[Identification of cardioprotective substances in Panax ginseng/P. notoginseng based on mitochondrial morphological characteristics and UPLC-Triple-TOF-MS].

Panax ginseng is reputed to be capable of replenishing healthy Qi and bolstering physical strength, and P. notoginseng can resolve blood stasis and alleviate pain. P. ginseng and P. notoginseng are frequently employed to treat ischemic heart diseases caused by blockages in the heart vessels. Mitochondrial dysfunction often coexists with abnormal mitochondrial morphology, and mitochondrial plasticity and dynamics play key roles in cardiovascular diseases. In this study, primary neonatal rat cardiomyocytes were exposed to 4 hours of hypoxia(H) followed by 2 hours of reoxygenation(R). MitoTracker Deep Red and Hoechst 33342 were used to label mitochondria and nuclei, respectively. Fluorescence images were then acquired using ImageXpress Micro Confocal. Automated image processing and parameter extraction/calculation were carried out using ImagePro Plus. Subsequently, representative parameters were selected as indicators to assess alterations in mitochondrial morphology and function. The active compounds of P. ginseng and P. notoginseng were screened out and identified based on the UPLC-Triple-TOF-MS results and mitochondrial morphometric parameters. The findings demonstrated that RS-2, RS-4, SQ-1, and SQ-4 significantly increased the values of three key morphometric parameters, including mitochondrial length, branching, and area, which might contribute to rescuing morphological features of myocardial cells damaged by H/R injury. Among the active components of the two medicinal herbs, 20(R)-ginsenoside Rg_3, ginsenoside Re, and gypenoside ⅩⅦ exhibited the strongest protective effects on mitochondria in cardiomyocytes. Specifically, 20(R)-ginsenoside Rg_3 might upregulate expression of optic atrophy 1(OPA1) and mitofusin 2(MFN2), and ginsenoside Re and gypenoside ⅩⅦ might selectively upregulate OPA1 expression. Collectively, they promoted mitochondrial membrane fusion and mitigated mitochondrial damage, thereby exerting protective effects on cardiomyocytes. This study provides experimental support for the discovery of novel therapeutic agents for myocardial ischemia-reperfusion injury from P. ginseng and P. notoginseng and offers a novel approach for large-scale screening of bioactive compounds with cardioprotective effects from traditional Chinese medicines.

Glycyrrhizic acid attenuates sorafenib resistance by inducing ferroptosis via targeting mTOR signaling in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most malignant cancer worldwide. Sorafenib (SRF) is a common therapeutic drug used for patients with advanced HCC. Nevertheless, drug resistance frequently occurs in patients treated with sorafenib. Glycyrrhizic acid (GRA) is a natural compound that is identified to exhibit anti-cancer effects. In this work, we aimed to investigate the effects of GRA on SRF-resistant HCC cells and the potential regulatory mechanisms. METHODS: We established SRF-resistant HCC cell lines and administrated GRA treatment. We performed CCK-8 and colony formation experiments to detect cell proliferation. The accumulation of lipid reactive oxygen species (ROS) and iron levels were measured to evaluate ferroptosis. The protein levels of ferroptosis suppressor glutathione peroxidase 4 (GPX4) and SLC7A11, and the activation of AKT and mTOR were measured with western blotting assay. RESULTS: GRA treatment notably suppressed the viability and proliferation of SRF-resistant HCC cells. SRF-resistant HCC cells exhibited repressed ferroptosis level activated AKT/mTOR cascade, and GRA treatment reversed these effects. Inhibition of ferroptosis and activation of mTOR reversed the anti-proliferation effects of GRA on SRF-resistant HCC cells. CONCLUSION: Treatment with GRA could effectively reverse the SRF resistance of HCC cells via inducing ferroptosis and inactivating the AKT/mTOR cascade.

From the Destruction of Two Lumbar Segments to Thoracic-Lumbar-Pelvic Fusion: A Case Caused by Congenital Insensitivity to Pain with Anhidrosis and Literature Review.

BACKGROUND: Congenital insensitivity to pain with anhidrosis (CIPA) with Charcot arthropathy is a rare combination in orthopaedic clinical practice. The experience dealing with such patients is limited. Here with this case of approximately 10 years follow-up, we wish to shed light on the choices of strategies of surgeries and alerting clinicians with post-surgery complications. The possible underlying reasons for the recurrent Charcot arthropathies as well as strategies for peri-operative management for such surgical cases are also discussed. CASE PRESENTATION: The patient underwent a surgery to correct her severe kyphosis caused by CIPA-related Charcot spine. Multiple post-surgery complications occurred during her follow-up, including hardware migration, adjacent segment disease (ASD), and loosening pedicle screws. Five revision surgeries were conducted consequently. From the limited experience on the management of CIPA-related Charcot spine, surgical correction is still the first-line treatment. CONCLUSIONS: Of all the 16 cases reviewed (including our case), loosening pedicle screws, hardware migration, and ASDs are the common post-surgery complications. Large-scale removal of damaged vertebrae and subsequent reconstruction are not recommended, which might increase the risk of hardware migration. A 360° long-segment fusion might be of help to reduce the risk of ASDs. In the meantime, comprehensive management including careful nursing, proper rehabilitation exercises, and treatments targeting bone mineral metabolism is also critical.

Dissection of mendelian predisposition and complex genetic architecture of craniovertebral junction malformation.

The craniovertebral junction (CVJ) is an anatomically complex region of the axial skeleton that provides protection of the brainstem and the upper cervical spinal cord. Structural malformation of the CVJ gives rise to life-threatening neurological deficits, such as quadriplegia and dyspnea. Unfortunately, genetic studies on human subjects with CVJ malformation are limited and the pathogenesis remains largely elusive. In this study, we recruited 93 individuals with CVJ malformation and performed exome sequencing. Manual interpretation of the data identified three pathogenic variants in genes associated with Mendelian diseases, including CSNK2A1, MSX2, and DDX3X. In addition, the contribution of copy number variations (CNVs) to CVJ malformation was investigated and three pathogenic CNVs were identified in three affected individuals. To further dissect the complex mutational architecture of CVJ malformation, we performed a gene-based rare variant association analysis utilizing 4371 in-house exomes as control. Rare variants in LGI4 (carrier rate = 3.26%, p = 3.3 × 10-5) and BEST1 (carrier rate = 5.43%, p = 5.77 × 10-6) were identified to be associated with CVJ malformation. Furthermore, gene set analyses revealed that extracellular matrix- and RHO GTPase-associated biological pathways were found to be involved in the etiology of CVJ malformation. Overall, we comprehensively dissected the genetic underpinnings of CVJ malformation and identified several novel disease-associated genes and biological pathways.

Emission factors and chemical profile of I/SVOCs emitted from household biomass stove in China.

Household combustion of biomass straw for cooking or heating is one of the most important emission sources of intermediate volatility and semi-volatile organic compounds (I/SVOCs). However, there are limited studies on the emission factors (EFs) and speciation profiles of I/SVOCs from household stoves burning biomass straw. In this study, experiments were conducted in a typical Chinese stove to test the EFs and species of I/SVOCs in three commonly used straws. It was revealed that EFs of I/SVOCs emitted from the burning of corn straw, rice straw, and wheat straw were 6.7, 1.9, and 9.8 g/kg, respectively, which accounted for 48.3 %, 36.8 %, and 48.6 % of total organic compounds emitted. Particulate organic compounds were dominated by ketones, oxygenated aromatics, acids, esters, and nitrogen-containing compounds, whereas the gaseous phase was dominated by aldehydes, acids, and aromatics. Although I/SVOCs only accounted for 18.1-23.6 % of the gaseous emissions from burning of straw, they represented 64.8-72.9 % of the secondary organic aerosol formation potential (SOAFP). The EFs of 16 priority polycyclic aromatic hydrocarbons (PAHs) were 362.0, 262.5, and 1145.2 mg/kg for corn straw, rice straw, and wheat straw, respectively, among which 3-ring and 4-ring PAHs were the main components. Thus, the results of this study provide new reliable I/SVOCs data that are useful for the development of an accurate emission inventory of organic compounds, simulation of secondary organic aerosol (SOA) formation, and health risk assessment.

Severe complications and management of a patient with myasthenia gravis undergoing anterior cervical spinal surgery: a case report.

Surgical management of patients with comorbid long-term myasthenia gravis (MG) is particularly challenging and MG thus represents an independent risk factor for perioperative complications. However, few studies have reported on the perioperative assessment, prevention measures, and risks in MG patients undergoing major surgery, especially for anterior cervical spine surgery. We herein report the rare case of a 62-year-old man with a 20-year history of MG, who was admitted to our hospital with diagnosis of degenerative cervical spondylosis. He safely underwent anterior cervical corpectomy of C4, discectomy of C5-6, and fusion of C3-6. Intraoperative motor evoked potential was recorded to detect significant improvement after decompression. However, the patient suffered from progressive dysphagia, bucking, and hyperpyrexia 20 days after the initial operation. Imaging revealed titanium cage sliding and graft dislodgement. Secondary surgery was performed for posterior internal fixation from C2-7 and anterior revision from C3-6 after Halo-Vest traction, antibiotic treatment, and immunoglobulin therapy. He underwent a series of postoperative treatments, including cervicothoracolumbosacral orthosis, atomization inhalation, chest physiotherapy, antibiotics, and nutritional support. His condition improved markedly and he had no recurrence of symptoms during the 6-month follow-up. It is the rare reported case of anterior cervical spinal surgery in a patient with MG. This rare case indicates a relative contraindication to anterior-only approaches especially with multiple levels for MG patients with cervical spondylosis. Posterior approach, intraoperative monitoring, osteoporosis, postoperative strong brace protection, and supportive management should be considered for patients who were on large doses of steroids for long duration of time, given the lack of sufficient bone mineral density.

Comparative proteomics analysis for identifying the lipid metabolism related pathways in patients with Klippel-Feil syndrome.

BACKGROUND: Klippel-Feil syndrome (KFS) represents the rare and complex deformity characterized by congenital defects in the formation or segmentation of the cervical vertebrae. There is a wide gap in understanding the detailed mechanisms of KFS because of its rarity, heterogeneity, small pedigrees, and the broad spectrum of anomalies. METHODS: We recruited eight patients of Chinese Han ethnicity with KFS, five patients with congenital scoliosis (CS) who presented with congenital fusion of the thoracic or lumbar spine and without known syndrome or cervical deformity, and seven healthy controls. Proteomic analysis by data-independent acquisition (DIA) was performed to identify the differential proteome among the three matched groups and the data were analyzed by bioinformatics tools including Gene Ontology (GO) categories and Ingenuity Pathway Analysis (IPA) database, to explore differentially abundant proteins (DAPs) and canonical pathways involved in the pathogenesis of KFS. RESULTS: A total of 49 DAPs were detected between KFS patients and the controls, and moreover, 192 DAPs were identified between patients with KFS and patients with CS. Fifteen DAPs that were common in both comparisons were considered as candidate biomarkers for KFS, including membrane primary amine oxidase, noelin, galectin-3-binding protein, cadherin-5, glyceraldehyde-3-phosphate dehydrogenase, peroxiredoxin-1, CD109 antigen, and eight immunoglobulins. Furthermore, the same significant canonical pathways of LXR/RXR activation and FXR/RXR activation were observed in both comparisons. Seven of DAPs were apolipoproteins related to these pathways that are involved in lipid metabolism. CONCLUSIONS: This study provides the first proteomic profile for understanding the pathogenesis and identifying predictive biomarkers of KFS. We detected 15 DAPs that were common in both comparisons as candidate predictive biomarkers of KFS. The lipid metabolism-related canonical pathways of LXR/RXR and FXR/RXR activation together with seven differentially abundant apolipoproteins may play significant roles in the etiology of KFS and provide possible pathogenesis correlation between KFS and CS.

Posterior fossa decompression with or without duraplasty for patients with chiari type I malformation and basilar impression: a meta-analysis.

BACKGROUND: To compare clinical effect and safety between posterior fossa decompression with duraplasty (PFDD) and posterior fossa decompression without duraplasty (PFD) in treatment of Chiari type I malformation and basilar impression. METHODS: A comprehensive computer search was conducted from 2000 to 2019. The quality assessment was performed by the QUADAS-2 tool. The clinical value of comparison between PFDD and PFD was evaluated by using the pooled estimate of sensitivity and specificity. In addition, sensitivity analysis and bias analysis were applied to ensure the accuracy of the results. RESULTS: Finally, 468 patients were enrolled in 6 studies and ultimately met the eligibility criteria. The PFDD and PFD groups were 282 and 186, respectively. The meta-analysis showed no significant difference in the Chicago Chiari Outcome Scale (COSS score) (MD = 0.14, 95% CI [-0.23, 0.50], P = 0.47; P = heterogeneity = 0.86, I2 = 0%). Meanwhile, Significant difference existed in length of stay (MD = -1.08, 95% CI [-1.32, -0.84], P = 0.001; heterogeneity P < 0.000001, I2 = 85%) and complications (OR = 0.35, 95%CI [0.20, 0.62], P = 0.0003; P for Heterogeneity = 0.04, I2 = 56%). CONCLUSION: PFD is a more efficient and safer therapy than PFDD in the treatment of Chiari type I malformation with basilar impression.

Neurofibromatosis Type 1 with Severe Dystrophic Kyphosis: Surgical Treatment and Prognostic Analysis of 27 Patients.

OBJECTIVE: The aim of the present study was to explore the surgical treatment and prognosis of 27 cases of neurofibromatosis type 1 with severe dystrophic kyphosis. METHODS: We performed surgical treatment for scoliosis and kyphosis caused by dystrophic curves at Peking Union Medical College Hospital, Beijing, China from December 2015 to December 2017. The study included 21 patients with moderate to severe kyphosis, 12 males and 9 females, with an average age of 14.95 ± 6.05 years. All patients had kyphosis angles greater than 70° and had more than four skeletal developmental defects. A total of 6 patients with severe kyphosis, 2 males and 4 females, with an average age of 12.5 years, had more than five skeletal developmental defects with a kyphosis angle greater than 90° or a lumbar kyphosis angle greater than 40°. According to the patient's own situation, we adopted a low-grade surgery scheme (grades 1 or 2) or a high-grade surgery scheme (grades 3-6). The low-grade surgery was mainly lower articular surface resection or pontodestomy, and the high-grade surgery was mainly apical vertebral body or upper discectomy. All patients were followed up to determine their prognosis. RESULTS: Statistical analysis showed that there was a significant difference in preoperative and postoperative scores between the two groups (P < 0.05), and scoliosis correction showed that surgical treatment had a significant effect on scoliosis kyphosis. The mean follow-up time was 66.7 months. Follow-up results showed that 50% of complications after internal fixation were related to high-level surgery. Complications included displacement of the titanium cage, removal of the lamina hook, formation of pseudoarthrosis, and internal fixation failure (with a rate of 7.7%-14.3%). In contrast, there were no associated symptoms for low-grade surgery. In addition, the results showed that gender, age, extent of resection, height, and body mass index had no significant effect on preoperative, postoperative, and prognostic indicators of patients (P > 0.05). CONCLUSION: Early identification of dysplastic scoliosis-related deformities plays an important role in surgical planning and prognosis, and low-level surgical procedures are more favorable for patients' prognosis.

Effectiveness of three-dimensional printed and virtual reality models in learning the morphology of craniovertebral junction deformities: a multicentre, randomised controlled study.

OBJECTIVES: To compare the effectiveness of three-dimensional printed (3DP), virtual reality (VR) and conventional normal physical (NP) models in clinical education regarding the morphology of craniovertebral junction (CVJ) deformities. DESIGN: Prospective, multicentre, randomised controlled study. SETTING: Three teaching hospitals in China. PARTICIPANTS: One hundred and fifty-three participants in their first year of a 3-year medical residency programme. INTERVENTIONS: All participants were randomised to one of the three groups to learn the morphology of CVJ deformities using 3DP, VR or NP models. PRIMARY OUTCOME MEASURES: The objective outcomes were evaluated using three-level objective testing. In the first-level test, the participants were required to identify 15 anatomical landmarks on radiographs without CVJ deformities. In the second-level test, all participants were asked to identify the same 15 landmarks on radiographs showing classic CVJ deformities. In the third-level test, the participants were required to describe the key features of three classic cases of CVJ deformities depicted on radiographs. Each participant was also asked to answer four subjective questions to evaluate the importance and usefulness of the educational materials. RESULTS: In the first-level test, the 3DP, VR and NP groups achieved similar correct rates. In the second-level test, the correct rate was higher in the 3DP group (82.1%±13.6%) than the VR and NP groups (76.9%±16.9% and 69.9%±20.0%, p=0.002). In the third-level test, the 3DP group achieved better correct rates regarding the description of key CVJ deformities features (66.2%±20.0%, p=0.049) than the other groups. The subjective tests showed that the 3DP model method was considered the most valuable approach for learning CVJ deformities. CONCLUSIONS: The objective and subjective results show that the 3DP model is more effective teaching instrument than the NP model for learning the pathomorphology of CVJ deformities. The VR model also showed great efficacy, second to 3DP model, in improving participants' understanding of CVJ deformities.

Comparison between surgical fusion and the growing-rod technique for early-onset neurofibromatosis type-1 dystrophic scoliosis.

BACKGROUND: Spinal deformities constitute one of the most common types of manifestations of neurofibromatosis type-1 (NF-1), which can lead to either dystrophic or non-dystrophic early-onset scoliosis (EOS). Surgical treatment for EOS with NF-1 is challenging, and the outcomes have rarely been reported. The anterior-posterior procedure is widely used, but posterior-only fusion is theoretically easier and safer to perform. Is it possible that a new surgery that accommodates growth is a better choice? A direct comparison between posterior fusion and growth-friendly surgery in terms of surgical outcomes has not yet been conducted in dystrophic EOS with NF-1 patients. METHODS: Baseline information was extracted from the NF-1 database at our institute with approval from the local ethics committee. All enrolled patients were diagnosed with NF-1. Clinical and radiographic data were recorded preoperatively, after the initial surgery, and at the final follow-up. Implant-related, alignment, neurological complication and unplanned revision surgery data were recorded. We compared the outcomes of these two groups in terms of curve correction, growth parameters, complications and unplanned revision surgeries. RESULTS: There were eight patients in the PF group and eight patients in the GR group, with a mean follow-up of 51.0 ± 17.5 months. The main curve size was similar (PF 67.38° ± 17.43° versus GR 75.1° ± 26.43°, P = 0.501), and there were no significant differences in the initial surgery correction rate or the rate of correction. However, the patients in the GR group exhibited more T1-S1 growth during the follow-up overall and per year than did those in the PF group. The operative time was significantly longer for the PF group than for the GR group (PF, 4.39 ± 1.38 vs. GR, 3.00 ± 0.42 h; p = 0.008). Significantly fewer segments were involved in the PF group (8.25 ± 3.20) than in the GR group (13.00 ± 1.60). CONCLUSION: For the initial treatment of dystrophic EOS in patients with NF-1, the GR technique is possibly a more appropriate treatment than is the PF technique in terms of trunk growth. However, the repeated procedures required for GR may be a considerable disadvantage. More studies with direct measurement of pulmonary function must be conducted to determine the effect of GR on pulmonary development. More studies with larger sample sizes and longer follow-up periods are needed to fully assess the treatment strategies.

Cement leakage following percutaneous kyphoplasty in a patient after a posterior lumbar fusion: a case report.

BACKGROUND: Percutaneous kyphoplasty (PKP) has become an important minimally invasive surgical technique for fracture stabilization and pain relief in patients with vertebral compression fractures. However, intraspinal cement leakage following PKP is a serious postoperative complication that can lead to morbidity and mortality. CASE PRESENTATION: We describe an uncommon case of epidural leakage of bone cement in an 81-year-old woman who underwent posterior lumbar decompression and fusion from L3-5 4 years prior and had an unremarkable postoperative course. The patient was admitted to Peking Union Medical College Hospital with complaints of muscle weakness and severe low back pain radiating to the left thigh 1 week after PKP of L5 due to an acute osteoporotic compression fracture. Computed tomographic imaging revealed massive leakage of cement into the spinal canal at L5-S1, and therefore, surgical decompression and removal of epidural cement were performed carefully without causing a dural tear. She improved remarkably and no neurologic deterioration was observed in the postoperative period during the one-year follow-up. CONCLUSIONS: We present the rare reported case, to our knowledge, of epidural cement leakage after PKP at the segment of internal fixation and discuss the most likely etiologies and preventive measures for this condition.

The mutational burden and oligogenic inheritance in Klippel-Feil syndrome.

BACKGROUND: Klippel-Feil syndrome (KFS) represents a rare anomaly characterized by congenital fusion of the cervical vertebrae. The underlying molecular etiology remains largely unknown because of the genetic and phenotypic heterogeneity. METHODS: We consecutively recruited a Chinese cohort of 37 patients with KFS. The clinical manifestations and radiological assessments were analyzed and whole-exome sequencing (WES) was performed. Additionally, rare variants in KFS cases and controls were compared using genetic burden analysis. RESULTS: We primarily examined rare variants in five reported genes (GDF6, MEOX1, GDF3, MYO18B and RIPPLY2) associated with KFS and detected three variants of uncertain significance in MYO18B. Based on rare variant burden analysis of 96 candidate genes related to vertebral segmentation defects, we identified BAZ1B as having the highest probability of association with KFS, followed by FREM2, SUFU, VANGL1 and KMT2D. In addition, seven patients were proposed to show potential oligogenic inheritance involving more than one variants in candidate genes, the frequency of which was significantly higher than that in the in-house controls. CONCLUSIONS: Our study presents an exome-sequenced cohort and identifies five novel genes potentially associated with KFS, extending the spectrum of known mutations contributing to this syndrome. Furthermore, the genetic burden analysis provides further evidence for potential oligogenic inheritance of KFS.

Posterior only instrumented fusion provides incomplete curve control for early-onset scoliosis in type 1 neurofibromatosis.

BACKGROUND: The mid-long term outcomes of posterior spinal fusion in pediatric neurofibromatosis type 1 (NF-1) patients are rarely reported, so does the effectiveness of itsorthopeidc maintenance function. This study aims to evaluate the mid-long term surgical outcomes of posterior only instrumented spinal fusion for early-onset scoliosis (EOS) in NF-1 patients. METHODS: A retrospective review was performed on a cohort of 10 NF-1 patients having EOS from 2008 to 2014 in our hospital, the age averaged at 7.8 years old when they underwent posterior only instrumented spinal fusion for their EOS. Both general clinical data and surgical specific data of the patients were collected and reviewed, and the dystrophic progression of EOS was evaluated during the follow-up. RESULTS: The average duration of follow-up was 54 months (24 to 88 months). All patients underwent posterior only instrumented spinal fusion at 1 stage. The primary curves of EOS were thoracic in 9 cases and 1 patient had lumbar scoliosis. Preoperative major curve was significantly corrected (from 66.1 to 31.1 degrees). However, the major curve deteriorated significantly to 40.1 degrees on average at the end of the follow-up. The T1-S1 distance increased 2.8 cm on average and kept increasing at a rate of 0.6 cm/year during the follow-up. CONCLUSIONS: Posterior only fusion surgery was not a good option to treat the EOS in NF-1 patients despite the relatively short segments involvement in the disease. The maintenance of orthopedic effect after treatment was not satisfactory.

Transcriptome-wide Sequencing Reveals Molecules and Pathways Involved in Neurofibromatosis Type I Combined With Spinal Deformities.

MINI: We identified differentially expressed genes (DEGs) that may be involved in the development of neurofibromatosis type I by whole-transcriptional sequencing. Seven hundred eighty DEGs were identified which include protein coding genes, miRNAs, and lncRNAs. The enrichment analysis may reveal pathways that these DEGs involved. A total of 383 protein-pairs for DEGs may unfold the possible mechanism how the disease is developed. STUDY DESIGN: This is a clinical basic study on neurofibromatosis type I (NF-1) with spinal deformity. OBJECTIVE: The current research focuses on screening key molecules affecting NF-1 with spinal deformity by transcriptome sequencing and discovering its underlying molecular biological mechanisms. SUMMARY OF BACKGROUND DATA: NF-1 is a complex multisystem human disorder, which is often found in spinal deformities patients. The success rate of orthopedic surgery for neurofibromatosis type I combined with spinal deformities patients was low because of the lack of molecular pathology. METHODS: In our study, the transcriptome-wide sequencing was preformed to identify the differentially expressed genes (DEGs) involved in this disease. RESULTS: Seven hundred eighty DEGs were identified which include protein coding genes, miRNAs, and lncRNAs. The DO, GO, KEGG and Reactome enrichment analysis may reveal pathways that these DEGs involved. And the 383 protein-pairs for DEGs that are involved in NF-1 combined with spinal deformities may unfold the possible mechanism how this disease is developed. CONCLUSION: The differentially expressed miRNAs and lncRNAs may contribute the ceRNA network. We focused on three key DEGs: FGFR2, MAP3K1 and STAT4. FGFR2 and MAP3K1 are members of the RAS/RAF/MEK/ERK-signaling pathway, and STAT4 were involved in the JAK/STAT pathway. The expression changes were verified by other researches and the functional cross-talk between the Ras/MAPK and JAK/STAT pathways may contribute in the disease development. This study took insight of the molecular mechanism of this disease. More detailed interactions between these factors are needed to be further explored. These key DEGs and involved pathways may provide clues in the clinical process for patients with NF-1, especially in prognosis prediction. LEVEL OF EVIDENCE: N/A.

This is a clinical basic study on neurofibromatosis type I (NF-1) with spinal deformity. The current research focuses on screening key molecules affecting NF-1 with spinal deformity by transcriptome sequencing and discovering its underlying molecular biological mechanisms. NF-1 is a complex multisystem human disorder, which is often found in spinal deformities patients. The success rate of orthopedic surgery for neurofibromatosis type I combined with spinal deformities patients was low because of the lack of molecular pathology. In our study, the transcriptome-wide sequencing was preformed to identify the differentially expressed genes (DEGs) involved in this disease. Seven hundred eighty DEGs were identified which include protein coding genes, miRNAs, and lncRNAs. The DO, GO, KEGG and Reactome enrichment analysis may reveal pathways that these DEGs involved. And the 383 protein-pairs for DEGs that are involved in NF-1 combined with spinal deformities may unfold the possible mechanism how this disease is developed. The differentially expressed miRNAs and lncRNAs may contribute the ceRNA network. We focused on three key DEGs: FGFR2, MAP3K1 and STAT4. FGFR2 and MAP3K1 are members of the RAS/RAF/MEK/ERK-signaling pathway, and STAT4 were involved in the JAK/STAT pathway. The expression changes were verified by other researches and the functional cross-talk between the Ras/MAPK and JAK/STAT pathways may contribute in the disease development. This study took insight of the molecular mechanism of this disease. More detailed interactions between these factors are needed to be further explored. These key DEGs and involved pathways may provide clues in the clinical process for patients with NF-1, especially in prognosis prediction. Level of Evidence: N/A.

Outcomes of 360° Osteotomy in the Cervicothoracic Spine (C7-T1) for Congenital Cervicothoracic Kyphoscoliosis in Children.

BACKGROUND: There have been many reports on the treatment of congenital kyphoscoliosis. However, congenital deformities in the cervicothoracic spine (C7-T1) have not been well described because of the rarity of these conditions. METHODS: The medical records and imaging studies of 25 children who were treated with 360° osteotomy for congenital deformities in the cervicothoracic spine (C7-T1) at a mean age of 11.4 years were reviewed. RESULTS: All 25 children presented with torticollis; 4 presented with neck pain; 10, with facial asymmetry; and 3, with preoperative neurological deficits. Twenty-three patients had congenital deformities in other regions of the spine. Six patients had a total of 8 intraspinal deformities. On average, the cervicothoracic curve was corrected from 53° preoperatively to 14° at the latest follow-up, the segmental kyphosis was corrected from 25° to 12°, and the head tilt improved from 25° to 5°. Nineteen patients had a total of 28 complications, including 1 transient cord injury together with a permanent C8 nerve root injury, 11 transient nerve root injuries, 1 transient Horner syndrome, 9 cases of decompensation of a compensatory curve, 2 implant failures, 2 cases of hemothorax, 1 dural tear, and 1 case of delayed wound-healing. CONCLUSIONS: Most congenital cervicothoracic deformities are fixed, and early surgical intervention may be needed. A 360° osteotomy is indicated for this type of rigid deformity and may provide satisfactory correction. However, 360° osteotomy in the cervicothoracic spine (C7-T1) is technically demanding with a higher risk of nerve root injuries, although most injuries tend to be transient. If the compensatory thoracic curve is severe and rigid, 1-stage or staged surgery in this region may be required. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Time-Resolved Intermediate-Volatility and Semivolatile Organic Compound Emissions from Household Coal Combustion in Northern China.

Coal combustion in low-efficiency household stoves results in the emission of large amounts of nonmethane organic compounds (NMOCs), including intermediate-volatility compounds (IVOCs) and semivolatile organic compounds (SVOCs). This conceptual picture is reasonably well established, however, quantitative assessment of I/SVOC emissions from household stoves is rare. We used a proton-transfer-reaction time-of-flight mass spectrometer (PTR-ToF-MS) to quantify the emissions of organic gases from a typical Chinese household coal stove operated with anthracite and bituminous coals. Most NMOCs (approximately 64-88%) were dominated by hydrocarbons and emitted during the ignition and flaming phases. The ratio of oxidized hydrocarbons increased during the flaming and smoldering stages due to the elevated combustion efficiency. The average emission factors of NMOCs were 121 ± 25.7 and 3690 ± 930 mg/kg for anthracite and bituminous coals, respectively. I/SVOCs contributed to approximately 30% of the total emitted NMOC mass during bituminous coal combustion, much higher than the contribution of biomass burning (approximately 1.5%). Furthermore, I/SVOCs may contribute over 70% of the secondary organic aerosol (SOA) mass formed from gaseous organic species emitted as a result of bituminous coal combustion. This study highlights the importance of inventorying coal-originated I/SVOCs when conducting SOA formation simulation studies.

Gasification of coal and biomass as a net carbon-negative power source for environment-friendly electricity generation in China.

Realizing the goal of the Paris Agreement to limit global warming to 2 °C by the end of this century will most likely require deployment of carbon-negative technologies. It is particularly important that China, as the world's top carbon emitter, avoids being locked into carbon-intensive, coal-fired power-generation technologies and undertakes a smooth transition from high- to negative-carbon electricity production. We focus here on deploying a combination of coal and biomass energy to produce electricity in China using an integrated gasification cycle system combined with carbon capture and storage (CBECCS). Such a system will also reduce air pollutant emissions, thus contributing to China's near-term goal of improving air quality. We evaluate the bus-bar electricity-generation prices for CBECCS with mixing ratios of crop residues varying from 0 to 100%, as well as associated costs for carbon mitigation and cobenefits for air quality. We find that CBECCS systems employing a crop residue ratio of 35% could produce electricity with net-zero life-cycle emissions of greenhouse gases, with a levelized cost of electricity of no more than 9.2 US cents per kilowatt hour. A carbon price of approximately $52.0 per ton would make CBECCS cost-competitive with pulverized coal power plants. Therefore, our results provide critical insights for designing a CBECCS strategy in China to harness near-term air-quality cobenefits while laying the foundation for achieving negative carbon emissions in the long run.