Comparison of En Bloc Resection and Intralesional Excision for Re-resection of Giant Cell Tumors of the Spine.

OBJECTIVE: Re-resection of spinal giant cell tumors is an exceedingly difficult procedure. Moreover, the prognosis of patients with en bloc resection or intralesional excision for re-resection has rarely been reported. This study aimed to compare the prognostic value of en bloc resection with that of intralesional excision in patients undergoing re-resection for giant cell tumors of the spine. METHODS: This retrospective analysis evaluated patients who underwent revision surgeries for relapse of giant cell tumors of the spine at our center between January 2005 and January 2021. Local progression-free survival represents the duration between en bloc resection or intralesional excision and tumor recurrence. Neurological recovery, survival rates, local control, and complications were evaluated. The Kaplan-Meier estimator was used for survival analysis. RESULTS: A total of 22 patients (nine men and 13 women) with a mean age of 34.1 (range 19-63) years were included. Significant statistical differences were found in the local tumor recurrence rate between patients treated with en bloc resection and those treated with intralesional excision (p < 0.05). The 5- and 10-year local progression-free survival rates were both 90% in the en bloc resection group, while in the intralesional excision group, the 5-year local progression-free survival rate was 80% with a 10-year rate of 45.7%. The en bloc resection group had a lower local tumor recurrence rate than that of the intralesional excision group (p < 0.05), but the former had a higher rate of complications (p = 0.015). CONCLUSIONS: This study revealed a low local recurrence rate in patients who underwent en bloc resection for giant cell tumors, while the perioperative complication rate was high.

Congenital Cervical Scoliosis Treated with Concave Side Distraction with Three-Dimensional Printed Titanium Cage.

STUDY DESIGN: Single-center, retrospective study. OBJECTIVE: Hemivertebra resection is the only treatment option for congenital cervical scoliosis (CCS). However, this procedure is complex and technically demanding. It often requires a considerably long operation, and there is substantial intraoperative bleeding. Therefore, we have attempted to treat CCS with a concave side distraction comprising a three-dimensional (3D) printed titanium cage. The purpose of this study is to evaluate the safety and efficacy of this technique for the treatment of patients with CCS. METHODS: A series of 22 patients with CCS who underwent a concave side distraction technique between 2019 and 2021 were retrospectively reviewed and analyzed. Radiological measurements included the Cobb angle of the distraction segments, the kyphosis angle, the range of movement, and the distraction correction angle. Student's t-test and Spearman correlation analysis were used for statistical analysis. p < 0.05 was considered statistically significant. RESULTS: The study included 12 males and 10 females whose ages ranged from 6 to 14 years old (9.8 ± 2.1 years old). Follow-up times ranged from 15 to 30 months (25.8 ± 3.6 months). Among 22 patients, two patients developed a postoperative C5 nerve root palsy and recovered after being treated with conservative treatment for 6 months. The duration of surgery ranged from 229 to 756 min (389 ± 112 min), and the estimated volume of blood loss ranged from 100 to 600mL (235 ± 121 mL). The coronal Cobb angle (p < 0.001), kyphosis angle (p < 0.05), and range of movement (p < 0.001) between the last follow-up and preoperative period were significantly different. A total of 28 segments were distracted, and the Cobb angle of the distraction segment ranged from 2.4 to 14.1° (8.5 ± 3.0°). There were six upper cervical spines (8.9 ± 1.9°) and 22 lower cervical spines (8.4 ± 3.2°) with no significant difference between them (p = 0.130). In addition, there was no correlation between the angle of the concave side distraction and patients' age (r = 0.018, p = 0.315). The fusion was solid between the bone and the customized 3D-printed pore metal cage at the final follow-up. CONCLUSION: The concave side distraction comprising a customized 3D-printed titanium cage implantation can provide satisfactory correction results and is a safe and reliable procedure for treating CCS.

Surgery for metastatic spinal differentiated thyroid cancer: feasibility, outcome, and prognostic factors.

Study design: A retrospective cohort study. Objectives: This study aims to report the surgical outcome of metastatic spinal differentiated thyroid cancer (MSDTC) and analyze the factors affecting the prognosis. Methods: Thirty-five patients were recruited in our single institution who underwent spinal surgery and adjuvant therapies from 2009 to 2019. Two surgical procedures, total en-bloc spondylectomy and debulking surgery, were undertaken. Their clinical data, postoperative events, and survival data were collected and analyzed. Survival time and associated factors were further analyzed. Results: The cohort had a median survival time of 60 months. The mean visual analog scale scores and the Karnofsky performance score improved postoperatively (p < 0.05). The patients' Frankel grade was elevated for cases with preoperative neurological deficits (p < 0.05). In 31 patients who underwent debulking surgery, 41.9% (n = 13) had local recurrences, and radiotherapy reduced the risk of local relapse (p < 0.05). Preoperative and postoperative Frankel grades and radioactive iodine (RAI) therapy were associated with the patients' survival in the univariate analysis (p < 0.05). Furthermore, a multivariate regression analysis showed the postoperative Frankel grade as an independent prognostic factor. Conclusion: Pain, quality of life, and neurological status of patients can be effectively improved after surgery. Radiotherapy can reduce the risk of local recurrences, whereas RAI therapy has a limited effect on local and extraspinal tumor control. Neurological status was independently associated with the patients' survival.

Implant Materials for Anterior Column Reconstruction of Cervical Spine Tumor.

The spine is the most common site of bone metastases. Many cancer patients will ultimately develop spinal metastatic disease with symptomatic epidural spinal cord compression. At present, the main treatment for cervical spine tumors is surgical resection combined with postoperative radiotherapy. Implant materials for cervical spine anterior column reconstruction need to meet amounts of different properties, such as biocompatibility, bioactivity and the ability to maintain long-term mechanical strength. The selection of different materials determines the surgical efficacy and prognosis of patients to a certain extent. This article provides an overview of a variety of implant materials used for anterior column reconstruction after cervical spine tumor resection, introduces and analyzes their properties, advantages, disadvantages, derivatives, and applications in clinical practice, and looks forward to the future development of implant materials.

The Outcomes of Surgical and Nonsurgical Treatment in Patients With Spinal Metastases of Lung Cancer: Protocol for a Prospective Cohort Study.

BACKGROUND: Spinal metastases of lung cancer (SMLC) usually have a high degree of malignancy and require multimodality treatment. Patients with SMLC who experience clinical symptoms (eg, local pain, emerging or potential spinal instability, and progressive neurological dysfunction) require surgical treatment. However, there are discrepancies in the comparison of outcomes between surgical treatment and nonsurgical treatment. OBJECTIVE: This paper presents the protocol for a study that aims to compare the clinical outcomes of surgical treatment and nonsurgical treatment for SMLC, explore the prognostic factors of SMLC, and establish a survival prediction model based on these prognostic factors. METHODS: This is a prospective cohort study, with an anticipated sample size of 240 patients (120 patients in the surgical group and 120 patients in the nonsurgical group). We will collect baseline data, including demographic, clinical, and radiological information, as well as data from patient-reported questionnaires. Patients will be followed up at 3, 6, 12, and 24 months after treatment, and survival status will be assessed every 3 months. The primary outcome is the overall survival period. Prognostic factors associated with overall survival will be analyzed by univariate and multivariate Cox proportional hazards regression. Odds ratios with 95% CIs will be presented. Statistical significance is set at P<.05. RESULTS: This study has been approved by our institute's Medical Science Research Ethics Committee (IRB00006761-M2021085) after a careful audit of the design and content. Patient enrollment began in June 2022 at our hospital. Data collection is expected to be completed by early 2026, and the study results will be published by mid-2027. CONCLUSIONS: In this study, we propose to set up a prospective cohort of patients with SMLC to investigate the outcomes between surgical treatment and nonsurgical treatment. We will explore the role of surgical treatment in SMLC and provide guidance to peer surgeons. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100048151; http://www.chictr.org.cn/showproj.aspx?proj=129450. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38273.

Prognostic Analysis of Spinal Metastasis Secondary to Lung Cancer after Surgeries: A Unicentric, Large-Cohort, Retrospective Study.

PURPOSE: Spinal metastases of lung cancer (SMLC) usually have high degree of malignancy and require surgical treatment. However, there are several controversies about the efficacy of surgery. This study aimed to investigate factors predicting prognosis of SMLC after surgery-based comprehensive treatment. METHODS: A cohort of 112 cases of SMLC who underwent surgical treatment between 2009 and 2020 were retrospectively reviewed and analyzed. The surgical strategies included total en-bloc spondylectomy, debulking surgery, palliative decompression, and vertebral augmentation procedures. The patients were regularly followed-up. Survival analysis was performed, as well as analysis of the patients' neurological recovery, pain relief, and improvement of Karnosky performance score (KPS). Cox regression was used to analyze influencing factors of survival time, and Kaplan-Meier method was performed in survival analysis. RESULTS: The cohort included 63 males and 49 females, with an average age of 60.6 ± 10.6 years. Median survival time was 16 months. A total of 86.7% of paralysis patients' neurological function recovered and 83.9% of patients with low KPS score (10-40) improved. Surgical method was significantly correlated with improvement of neurological function (p < 0.001) and KPS (p < 0.001). The mean bleeding volume was 502 ml and operative time was 170 min. The survival rates at 3, 6, 12, 24, and 36 months were 92.0%, 80.4%, 63.4%, 63.4%, and 22.6%, respectively. Postoperative Frankel grade (p < 0.001), postoperative KPS score (p = 0.001), and application of molecular targeted drugs (p < 0.001) were significantly correlated with survival time in univariate analysis, while application of molecular targeted drugs was an independent predictor for a longer survival by a multivariate analysis. CONCLUSION: Surgery-based comprehensive treatment brought a fair outcome, with elongated survival time. Surgery can significantly improve patients' neurological function and physical performance status. Adjuvant targeted therapy is an independent positive factor for patients' survival.

Cross-cultural adaptation and validation of the Chinese version of the Spine Oncology Study Group Outcomes Questionnaire.

Background context: Patients with spinal metastases always have a poor health-related quality of life (HRQoL) and disease- and treatment-related adverse outcomes. The Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ) has been verified and validated in English for patients with spinal metastases but not in Chinese. Purpose: This paper aimed to complete the cross-cultural adaptation of the Chinese version of the SOSGOQ, to verify its reliability and validity, and to report on the HRQoL of Chinese patients with spinal metastases. Study design/setting: This is a single-center, prospective, observational cross-sectional study. Patient sample: Seventy-six patients were enrolled in this study. Outcome measures: The SOSGOQ is made up of five HRQoL domains (physical function, neurological function, pain, mental health, social function) and post-therapy questions. The EQ-5D 3L questionnaire covers five items in mobility, self-care, usual activities, pain discomfort, and anxiety-depression, each with three answer options. The SF-36 comprises 36 items divided into eight domains. Methods: A single-center, prospective, observational cross-sectional study involving patients with spinal metastases who underwent surgery was conducted. HRQoL was evaluated using the Chinese version of the SOSGOQ, the Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36), and the EuroQol 5-Dimension questionnaire (EQ-5D). Demographic, tumor, symptom, and treatment data, as well as Eastern Cooperative Oncology Group (ECOG) information, were collected. Internal consistency reliability, convergent validity, concurrent validity, and clinical validity were used to evaluate reliability. A Spearman's correlation analysis was used to analyze the relationship between variables. Results: This study enrolled 76 patients, with a mean age of 55.8 years. The kidney was the most common primary tumor site, and the thoracic spine was the most affected. The internal consistency of the overall SOSQOQ (0.907) was higher than the EQ-5D (0.819), and all items of the SOSQOQ had a high convergent validity (>0.40). The SOSGOQ was significantly correlated with the EQ-5D in respective domains (p < 0.001) and overall score (p < 0.001), whereas the SF-36 was related to the overall SOSGOQ score and most domains. Total SOSGOG was significantly sensitive to changes in ECOG (p = 0.017), prior surgery (p = 0.001), and tumor type (p = 0.026). Conclusions: The SOSGOQ is a reliable and effective tool for evaluating HRQoL in patients with spinal metastases, with high sensitivity and specificity. Surgical treatment can significantly improve patients' HRQoL.

The effectiveness of percutaneous endoscopic decompression compared with open decompression and fusion for lumbar spinal stenosis: protocol for a multicenter, prospective, cohort study.

BACKGROUND: Lumbar spinal stenosis (LSS) is one of the most frequent indications for spine surgery. Open decompression and fusion surgery was the most common treatment and used to be regarded as the golden standard treatment for LSS. In recent years, percutaneous endoscopic decompression surgery was also used for LSS. However, the effectiveness and safety of percutaneous endoscopic decompression in the treatment of LSS have not been supported by high-level evidence. Our aim is to 1) compare the effectiveness of percutaneous endoscopic decompression surgery and open decompression and fusion for the treatment of LSS. 2) Investigate the prognosis risk factors for LSS. 3) Evaluate the influence of percutaneous endoscopic decompression for the stability of operative level, and degeneration of adjacent level. METHODS: It's a prospective, multicenter cohort study. The study is performed at 4 centers in Beijing. This study plans to enroll 600 LSS patients (300 patients in the percutaneous endoscopic decompression group, and 300 patients in the open decompression and fusion group). The demographic variables, healthcare variables, symptom related variables, clinical assessment (Visual analogue score (VAS), Oswestry disability index (ODI), Japanese Orthopaedic Association score (JOA)), and radiological assessment (dynamic X-ray, CT, MRI) will be collected at baseline visit. Patients will follow up at 3, 6, 12 months. The primary outcome is the difference of improvement of ODI between baseline and 12-month follow-up between the two groups. The secondary outcome is the score changes of preoperative and postoperative VAS, the recovery rate of JOA, MacNab criteria, patient satisfaction, degeneration grade of adjacent level, ROM of operative level and adjacent level, complication rate. DISCUSSION: In this study, we propose to conduct a prospective registry study to address the major controversies of LSS decompression under percutaneous spinal endoscopy, and investigate the clinical efficacy and safety of percutaneous endoscopic decompression and open decompression in the treatment of LSS. TRIAL REGISTRATION: This study has been registered on clinicaltrials.gov in January 15, 2020 ( NCT04254757 ). (SPIRIT 2a).

A sheep model of chronic cervical compressive myelopathy via an implantable wireless compression device.

PURPOSE: This study aimed to establish an animal model in which we can precisely displace the spinal cord and therefore mimic the chronic spinal compression of cervical spondylotic myelopathy. METHODS: In vivo intervertebral compression devices (IVCDs) connected with subcutaneous control modules (SCCMs) were implanted into the C2-3 intervertebral disk spaces of sheep and connected by Bluetooth to an in vitro control system. Sixteen sheep were divided into four groups: (Group A) control; (Group B) 10-week progressive compression, then held; (Group C) 20-week progressive compression, then held; and (Group D) 20-week progressive compression, then decompression. Electrophysiological analysis (latency and amplitude of the N1-P1-N2 wave in somatosensory evoked potentials, SEP), behavioral changes (Tarlov score), imaging test (encroachment ratio (ER) of intraspinal invasion determined by X-ray and CT scan), and histological examinations (hematoxylin and eosin, Nissl, and TUNEL staining) were performed to assess the efficacy of our model. RESULTS: Tarlov scores gradually decreased as compression increased with time and partially recovered after decompression. The Pearson correlation coefficient between ER and time was r = 0.993 (p < 0.001) in Group B at 10 weeks and Groups C and D at 20 weeks. And ER was negatively correlated with the Tarlov score (r = -0.878, p < 0.001). As compression progressed, the SEP latency was significantly extended (p < 0.001), and the amplitude significantly decreased (p < 0.001), while they were both partially restored after decompression. The number of abnormal motor neurons and TUNEL-positive cells increased significantly (p < 0.001) with compression. CONCLUSION: Our implantable and wireless intervertebral compression model demonstrated outstanding controllability and reproducibility in simulating chronic cervical spinal cord compression in animals.

Long-Term Follow-Up of Multilevel Thoracic Ossification of the Posterior Longitudinal Ligament Following Circumferential Decompression via Posterior Approach: A Retrospective Study.

OBJECTIVE: To examine the postoperative progression of multilevel thoracic posterior longitudinal ligament (OPLL) at circumferential decompression (CD) levels and evaluate the long-term results after CD via the posterior approach. METHODS: Clinical data from 16 patients with thoracic myelopathy secondary to OPLL who underwent CD at a single center were evaluated retrospectively from 2007 to 2014 and were followed up for more than 60 months. Patients of all sexes and ages were included in the study. Thin-slice computed tomography scans obtained at the time of surgery and the most recent follow-up were analyzed. The ossified area was measured on the axial reconstructed scan of the most obvious protrusion of ossification at the CD level. The neurological outcomes were evaluated using modified Japanese Orthopaedic Association (JOA) scores and Hirabayashi recovery rates (HRRs). Continuous variables were presented as the mean ± standard deviation and were analyzed using the Student's t-test, while categorical variables were tested using Fisher's exact test. RESULTS: Among all patients, the most predominant type was the mixed type (9/16, 56.3%), while the circumscribed type was only found in two patients (12.5%), and the continuous type was found in five patients (31.2%). Six cases were associated with ossification of the ligamentum flavum, and two cases were combined with cervical OPLL. The OPLL area at the CD level increased in all patients. The mean follow-up period was 5.5 ± 0.92 years (range 5-8 years). The mean area of ossification increased from 35.63 ± 39.23 mm2 at the time of surgery to 99.94 ± 65.39 mm2 at the last follow-up visit (P < 0.01). There was no internal fixation disorder on any computed tomography scan after the operation. The average JOA score of all patients improved from 4.2 ± 2.2 points before surgery to 8.4 ± 2.6 points at the final follow-up (P < 0.01). The overall HRR was 61.8%. None of the patients exhibited any neurological deterioration due to OPLL progression. One patient developed a severe gait disturbance due to worsening lumbar canal stenosis, an unrelated cause, but the other 15 experienced gait disturbance improvements. CONCLUSIONS: According to the long-term follow-up results, although OPLL progression did not decrease or stop after removing the OPLL mass, CD is a safe and effective procedure that can provide adequate reserve ventral space to cope with postoperative OPLL progression.

Reconstruction after resection of C2 vertebral tumors: A comparative study of 3D-printed vertebral body versus titanium mesh.

Background: Surgical resection of C2 vertebral tumors is challenging owing to the complex anatomy of C2 vertebrae and the challenges to surgical exposure. Various surgical approaches are available, but some are associated with excessively high risks of complications. An additional challenge is reconstruction of the upper cervical spine following surgery. In the last decade, additive-manufacturing personalized artificial vertebral bodies (AVBs) have been introduced for the repair of large, irregular bony defects; however, their use and efficacy in upper cervical surgery have not been well addressed. Therefore, in this study, we compared instrumented fixation status between patients who underwent conventional titanium mesh reconstruction and those who underwent the same resection but with personalized AVBs. Methods: We performed a retrospective comparative study and recruited a single-institution cohort of patients with C2 vertebral tumors. Clinical data and imaging findings were reviewed. Through data processing and comparative analysis, we described and discussed the feasibility and safety of surgical resection and the outcomes of hardware implants. The primary outcome of this study was instrumented fixation status. Results: The 31 recruited patients were divided into two groups. There were 13 patients in group A who underwent conventional titanium mesh reconstruction and 18 group B patients who underwent personalized AVBs. All patients underwent staged posterior and anterior surgical procedures. In the cohort, 9.7% achieved total en bloc resection of the tumor, while gross total resection was achieved in the remaining 90.3%. The perioperative complication and mortality rates were 45.2% and 6.5%, respectively. The occurrence of perioperative complications was related to the choice of anterior approach (p < 0.05). Group A had a higher complication rate than group B (p < 0.05). Four patients (4/13, 30.8%) developed hardware problems during the follow-up period; however, this rate was marginally higher than that of group B (1/18, 5.6%). Conclusions: Total resection of C2 vertebral tumors was associated with a high risk of perioperative complications. The staged posterior and retropharyngeal approaches are better surgical strategies for C2 tumors. Personalized AVBs can provide a reliable reconstruction outcome, yet minor pitfalls remain that call for further modification.

VPS34 regulates dynamin to determine the endocytosis of mitochondria-targeted zinc oxide nanoparticles in human osteosarcoma cells.

In our previous study, zinc oxide nanoparticles (ZnO NPs) presented satisfying therapeutic effects with cancer cell selectivity in osteosarcoma cells and, thus, have been considered as a potential nanomedicine for human osteosarcoma treatment. However, the poorly investigated internalization process, including their endocytic pathway into tumor cells and intracellular fate, limits the clinical application. Here, we further clarified these aspects. First, ZnO NPs were rapidly internalized by osteosarcoma cells and accumulated in mitochondria, before being entrapped into lysosomes. Second, dynasore (a dynamin inhibitor) was demonstrated to be the most effective in blocking ZnO NP uptake and rescuing ZnO NP-induced osteosarcoma cell autophagic death and apoptosis. Third, we confirmed the key role of dynamin 2 in ZnO NP endocytosis and subsequent autophagic cell death in vitro and in vivo. Furthermore, we proved that VPS34 transferred from cell cytoplasm to cell membrane to interact with dynamin under ZnO NP treatment. Altogether, combined with our previous study, the current research further revealed that ZnO NPs entered human osteosarcoma cells through the VPS34/dynamin 2-dependent endocytic pathway, directly targeting and damaging the mitochondria before being entrapped into the lysosomes, thereby initiating mitophagy-Zn2+-reactive oxygen species-mitophagy axis mediated cell apoptosis.

Bone Marrow Mesenchymal Stem Cells-Derived Exosomal MicroRNA-150-3p Promotes Osteoblast Proliferation and Differentiation in Osteoporosis.

At present, much more studies have focused on the role of microRNAs in osteoporosis, but the more specific role of microRNA-150-3p (miR-150-3p) in osteoporosis still needs full exploration. We aim at investigating the role of miR-150-3p in osteoporosis and at exploring the related mechanisms. Bone marrow mesenchymal stem cells (BMSCs) were cultured, from which exosomes were isolated. Osteoporosis models were established by ovariectomy and injected with transfected BMSCs exosomes. Bone formation markers in serum, histopathological changes and miR-150-3p, runt-related transcription factor 2 (Runx2) and Osterix expression, and osteoblast apoptosis in femoral tissues were detected. Osteoblasts were isolated and co-cultured with the transfected BMSCs-derived exosomes. Osteoblast proliferation, cell differentiation, and apoptosis, along with miR-150-3p, Runx2, and Osterix expression in osteoblasts were detected. In vivo experiment demonstrated that miR-150-3p, Runx2, and Osterix expression was decreased whereas bone formation markers were decreased in osteoporosis. BMSCs exosomes attenuated osteoporosis, which was further improved by upregulated miR-150-3p in exosomes whereas it was impaired by downregulated miR-150-3p in exosomes. In vitro experiments declared decreased miR-150-3p, Runx2, and Osterix expression; suppressed proliferation; and encouraged apoptosis in osteoblasts in osteoporosis. BMSCs exosomes promoted osteoblast proliferation and differentiation and inhibited apoptosis, which was strengthened by raised exosomal miR-150-3p whereas it was disrupted by inhibited exosomal miR-150-3p. Our study elucidates that exosomal miR-150-3p promotes osteoblast proliferation and differentiation in osteoporosis and provides a new clue for the treatment of patients with osteoporosis.

DPP4 Activities Are Associated with Osteopenia/Osteoporosis and Fracture Risk in Newly Diagnosed Type 2 Diabetes.

BACKGROUND: Recent studies have shown the beneficial effect of dipeptidyl peptidase-4 (DPP4) inhibitor on bone turnover in diabetes mellitus. However, little clinical evidence for DPP4 activity in newly diagnosed type 2 diabetes is available. This study was designed to investigate the relationship between plasma DPP4 activity and osteoporosis/osteopenia and fracture risk in newly diagnosed type 2 diabetes. METHODS: A total of 147 subjects with newly diagnosed type 2 diabetes were enrolled for this cross-sectional study. The bone mineral density (BMD) at the lumbar spine (L1-4) and femoral neck (FN) was measured by dual-energy X-ray absorptiometry (DXA). The 10-year probability of major osteoporotic fracture (MOF) and hip fracture (HF) was assessed by a modified fracture risk algorithm (FRAX) tool. The plasma DPP4 activity and clinical variables were measured. Correlation analyses between DPP4 activity and osteoporosis/osteopenia and fracture risk were performed. RESULTS: Elevated plasma DPP activities were significantly associated with a higher proportion of osteoporosis/osteopenia (50% for quartile-1, 56.4% for quartile-2, 65.8% for quartile-3 and 72.2% for quartile-4). With increasing plasma DPP activities, the incidence rate of osteoporosis/osteopenia is gradually increasing (P for the trend between quartiles = 0.04). Of note, a statistically significant linear correlation was found between plasma DPP4 activities and modified FRAX MOF (r = 0.20, P=0.02). Moreover, plasma DPP4 activities were also positively related to modified FRAX HF in newly diagnosed type 2 diabetic patients (r = 0.21, P=0.01). CONCLUSIONS: Elevated plasma DPP4 activity tended to be associated with a higher proportion of osteoporosis/osteopenia and increased the fracture risk in newly diagnosed type 2 diabetes.

SpxB-mediated H2 O2 induces programmed cell death in Streptococcus sanguinis.

Streptococcus sanguinis (S. sanguinis) is a commensal oral streptococci that produces hydrogen peroxide (H2 O2 ), and this production is dependent on pyruvate oxidase (SpxB) activity. In addition to its well-known role in intraspecies or interspecies competitions, recent studies have shown that H2 O2 produced by S. sanguinis under aerobic conditions not only upregulates biofilm formation and eDNA release but also regulates cell death without obvious cell lysis. Here, we report that S. sanguinis exhibits characteristic hallmarks of eukaryotic apoptosis when it encounters endogenous and exogenous H2 O2 . As the most common mode of programmed cell death (PCD), apoptosis is accompanied by a series of biochemical and morphological events, including DNA fragmentation, chromosome condensation, membrane potential depolarization, phosphatidylserine (PS) exposure, and caspase substrate binding protein activity changes. In addition, we also provide genetic evidence that there is decreased expression of the related DNA repair genes comEA, recA, dnaC, dinG, and pcrA in the wild-type compared to the isogenic spxB mutant in S. sanguinis. Our data suggest that endogenous H2 O2 is the most important agent in this development process in S. sanguinis.