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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Spheroid Formation Enhances the Regenerative Capacity of Nucleus Pulposus Cells via Regulating N-CDH and ITGß1 Interaction.

Background: Nucleus pulposus (NP) degeneration is the core pathological change of intervertebral disc (IVD) degenerative diseases, but currently, no effective therapy is available. With the rapid development of biomaterials and tissue engineering in recent years, biomaterial-assisted cell transplantation becomes a promising therapy for IVD degeneration. However, the application is severely limited by the weak biological characteristics of NP cells (NPCs), such as a moderate proliferation ability, weak self-renewal capacity, and minimal extracellular matrix (ECM) synthesis capacity, caused by the current inappropriate cell seeding or grafting methods. Methods: Here, we developed a three-dimensional (3D) spheroidizing culture method to construct NPC spheroids and investigated repair and regeneration potential of these spheroids in vitro and in vivo. The in vitro biological characteristics (including cell viability and proliferation), and in vivo functions (including anti-degeneration potential and ability to induce tissue repair) of NPC spheroids and monolayer-cultured NPCs were compared. Furthermore, an RNA-seq-based transcriptome analysis and a series of function experiments were performed to elucidate the potential mechanisms of their differences that were involved in the tissue regeneration process. Results: NPC spheroids exhibited obviously superior self-renewal and ECM synthesis capacities compared to monolayers of NPCs in vitro. In vivo, NPC spheroids generated more functional ECM components, primarily aggrecan (ACAN) and collagen type II (Col2), and markedly promoted NP regeneration in the disc degeneration model induced by partial NP excision. Additionally, the biological characteristics and functions of NPC spheroids were to some extent regulated by the interaction of N-cadherin (N-CDH) and Integrinß1 (ITGß1), two key mechanosensing ECM-receptors expressed on NPCs. Conclusions: The NPC spheroidizing culture method is beneficial for cell renewal and the generation of functional ECM in NP tissue. The molecular mechanism involved in this regeneration process is closely associated with the regulation of the N-CDH and ITGß1 interaction-mediated ECM homeostesis. Moreover, the strategy of hydrogel-assisted NPC spheroids transplantation may potentially be used in the future treatment of IVD degeneration.

Comparison between Dynamic Stabilization and Instrumented Fusion in the Treatment of Spinal Stenosis with Degenerative Lumbar Scoliosis.

Objective: Posterior instrumented fusion is the most widely accepted surgical treatment for spinal stenosis with degenerative lumbar scoliosis (DLS). However, long fusion can affect daily activities due to lumbar stiffness. Dynamic stabilization has been introduced to overcome the drawbacks of fusion in recent years. This study aimed to compare the outcomes of dynamic stabilization (Dynesys system) with posterior instrumented fusion for the management of spinal stenosis with DLS. Methods: This study retrospectively reviewed 65 consecutive patients with spinal stenosis and DLS who were undergoing surgical treatment between January 2013 and December 2017. Among them, 34 patients (Dynesys group) had fenestration decompression and Dynesys stabilization, whereas 31 patients (fusion group) underwent posterior instrumented fusion. Clinical outcomes, radiographic data, and postoperative complications were compared between the two groups. Results: The mean number of fixed segments was 3.6 ± 0.9 in the Dynesys group and 4.2 ± 1.0 in the fusion group. Lower average values of operating time and blood loss were observed in the Dynesys group (P < 0.05). At an average follow-up of 42 months, there were no significant differences in the visual analog scale for the leg pain (VASleg), the scoliosis Cobb's angle, and the lumbar lordosis between the two groups (P > 0.05). The visual analog scale for back pain (VASback), oswestry disability index (ODI), and lumbar stiffness disability index (LSDI) scores of the Dynesys group were lower compared with the fusion group (P < 0.05). The range of motion (ROM) of implanted segments was significantly higher in the Dynesys group as compared to the fusion group (P < 0.05). The overall complications were less in the Dynesys group, but the difference was not statistically significant (P > 0.05). Conclusion: Both dynamic stabilization and instrumented fusion can improve the clinical outcomes of patients with spinal stenosis and mild DLS. Compared to instrumented fusion, dynamic stabilization has the advantages of less invasion and motion preservation.

A Modified Transverse Process-Pedicle Approach Applied to Unilateral Extrapedicular Percutaneous Vertebroplasty.

OBJECTIVE: To introduce a modified transverse process-pedicle puncture technique applied to unilateral extrapedicular percutaneous vertebroplasty (PVP) for the treatment of osteoporotic lumbar vertebral compression fractures. METHODS: A retrospective study was performed on 91 patients with osteoporotic vertebral compression fractures (OVCFs) who underwent unilateral extrapedicular PVP from June 2016 to September 2018. Lumbar and back pain was assessed through the visual analogue scale (VAS). Function recovery was assessed through the Oswestry disability index (ODI). Radiologic outcomes were assessed mainly on the basis of bone cement distribution and anterior vertebral height. RESULTS: A total of 101 fractured vertebrae were successfully treated using the extrapedicular technique without any recognized clinical complications. The postoperative VAS and ODI values were significantly lower than the corresponding preoperative values (P < 0.01). Radiologic outcomes in all fractured vertebrae showed that the diffusion of bone cement could exceed the midline of the vertebral body. There was no significant difference between preoperative and postoperative anterior vertebral heights (P < 0.05). CONCLUSION: The modified transverse process-pedicle approach applied to unilateral extrapedicular percutaneous vertebroplasty is a simple, safe, and effective surgical method.

Postoperative Management Strategy of Surgical Site Infection following Lumbar Dynesys Dynamic Internal Fixation.

AIM: To research the incidence of surgical site infection (SSI) following lumbar Dynesys dynamic internal fixation and its management strategy. METHODS: We retrospectively analyzed all cases of lumbar Dynesys dynamic internal fixation performed from January 2010 to December 2019, and the data from patients with SSI were collected. The observational indicators included the incidence of SSI, general information of the patients, surgical details, inflammatory indicators, pathogenic bacteria, and treatment. SSI was defined as both early infection and delayed infection, and the cases were divided into Groups A and B, respectively. The relevant indicators and treatment were compared between the two groups. RESULTS: A total of 1125 cases of lumbar Dynesys dynamic internal fixation were followed up. Twenty-five cases of SSI occurred, and the incidence of SSI was 2.22% (25/1125). There were 14 cases of early infection (1.24%) and 11 cases of delayed infection (0.98%). Fourteen cases of early infection occurred 12.3 ± 8.3 days postoperatively (3-30), and 11 cases of delayed infection occurred 33.3 ± 18.9 months postoperatively (3-62). The inflammatory indicators of Group A were significantly higher than those of Group B (all P < 0.05), except for procalcitonin. The main infection site in Group A was located on the skin and subcutaneous tissue and around the internal instrument, while the main infection site in Group B was around the internal instrument. The main treatment for Group A was debridement and implant replacement, and the main treatment for Group B was implant removal. Summary. The incidence of SSI following lumbar Dynesys dynamic internal fixation was 2.22%, the incidence of early SSI was 1.24%, and the incidence of delayed SSI was 0.98%. If the main infection site of early infection is in the incision, debridement should be the main treatment method; if the infection site is around the internal fixation, implant replacement is recommended on the basis of debridement. Once delayed infection is diagnosed, implant removal is suggested.

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.

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.

The Physiological Significance of A-Waves in Early Diabetic Neuropathy: Assessment of Motor Nerve Fibers by Neurophysiological Techniques.

Objective: This study aimed to investigate how early A-waves could occur in type II diabetes, and what it implied functionally. Methods: We performed conduction velocity distribution (CVD) test in peroneal nerves of 37 type II diabetic patients with normal nerve conduction study (NCS) and 22 age-matched controls. The electrophysiological data and clinical information were analyzed. Results: A-waves were observed in 45.9% of diabetic patients and only in 1 person in healthy controls, all detected in the tibial nerves. The diabetic patients with A-waves showed faster conduction velocity in all quartiles in the motor peroneal nerves compared to the patients without A-waves, and their CVD histograms were shifted to the right side, consisting of a significantly larger percentage of fast conducting fibers. There was no significant difference in the CVD values of the upper extremity nerves among the patients with and without A-waves and the healthy controls. Conclusion: A-waves could occur in type II diabetes as early as when NCS showed normal, and represented as a sign of neuropathy as well as a sign of rescued motor nerve function.

Single-cell transcriptomic landscape reveals the differences in cell differentiation and immune microenvironment of papillary thyroid carcinoma between genders.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the main pathological type of thyroid carcinoma (TC). Gender is a prominent background parameter for patients with PTC. Here, we aimed to delineate the differences in cell clusters and immune microenvironment in relation to gender in PTC. METHODS: We generated 6720, 14,666, and 33,373 single-cell transcriptomes that were pooled from the tissues of four male patients with PTC, seven female patients with PTC, and three patients with nodular goiter, respectively. We performed single-cell RNA-sequencing (scRNA-seq) based on BD Rhapsody and characterized the first single-cell transcriptomic landscape of PTC involving gender. The differential cell clusters and their gene profiles were identified and analyzed via a multi-resolution network in male and female patients. The interactions of fibroblasts and endothelial cells with malignant epithelial cells and the difference in the immune infiltration of B and T lymphocytes according to gender were assessed. RESULTS: Malignant epithelial cells were divided into two distinct subsets in male and female patients with PTC. Moreover, significant differences involving inferred copy-number variations (CNVs), gene profiles, and cell differentiation were detected between male and female patients. Regarding the interactions of fibroblasts and endothelial cells with malignant epithelial cells, members of the human leukocyte antigen (HLA) family and their receptors were considered as typical in female patients with PTC, while transforming growth factor beta 1 (TGFB1) and its receptors were typical of male patients with PTC. The characteristics of B cells, including cell clusters, cell differentiation, and dominant gene sets, were significantly different between genders. CONCLUSIONS: Our data revealed the detailed differences in cell clusters and immune microenvironment in PTC according to gender at the single-cell level, which provided new insights into the understanding of the impact of gender on PTC.