCR analysis of clinical MM specimens were utilized to explore the role of BRD9 associated with IMiDs resistance and MM progression. Results We identified a novel cereblon (CRBN)-dependent lead degrader with phthalazinone scaffold, MGD-4, which induced the degradation of Ikaros proteins. We further developed a novel potent candidate, MGD-28, significantly inhibited the growth of hematological cancer cells and induced the degradation of IKZF1/2/3 and CK1α with nanomolar potency via a Cullin-CRBN dependent pathway. Oral administration of MGD-4 and MGD-28 effectively inhibited MM tumor growth and exhibited significant synergistic effects with standard of care agents. MGD-28 exhibited preferentially profound cytotoxicity towards MM PDCs at different disease stages and broad antiproliferative activity in multiple solid malignancies. BRD9 modulated IMiDs resistance, and the expression of BRD9 was significant positively correlated with IKZF1/2/3 and CK1α in MM specimens at different stages. We also observed pronounced synergetic efficacy between the BRD9 inhibitor and MGD-28 for MM treatment. Conclusions Our findings present a strategy for the multi-targeted degradation of Ikaros proteins and CK1α against hematological cancers, which may be expanded to additional targets and indications. This strategy may enhance efficacy treatment against multiple hematological cancers and solid tumors.

Abstract Ferroptosis, a nonapoptotic form of programmed cell death characterized by significant iron-dependent peroxidation of phospholipids, is regulated by cellular metabolism, redox homeostasis, and various cancer-related signaling pathways. Recently, considerable progress has been made in demonstrating the critical role of lipid metabolism in regulating ferroptosis, indicating the potential of combinational strategies for treating cancer in the future. In this study, we explored the combinational effects of lipid metabolism compounds and ferroptosis inducers on renal cell carcinoma (RCC) cells. We found potent synergy of the fatty acid amide hydrolase (FAAH) inhibitor URB597 with ferroptosis inducer (1S, 3R)-RSL3 (RSL3) in inhibiting the growth and metastasis of RCC cells both in vitro and in vivo via induction of G1 cell cycle arrest and promotion of the production of lipid peroxides, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and cytosolic reactive oxygen species (ROS). In addition, inhibition of FAAH increased the sensitivity of RCC cells to ferroptosis. Genome-wide RNA sequencing indicated that the combination of URB597 and RSL3 has more significant effects on regulation of the expression of genes related to cell proliferation, the cell cycle, cell migration and invasion, and ferroptosis than either single agent alone. Moreover, we found that combinational treatment modulated the sensitivity of RCC cells to ferroptosis via the phosphatidylinositol 3 kinase (PI3K)-AKT signaling pathway. These data demonstrate that dual targeting of FAAH and ferroptosis could be a promising strategy for treating RCC.

Background: As a population ages, blood pressure levels gradually increase, leading to a higher incidence of hypertension and increased cardiovascular diseases risk. This study examines factors affecting hypertension grading among centenarians in the Hainan Province. Methods: Data from 2014 to 2016 were accessed from the cross-sectional database “Hypertension Levels and Epidemiological Characteristics of the Elderly and Centenarians in Hainan province of China”. This study included 690 centenarians with hypertension. Hypertension grading was the dependent variable, analyzed against independent variables including demographic information (sex, age, ethnicity, education level, marital status, cohabitation, and regional distribution), lifestyle factors (smoking, alcohol consumption, and physical activity), body mass index (BMI), and comorbid conditions (diabetes and hyperlipidemia). Logistic regression models, adjusted for these factors, were used to assess the determinants of hypertension grading among the participants. Results: Multivariate regression analysis, after adjusting for other variables, revealed significant associations between BMI, low-density lipoprotein (LDL) levels, and hypertension grades. Individuals with BMI below 18.5 kg/m2 had a 0.614-fold lower risk of developing grade III hypertension (odds ratio [OR]: 0.614, 95% confidence interval [CI]: 0.390–0.966, p = 0.0350) and a 0.586-fold lower risk for grade II hypertension (OR: 0.586, 95% CI: 0.402–0.852, p = 0.0052). Furthermore, individuals with elevated LDL levels had a 6.087-fold greater risk of progressing from grade I to grade III hypertension (OR: 6.087, 95% CI: 1.635–22.660, p = 0.0071) and a 4.356-fold greater risk of progressing from grade II to grade III hypertension (OR: 4.356, 95% CI: 1.052–18.033, p = 0.0423). Additionally, individuals of Li ethnicity had 1.823-fold greater risk of progressing from grade I to grade II hypertension compared to those of Han ethnicity (OR: 1.823, 95% CI: 1.033–3.218, p = 0.0383). Conclusions: A BMI below 18.5 kg/m2, elevated LDL, and ethnicity emerged the primary factors associated with hypertension grading in centenarians. To reduce the risk of hypertension, it is crucial for centenarians to maintain a healthy weight, normal LDL levels, and adopt dietary habits including a low-cholesterol and low-fat diet.

Objectives: The present study aimed to develop a random forest (RF) based prediction model for hyperuricemia (HUA) and compare its performance with the conventional logistic regression (LR) model. Methods: This cross-sectional study recruited 91,690 participants (14,032 with HUA, 77,658 without HUA). We constructed a RF-based prediction model in the training sets and evaluated it in the validation sets. Performance of the RF model was compared with the LR model by receiver operating characteristic (ROC) curve analysis. Results: The sensitivity and specificity of the RF models were 0.702 and 0.650 in males, 0.767 and 0.721 in females. The positive predictive value (PPV) and negative predictive value (NPV) were 0.372 and 0.881 in males, 0.159 and 0.978 in females. AUC of the RF models was 0.739 (0.728-0.750) in males and 0.818 (0.799-0.837) in females. AUC of the LR models were 0.730 (0.718-0.741) for males and 0.815 (0.795-0.835) for females. The predictive power of RF was slightly higher than that of LR, but was not statistically significant in females (Delong tests, P=0.0015 for males, P=0.5415 for females). Conclusion: Compared with LR, the good performance in HUA status prediction and the tolerance of features associations or interactions showed great potential of RF in further application. A prospective cohort is necessary for HUA developing prediction. People with high risk factors should be encouraged to actively control to reduce the probability of developing HUA. [ABSTRACT FROM AUTHOR]

Background and Aims: The protective effect of garlic against nonalcoholic fatty live r disease (NAFLD) has been reported in animal studies. However, in humans, the association between garlic consumption and NAFLD is unclear. The study sought to explore the association between habitual raw garlic i ntake and newly diagnosed NAFLD among Chinese adults. Methods: We performed a study of 11,326 men and 12,780 women aged 20-90 years. Habitual food intake was assessed using a validated and standardized 100-item food frequ ency questionnaire. Diagnosis of NAFLD was based on the liver ultrasonography and self-reported alcohol intake. Multiple logistic regression was used to evaluate the association of raw garlic intake with newly diagnosed NAFLD. Results: The prevalence of newly diagnosed NAFLD was 28.9% in men and 1 0.1% in women, respectively. In men, the fully adjusted odds ratios (95% confidence interval) of having N AFLD across increasing frequency of raw garlic intake were 1.00 (reference) for <1 time/week, 0.81 (0.73, 0.90) for 1-3 times/week, 0.66 (0.54, 0.80) for 4-6 times/week, and 0.71 (0.55, 0.90) for =7 times/week (P for trend <0.0001). The odds ratio for NAFLD associated with each 1 g of raw garlic/1000 kcal was 0.93 (0.90, 0.97) in men. In women, no significant association between raw garlic intake and NAFLD was identified. These associations between raw garlic inta ke and NAFLD were consistent in several sensitivity analyses. Conclusions: Frequent consumption of raw garlic is inversely associated wit h NAFLD in Chinese men. Further investigations are needed to confirm this finding. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatocellular carcinoma (HCC) is a common cause of cancer mortality worldwide. Recent studies have shown that the polytopic enzyme membrane associated ring-CH-type finger 6 (MARCH6) participates in tumorigenesis, but its function in HCC development needs to be investigated. This study aimed to explore the role of MARCH6 in HCC. Methods Expression of MARCH6 in human HCC samples was checked by immunohistochemical staining assay. Clinical relevance of MARCH6 and activating transcription factor 2 (ATF2) was analyzed from TCGA database. CCK-8, EdU staining, colony formation and transwell were performed to assess cell proliferation, growth and migration. Xenografted tumorigenesis was used to examine in vivo role MARCH6. Immunoblotting was applied to detect protein abundance. Results We found that MARCH6 expression was elevated in human HCC samples. Over-expression of MARCH6 was associated with poor prognosis of HCC patients. Up-expression of MARCH6 promoted cell growth and migration of HCC cells. In contrast, the HCC cell growth and migration were suppressed by MARCH6 knockdown. Furthermore, the DNA synthesis was enhanced by MARCH6. The expression of ATF2 was potentiated by MARCH6 over-expression, while it was suppressed by MARCH6 silencing. TCGA database showed positive correlation between the expression of MARCH6 and ATF2. Importantly, ATF2 expression contributed to the oncogenic function of HCC cells. Conclusion Our findings suggest that MARCH6-mediated ATF2 up-regulation contributes to HCC development. MARCH6 may be a promising target for the diagnosis and treatment of HCC.

New strategies for molecular-targeted drug therapy for advanced hepatocellular carcinoma (HCC) ignore the contribution of the nutritional status of patients and nutritional support to improve physical status and immunity. We aimed to elucidate the role of a single nucleotide mixture (SNM) in the anti-tumor therapy of HCC, and to explore the importance of a SNM as adjuvant therapy for HCC. Compared with a lipid emulsion (commonly used nutritional supplement for HCC patients), the SNM could not induce metabolic abnormalities in HCC cells (Warburg effect), and did not affect expression of metabolic abnormality-related factors in HCC cells. The SNM could also attenuate the lymphocyte injury induced by antitumor drugs in vitro and in vivo, and promote the recruitment and survival of lymphocytes in HCC tissues. Using HCC models in SCID (server combined immune-deficiency) mice or BalB/c mice, the SNM had anti-tumor activity, and could significantly upregulate the antitumor activity of molecular-targeted drugs (tyrosine-kinase inhibitors [TKI] and immune-checkpoint inhibitors [ICI]) against HCC. We employed research models in vivo and in vitro to reveal the anti-tumor activity of the SNM on HCC. Our findings expand understanding of the SNM and contribute to HCC (especially nutritional support) therapy.

The protein kinase, TANK-binding kinase 1 (TBK1), not only regulates various biological processes but also functions as an important regulator of human oncogenesis. However, the detailed function and molecular mechanisms of TBK1 in hepatocellular carcinoma (HCC), especially the resistance of HCC cells to molecular-targeted drugs, are almost unknown. In the present work, the role of TBK1 in regulating the sensitivity of HCC cells to molecular-targeted drugs was measured by multiple assays. The high expression of TBK1 was identified in HCC clinical specimens compared with paired non-tumor tissues. The high level of TBK1 in advanced HCC was associated with a poor prognosis in patients with advanced HCC who received the molecular-targeted drug, sorafenib, compared to patients with advanced HCC patients and a low level of TBK1. Overexpression of TBK1 in HCC cells induced their resistance to molecular-targeted drugs, whereas knockdown of TBK1 enhanced the cells’ sensitivity to molecular-targeted dugs. Regarding the mechanism, although overexpression of TBK1 enhanced expression levels of drug-resistance and pro-survival-/anti-apoptosis-related factors, knockdown of TBK1 repressed the expression of these factors in HCC cells. Therefore, TBK1 is a promising therapeutic target for HCC treatment and knockdown of TBK1 enhanced sensitivity of HCC cells to molecular-targeted drugs.

The transcription factor, sterol regulatory element binding protein 1 (SREBP-1), plays important roles in modulating the proliferation, metastasis, or resistance to antitumor agents by promoting cellular lipid metabolism and related cellular glucose-uptake/Warburg Effect. However, the underlying mechanism of SREBP-1 regulating the proliferation or drug-resistance in lung squamous cell carcinoma (LUSC) and the therapeutic strategies targeted to SREBP-1 in LUSC remain unclear. In this study, SREBP-1 was highly expressed in LUSC tissues, compared with the paired non-tumor tissues (the para-tumor tissues). A novel small-molecule inhibitor of SREBP-1, MSI-1 (Ma’s inhibitor of SREBP-1), based on natural product monomers, was identified by screening the database of natural products. Treatment with MSI-1 suppressed the activation of SREBP-1-related pathways and the Warburg effect of LUSC cells, as indicated by decreased glucose uptake or glycolysis. Moreover, treatment of MSI-1 enhanced the sensitivity of LUSC cells to antitumor agents. The specificity of MSI-1 on SREBP-1 was confirmed by molecular docking and point-mutation of SPEBP-1. Therefore, MSI-1 improved our understanding of SREBP-1 and provided additional options for the treatment of LUSC.

Infectious mononucleosis (IM) due to Epstein-Barr virus infection is common. Uric acid (UA) is an important endogenous antioxidant. To the best of our knowledge, the association between UA and IM has not been comprehensively investigated to date. The aim of the present study was to investigate this association in Chinese patients. A total of 95 patients (47 men and 48 women) with IM were recruited, along with 95 healthy controls. Clinical data were classified by patient sex. Receiver operating characteristic (ROC) curve analysis was adopted to determine the cut-off values of UA for IM diagnosis and prediction. Crude and adjusted odds ratios (ORs) of UA for IM were analyzed by binary logistic regression. The UA levels were significantly lower in IM patients compared with those in controls. In addition, UA levels in men were significantly higher compared with those in women. The ROC curve demonstrated good diagnostic and predictive values of UA for IM in both sexes. The UA cut-off values were 326.00 and 243.50 μmol/l for diagnosing IM in men and women, respectively, with a diagnostic accuracy of 76.596 and 80.208%, respectively. Binary logistic regression analysis revealed a significant risk of IM in the low UA quartiles in both sexes. Following adjustments, the ORs even increased. Women with low UA levels appeared to be more susceptible to IM. For example, the crude ORs in quartile 1 were 24.000 and 52.500 for men and women, respectively, and the respective adjusted ORs were 31.437 and 301.746 (all P<0.01). To the best of our knowledge, the present study is the first to demonstrate the inverse association between UA and IM, suggesting a progressive decrease of antioxidant reserve in IM. Moreover, low UA was suggestive of IM, particularly in women. [ABSTRACT FROM AUTHOR]