SIMarker: Cellular similarity detection and its application to diagnosis and prognosis of liver cancer.

BACKGROUND: The emergence of single-cell technology offers a unique opportunity to explore cellular similarity and heterogeneity between precancerous diseases and solid tumors. However, there is lacking a systematic study for identifying and characterizing similarities at single-cell resolution. METHODS: We developed SIMarker, a computational framework to detect cellular similarities between precancerous diseases and solid tumors based on gene expression at single-cell resolution. Taking hepatocellular carcinoma (HCC) as a case study, we quantified the cellular and molecular connections between HCC and cirrhosis. Core analysis modules of SIMarker is publicly available at https://github.com/xmuhuanglab/SIMarker ("SIM" means "similarity" and "Marker" means "biomarkers). RESULTS: We found PGA5+ hepatocytes in HCC showed cirrhosis-like characteristics, including similar transcriptional programs and gene regulatory networks. Consequently, the genes constituting the gene expression program of these cirrhosis-like subpopulations were designated as cirrhosis-like signatures (CLS). Strikingly, our utilization of CLS enabled the development of diagnosis and prognosis biomarkers based on within-sample relative expression orderings of gene pairs. These biomarkers achieved high precision and concordance compared with previous studies. CONCLUSIONS: Our work provides a systematic method to investigate the clinical translational significance of cellular similarities between HCC and cirrhosis, which opens avenues for identifying similar paradigms in other categories of cancers and diseases.

Staged osteotomy in lateral position for the treatment of severe kyphotic deformity secondary to ankylosing spondylitis: a retrospective study.

BACKGROUND: Patients with severe kyphotic deformity (Cobb > 100°) secondary to ankylosing spondylitis (AS) occasionally cannot undergo corrective surgery in the prone position. Osteotomy in the lateral position might provide a possible solution. In this study, we aim to evaluate the clinical efficacy and safety of staged osteotomy in the lateral position for the treatment of AS-related severe kyphosis with a minimum of 2-year follow-up. METHODS: In total, 23 patients who underwent staged osteotomy in the lateral position from October 2015 to June 2017 were analyzed. In the first stage of surgery, all but one patient underwent a single-level Ponte osteotomy, which was followed by a pedicle subtraction osteotomy in the second stage. Mean follow-up was 30.8 ± 4.6 months. Global kyphosis (GK), thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), osteotomized vertebra intervertebral angle (OVI), chin-brow vertical angle (CBVA), Oswestry Disability Index (ODI) score and Scoliosis Research Society-22 Patient Questionnaire (SRS-22) were all compared pre- and postoperation. RESULTS: All kyphosis parameters were significantly improved (all P < 0.05). GK was corrected from 115.0 ± 13.4° to 46.5 ± 9.0° postoperatively, with a mean correction of 68.5°. SVA was improved from 21.2 ± 5.1 cm to 5.1 ± 1.8 cm postoperatively. After surgery, CBVA was adjusted from 64.1 ± 23.2° to 5.7 ± 10.6° and OVI was changed from 9.0 ± 2.7° to - 20.1 ± 5.6°. Both the ODI and SRS-22 showed substantial improvements (all P < 0.05). Four patients with mild complications were observed perioperatively. CONCLUSION: In AS patients with severe kyphosis, satisfactory correction can be safely achieved with staged osteotomy in the lateral position, which can not only correct the sagittal imbalance of the spine with acceptable complications but also facilitate the placement of the intraoperative position.

A novel surgical strategy of three column osteotomy at non-lesioned area for correcting severe angular kyphosis due to Pott's disease: a retrospectively study.

Severe sharp angular kyphosis resulting from Pott's disease typically necessitates surgical intervention. The deployment of three-column osteotomy within the lesion and apical regions has been validated as an effective modality for the amelioration of angular kyphosis. Nonetheless, a propensity for residual kyphosis persists, accompanied by a significant perioperative risk profile. In pursuit of optimizing correctional outcomes and diminishing complication rates, we proposed an innovative surgical approach, utilizing osteotomy in the non-lesioned zones for the rectification of severe angular kyphosis associated with Pott's disease. This retrospective investigation encompasses 16 subjects who underwent this novel surgical tactic, involving osteotomies in non-lesioned vertebral segments, at our institution from 2016 to 2018. Radiographic measures, encompassing kyphotic angle and sagittal vertical axis (SVA), were documented at baseline and during terminal follow-up. Neurological status was evaluated via the American Spinal Injury Association (ASIA) grading system. Operative duration, volume of hemorrhage, and perioperative complications were systematically recorded. The cohort included 6 males and 10 females with an average age of 30.7 ± 11.41 years. Follow-up intervals spanned 24 to 42 months. Mean operative time and blood loss were 492 ± 127.3 min and 1791 ± 788.8 ml, respectively. The kyphotic angle improved from 97.6 ± 14.6° to 28.8 ± 18.70°. In cases with lumbar afflictions, vertebral restoration was achieved (L1-L5 and L2-S1). Initial mean SVA of 6.7 ± 3.58 cm was reduced to 3.3 ± 1.57 cm at follow-up. Neurological function enhancement was observed in six patients, while ten maintained baseline status. Complication rates, including wound infection and rod fracture at 12 months, were observed in approximately 11.8% of cases. Our findings suggest that the surgical strategy is both effective and safe for addressing severe angular kyphosis due to Pott's disease, contingent upon the expertise of the surgical unit.

Single-cell transcriptional regulation and genetic evolution of neuroendocrine prostate cancer.

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer, with a 10% five-year survival rate. However, little is known about its origin and the mechanisms governing its emergence. Our study characterized ADPC and NEPC in prostate tumors from 7 patients using scRNA-seq. First, we identified two NEPC gene expression signatures representing different phases of trans-differentiation. New marker genes we identified may be used for clinical diagnosis. Second, integrative analyses combining expression and subclonal architecture revealed different paths by which NEPC diverges from the original ADPC, either directly from treatment-naïve tumor cells or from specific intermediate states of treatment-resistance. Third, we inferred a hierarchical transcription factor (TF) network underlying the progression, which involves constitutive regulation by ASCL1, FOXA2, and selective regulation by NKX2-2, POU3F2, and SOX2. Together, these results defined the complex expression profiles and advanced our understanding of the genetic and transcriptomic mechanisms leading to NEPC differentiation.

[Classification, diagnosis, and treatment system of posteromedial structure and posterolateral corner injury in knee dislocation].

Objective: To review the research progress of diagnosis and treatment system for knee dislocation (KD) based on the stage and classification of posteromedial structure and posterolateral corner injury, so as to provide guidance for clinical work. Methods: The relevant literature on the classification, diagnosis and treatment was extensively reviewed. Results: At present, the criterion of the stage and classification of KD mainly include classification based on the size of the injury energy, Kennedy classification, and the improved Schenck classification, but they are not perfect because of no stage and classification of multiple ligament injury and no standardized treatment of different injuries. Hua Xi Knee Dislocation and Multiple Ligament Injury (HX-KDMLI) has optimum plan for injury treatment of posteromedial structure and posterolateral corner injury in KD based on stage and classification. Conclusion: At present, there is no unified opinion on stages and classifications of the posteromedial structure and posterolateral corner injury in KD as well as on diagnosis and treatment. HX-KDMLI has certain feasibility for the stage and classification of the posteromedial structure and posterolateral corner injury in KD, to a certain extent, it can be used as reference for the diagnosis and treatment of KD.