Targeting POLRMT by a first-in-class inhibitor IMT1 inhibits osteosarcoma cell growth in vitro and in vivo.

Osteosarcoma (OS) is a highly aggressive form of bone cancer that predominantly affects adolescents and young adults. In this study, we have undertaken an investigation into the potential anti-OS cell activity of IMT1 (inhibitor of mitochondrial transcription 1), a first-in-class inhibitor of RNA polymerase mitochondrial (POLRMT). IMT1 exhibited a profound inhibitory effect on cell survival, proliferation, cell cycle progression, and migration in primary and immortalized OS cells. Furthermore, this POLRMT inhibitor elicited apoptosis in the OS cells, without, however, inducing cytotoxicity in human osteoblasts or osteoblastic cells. IMT1 disrupted mitochondrial functions in OS cells, resulting in mitochondrial depolarization, oxidative injury, lipid peroxidation, and ATP reduction in OS cells. Silencing POLRMT using targeted shRNA closely mimicked the actions of IMT1 and exerted potent anti-OS cell activity. Importantly, IMT1's effectiveness was diminished in POLRMT-silenced OS cells. Subsequent investigations revealed that IMT1 suppressed the activation of the Akt-mammalian target of rapamycin (mTOR) cascade in OS cells. IMT1 treatment or POLRMT silencing in primary OS cells led to a significant reduction in Akt1-S6K-S6 phosphorylation. Conversely, it was enhanced upon POLRMT overexpression. The restoration of Akt-mTOR activation through the introduction of a constitutively active S473D mutant Akt1 (caAkt1) mitigated IMT1-induced cytotoxicity in OS cells. In vivo, oral administration of IMT1 robustly curtailed the growth of OS xenografts in nude mice. Furthermore, IMT1 suppressed POLRMT activity, impaired mitochondrial function, repressed Akt-mTOR activation, and induced apoptosis within xenograft tissues. Collectively, these findings underscore the potent growth-inhibitory effects attributed to IMT1 via targeted POLRMT inhibition. The utilization of this POLRMT inhibitor carries substantial therapeutic promise in the context of OS treatment.

A biphasic calcium phosphate/acylated methacrylate gelatin composite hydrogel promotes osteogenesis and bone repair.

PURPOSE/AIM: Bone defects caused by trauma, tumors, congenital malformation, or inflammation are very common in orthopedics. In recent years, mimicking the composition and structure of natural bone tissue has become a hot topic in biomaterial research, with the aim of developing an ideal biomaterial for bone defect transplantation. Here, the feasibility of a biphasic calcium phosphate (BCP)/acylated methacrylate gelatin (GelMA) composite hydrogel to repair bone defects was evaluated in vitro and in rats. MATERIALS AND METHODS: The biocompatibility of a biphasic calcium phosphate (BCP)/acylated methacrylate gelatin (GelMA) composite hydrogel was evaluated by cytoskeleton staining, live/dead cell staining and cell proliferation assays. The in vitro osteogenic activities of the composite hydrogel were evaluated by alkaline phosphatase and alizarin red staining, as well as osteogenic gene expression analysis at both transcript and protein levels. The in vivo bone repair activities were evaluated using the rat skull defect model. RESULTS: The BCP/GelMA composite hydrogel displayed excellent biocompatibility and promoted osteogenesis of bone marrow mesenchymal stem cells in vitro. In addition, the BCP/GelMA composite hydrogel markedly promoted new bone formation in the rat skull-defect model. CONCLUSIONS: BCP/GelMA composite hydrogel may be an effective artificial material for bone tissue engineering.

Effects of silicate application on rice growth, yield and quality under nighttime warming in southern China.

The main feature of climate warming is that nighttime warming is higher than the daytime warming. Nighttime warming reduced single rice production in southern China, while silicate application increased rice yield and stress resistance. It is still unclear regarding the effects of silicate application on growth, yield, and especially quality in rice under nighttime warming. We performed a field simulation experiment to investigate the effects of silicate application on tiller number, biomass, yield and quality of rice. Warming was set at two levels, ambient temperature (control, CK) and nighttime warming (NW). The open passive nighttime warming method was used, with rice canopy being covered with aluminum foil reflective film at night (19:00-6:00) to simulate nighttime warming. Silicate fertilizer (steel slag) was applied at two levels, i.e., Si0(0 kg SiO2·hm-2) and Si1(200 kg SiO2·hm-2). The results showed that, compared with the control (ambient temperature), average temperature at nighttime on rice canopy and at 5 cm soil layer increased by 0.51-0.58 ℃ and 0.28-0.41 ℃ during rice growing season, respectively. Nighttime warming decreased tiller number and chlorophyll content by 2.5%-15.9% and 0.2%-7.7%, respectively. In contrast, silicate application increased tiller number and chlorophyll content by 1.7%-16.2% and 1.6%-16.6%, respectively. Under nighttime warming, silicate application increased dry weight of shoot, total dry weight of the whole plant, and yield at grain filling-maturity stage by 64.1%, 55.3%, and 7.1%, respectively. Under nighttime warming, silicate application significantly increased milled rice rate, head rice rate, and total starch content by 2.3%, 2.5%, and 41.8%, respectively. Nighttime warming reduced rice yield by decreasing the number of effective panicles, seed setting rate, and 1000-grain weight, but increasing empty grains. Silicate application increased rice yield by increasing the number of effective panicles, filled grains per panicle, seed setting rate and 1000-grain weight, but reducing empty grains. In conclusion, silicate application could effectively alleviate the suppressive effects of nighttime warming on growth, yield, and quality of single rice in Southern China.

Exploring the mechanism of Self-Consistent balance between microbiota and high efficiency in wastewater treatment.

Sewage treatment mediated by microbial organisms is a promising green trend. However, the complex balance between microbiota stability and highly efficient wastewater treatment requires investigation. This study successfully improved the effectiveness of sewage treatment by resetting the microbial community structure in the activated sludge. Truepera, Methylophaga, unclassified_Fodinicurvataceae, and unclassified_Actinomanarales were the dominant genera, while salinity and NH3-N content were identified as the key environmental factors governing the microbial structure. By optimizing the microflora structure driven by environmental factors, the key minor genera were activated and coordinated with the aforementioned genera, thereby promoting wastewater treatment. Finally, the chemical oxygen demand, NH3-N, and total phosphorus removal rates were improved to 86.8 ± 1.9%, 82.4 ± 4.1%, and 94.8 ± 3.8%, respectively. It provides a new insight to improve the wastewater treatment through setting microbiota by environmental factor driven.

Runx1 is a key regulator of articular cartilage homeostasis by orchestrating YAP, TGFß, and Wnt signaling in articular cartilage formation and osteoarthritis.

Runt-related transcription factor 1 (Runx1) plays a key role in cartilage formation, but its function in articular cartilage formation is unclear. We generated non-inducible and inducible Runx1-deficient mice (Runx1f/fCol2α1-Cre and Runx1f/fCol2α1-CreER mice) and found that chondrocyte-specific Runx1-deficient mice developed a spontaneous osteoarthritis (OA)-like phenotype and showed exacerbated articular cartilage destruction under OA, characterized by articular cartilage degradation and cartilage ossification, with decreased Col2α1 expression and increased Mmp13 and Adamts5 expression. RNA-sequencing analysis of hip articular cartilage from the Runx1f/fCol2α1-Cre mice compared to that from wild-type mice and subsequent validation analyses demonstrated that Runx1 is a central regulator in multiple signaling pathways, converging signals of the Hippo/Yap, TGFß/Smad, and Wnt/ß-catenin pathways into a complex network to regulate the expression of downstream genes, thereby controlling a series of osteoarthritic pathological processes. RNA-sequencing analysis of mutant knee joints showed that Runx1's role in signaling pathways in articular cartilage is different from that in whole knee joints, indicating that Runx1 regulation is tissue-specific. Histopathologic analysis confirmed that Runx1 deficiency decreased the levels of YAP and p-Smad2/3 and increased the levels of active ß-catenin. Overexpression of Runx1 dramatically increased YAP expression in chondrocytes. Adeno-associated virus-mediated Runx1 overexpression in the knee joints of osteoarthritic mice showed the protective effect of Runx1 on articular cartilage damaged in OA. Our results notably showed that Runx1 is a central regulator of articular cartilage homeostasis by orchestrating the YAP, TGFß, and Wnt signaling pathways in the formation of articular cartilage and OA, and targeting Runx1 and its downstream genes may facilitate the design of novel therapeutic approaches for OA.

Effect of Different Anesthesia and Puncture Methods of Percutaneous Kyphoplasty on More Than 90-Year-Old Osteoporotic Vertebral Fracture: Advantages of the ERAS Concept.

Background: Percutaneous kyphoplasty (PKP) is an effective minimally invasive technique for the treatment of osteoporotic vertebral fracture (OVF) in recent years. This study focuses on the analysis of PKP surgery and anesthesia in osteoporotic vertebral facture patients over 90 years old with the concept of "enhanced recovery after surgery." Methods: This study reviewed 239 patients who were diagnosed with OVF retrospectively between October 2015 and June 2019. According to the method of anesthesia, these patients were divided into Group A (n = 125) and Group B (n = 114). According to the pedicle puncture approach, these patients were divided into Group C (n = 102) and Group D (n = 137). The anterior vertebral height (AVH) and local kyphosis angle (LKA) were used to evaluate the degree of vertebral damage and restoration. The visual analogue scale (VAS) and the Oswestry Disability Index (ODI) scores were used for assessing functional outcomes. Some parameters were used to assess the perioperative conditions such as operation time, amount of bone cement perfusion, intraoperative fluoroscopy times, anesthesia recovery time, time out of the bed, hospital stay, hospitalization cost, and complications. Results: The visual analogue scale (VAS), Oswestry Disability Index (ODI), anterior vertebral height (AVH), and local kyphosis angle (LKA) 1 day, 1 year after surgery, and at the last follow-up all showed significant improvement (P < 0.05) in comparison with those before surgery both in Groups A and B and Groups C and D. The ODI 1 day after surgery was significantly better in Group B than Group A (P < 0.05). Compared with Group B, Group A required longer time of anesthesia, operation time, anesthesia recovery time, time to get out of bed, and length of hospital stay and more hospitalization costs (P < 0.05). Group D required longer operation time, longer time to get out of bed, more bone cement volume, fluoroscopy time, and more operation hospitalization costs compared with Group C (P < 0.05). Conclusion: We recommend unilateral puncture under local anesthesia for OVF in the patients aged over 90 from the perspective of rapid recovery.

Outcome of percutaneous compression plate for treatment of femoral neck fractures: mean follow-up of 4.4 years.

PURPOSE: Percutaneous compression plate (PCCP) provides superior anti-rotational abilities and mechanical strength in femoral neck fractures (FNFs). The first series reporting its utilization of FNFs was promising. Since the long-term outcome regarding the implant has not been reported, the purpose of this study was to evaluate the long-term functional outcomes and complications after fixation using PCCP in FNFs. MATERIALS AND METHODS: From 2010 to 2019, 51 patients aged from 18 to 87 years were evaluated; 11 patients were excluded from this study. Demographic data, fracture classification, and complications were analyzed. Besides plain radiographs and CT, uptake ratios using bone scintigraphy and/or SPECT were also collected and analyzed. RESULTS: At a mean follow-up of 4.4 ± 2.0 years (range, 2-10 years), the mean Harris hip score was 88, with 44 patients (86.3%) achieving excellent or good outcomes. The rate of complication was 13.7% (7/51), with five cases of osteonecrosis of the femoral head (OFNH). Hip replacements were performed in four (7.8%) cases. After confirmation of normal transfusion status, 11 patients underwent elective removal of the implant without further complications. CONCLUSION: Closed reduction and internal fixation using PCCP in FNFs resulted in satisfactory outcomes with low complication rates. Longer follow-up (3-5 years) and sequential bone scintigraphy or SPECT after surgery are recommended after internal fixation using PCCP.

Catching the circadian rhythm of intervertebral disc and association with clinical outcomes by twice-a-day magnetic resonance imaging.

OBJECTIVES: We conducted a prospective magnetic resonance imaging(MRI) surveillance program of the whole spine twice a day to aim at investigating the diurnal prevalence of MRI parameters of intervertebral discs and their associations with relevant symptoms. METHODS: Sixty-four young volunteers underwent MRI of the whole spine twice on the same day (in the morning and evening). Sagittal T2-weighted MRIs of the whole spine were compared and analyzed. Two independent observers assessed the images for the disc height, anterior-posterior distance, and T2 values. Subject demographics and clinical findings were assessed by standardized questionnaires. RESULTS: There was a statistically significant diurnal disc height change in all the disc level groups. Except four lumbar levels, there was no statistically significant diurnal disc AP distance change seen in other levels. There were statistically significant diurnal T2 value changes in all intervertebral discs except T3/4 levels. The multivariate linear regression analysis showed a positive linear trend association between BMI and the diurnal variations of T1/2 T2 value, T12/L1, L1/2, L2/3, L3/4,L4/5 and L5/S1 disc heights (p < 0.05) . Smoking and passive smoking affected cervical levels of T2 value changes. Interestingly, a reverse trend was observed in all disc changes in the case of more than ten years shift work history. CONCLUSION: Smoking and passive smoking are associated with cervical disc T2 value diurnal changes and BMI is associated with lumbar disc height changes. Long time disruption of circadian clock may cause reverse changes of discs, however not in short or medium-time shift workers.

[Effect of Laportea bulbifera extract on CYP450 enzyme activities in rats by Cocktail probe drug method].

The Cocktail probe drug method was used to evaluate the effect of Laportea bulbifera extract on the different subtypes of CYP450 enzyme activities in rats, and to provide references for its clinical rational drug use. The rats were randomly divided into a high-dose L. bulbifera group(0.45 g·kg~(-1)·d~(-1)) and a low-dose L. bulbifera group(0.09 g·kg~(-1)·d~(-1)). After continuous gavage for 7 and 14 days, the Cocktail probe mixing solution, including caffeine, midazolam, tolbutamide, omeprazole, metoprolol, and chlorzoxazone, was injected into the tail vein, and the blood sample was obtained from the tail vein at different time points. Ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS) was established to determine the concentration of six probe drugs in rat plasma. DAS 2.0 was used to calculate its pharmacokinetic parameters, and the effect of L. bulbifera extract on CYP1 A2, CYP2 C9, CYP2 C19, CYP2 D6, CYP2 E1, and CYP3 A4 in rats was investigated. As compared with the blank control group, under the omeprazole index, the AUC_(0-t) and AUC_(0-∞) of the 7-day administration groups and the 14-day high-dose group were significantly decreased, and the CLz and Vz were significantly increased. Under the midazolam index, the AUC_(0-t) and AUC_(0-∞) of the 7-day low-dose group and the 14-day administration group were significantly decreased, and the CLz was significantly increased. In addition, the AUC_(0-∞) of the 7-day high-dose group was also significantly decreased. Under the index of metoprolol, the AUC_(0-t) and AUC_(0-∞) of each experimental group were decreased significantly, and the CLz and Vz of the 7-day low-dose group and the 14-day low-dose group were increased significantly. Under the caffeine index, the AUC_(0-t) and AUC_(0-∞) of the 7-day administration groups were increased significantly, the CLz was decreased significantly, and the t_(1/2 z) of the 14-day high-dose group was increased significantly. Under the chlorzoxazone index, the AUC_(0-t) and AUC_(0-∞) of the 7-day low-dose group were increased significantly, and the CLz was decreased significantly. Under the tolbutamide index, there was no statistical difference in the pharmacokinetic parameters. In conclusion, L. bulbifera extract induces the activities of CYP2 C19, CYP3 A4, and CYP2 D6, inhibits the activities of CYP1 A2 and CYP2 E1, and does not affect the activity of CYP2 C9.

Balloon kyphoplasty as palliative care for painful pathological spinal fracture followed by lung cancer metastasis: A cohort study.

Background: Pathological spine fractures caused by metastases of lung cancer have brought great suffering to patients. Percutaneous kyphoplasty (PKP) has been considered a preferred alternative for painful spinal metastases. The clinical efficacy and safety of PKP for metastatic spinal lesions are urgently to be evaluated. Methods: A cohort study was conducted on 54 cases with pathologic spine fractures caused by metastasis of lung cancer. The correction of kyphosis was assessed by the Cobb angle. The life dependence and quality of the patients were evaluated by the Barthel Index of activities of daily living (ADL) and the quality-adjusted life year (QALY). Patients' survival was carefully recorded. Results: PKP significantly corrected the kyphosis compared with conservative treatment. The ratio of moderate dependence after fracture was clearly increased by PKP. QALY indicated a better life quality brought by PKP. However, PKP could not improve the survival rate of patients. Conclusion: PKP can be used as an effective palliative care treatment for patients with metastatic pathologic spinal fractures of lung cancer.

Comparative Analysis of Cage Subsidence in Anterior Cervical Decompression and Fusion: Zero Profile Anchored Spacer (ROI-C) vs. Conventional Cage and Plate Construct.

Background: Anterior cervical discectomy and fusion (ACDF) has been widely performed to treat cervical generative diseases. Cage subsidence is a complication after ACDF. Although it is known that segmental kyphosis, acceleration of adjacent segmental disease, and restenosis may occur due to cages subsidence; however detailed research comparing zero-profile cages (ROI-C) and conventional plate and cage construct (CPC) on cage subsidence has been lacking. Objective: The objectives of this study was to compare the rate of postoperative cage subsidence between zero profile anchored spacer (ROI-C) and conventional cage and plate construct (CPC) and investigate the risk factors associated with cage subsidence following ACDF. Methods: Seventy-four patients with ACDF who received either ROI-C or CPC treatment from October 2013 to August 2018 were included in this retrospective cohort study. Clinical and radiological outcomes and the incidence of cage subsidence at final follow up-were compared between groups. All patients were further categorized into the cage subsidence (CS) and non-cage subsidence (NCS) groups for subgroup analysis. Results: The overall subsidence rate was higher in the ROI-C group than in the CPC group (66.67 vs. 38.46%, P = 0.006). The incidence of cage subsidence was significantly different between groups for multiple-segment surgeries (75 vs. 34.6%, P = 0.003), but not for single-segment surgeries (54.55 vs. 42.30%, P = 0.563). Male sex, operation in multiple segments, using an ROI-C, and over-distraction increased the risk of subsidence. Clinical outcomes and fusion rates were not affected by cage subsidence. Conclusion: ROI-C use resulted in a higher subsidence rate than CPC use in multi-segment ACDF procedures. The male sex, the use of ROI-C, operation in multiple segments, and over-distraction were the most significant factors associated with an increase in the risk of cage subsidence.

Effects of different pedicle screw insertion depths on sagittal balance of lumbar degenerative spondylolisthesis, a retrospective comparative study.

BACKGROUND: Few reports to date have evaluated the effects of different pedicle screw insertion depths on sagittal balance and prognosis after posterior lumbar interbody and fusion (PLIF) in patients with lumbar degenerative spondylolisthesis (LDS). METHODS: A total of 88 patients with single-level PLIF for LDS from January 2018 to December 2019 were enrolled. Long screw group (Group L): 52 patients underwent long pedicle screw fixation (the leading edge of the screw exceeded 80% of the anteroposterior diameter of vertebral body). Short screw group (Group S): 36 patients underwent short pedicle screw fixation (the leading edge of the screw was less than 60% of the anteroposterior diameter of vertebral body). Local deformity parameters of spondylolisthesis including slip degree (SD) and segment lordosis (SL), spino-pelvic sagittal plane parameters including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) and lumbar lordosis (LL), Oswestry Disability Index (ODI), and Visual Analog Scale (VAS) for back pain of both groups were compared. Postoperative complications, including vertebral fusion rate and screw loosening rate, were recorded. RESULTS: Except that PI in Group S at the final follow-up was not statistically different from the preoperative value (P > 0.05), other parameters were significantly improved compared with preoperative values one month after surgery and at the final follow-up (P < 0.05). There was no significant difference in parameters between Group L and Group S before and one month after surgery (P > 0.05). At the final follow-up, SD, SL, LL, PT and PI-LL differed significantly between the two groups (P < 0.05). Compared with the preoperative results, ODI and VAS in both groups decreased significantly one month after surgery and at the final follow-up (P < 0.05). Significant differences of ODI and VAS were found between the two groups at the final follow-up (P < 0.05). Postoperative complications were not statistically significant between the two groups (P > 0.05). CONCLUSIONS: PLIF can significantly improve the prognosis of patients with LDS. In terms of outcomes with an average follow-up time of 2 years, the deeper the screw depth is within the safe range, the better the spino-pelvic sagittal balance may be restored and the better the quality of life may be.

Association Analysis of Hyperlipidemia with the 28-Day All-Cause Mortality of COVID-19 in Hospitalized Patients.

Objective This study aimed to determine the association of hyperlipidemia with clinical endpoints among hospitalized patients with COVID-19, especially those with pre-existing cardiovascular diseases (CVDs) and diabetes. Methods This multicenter retrospective cohort study included all patients who were hospitalized due to COVID-19 from 21 hospitals in Hubei province, China between December 31, 2019 and April 21, 2020. Patients who were aged < 18 or ≥ 85 years old, in pregnancy, with acute lethal organ injury (e.g., acute myocardial infarction, severe acute pancreatitis, acute stroke), hypothyroidism, malignant diseases, severe malnutrition, and those with normal lipid profile under lipid-lowering medicines (e.g., statin, niacin, fenofibrate, gemfibrozil, and ezetimibe) were excluded. Propensity score matching (PSM) analysis at 1:1 ratio was performed to minimize baseline differences between patient groups of hyperlipidemia and non-hyperlipidemia. PSM analyses with the same strategies were further conducted for the parameters of hyperlipidemia in patients with increased triglyceride (TG), increased low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C). Mixed-effect Cox model analysis was performed to investigate the associations of the 28-days all-cause deaths of COVID-19 patients with hyperlipidemia and the abnormalities of lipid parameters. The results were verified in male, female patients, and in patients with pre-existing CVDs and type 2 diabetes. Results Of 10 945 inpatients confirmed as COVID-19, there were 9822 inpatients included in the study, comprising 3513 (35.8%) cases without hyperlipidemia and 6309 (64.2%) cases with hyperlipidemia. Based on a mixed-effect Cox model after PSM at 1:1 ratio, hyperlipidemia was not associated with increased or decreased 28-day all-cause death [adjusted hazard ratio (HR), 1.17 (95% CI, 0.95-1.44), P =0.151]. We found that the parameters of hyperlipidemia were not associated with the risk of 28-day all-cause mortality [adjusted HR, 1.23 (95% CI, 0.98-1.55), P = 0.075 in TG increase group; 0.78 (95% CI, 0.57-1.07), P = 0.123 in LDL-C increase group; and 1.12 (95% CI, 0.9-1.39), P = 0.299 in HDL-C decrease group, respectively]. Hyperlipidemia was also not significantly associated with the increased mortality of COVID-19 in patients accompanied with CVDs or type 2 diabetes, and in both male and female cohorts. Conclusion Our study support that the imbalanced lipid profile is not significantly associated with the 28-day all-cause mortality of COVID-19 patients, even in those accompanied with CVDs or diabetes. Similar results were also obtained in subgroup analyses of abnormal lipid parameters. Therefore, hyperlipidemia might be not a major causative factor for poor outcome of COVID-19, which provides guidance for the intervention of inpatients during the epidemic of COVID-19.

Stiffness of the extracellular matrix affects apoptosis of nucleus pulposus cells by regulating the cytoskeleton and activating the TRPV2 channel protein.

It is known that nucleus pulposus cells (NPs) play an important role in intervertebral disc degeneration (IVDD), and a previous study indicated that the stiffness of NP tissue changes during the degeneration process. However, the mechanism underlying the cellular response to ECM stiffness is still unclear. To analyze the effects of extracellular matrix (ECM) with different degrees of stiffness on NPs, we prepared polyacrylamide (PA) gels with different elastic moduli, and cells grown under different stiffness conditions were obtained and analyzed. The results showed that the spreading morphology of NPs changed significantly under increased ECM elastic modulus conditions and that TRPV2 and the PI3K / AKT signaling pathway were activated by stiffer ECM. At the same time, mitochondria released cytochrome c (Cyt c) and activated caspase proteins to promote the apoptosis of NPs. After TRPV2 was specifically knocked out, the activation of the PI3K / AKT signaling pathway decreased, and the release of Cyt c and NP apoptosis were reduced. These results indicate that TRPV2 is closely linked to the detection of extracellular mechanical signals, and that conversion of mechanical and biological signals plays an important role in regulating the biological behavior of cells. This study offers a new perspective on the cellular and biochemical events underlying IVDD which could result in novel treatments.

Percutaneous vertebroplasty versus kyphoplasty for the treatment of neurologically intact osteoporotic Kümmell's disease.

BACKGROUND: Percutaneous vertebroplasty (PVP) and kyphoplasty (PKP) have been widely used to treat neurologically intact osteoporotic Kümmell's disease (KD), but it is still unclear which treatment is more advantageous. Our study aimed to compare and investigate the safety and clinical efficacy of PVP and PKP in the treatment of KD. METHODS: The relevant data that 64 patients of neurologically intact osteoporotic KD receiving PVP (30 patients) or PKP (34 patients) were analyzed. Surgical time, operation costs, intraoperative blood loss, volume of bone cement injection, and fluoroscopy times were compared. Occurrence of cement leakage, transient fever and re-fracture were recorded. Universal indicators of visual analogue scale (VAS) and Oswestry disability index (ODI) were evaluated separately before surgery and at 1 day, 6 months, 1 year, 2 years and the final follow-up after operation. The height of anterior edge of the affected vertebra and the Cobb's angle were assessed by imaging. RESULTS: All patients were followed up for at least 24 months. The volume of bone cement injection, intraoperative blood loss, occurrence of bone cement leakage, transient fever and re-fracture between two groups showed no significant difference. The surgical time, the operation cost and fluoroscopy times of the PKP group was significantly higher than that of the PVP group. The post-operative VAS, ODI scores, the height of the anterior edge of the injured vertebrae and kyphosis deformity were significantly improved in both groups compared with the pre-operation. The improvement of vertebral height and kyphosis deformity in PKP group was significantly better than that in the PVP group at every same time point during the follow-up periods, but the VAS and ODI scores between the two groups showed no significant difference. CONCLUSION: PVP and PKP can both significantly alleviate the pain of patients with KD and obtain good clinical efficacy and safety. By contrast, PKP can achieve better imaging height and kyphosis correction, while PVP has the advantages of shorter operation time, less radiation volume and operation cost.

Cadmium exposure alters expression of protective enzymes and protein processing genes in venom glands of the wolf spider Pardosa pseudoannulata.

Cadmium (Cd) pollution is currently the most serious type of heavy metal pollution throughout the world. Previous studies have shown that Cd elevates the mortality of paddy field spiders, but the lethal mechanism remains to be explored profoundly. In the present study, we measured the activities of protective enzymes (acetylcholinesterase, glutathione peroxidase, phenol oxidase) and a heavy metal chelating protein (metallothionein) in the pond wolf spider Pardosa pseudoannulata after Cd exposure. The results indicated that Cd initially increased the enzyme activities and protein concentration of the spider after 10- and 20-day exposure before inhibiting them at 30-day exposure. Further analysis showed that the enzyme activities in the cephalothorax were inhibited to some extent. Since the cephalothorax region contains important venom glands, we performed transcriptome sequencing (RNA-seq) analysis of the venom glands collected from the spiders after long-term Cd exposure. RNA-seq yielded a total of 2826 differentially expressed genes (DEGs), and most of the DEGs were annotated into the process of protein synthesis, processing and degradation. Furthermore, a mass of genes involved in protein recognition and endoplasmic reticulum (ER) -associated protein degradation were down-regulated. The reduction of protease activities supports the view that protein synthesis and degradation in organelles and cytoplasm were dramatically inhibited. Collectively, our outcomes illustrate that Cd poses adverse effects on the expression of protective enzymes and protein, which potentially down-regulates the immune function in the venom glands of the spiders via the alteration of protein processing and degradation in the ER.

Low energy extracorporeal shock wave therapy combined with low tension traction can better reshape the microenvironment in degenerated intervertebral disc regeneration and repair.

BACKGROUND: Low-tension traction is more effective than high-tension traction in restoring the height and rehydration of a degenerated disc and to some extent the bony endplate. This might better reshape the microenvironment for disc regeneration and repair. However, the repair of the combination of endplate sclerosis, osteophyte formation, and even collapse leading to partial or nearly complete occlusion of the nutrient channel is greatly limited. PURPOSE: To evaluate the effectiveness of low-intensity extracorporeal shock wave therapy (ESWT) combined with low tension traction for regeneration and repair of moderately and severely degenerated discs; to explore the possible mechanism of action. STUDY DESIGN: Animal study of a rat model of degenerated discs. METHODS: A total of thirty-five 6-month old male Sprague-Dawley rats were randomly assigned to one of five groups (n=7, each group). In Group A (model group), caudal vertebrae were immobilized using a custom-made external device to fix four caudal vertebrae (Co7-Co10) whereas Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration. In Group B (experimental control group), as in Group A, disc degeneration was successfully induced after which the fixed device was removed for 8 weeks of self-recovery. The remaining three groups of rats represented the intervention Groups (C-E): after successful generation of disc degeneration in Group C (com - 4w/tra - 4w) and Group D (com - 4w/ESWT), as described for group A, low-tension traction (in-situ traction) or low-energy ESWT was administered for 4 weeks (ESWT parameters: intensity: 0.15 Mpa; frequency: 1 Hz; impact: 1,000 each time; once/week, 4 times in total); Group E (com - 4w/tra - 4w/ESWT): disc degeneration as described for group A, low-tension traction combined with low-energy ESWT was conducted (ESWT parameters as Group D). After experimentation, caudal vertebrae were harvested and disc height, T2 signal intensity, disc morphology, total glycosaminoglycan (GAG) content, gene expression, structure of the Co8-Co9 bony endplates and elastic moduli of the discs were measured. RESULTS: After continuous low-tension traction, low energy ESWT intervention or combined intervention, the degenerated discs effectively recovered their height and became rehydrated. However, the response in Group D was weaker than in the other intervention groups in terms of restoration of intervertebral disc (IVD) height, whereas Group E was superior in disc rehydration. Tissue regeneration was evident in Groups C to E using different interventions. No apparent tissue regeneration was observed in the experimental control group (Group B). The histological scores of the three intervention groups (Groups C-E) were lower than those of Groups A or B (p<.0001), and the scores of Groups C and E were significantly lower than those of Group D (p<.05), but not Group C versus Group E (p>.05). Compared with the intervention groups (Groups C-E), total GAG content of the nucleus pulposus (NP) in Group B did not increase significantly (p>.05). There was also no significant difference in the total GAG content between Groups A and B (p>.05). Of the three intervention groups, the recovery of NP GAG content was greatest in Group E. The expression of collagen I and II, and aggrecan in the annulus fibrosus (AF) was up-regulated (p<.05), whereas the expression of MMP-3, MMP-13, and ADAMTS-4 was down-regulated (p<.05). Of the groups, Group E displayed the greatest degree of regulation. The trend in regulation of gene expression in the NP was essentially consistent with that of the AF, of which Group E was the greatest. In the intervention groups (Groups C-E), compared with Group A, the pore structure of the bony endplate displayed clear changes. The number of pores in the endplate in Groups C to E was significantly higher than in Group A (p<.0001), among which Group C versus Group D (p=.9724), and Group C versus Group E (p=.0116). There was no significant difference between Groups A and B (p=.5261). In addition, the pore diameter also increased, the trend essentially the same as that of pore density. There was no significant difference between the three intervention groups (p=.7213). It is worth noting that, compared with Groups A and B, peripheral pore density and size in Groups D and E of the three intervention groups recovered significantly. The elastic modulus and diameter of collagen fibers in the AF and NP varied with the type of intervention. Low tension traction combined with ESWT resulted in the greatest impact on the diameter and modulus of collagen fibers. CONCLUSIONS: Low energy ESWT combined with low tension traction provided a more stable intervertebral environment for the regeneration and repair of moderate and severe degenerative discs. Low energy ESWT promoted the regeneration of disc matrix by reducing MMP-3, MMP-13, and ADAMTS-4 resulting in inhibition of collagen degradation. Although axial traction promoted the recovery of height and rehydration of the IVD, combined with low energy ESWT, the micro-nano structure of the bony endplate underwent positive reconstruction, tension in the annulus of the AF and nuclear stress of the NP declined, and the biomechanical microenvironment required for IVD regeneration and repair was reshaped.

Treatment of Kümmell's disease with sequential infusion of bone cement: A retrospective study.

BACKGROUND: Percutaneous vertebroplasty (PVP) is an effective method for the treatment of neurologically intact Kümmell's disease, but bone cement leakage during surgery is a problem that deserves attention. AIM: To reduce bone cement leakage and evaluate the effect of the sequential infusion of bone cement during PVP for the treatment of stage I or II Kümmell's disease. METHODS: Patients with Kümmell's disease treated in our hospital from September 2015 to September 2018 were retrospectively analyzed. Patients meeting the inclusion and exclusion criteria were divided into two groups: Traditional single infusion and sequential infusion (SI). The visual analog scale (VAS) and Oswestry disability index (ODI) were evaluated and compared, and duration of operation, bone cement content and complications were recorded. RESULTS: Forty-five patients were included in this study; there were 24 in the traditional single infusion group and 21 in the SI group. The VAS and ODI were significantly different for both groups when compared pre- and postoperatively, whereas the differences between 1 wk postoperatively and at the final follow-up were not statistically. When the VAS and ODI of the two groups were compared, there were no significant differences at any time point. The leakage rate of bone cement was significantly lower in the SI group (14.3%, 3 of 21) than that in the traditional single infusion group (41.7%, 10 of 24). CONCLUSION: SI in unipedicular PVP is a safe and effective procedure for neurologically intact Kümmell's disease, and this technique could decrease the incidence of bone cement leakage.

Single door laminoplasty plus posterior fusion for posterior atlantoaxial dislocation with congenital malformation: A case report and review of literature.

BACKGROUND: Posterior atlantoaxial dislocation (PAD) is a rare type of upper cervical spine disease. We sought to describe a unreported case of old PAD with os odontoideum (OO) and atlas hypoplasia (AH) and our unique treatment approach consisting of C1 single door laminoplasty with C1-3 posterior fixation and fusion. CASE SUMMARY: A 70-year-old male patient who suffered from progressive aggravating numbness and limb weakness for 4 years without trauma, was diagnosed with old PAD with OO and AH. The patient underwent closed reduction and C1 single door laminoplasty with C1-3 posterior fixation and fusion instead of C1 laminectomy with occipitocervical fusion. During the 3-year follow-up, he was able to walk by himself instead of using a wheelchair and with a ± 25° range of head rotation as well as a ± 10° range of flexion-extension. Three-year follow-up images showed satisfactory reduction and fusion. CONCLUSION: C1 single door laminoplasty with cervical fusion in PAD combined with spinal cord compression could be a suitable and effective surgical option. Compared with laminectomy and occipitocervical fusion, it retains more cervical range of motion, has a smaller incision and provides an adequate bone grafting space for atlantoaxial fusion.

Exploratory meta-analysis on dose-related efficacy and complications of rhBMP-2 in anterior cervical discectomy and fusion: 1,539,021 cases from 2003 to 2017 studies.

BACKGROUND/OBJECTIVE: Anterior cervical discectomy and fusion (ACDF), commonly using autogenous iliac bone graft may be limited by donor site availability, donor-site morbidity, lower fusion rate among specific patients and longer surgical time. Surgeons used rhBMP-2 as an alternative in order to fill these clinical needs. However, studies comparing with and without rhBMP-2 in ACDF have reported conflicting results on efficacy and complications. Therefore, the purpose of this article was to evaluate efficacy and complications through dose-related rhBMP-2 and surgical level-dependence in ACDF. METHODS: We comprehensively searched PubMed and the Cochrane Library and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs), prospective and retrospective comparative studies assessing with and without rhBMP-2 treatments. RESULTS: 1 RCTs, 4 prospective studies and 24 retrospective studies including a total of 1,539,021 cases were identified. Patients in ACDF with rhBMP-2 might benefit from significantly higher fusion rates than that in non-rhBMP-2, not only total value but also in 3 tiers of rhBMP-2 doses. It is worth noting that the low dose of rhBMP-2 (<0.7 mg/level) showed highest fusion rate among all rhBMP-2 doses. Patients in rhBMP-2 also experienced higher complication rate, dysphagia and wound infections than that in non-rhBMP-2. In 2-level ACDF, the fusion rate was significantly better in rhBMP-2 than non-rhBMP-2 but not for complication rate. Surgery operative time, lengths of hospital stay and neurologic symptoms did not differ significantly between two treatments. CONCLUSIONS: rhBMP-2 chosen in ACDF offered higher fusion, but also higher complication rate with more dysphagia and wound infections than non-rhBMP-2. To gain the efficacy and safety, rhBMP-2 dosing recommendations for ACDF would be better < 0.7 mg/level. Moreover, rhBMP-2 may be an option to improve nonunion in high risk of multi-level ACDF. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This article indicated that the product development of facilities used in ACDF, the dose of rhBMP-2 may be lower than 0.7 mg/level was enough to gain the good fusion rates. However, the complications were higher in patients used rhBMP-2, therefore the manufacturers should pay attention to mitigate such side effects.