Limited knowledge and distrust are important social factors of out-patient' s 'inappropriate diagnosed seeking behaviour': a qualitative research in Shanghai.

AIMS: This study is designed to present out-patient's 'inappropriate diagnosed seeking behaviour' in tertiary hospitals and interpret its association with some potential social factors. METHODS: A qualitative study based on grounded theory was designed in this paper. The participates were recruited by a two-stage process. The field observation and in-depth interview were adopted for data collection. Multi-round (five rounds) sampling and continuing data analysis were adopted as well. RESULTS: Totally 26 out-patients from three tertiary hospitals in Shanghai were involved. Four focused codes, including 'limited policy-related knowledge', 'limited health-related knowledge', 'distrust on related policy' and 'distrust on medical networks', were identified. Then, a theoretical model about the association of out-patient's 'limited knowledge' with 'distrust' and its relationship with 'inappropriate first-diagnosed seeking behaviour' in tertiary hospitals was developed. CONCLUSION: 'Inappropriate first-diagnosed seeking behaviour' of the out-patients in tertiary hospitals is closely associated with their limited knowledge and related distrust. Great effort on improving publics' knowledge and rebuilding a benign trust relationship with out-patients and the medical networks is found to be essential for guiding publics' appropriate first-diagnosed health behaviour in various levels of medical institutions.

The effect of type 2 diabetes mellitus on the prognosis of osteoporotic vertebral compression fracture with osteoporotic fracture classification after vertebroplasty.

BACKGROUND: To analyze the clinical and radiological effects of type 2 diabetes mellitus on the prognosis of osteoporotic vertebral compression fracture after percutaneous vertebroplasty, and explore the prognostic value of osteoporotic fracture classification. METHODS: Osteoporotic vertebral compression fracture patients who received vertebroplasty from January 1, 2016 to June 30, 2021 were divided into type 2 diabetes mellitus group and control group in this retrospective cohort study. Visual analogue scale, Oswestry Disability Index, bone cement leakage, new compression fracture, anterior, middle, and posterior portion heights of vertebral body and local Cobb angle on X-ray before surgery, 2 days after surgery, 6 months, and 12 months after surgery were recorded, and the osteoporotic fracture classification was performed. P < 0.05 was set as statistical significance. RESULTS: A total of 261 vertebral bodies were included, containing 68 in the type 2 diabetes mellitus group and 193 in the control group. There were no differences in baseline characteristics between the two groups. At 6 months after vertebroplasty, the local Cobb angle of the type 2 diabetes mellitus group was 8.29 ± 4.90° greater than that of the control group 6.05 ± 5.18° (P = 0.002). At 12 months, compared with pre-operation, the anterior portion height recovered 8.13 ± 12.90%, which was less than 12.51 ± 14.92% of the control group (P = 0.032), and 19.07 ± 16.47% of the middle portion height recovery was less than the control group's 24.63 ± 17.67% (P = 0.024). Compared with the control group, osteoporotic fracture 2 vertebral bodies of the type 2 diabetes mellitus group at 12 months postoperatively in middle portion height (14.82 ± 14.71% vs 24.78 ± 18.16%, P = 0.023) and local Cobb angle (5.65 ± 4.06° vs 3.26 ± 4.86°, P = 0.043) restored significantly worse. Besides, osteoporotic fracture 3 with type 2 diabetes mellitus restored worse in anterior portion height (5.40 ± 11.02% vs 13.57 ± 12.79%, P = 0.008), middle portion height (11.22 ± 15.53% vs 17.84 ± 12.36%, P = 0.041) and local Cobb angle (10.85 ± 3.79 vs 7.97 ± 3.83°, P = 0.002) at 12 months postoperatively. There was no difference in radiological outcomes of osteoporotic fracture 4 between the two groups. CONCLUSIONS: The degree of fractured vertebral compression, the recovery of the height and angle obtained immediately after surgery and the clinical symptoms in type 2 diabetes mellitus patients were not different from those in the control. However, vertebral body morphology of type 2 diabetes mellitus patients was worse since the sixth month after surgery. Osteoporotic fracture classification has a good prognostic reference value for both the control and the type 2 diabetes mellitus population.

Celecoxib activates autophagy by inhibiting the mTOR signaling pathway and prevents apoptosis in nucleus pulposus cells.

BACKGROUND: Intervertebral disc degeneration results from a variety of etiologies, including inflammation and aging. Degenerated intervertebral discs feature down-regulated extracellular matrix synthesis, resulting in losing their ability to retain water and absorb compression. Celecoxib is a well-known selective cyclooxygenase-2 inhibitor for treating arthritis and relieving pain. Nevertheless, the mechanism of Celecoxib for treating inflammation-related intervertebral disc degeneration has not yet been clarified. METHOD: Protein synthesis was analyzed by western blot. Fluorescent probes DCFH-DA and MitoSox Red detected reactive oxygen species and were measured by flow cytometry. The activity of the kinase pathway was evaluated by protein phosphorylation. Autophagy was monitored by mRFP-GFP-LC3 transfection and LC3 analysis. Mitochondrial apoptotic proteins were analyzed by western blot and cell membrane integrity was measured by flow cytometry. The autophagic gene was silenced by siRNA. RESULTS: In this study, interleukin-1ß stimulation reduced the synthesis of aggrecan, type I and II collagen and caused excessive production of reactive oxygen species. We looked for a therapeutic window of Celecoxib for nucleus pulposus cells to regain extracellular matrix synthesis and reduce oxidative stress. To look into nucleus pulposus cells in response to stimuli, enhancement of autophagy was achieved by Celecoxib, confirmed by mRFP-GFP-LC3 transfection and LC3 analysis. The mammalian target of rapamycin and a panel of downstream proteins responded to Celecoxib and propelled autophagy machinery to stabilize homeostasis. Ultimately, inhibition of autophagy by silencing autophagy protein 5 disrupted the protective effects of Celecoxib, culminating in apoptosis. CONCLUSION: In summary, we have demonstrated a new use for the old drug Celecoxib that treats intervertebral disc degeneration by enhancing autophagy in nucleus pulposus cells and opening a door for treating other degenerative diseases.

Establishment and validation of an individualized nomogram to predict distant metastasis in chondrosarcoma patients: a population-based study.

Background: Distant metastasis is a significant factor influencing chondrosarcoma (CHS) patients' treatment and prognosis. We aimed to establish a consistent and effective nomogram to better predict distant metastases of CHS individuals. Methods: The Surveillance, Epidemiology and End Results (SEER) database was used to obtain the demographics and clinicopathological characteristics of CHS patients from 2010 to 2018. Independent risk factors were identified via univariate and multivariate logistic regressive analysis. A nomogram that predicts metastasis risk was established based on the training cohort, and its accuracy was validated through the validation cohort. The performance of this predictive model was assessed by the receiver operating characteristic (ROC) curve and Harrell's concordance index (C-index). Finally, decision curve analysis (DCA) was conducted to test its clinical reliability. Results: Data of 1,066 patients were extracted, of these, 66 cases (6.19%) were with distant metastasis at initial diagnosis. The following features were shown to be linked to an increased risk of metastasis: high-grade tumor, T3 stage, and large tumor size; whereas unmarried and use of surgery were independent protective factors. Marital status, tumor grade, T stage, use of cancer-directed surgery and tumor size were incorporated to develop the novel nomogram. The ROC curves showed the effectiveness of the nomogram with the high area under the curves, the C-indices were 0.931 and 0.951 in the internal and external validation, respectively. The calibration plots indicated a good consistency and agreement of the nomogram, while the DCA illustrated that the nomogram had favorable potential clinical applicability due to great positive net benefit with wide ranges of the threshold probabilities. Conclusions: This work developed a novel nomogram for predicting distant metastasis in CHS patients, which might assist clinicians to determine the optimal treatment plan by precisely predicting individualized metastatic risk.

Health-Related Perceptions of Older Adults/Patients with Degenerative Lumbar Diseases (ODLs) are associated with their Quality of Life: a Mixed-Methods Study.

PURPOSE: This study aimed to elucidate the quality of life of older adults/patients with degenerative lumbar diseases (ODLs) and analyse its association with some of their health-related perceptions. MATERIALS AND METHODS: This mixed-methods study consisted of a questionnaire survey and an in-depth interview, which was designed within this study. ODLs were recruited from January 12, 2017 to June 27, 2018. The independent sample t-test and grounded theory coding method were employed for data analysis. RESULTS: Of the 125 participants who returned valid questionnaires, 18 were included in the in-depth interviews. ODLs' quality of life was associated with the following health-related perceptions: "life barriers", "subjective health status", and "treatment outcomes" across the domains of physiology, psychology, social relations, and environment. CONCLUSION: Our findings indicate that ODLs' quality of life is associated with their health-related perceptions. Thus, to improve older adults' quality of life, more attention should be paid to enhancing non-medical factors such as their health-related perceptions.

Osteoporosis and Endplate Damage Correlation Using a Combined Approach of Hounsfield Unit Values and Total Endplate Scores: A Retrospective Cross-Sectional Study.

PURPOSE: Osteoporosis and endplate damage, two primary orthopedic disorders that have adverse effects on the quality of life of older adults, may have some previously unknown relationship. The purpose of this study was to determine the potential association between osteoporosis and endplate damage with two specific imaging scoring systems and analyze the underlying mechanisms. PATIENTS AND METHODS: A cross-sectional study including 156 patients with degenerative disc disease (DDD) who visited our department in 2018 was performed. Data including age, sex, body mass index, Hounsfield unit (HU) values utilizing computed tomography (CT), and total endplate scores (TEPSs) using magnetic resonance imaging (MRI) of all patients were retrospectively collected and analyzed. The average HU value and TEPS of L1-L4 were used to represent the degrees of bone mineral density (BMD) and endplate damage, respectively. Patients with an HU value < 110 were defined as having osteoporosis and placed in the low-BMD group; otherwise, they were placed in the normal-BMD group. Multivariate logistic regression models were used to determine the independent factors of endplate damage. RESULTS: The TEPSs in the low-BMD group were significantly higher (6.4 ± 1.6 vs 5.0 ± 0.9, p < 0.001) overall and in every segment of L1-L4 (p < 0.01). A significant negative correlation was found between TEPS and HU values (p < 0.001). The HU value (odds ratio [OR] 0.221; 95% confidence interval [CI], 0.148-0.295, p < 0.001), age (OR 0.047; 95% CI, 0.029-0.224, p < 0.001), and BMD (OR 3.796; 95% CI, 2.11-7.382, p < 0.05) were independent factors influencing endplate damage. CONCLUSION: A significantly positive correlation was observed between osteoporosis and endplate damage, indicating the requirement for a more comprehensive therapeutic regimen for treating patients with DDD complicated with osteoporosis.

Jintiange Capsules Ameliorate Osteoarthritis by Modulating Subchondral Bone Remodeling and Protecting Cartilage Against Degradation.

Osteoarthritis (OA) is the most prevalent joint disease worldwide, making it a major cause of pain and disability. Identified as a chronic and progressive disease, effective treatment at the early stages of OA has become critical to its management. Jintiange (Jtg) capsules are a traditional Chinese medicine produced from multiple organic components of various animal bones and routinely used to treat osteoporosis in China. However, the effect of Jtg on subchondral bone and cartilage degeneration in OA remains unknown. The purpose of the present study was to investigate the biomolecular role and underlying mechanisms of Jtg in OA progression. Herein, we found that Jtg inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and it functions through the NF-κB signaling pathway. Jtg also inhibited chondrocyte apoptosis via reducing the reactive oxygen species concentration in these cells. Moreover, in vivo evaluation revealed that Jtg significantly attenuates subchondral bone remodeling and cartilage destruction in anterior cruciate ligament transection (ACLT) mouse models. Taken together, our data demonstrate that Jtg inhibits osteoclast differentiation in subchondral bone and chondrocyte apoptosis in cartilage, supporting its potential therapeutic value for treating OA.

The Effect of Daily Teriparatide versus One-Time Annually Zoledronic Acid Administration After Transforaminal Lumbar Interbody Fusion in Osteoporotic Patients.

PURPOSE: The research aimed to compare the therapeutic effect of teriparatide (TPTD) and zoledronic acid (ZOL) therapy on bone formation and spinal fusion in patients with osteoporosis (OP) who underwent transforaminal lumbar interbody fusion (TLIF). METHODS: On the basis of different anti-OP treatment options, the TPTD group was treated daily with TPTD (20 µg. ih. qd) for at least 6 months, while the ZOL group was treated with a single dose of ZOL (5 mg. ivgtt. st) postoperatively. The visual analogue scale (VAS), Oswestry Disability Index (ODI), bone mineral density (BMD), and concentration of bone turnover markers before, 6, and 12 months after surgery were evaluated. X-ray and three-dimensional computed tomography scans were performed at 6 and 12 months postoperatively to assess interbody fusion. RESULTS: The number of patients in the TPTD and ZOL groups was 29 and 38 patients, respectively. The VAS and ODI scores in both groups were significantly reduced at 6 and 12 months after TLIF. Compared with that of baseline, the lumbar spine BMD of TPTD patients increased significantly from 0.716±0.137 g/cm2 to 0.745±0.124 g/cm2 and 0.795±0.123 g/cm2 at 6 and 12 months, respectively, and was significantly higher than that of the ZOL group at 12 months (0.720±0.128 g/cm2). The bone formation marker, P1NP, in the TPTD group increased significantly (145.48±66.64 ng/mL and 119.55±88.27 ng/mL) compared with baseline (44.67±25.15 ng/mL) and in the ZOL group (28.82±19.76 ng/mL and 29.94±20.67 ng/mL) at 6 and 12 months, respectively. The fusion rates in the TPTD and ZOL groups were 57% and 45% at 6 months, without statistical significance. However, TPTD had a more statistically significant positive influence on fusion rate than ZOL at 12 months (86% vs 70%). CONCLUSION: TPTD was more efficient than ZOL in bone formation and spinal fusion in OP patients who underwent TLIF.

TNF-α-stimulated nucleus pulposus cells induce cell apoptosis through the release of exosomal miR-16 targeting IGF-1 and IGF-1R in rats.

BACKGROUND: Exosomes may contain excess cellular components released by cells in response to harmful external stimuli to maintain cellular homeostasis. Inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), can induce cell apoptosis, alter cellular component expression levels, and stimulate exosome release. In this study, we examined whether exosomes released from nucleus pulposus cells (NPCs) under inflammatory conditions could induce normal NP cell apoptosis in rats and its underlining mechanism. METHODS: Exosomes were isolated from TNF-α-treated NPCs and used to treat normal NPCs. The effects were assessed by flow cytometry and western blot analysis. Anti-apoptotic insulin-like growth factor-1 (IGF-1) expression in NPCs was assessed by western blot analysis. Given the exosomal miRNAs might be the key factors of exosomes, bioinformatics approaches and quantitative real-time polymerase chain reaction (qRT-PCR) were used to identify IGF-1-regulating micro RNAs (miRNAs), including miR-16. Luciferase reporter assay assessed miR-16 regulation of IGF-1 and IGF-1 receptor (IGF-1R). NPCs were transfected with miR-16 mimic, and exosomes were applied to normal NPCs. NPCs were pretreated with 10 ng/mL TNF-α, transfected with miR-16 inhibitors, and the exosomes were isolated. Cell and exosome miR-16 levels were detected by qRT-PCR. Western blot analysis determined IGF-1, IGF-1R, and apoptotic marker levels in exosome-treated NPCs. RESULTS: Exosomes from TNF-α-treated NPCs induced apoptosis in normal NPCs and repressed IGF-1 expression. Exosomal miR-16 regulated IGF-1 and induced NPC apoptosis. The dual-luciferase reporter assay revealed that miR-16 binds the 3' untranslated regions (3'-UTRs) of IGF-1 and IGF-1R. Exosomal miR-16 repressed IGF-1 and the IGF-1R/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway which therefore induced NPC apoptosis. Rescue experiments using miR-16 inhibitors further validated these findings. CONCLUSIONS: The inflammatory factor TNF-α stimulated exosome release from NPCs, which induced the apoptosis of normal NPCs through the actions of exosomal miR-16. Exosomal miR-16 directly repressed the anti-apoptotic IGF-1/IGF-1R pathway, increasing the apoptosis of NPCs.