N-cadherin Alleviates Apoptosis and Senescence of Nucleus Pulposus Cells via Suppressing ROS-dependent ERS in the Hyper-osmolarity Microenvironment.

The in-situ osmolarity is an important physicochemical factor that regulates cell fate of nucleus pulposus cells (NPCs). Our previous studies demonstrated that reduced N-cadherin (NCDH) expression in nucleus pulposus cells is associated with cellular damage under hyper-osmolarity microenvironment. This study was aimed at exploring the impacts of NCDH on senescence and apoptosis of NPCs, as well as the potential molecular mechanism. By comparing NPCs from patients with lumbar fractures and lumbar disc herniation, we identified a correlation between decreased NCDH expression and increased endoplasmic reticulum stress (ERS), resulting in undesirable cell fate (senescence and apoptosis). After blocking Reactive oxygen species (ROS) or ERS, it was indicated that hyper-osmolarity microenvironment induced ERS was ROS-dependent. Further results demonstrated the correlation in rat NPCs. Upregulation of NCDH expression reduced ROS-dependent ERS, thus limiting undesirable cell fates in vitro. This was further confirmed through the rat tail acupuncture injection model. NCDH overexpression successfully mitigated ERS, preserved extracellular matrix production and alleviating intervertebral disc degeneration in vivo. Together, NCDH can alleviate senescence and apoptosis of NPCs by suppressing ROS-dependent ERS via the ATF4-CHOP signaling axis in the hyper-osmolarity microenvironment, thus highlighting the therapeutic potential of NCDH in combating degenerative disc diseases.

Glucose-dependent insulinotropic polypeptide modifies adipose plasticity and promotes beige adipogenesis of human omental adipose-derived stem cells.

The adipocyte precursors (APs) located in white adipose tissue (WAT) are functionally significant in adipose plasticity and browning. Modifying adipogenesis or WAT browning targeted on APs is a promising mechanism for anti-obesity drug. We herein explored the in vitro actions and mechanisms of glucose-dependent insulinotropic polypeptide (GIP), a gut-derived peptide, in human adipose-derived mesenchymal stem cells (hADSCs) isolated from omentum. The hADSCs were cotreated with 100 nM GIP with or without equimolar concentration of GIP3-42 (a GIP receptor antagonist), and subsequently examined in vitro. CCK-8, EdU incorporation, and flow cytometry assays were used to assess cellular proliferation. Annexin V FTIC/PI double stain, TUNEL staining, and Western blot were applied for apoptosis evaluation. Adipogenesis was reflected by Western blot, real-time PCR, Oil Red O staining, mitochondrial staining, and mitochondrial DNA analysis. Results showed that GIP promoted proliferation and inhibited apoptosis of hADSCs via pleiotropic effects. Besides, GIP facilitated de novo beige adipogenesis, by accelerating mitotic clonal expansion (MCE), upregulating core adipogenic regulators (C/EBPα and PPARγ), augmenting beige-related genes (UCP1, PGC1α, and PRDM16), increasing mitochondrial content and improving beige adipocyte functionalities. Above all, our study expands knowledge on the mechanisms of GIP modifying adipogenesis especially in inducing beige adipogenesis, and thus provides a theoretical support for clinical usage of GIP on obesity treatment.

Mid- and Long-Term Efficacy of Surgical Treatment of L1-2 Vertebral Tuberculosis with Subdiaphragmatic Extraperitoneal Approach.

BACKGROUND The L1-2 vertebral segment is the most common site of spinal tuberculosis. Traditional thoracoabdominal surgery in this segment risks trauma and complications. This study analyzed the surgical efficacy of the subdiaphragmatic extraperitoneal approach in the treatment of L1-2 spinal tuberculosis. MATERIAL AND METHODS Retrospective analysis of 67 patients with L1-2 vertebral tuberculosis who underwent posterior internal fixation was performed: 35 patients underwent the subdiaphragmatic extraperitoneal approach (group A) and 32 underwent the thoracoabdominal approach (group B). Operation time, intraoperative blood loss, postoperative hospital stay, postoperative nerve function recovery, deformity correction, bone graft fusion, lesion healing, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complications were observed. RESULTS In group A and group B, intraoperative blood loss was 712.00±64.66 mL and 1104.38±131.34 mL; average operation time was 3.16±0.67 h and 5.16±1.07 h; and postoperative hospital stay was 9.60±2.64 days and 13.69±3.87 days, respectively. At 6 months and 5 years after surgery, neurological function, visual analog scale score, and Cobb angle of all patients were significantly improved compared with those before surgery; ESR and CRP decreased to normal levels; lesions completely cured; and all patients had good bone graft fusion. Pulmonary complications occurred in 2 patients in group A and in 14 patients in group B. CONCLUSIONS The efficacy of subdiaphragmatic extraperitoneal approach was similar to that of the thoracoabdominal approach for L1-2 spinal tuberculosis, but the former has the advantages of less surgical trauma, shorter operation time, less intraoperative bleeding, and fewer postoperative pulmonary complications.

Prior bariatric surgery and perioperative cardiovascular outcomes following noncardiac surgery in patients with type 2 diabetes mellitus: hint from National Inpatient Sample Database.

BACKGROUND: Both diabetes and obesity are risk factors for perioperative major adverse events. This study aims to evaluate the association between prior bariatric surgery (prior-BS) and perioperative cardiovascular outcomes following noncardiac surgery in patients with type 2 diabetes mellitus (T2DM). METHODS: We used the National Inpatient Sample Database to identify T2DM patients undergoing major noncardiac surgery from 2006 to 2014. The primary outcome was major perioperative adverse cardiovascular and cerebrovascular events (MACCEs), which include death, acute myocardial infarction and acute ischaemic stroke. In-hospital outcomes between patients with prior BS and morbid obesity were compared using unadjusted logistic, multivariable logistic and propensity score matching analyses. RESULTS: A weighted of 1,526,820 patients diagnosed with T2DM who underwent noncardiac surgery were included. The rates of both prior BS and morbid obesity significantly increased during the study period (P < 0.0001). Patients with prior BS were younger, were more likely to be female, and had lower rates of cardiovascular risk factors but had higher rates of smoking, alcohol abuse, anaemia, prior venous thromboembolism and prior percutaneous coronary intervention. The incidence of MACCEs was 1.01% and 3.25% in patients with prior BS and morbid obesity, respectively. After multivariable adjustment, we found that prior BS was associated with a reduced risk of MACCEs (odds ratio [OR] = 0.71; 95% confidence interval [CI] 0.62-0.81), death (OR = 0.64, 95% CI 0.52-0.78), acute kidney injury (OR = 0.66, 95% CI 0.62-0.70) and acute respiratory failure (OR: 0.46; 95% CI 0.42-0.50). CONCLUSIONS: Prior bariatric surgery in T2DM patients undergoing noncardiac surgery is associated with a lower risk of MACCEs. Prospective studies are needed to verify the benefits of bariatric surgery in patients undergoing noncardiac surgery.

The methods for inserting lumbar bicortical pedicle screws from the anatomical perspective of the prevertebral great vessels.

BACKGROUND: At present, bicortical pedicle screws (BPSs) are not used clinically because they carry the potential risk of damaging the prevertebral great vessels (PGVs). The authors observed the anatomical relationship between the PGVs and simulated BPSs at different transverse screw angles (TSAs), exploring the insertion method of the BPS. METHODS: Computed tomography angiography (CTA) images from 65 adults were collected. A total of 4-5 TSAs of the BPSs were simulated on the left and right sides of L1-L5 (L1-L3: 0°, 5°, 10°, 15°; L4-L5: 0°, 5°, 10°, 15°, 20°). There were three types of distances from the anterior vertebral cortex (AVC) to the PGVs (DAVC-PGV); DAVC-PGV < 0.50 cm, DAVC-PGV ≥ 0.50 cm, and DAVC-PGV↑; these distances represented close, distant, and noncontact PGV, respectively. RESULTS: The ratio of every type of PGV was calculated, and the appropriate TSA of the BPS was recommended. In L1, the recommended left TSA of the BPS was 0°, and the ratio of the close PGV was 7.69%, while the recommended right TSA was 0°-10°, and the ratio of the close PGV was 1.54-4.62%. In L2, the recommended left TSA of the BPS was 0° and the ratio of the close PGV was 1.54%, while the recommended right TSA was 0°-15° and the ratio of the close PGV was 3.08-9.23%. In L3, the recommended left TSA was 0°-5°, and the ratio of the close PGV was 1.54-4.62%. In L4, the recommended left TSA was 0°, and the ratio of the close PGV was 4.62%. BPS use was not recommended on the right side of either L3 or L4 or on the either side of L5. CONCLUSIONS: From the anatomical perspective of the PGVs, BPSs were not suitable for insertion into every lumbar vertebra. Furthermore, the recommended methods for inserting BPSs were different in L1-L4.

Dipeptidyl peptidase-4 (DPP-4): Localization and activity in human and rodent islets.

Dipeptidyl peptidase 4 (DPP-4) was recently found to be expressed in human and mouse islets with different expression patterns. However, whether species-dependent expression pattern is a generalized phenomenon and whether islet DPP-4 activity is regulated are not known. This study was conducted to investigate DPP-4 localization in several different species, and to examine the impact of glucose, incretin hormones, and insulin on islet DPP-4 activity. It was shown by immuofluorescent staining that there were two distinct species-specific expression patterns of islet DPP-4. The enzyme was expressed exclusively in α-cells in human and pig islets, but primarily in ß-cells in mouse and rat islets. INS-1 832/13 cells also expressed DPP-4, and inhibition of DPP-4 enhanced insulin secretion in the presence of glucagon-like peptide-1 (GLP-1) in the cells. DPP-4 activity was remarkably robust when cultured with high glucose, incretin hormones, and insulin in mouse and human islets as well as INS-1 832/13 cells and islet DPP-4 activity and expression pattern was not altered in double incretin receptor knockout mice, compared to wild type mice. We conclude that islet DPP-4 is species-specifically expressed in α-cell and ß-cell dominant patterns in several species and both patterns remained robust in enzyme activity during short-term metabolic challenge.

Biomechanical comparison of anterior lumbar screw-plate fixation versus posterior lumbar pedicle screw fixation.

Anterior lumbar interbody fusion (ALIF) followed by posterior pedicle screw fixation (PSF) in a second procedure is mostly used to implement lumbar spine fusion. ALIF followed by anterior lumbar screw-plate has a lot of advantages, but its biomechanical stability requires confirmation. This study evaluated the biomechanical stability of a novel anterior lumbar locked screw-plate (ALLSP) by comparison with posterior lumbar PSF. Twelve fresh human cadaveric lumbar specimens (L4-L5) were assigned to four groups: ALIF+PSF group, ALIF+ALLSP (both fixed) group, ALIF group and an untreated control (both non-fixed) group. The first three groups received implantation of a rectangular titanium cage. Tests under axial compression, flexion, extension, lateral bending, or rotation showed that the fixed groups had significantly stronger stability than the non-fixed groups (P=0.000 for all). The ALIF+ALLSP group had significantly greater axial stiffness under applied axial compression and significantly less angular displacement under rotational forces than the ALIF+PSF group. The angular displacement of the ALIF+ALLSP group was less under flexion than that of the ALIF+PSF, and the angular displacement under lateral bending and extension was greater, but these differences were not statistically significant. In summary, the ALLSP conforms to the anterior lumbar spine and has good biomechanical stability. It is a reliable choice for enhancing the stability of ALIF.

Study on the anatomy of the lumbosacral anterior great vessels pertinent to L5/S1 anterior interbody surgery with computer tomography angiography.

We investigate the anatomy of the lumbosacral anterior great vessels using computer tomography (CT) angiography before L5/S1 anterior interbody surgery. Sixty-two adult patients were selected. The location of the abdominal aortic bifurcation and common iliac venous confluence in the lumbar vertebrae and the anatomic parameters of the iliac vascular space (e.g., distances from the included angle vertex of the iliac vascular space to the median sagittal plane and to the inferior boundary of L5 and distances between the left and right iliac vessels on the inferior boundary of L5 and on the superior boundary of S1) were analysed. Overall, 67.73% of the 62 cases had an abdominal aortic bifurcation located at L4 and L4/5 intervertebral disc; 61.29%, the common iliac venous confluence located at L5. The four distances mentioned above were 0.98 cm ± 0.38 cm, 2.01 cm ± 1.26 cm, 3.11 cm ± 1.35 cm and 4.34 cm ± 1.10 cm, respectively. A classification system of types A, B and C was developed. The calculated L5/S1 intervertebral space exposure percentages of types A, B and C were 32.21%, 82.58% and 54.68%, respectively. During L5/S1 anterior interbody surgery, type B intervertebral discs can be exposed conveniently, preventing injury of the iliac vessels, which was also observed in 54.68% and 32.21% of the type C and type A discs, respectively. Because the type A intervertebral disc has minimal exposure, the risk of iliac vascular injury is relatively high in these patients.

Decreased circulating dipeptidyl peptidase-4 activity after short-term intensive insulin therapy predicts clinical outcomes in patients with newly diagnosed type 2 diabetes.

Background: This study aims to investigate the changes in circulating dipeptidyl peptidase-4 (DPP-4) activity following short-term intensive insulin therapy (SIIT) in newly diagnosed type 2 diabetes (T2D) patients and to assess its potential in predicting long-term remission. Methods: Ninety-five patients underwent SIIT for 2-3 weeks to attain and sustain near-normal glycemia. Insulin was then discontinued, and patients were followed for a year to evaluate glycemic outcomes. Biochemical tests, serum DPP-4 activity, and mixed meal tolerance tests were conducted at baseline, post-SIIT, and the 3-month follow-up. Results: DPP-4 activity decreased from 44.08 ± 9.58 to 40.53 ± 8.83 nmol/min/mL after SIIT (P<0.001). After three months post-SIIT, DPP-4 activity remained stable in the remission group (39.63 ± 8.53 nmol/L) but increased in the non-remission group (42.34 ± 6.64 nmol/L). This resulted in a more pronounced decrease in DPP-4 activity from baseline in the remission group (-3.39 ± 8.90 vs. -1.10 ± 8.95, P = 0.035). Logistic regression analyses showed that patients with greater DPP-4 activity reduction had a higher likelihood of 1-year remission (70% vs. 51.1%, OR: 7.939 [1.829, 34.467], P = 0.006 in the fully adjusted model). A non-linear relationship between △DPP-4 and 1-year remission rate was observed, with a clear threshold and saturation effect. Conclusion: Circulating DPP-4 activity significantly decreases after SIIT. The change in circulating DPP-4 activity during the 3-month post-treatment phase has the potential to predict long-term remission.

Fasting plasma glucose after intensive insulin therapy predicted long-term glycemic control in newly diagnosed type 2 diabetic patients.

Short term intensive insulin therapy has been reported to induce long term euglycemia remission in patients with newly diagnosed type 2 diabetes mellitus, but the factors that are responsible for long-term remission or hyperglycemia relapse are unknown. Original data of 188 patients with newly diagnosed type 2 diabetes treated with short term intensive insulin therapy was reanalyzed. Patients who maintained glycemic control for 12 months with only life style intervention were defined as remission while those who failed to maintain glycemic control for 12 months as hyperglycemia relapse. Relationships of metabolic control, ß cell function and insulin sensitivity with remission time and hyperglycemia relapse were explored. Totally 93 patients achieved 12-month euglycemic remission. Substantial improvement in blood glucose, parameters of ß cell function and insulin sensitivity were obtained in both remission and relapse patients. The duration of remission was correlated with fasting plasma glucose measured after cessation of continuous subcutaneous insulin infusion (CSII) therapy (fasting plasma glucose (FPG) after CSII, r= -0.349, p<0.0001). Multivariate logistic regression show that FPG after CSII was independent predictor of hyperglycemic relapse (Odds ratio=1.585, p=0.001). All patients were stratified into three groups according FPG after CSII. As multivariate Cox proportional hazards regression demonstrated, compared with the patients with FPG<6.1mmol/L, risk for hyperglycemia relapse was increased 60% in those with 6.1 mmol/L≤FPG≤7.0 mmol/L (Hazard ratio=1.60, p=0.049), and 1.69 folds in those with FPG>7.0 mmol/L (Hazard ratio=2.69, p<0.0001). Our study demonstrated that fasting plasma glucose after intensive insulin therapy is a convenient and significant predictor for hyperglycemic relapse.

Efficacy and Safety of Meal Replacement in Patients With Type 2 Diabetes.

CONTEXT: Meal replacement (MR) is beneficial for the management of type 2 diabetes (T2D). However, MR prescription and patient characteristics vary substantially between studies using MR in T2D patients. OBJECTIVE: This work aimed to evaluate the efficacy and safety of MR in T2D patients by meta-analysis, with a focus on subgroup analysis of variable participant characteristics and MR prescription. METHODS: We searched PubMed, CENTRAL, Embase, Web of Science, and the clinical trial registration database up to March 2022. We included randomized controlled trials (RCTs) of 2 weeks or more assessing the effect and safety of MR in T2D patients in comparison with conventional diabetic diets (CDs). RESULTS: A total of 17 RCTs involving 2112 participants were ultimately included. Compared with CDs, MR significantly reduced glycated hemoglobin A1c (HbA1c) (MD -0.46%; P < .001), fasting blood glucose (FBG, -0.62 mmol/L; P < .001), body weight (-2.43 kg; P < .001), and body mass index (BMI, -0.65; P < .001), and improved other cardiometabolic risk factors. In subgroup analyses, total MR showed greater improvement in HbA1c (-0.72% vs -0.32%; P = .01), FBG (-1.45 vs -0.56 mmol/L; P = .02), body weight (-6.57 vs -1.58 kg; P < .001), and BMI (-2.78 vs -0.37; P < .001) than partial MR. MR with caloric restriction showed more reduction in body weight (-3.20 vs -0.75 kg; P < .001) and BMI (-0.84 vs -0.24; P = .003) compared with those without caloric restriction. MR showed similar benefits in studies that included patients using insulin and those that did not. Both partial and total MR were well tolerated. CONCLUSION: Compared with CDs, the MR-based dietary pattern further improved the glycemic control and adipose indicators in T2D patients. Appropriate calorie restriction and total MR might be more beneficial, while both patients treated with or without insulin treatment could similarly benefit from MR usage.

Evaluating the role of time in range as a glycemic target during short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes.

BACKGROUND: Tight glycemic control during short-term intensive insulin therapy (SIIT) is critical for inducing diabetes remission in patients with newly diagnosed type 2 diabetes (T2D). This work aimed to investigate the role of time in range (TIR) during SIIT as a novel glycemic target by predicting clinical outcomes. METHODS: SIIT was given to 116 patients with newly diagnosed T2D, with daily eight-point capillary glucose monitored. Glycemic targets (fasting/premeal glucose, 3.9-6.0 mmol/L; 2 h postprandial blood glucose, 3.9-7.8 mmol/L) were achieved and maintained for 2 weeks. TIRPIR was calculated as the percentage of glucose points within these glycemic targets during the maintenance period and was compared to TIR3.9-7.8mmol/L and TIR3.9-10.0mmol/L . Acute insulin response (AIR), HOMA-IR, HOMA-B, and disposition index (DI) were measured. Patients were followed up for 1 year to observe clinical outcomes. RESULTS: TIRPIR , TIR3.9-7.8mmol/L , and TIR3.9-10.0mmol/L were 67.2 ± 11.2%, 80.8 ± 9.2%, and 90.1 ± 6.2%, respectively. After SIIT, ß-cell function and insulin sensitivity improved remarkably, and the 1-year remission rate was 55.2%. △AIR and △DI were positively correlated with all the TIR values, whereas only TIRPIR was correlated with △HOMA-IR (r = -0.22, p = 0.03). Higher TIRPIR but not TIR3.9-7.8mmol/L or TIR3.9-10.0mmol/L was robustly associated with diabetes remission; patients in the lower TIRPIR tertile had an elevated risk of hyperglycemia relapse (hazard ratio 3.4, 95% confidence interval 1.6-7.2， p = .001). Only those with TIRPIR ≥ 65% had a one-year remission rate of over 60%. CONCLUSIONS: These findings advocate TIRPIR ≥ 65% as a novel glycemic target during SIIT for clinical decision-making.

Injectable, Hierarchically Degraded Bioactive Scaffold for Bone Regeneration.

Bioactive materials play vital roles in the repair of critical bone defects. However, bone tissue engineering and regenerative medicine are still challenged by the need to repair bone defects evenly and completely. In this study, we functionally simulated the natural creeping substitution process of autologous bone repair by constructing an injectable, hierarchically degradable bioactive scaffold with a composite hydrogel, decalcified bone matrix (DBM) particles, and bone morphogenetic protein 2. This composite scaffold exhibited superior mechanical properties. The scaffold promoted cell proliferation and osteogenic differentiation through multiple signaling pathways. The hierarchical degradation rates of the crosslinked hydrogel and DBM particles accelerated tissue ingrowth and bone formation with a naturally woven bone-like structure in vivo. In the rat calvarial critical defect repair model, the composite scaffold provided even and complete repair of the entire defect area while also integrating the new and host bone effectively. Our results indicate that this injectable, hierarchically degradable bioactive scaffold promotes bone regeneration and provides a promising strategy for evenly and completely repairing the bone defects.

A plasma 3-marker microRNA biosignature distinguishes spinal tuberculosis from other spinal destructive diseases and pulmonary tuberculosis.

Accurate spinal tuberculosis (TB) diagnosis is of utmost importance for adequately treating and managing the disease. Given the need for additional diagnostic tools, this study aimed to investigate the utility of host serum miRNA biomarkers for diagnosing and distinguishing spinal tuberculosis (STB) from pulmonary tuberculosis (PTB) and other spinal diseases of different origins (SDD). For a case-controlled investigation, a total of 423 subjects were voluntarily recruited, with 157 cases of STB, 83 cases of SDD, 30 cases of active PTB, and 153 cases of healthy controls (CONT) in 4 clinical centers. To discover the STB-specific miRNA biosignature, a high-throughput miRNA profiling study was performed in the pilot study with 12 cases of STB and 8 cases of CONT using the Exiqon miRNA PCR array platform. A bioinformatics study identified that the 3-plasma miRNA combination (hsa-miR-506-3p, hsa-miR-543, hsa-miR-195-5p) might serve as a candidate biomarker for STB. The subsequent training study developed the diagnostic model using multivariate logistic regression in training data sets, including CONT(n=100) and STB (n=100). Youden's J index determined the optimal classification threshold. Receiver Operating Characteristic (ROC) curve analysis showed that 3-plasma miRNA biomarker signatures have an area under the curve (AUC) = 0.87, sensitivity = 80.5%, and specificity = 80.0%. To explore the possible potential to distinguish spinal TB from PDB and other SDD, the diagnostic model with the same classification threshold was applied to the analysis of the independent validation data set, including CONT(n=45), STB(n=45), brucellosis spondylitis (BS, n=30), PTB (n=30), spinal tumor (ST, n=30) and pyogenic spondylitis (PS, n=23). The results showed diagnostic model based on three miRNA signatures could discriminate the STB from other SDD groups with sensitivity=80%, specificity=96%, Positive Predictive Value (PPV)=84%, Negative Predictive Value (NPV)=94%, the total accuracy rate of 92%. These results indicate that this 3-plasma miRNA biomarker signature could effectively discriminate the STB from other spinal destructive diseases and pulmonary tuberculosis. The present study shows that the diagnostic model based on 3-plasma miRNA biomarker signature (hsa-miR-506-3p, hsa-miR-543, hsa-miR-195-5p) may be used for medical guidance to discriminate the STB from other spinal destructive disease and pulmonary tuberculosis.

Plasma extrachromosomal circular DNA is a pathophysiological hallmark of short-term intensive insulin therapy for type 2 diabetes.

BACKGROUND: Extrachromosomal circular DNA (eccDNA) has emerged as a promising biomarker for disease diagnosis and prognosis prediction. However, its role in type 2 diabetes remains unexplored. OBJECTIVE: To investigate the characteristics and dynamics of circulating eccDNAs in newly diagnosed type 2 diabetes mellitus (T2DM) patients undergoing short-term intensive insulin therapy (SIIT), a highly effective treatment for inducing long-term glycemic remission. METHODS: We conducted Circle-Seq analysis on plasma samples from 35 T2DM patients at three time points: pre-SIIT, post-SIIT, and 1-year post-SIIT. Our analysis encompassed the characterization of eccDNA features, including GC content, eccDNA length distribution, genomic distribution, and the genes in eccDNAs. RESULTS: Following SIIT, we observed an increase in plasma eccDNA load, suggesting metabolic alterations during therapy. Notably, a correlation was identified between eccDNA profiles and glycemia in T2DM, both quantitatively and genetically. Our analysis also revealed the frequent presence of metabolism-related genes within T2DM plasma eccDNAs, some of which spanned gene exons and/or fractions. CONCLUSION: This study represents the first report of cell-free eccDNA in T2DM and underscores a compelling association between cell-free eccDNA and profound glycemic changes. These findings highlight the potential of eccDNAs as crucial players in the context of T2DM and glycemic control.

Steroidogenic factor 1 protects mice from obesity-induced glucose intolerance via improving glucose-stimulated insulin secretion by beta cells.

As a potential druggable nuclear receptor, steroidogenic factor 1 (SF1) regulates obesity and insulin resistance in the ventromedial hypothalamic nucleus. Herein, we sought to demonstrate its expression and functions in islets in the development of obesity-induced diabetes. SF1 was barely detected in the beta cells of lean mice but highly expressed in those of non-diabetic obese mice, while decreased in diabetic ones. Conditional deletion of SF1 in beta cells predisposed diet-induced obese (DIO) mice to glucose intolerance by perturbing glucose-stimulated insulin secretion (GSIS). Consistently, forced expression of SF1 restored favorable glucose homeostasis in DIO and db/db mice by improving GSIS. In isolated islets and MIN6, overexpression of SF1 also potentiated GSIS, mediated by improvement of mitochondrial ATP production. The underlying mechanisms may involve oxidative phosphorylation and lipid metabolism. Collectively, SF1 in beta cell preserves GSIS to promote beta-cell adaptation to obesity and hence is a potential therapeutic target for obesity-induced diabetes.

Clinical expert consensus on the assessment and protection of pancreatic islet ß-cell function in type 2 diabetes mellitus.

Islet ß-cell dysfunction is a basic pathophysiological characteristic of type 2 diabetes mellitus (T2DM). Appropriate assessment of islet ß-cell function is beneficial to better management of T2DM. Protecting islet ß-cell function is vital to delay the progress of type 2 diabetes mellitus. Therefore, the Pancreatic Islet ß-cell Expert Panel of the Chinese Diabetes Society and Endocrinology Society of Jiangsu Medical Association organized experts to draft the "Clinical expert consensus on the assessment and protection of pancreatic islet ß-cell function in type 2 diabetes mellitus." This consensus suggests that ß-cell function can be clinically assessed using blood glucose-based methods or methods that combine blood glucose and endogenous insulin or C-peptide levels. Some measures, including weight loss and early and sustained euglycemia control, could effectively protect islet ß-cell function, and some newly developed drugs, such as Sodium-glucose cotransporter-2 inhibitor and Glucagon-like peptide-1 receptor agonists, could improve islet ß-cell function, independent of glycemic control.

Surgical Reduction and Direct Repair Using Pedicle Screw-Rod-Hook Fixation in Adult Patients with Low-Grade Isthmic Spondylolisthesis.

Background: Although direct pars repair using a pedicle screw-rod-hook system has achieved satisfactory results in patients with spondylolysis, its application in adults with low-grade isthmic spondylolisthesis is rarely reported. Objective: To assess the surgical effect of reduction and direct repair surgery with a pedicle screw-rod-hook system combined with autogenous bone grafts in adult patients with low-grade isthmic spondylolisthesis. Methods: Sixty-four adult patients with low-grade isthmic spondylolisthesis underwent reduction and direct repair using a pedicle screw-rod-hook system in our department from September 2009 to April 2018. The clinical efficacy was evaluated by clinical and radiological assessments. Results: The average follow-up was 52.15 ± 9.96 months. The visual analog scale (VAS) scores (VAS-lumbar and VAS-leg) and Oswestry Disability Index (ODI) at the final follow-up (FFU) were significantly lower than the preoperative levels (P < 0.05). The modified Prolo score was "excellent" for 60 patients (93.75%) and "good" for 4 patients (6.25%). The slip distance and slipping percentage showed significant decreases postoperatively and FFU compared to preoperatively (P < 0.05). There were no significant differences in the disc height, slip angle, and range of motion of the surgical intervertebral space or upper intervertebral space between preoperation and FFU (P < 0.05). Successful bony fusion had a 96.86% success rate. Conclusion: Reduction of slip and direct repair using pedicle screw-rod-hook fixation combined with autogenous iliac bone grafting in adult patients with low-grade isthmic spondylolisthesis is a safe and effective technique.

Soil conditions on bacterial wilt disease affect bacterial and fungal assemblage in the rhizosphere.

Natural soil has the ability to suppress the soil-borne pathogen to a certain extent, and the assemblage of soil microbiome plays a crucial role in maintaining such ability. Long-term monoculture accelerates the forms of soil microbiome and leads to either disease conducive or suppressive soils. Here, we explored the impact of soil conditions on bacterial wilt disease (healthy or diseased) under long-term tobacco monoculture on the assemblage of bacterial and fungal communities in bulk and rhizosphere soils during the growth periods. With Illumina sequencing, we compared the bacterial and fungal composition of soil samples from tobacco bacterial wilt diseased fields and healthy fields in three growth periods. We found that Proteobacteria and Ascomycota were the most abundant phylum for bacteria and fungi, respectively. Factors of soil conditions and tobacco growth periods can significantly influence the microbial composition in bulk soil samples, while the factor of soil conditions mainly determined the microbial composition in rhizosphere soil samples. Next, rhizosphere samples were further analyzed with LEfSe to determine the discriminative taxa affected by the factor of soil conditions. For bacteria, the genus Ralstonia was found in the diseased soils, whereas the genus Flavobacterium was the only shared taxon in healthy soils; for fungi, the genus Chaetomium was the most significant taxon in healthy soils. Besides, network analysis confirmed that the topologies of networks of healthy soils were higher than that of diseased soils. Together, our results suggest that microbial assemblage in the rhizosphere will be largely affected by soil conditions especially after long-term monoculture.

miR-1275 Inhibits Human Omental Adipose-Derived Stem Cells Differentiation Toward the Beige Phenotype via PRDM16.

Beige adipocytes have recently attracted attention for their potential as new therapeutic targets in the management of obesity and related metabolic disorders. MicroRNAs (miRNAs) have been reported as transcriptional regulators or biomarkers of brown and beige adipogenesis. Nevertheless, the effects of miRNAs involved in beige differentiation of human visceral adipocytes remain to be investigated. In this study, microarray screening showed that miR-1275 was significantly decreased during the differentiation of beige adipocytes induced by human omental adipose-derived stem cells (hASCs). Overexpression of miR-1275 suppressed the "brown-like" differentiation of hASCs by inhibiting the key transcriptional factor PR domain containing 16 (PRDM16) without affecting the proliferation. Adipogenesis and mitochondrial biogenesis of beige adipocytes derived from hASCs were impaired by miR-1275 overexpression. The regulatory effect of miR-1275 was determined by direct binding to the 3'-untranslated region of PRDM16, which was demonstrated by a dual-luciferase assay. Taken together, this study identified miR-1275 as a negative regulator of beige cell development in hASCs by inhibiting PRDM16. Thus, miR-1275 might be a potential target in the management of visceral obesity and related metabolic diseases.