The selection of a surgical strategy for the treatment of adult degenerative scoliosis with "pear-shaped" decompression under open spinal endoscopy.

The prognoses of patients who undergo open spinal endoscopy (OSE) decompression significantly differ by scoliosis type and symptom despite the use of uniform standards and procedures for the decompression surgery. These differences may be directly related to the selection and formulation of surgical strategies but their cause remains unclear. The aim of this study was to verify and evaluate the efficacy of the "Symptom, Stenosis and Segment classification (SSS classification)" in determining an appropriate surgical strategy and to analyze the differences in the outcomes of different patients after receiving the selected surgical strategy. The results of this study ultimately provide a theoretical basis for the specific optimization of surgical strategies guided by the "SSS classification". This work was a retrospective study. We reviewed 55 patients with scoliosis and spinal stenosis who underwent "pear-shaped" decompression under OSE from May 2021 to June 2023 treated by our surgical team. To classify different types of patients, we defined the "SSS classification" system. The permutation and combination of subtypes in Symptom (including three subtypes: Convex = v, Concave = c and Bilateral = b), Stenosis (including three subtypes: Convex = v, Concave = c and Bilateral = b), and Segment (including two subtypes: Edge = e and Inside = i) yields 18 possible types (details in Table 1) in this classification system. To classify different types of surgeries, we also defined the operation system. The VAS Back and VAS Leg scores after surgical treatment were significantly lower in all patients 3 months after surgery than before surgery. (**P < 0.05). The Svve type accounted for the greatest proportion of patients (62.50%) in the VAS back remission group, and the Scce type accounted for the greatest proportion (57.14%) in the VAS back ineffective group. According to the VAS leg score, the percentage of patients in whom Svve was detected in the VAS leg remission group reached 60.87%, and the percentage of patients in whom Svve was detected in the VAS leg ineffective group reached 44.44%. Svve accounted for the greatest proportion of cases (61.22%) in the JOA-effective group, and Scce accounted for the greatest proportion of cases (50.00%) in the JOA-ineffective group. In the JOA-effective group, the Ovv type accounted for the greatest proportion (up to 79.59%), while in the JOA-ineffective group, Occ and Ovv accounted for 50.00% of the cases each. The proportions of Svve type were the highest in the healthy group (up to 60.00%) and the ODI-effective group (up to 50.00%). The Ovv type accounted for the greatest proportion of patients in the ODI-effective group (up to 80.00%), and the Occ type accounted for the greatest proportion of patients in the ODI-ineffective group (up to 60.00%). Most of the surgical plans formulated by the "SSS classification" method were considered appropriate, and only when the symptoms of patients were located on the concave side did the endoscopic decompression plan used in the present study have a limited ability to alleviate symptoms.

Closed Reduction for the Treatment of Traumatic Thoracolumbar Spondylolisthesis.

OBJECTIVE: Thoracolumbar traumatic spondylolisthesis is a relatively rare phenomenon and has poor prognosis due to serious spinal cord or cauda equina injuries. In such cases, closed reduction is a method for restoring the vertebral sequence and may play an important role in the treatment process, although whether it is actually feasible for patients with this condition requires further investigation. The present study included 9 patients with serious thoracolumbar traumatic spondylolisthesis to determine the advantages of closed reduction over total reduction through open surgery. METHODS: Data from 9 patients (cases 1-9), diagnosed with severe thoracolumbar traumatic spondylolisthesis between June 2012 and August 2023, were retrospectively reviewed. Five patients were treated with closed reduction in an emergency department and subsequently underwent delayed internal fixation surgery at least 48 hours after the injury, and 4 with similar serious injuries underwent emergency surgery. The incidence of complications and recovery of the spinal cord or cauda equina were compared between groups. RESULTS: There were no significant differences in demographic characteristics or adverse events between the 2 groups. The reduction group had a shorter surgical duration and less blood loss than the surgery group. Although patients in the surgery group may have experienced more pain, there were no significant differences between the groups in Oswestry Disability Index or Japanese Orthopaedic Association scores. Thus, regardless of whether closed reduction was chosen, patients experienced a similar quality of life for a relatively prolonged period. CONCLUSIONS: Closed reduction may be feasible for serious thoracolumbar traumatic spondylolisthesis, although the safety of this method requires further research.

MACF1 mutations predict poor prognosis: a novel potential therapeutic target for breast cancer.

OBJECTIVE: Microtubule actin cross-linking factor 1 (MACF1) mutations are known to play an important role in the progression of various cancers. However, its role in breast cancer remains to be determined. In this study, we investigated how MACF1 mutations may play a role in breast cancer development. METHODS: The gene-expression profile data of patients with breast cancer were obtained from The Cancer Genome Atlas (TCGA)-Breast cancer cohort. We estimated the influence of MACF1 mutations on patient clinical prognosis using the Kaplan-Meier method. Further, patients with MACF1-mutant (MACF1-MT) and MACF1-wild-type (MACF1-WT) were compared to identify the differentially expressed genes (DEGs). We also performed functional enrichment analyses, constructed protein-protein interaction (PPI) and competing endogenous RNA (ceRNA) networks, and investigated the correlation between MACF1 mutations and immune-cell infiltration. To explore the prognostic value of MACF1 mutations, a nomogram was developed based on MACF1 mutations and other clinicopathological parameters. RESULTS: Patients with MACF1-MT had a worse prognosis and higher tumor mutation burden score (P < 0.05) than patients with MACF1-WT. MACF1 mutations were demonstrated to upregulate the mTOR signaling pathway and alter energy metabolism and tumor immune microenvironment. Thus, MACF1 mutations might affect immunogenicity and result in a lower response to immunotherapy. By analyzing the Genomics of Drug Sensitivity in Cancer (GDSC), the sensitivity of breast cancer cells to 13 drugs was found to be significantly enhanced by MACF1 mutations. The prognostic model was verified in predicting the outcome of breast cancer patients. CONCLUSION: MACF1 mutations might be a potential prognostic biomarker and a therapeutic target for breast cancer.

Research into the biological differences and targets in lung cancer patients with diverse immunotherapy responses.

Background: Immunotherapy has gradually become an important therapy option for lung cancer patients. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were responsible for all the public data. Results: In our study, we firstly identified 22 characteristic genes of NSCLC immunotherapy response using the machine learning algorithm. Molecule subtyping was then conducted and two patient subtypes were identified Cluster1 and Cluster2. Results showed that Cluster1 patients had a lower TIDE score and were more sensitive to immunotherapy in both TCGA and combined GEO cohorts. Biological enrichment analysis showed that pathways of epithelial-mesenchymal transition (EMT), apical junction, KRAS signaling, myogenesis, G2M checkpoint, E2F targets, WNT/ß-catenin signaling, hedgehog signaling, hypoxia were activated in Cluster2 patients. Genomic instability between Cluster1 and Cluster2 patients was not significantly different. Interestingly, we found that female patients were more adaptable to immunotherapy. Biological enrichment revealed that compared with female patients, pathways of MYC target, G2M checkpoints, mTORC1 signaling, MYC target, E2F target, KRAS signaling, oxidative phosphorylation, mitotic spindle and P53 pathway were activated. Meanwhile, monocytes might have a potential role in affecting NSCLC immunotherapy and underlying mechanism has been explored. Finally, we found that SEC14L3 and APCDD1L were the underlying targets affecting immunotherapy, as well as patients survival. Conclusions: These results can provide direction and guidance for future research focused on NSCLC immunotherapy.

[Imaging study and clinical application of unilateral biportal endoscopy technique for upper lumbar disc herniation via contralateral approach].

Objective: To investigate the relationships between the bony structures, nerve, and indentations of ligamentum flavum of the upper lumbar spine by using CT three-dimensional reconstruction technique, in order to guide the unilateral biportal endoscopy (UBE) technique via contralateral approach in the treatment of upper lumbar disc herniation (ULDH). Methods: Twenty-one ULDH patients who were admitted between June 2019 and July 2021 and met the selection criteria were selected as the research subjects. There were 12 males and 9 females with an average age of 62.1 years (range, 55-72 years). The disease duration was 1-12 years (mean, 5.7 years). There was 1 case of L 1, 2, 4 cases of L 2, 3, and 16 cases of L 3, 4. The CT myelography data of T 12-S 3 segment was saved in DICOM format and imported into Mimics21.0 software for three-dimensional reconstruction. The relationship between the intersection (point Q) of spinous process and the inferior margin of lamina, the indentation of superior margin of ligamentum flavum, the inferior margin of nerve root origin, intervertebral space, and foramen were observed. The Mimics21.0 software was used to create a 3-mm-diameter cylinder to simulate the UBE channel and measure its abduction angle (∠b1), as well as measure the following lumbar vertebra-related indicators: in L 1,2-L 3,4 segments, the vertical distance from the point Q to the inferior margin of the contralateral lumbar pedicle of the same lumbar vertebra (a1), the superior margin of the contralateral pedicle of the lower lumbar vertebra (a2), the lower endplate of the same lumbar vertebra (a3), the upper endplate of the lower lumbar vertebra (a4); the vertical distance from the lower endplate of lumbar vertebra to the inferior margin of the lumbar pedicle (c1), the vertical distance from the upper endplate of the lower lumbar vertebra to the superior margin of the lumbar pedicle (c2); the vertical distance from the inferior margin of the nerve root origin to the superior margin (d1) and the inferior margin (d2) of the lumbar pedicle, respectively; the vertical distance from the intersection (point P) of the indentation of superior margin of ligamentum flavum and the medial margin of the lumbar pedicle to the superior margin (e1) and the inferior margin (e2) of the lumbar pedicle, respectively; the horizontal distance from the lateral margin of the dural mater (f1) and the narrowest part of the lumbar isthmus (f2) to the facet joint space, respectively. Thirteen of the patients included in the study chose the UBE surgery via contralateral approach. There were 8 males and 5 females with an average age of 63.3 years (range, 55-71 years). The disease duration was 2-12 years, with an average of 6.2 years. There were 3 cases of L 2, 3 and 10 cases of L 3, 4. The perioperative complications and surgical decompression were recorded. And the effectiveness were evaluated by visual analogue scale (VAS) score, Oswestry disability index (ODI), and short form-36 health survey (SF-36) score. Results: The imaging results showed that there was no significant difference in a1, a3, a4, e1, e2, f1, and f2 between segments ( P>0.05), and there were significant differences ( P<0.05) in a2 and c2 between L 1, 2 and L 3, 4 segments, in ∠b1 and d2 between L 1, 2, L 2, 3 segments and L 3, 4 segments, and in c1 and d1 between L 1, 2 and L 2, 3, L 3, 4 segments. The 87.30% (110/126) of point Q of L 1, 2-L 3, 4 segments corresponded to the inferior articular process, and 78.57% (99/126) of the lower endplate corresponded to the level of the isthmus. All 13 patients completed the UBE surgery via contralateral approach, and none were converted to open surgery. All patients were followed up 12-17 months (mean, 14.6) months. The VAS score of low back pain and leg pain, ODI, and SF-36 score at 6 and 12 months after operation significantly improved when compared with those before operation ( P<0.05), and further improved at 12 months after operation when compared with 6 months after operation ( P<0.05). The imaging review results showed that the herniated disc was removed and the dura mater was decompressed adequately. Conclusion: The point Q, the superior margin of ligamentum flavum, and lumbar pedicle can be used as the markers for the treatment of ULBD with UBE surgery via contralateral approach, making the procedure safer, more precise, and more effective.

Phase I 270° single-incision percutaneous spinal endoscopy for decompression treatment of thoracic spinal stenosis.

This study aimed to explore the feasibility of Phase I percutaneous spinal endoscopy with a 270° single incision in the ventral and dorsal dura mater for decompression treatment of thoracic spinal stenosis (TSS). Phase I percutaneous spinal endoscopy with a two-path (posterior and posterolateral approaches) single incision with a 270° decompression was performed in four cases of TSS with compression in the ventral and dorsal dura mater. The affected intervertebral space was located during the surgery, and the ossified ligamentum flavum in the ventral and dorsal dura mater was removed via laminectomy, which formed a decompression space in the thoracic cord. Next, posterolateral transforaminal expansion and plasty were performed to remove the ventral intervertebral disk. The visual analogue scale (VAS) score, thoracic spinal cord function score of the Japanese Orthopaedic Association (JOA) (11-point method), and Oswestry Disability Index (ODI) scores were used to evaluate the clinical efficacy. No dura mater or thoracic nerve injury occurred during the surgery. The symptoms of weakness in the lower extremities improved after the surgery. The postoperative magnetic resonance imaging and computed tomography examinations showed compression removal and dura mater bulging. The postoperative VAS, JOA, and ODI scores improved compared with the preoperative scores. Two surgical trajectories, posterior and posterolateral approaches, were established by a single incision using thoracic spinal canal decompression with Phase I 270° single-incision percutaneous spinal endoscopy. The posterior approach was performed mainly by translaminar unilateral fenestration and bilateral decompression in the ventral and dorsal dura mater, whereas the posterolateral approach was performed by decompression in the ventral dura mater to the midline of the vertebrae. This surgical method could be applied as a safe and feasible minimally invasive treatment for TSS with compression on both the ventral and dorsal dura mater.

Identification of methylation markers for diagnosis of autism spectrum disorder.

Autism spectrum disorder (ASD) is a hereditary heterogeneous neurodevelopmental disorder characterized by social and speech dysplasia. We collected the expression profiles of ASD in GSE26415, GSE42133 and GSE123302 from the gene expression omnibus (GEO) database, as well as methylation data of GSE109905. Differentially expressed genes (DEGs) between ASD and controls were obtained by differential expression analysis. Enrichment analysis identified the biological functions and signaling pathways involved by common genes in three groups of DEGs. Protein-protein interaction (PPI) networks were used to identify genes with the highest connectivity as key genes. In addition, we identified methylation markers by associating differentially methylated positions. Key methylation markers were identified using the least absolute shrink and selection operator (LASSO) model. Receiver operating characteristic curves and nomograms were used to identify the diagnostic role of key methylation markers for ASD. A total of 57 common genes were identified in the three groups of DEGs. These genes were mainly enriched in Sphingolipid metabolism and PPAR signaling pathway. In the PPI network, we identified seven key genes with higher connectivity, and used qRT-PCR experiments to verify the expressions. In addition, we identified 31 methylation markers and screened 3 key methylation markers (RUNX2, IMMP2L and MDM2) by LASSO model. Their methylation levels were closely related to the diagnostic effects of ASD. Our analysis identified RUNX2, IMMP2L and MDM2 as possible diagnostic markers for ASD. Identifying different biomarkers and risk genes will contribute to the diagnosis of ASD and the development of new clinical and drug treatments.

[Application of three-dimensional reconstruction simulation to define the starting point of lumbar cortical bone trajectory].

OBJECTIVE: CT three-dimensional reconstruction technology was used to simulate the placement of the lumbar cortical bone trajectory (CBT), to determine the starting point and direction of the screw trajectory. METHODS: Between February 2017 and April 2018, 24 patients with lumbar CT were selected as the study object. There were 7 males and 17 females, with an average age of 50.4 years (range, 37-68 years). The CT DICOM data of patients were imported into Mimics 16.0 software, and the three-dimensional model of lumbar spine was established. A 5 mm diameter cylinder was set up to simulate the CBT by using Mimics 16.0 software. According to the different implant schemes, the study was divided into groups A, B, and C, the track of the screw respectively passed through the upper edge, the medial edge, and the lower edge of the isthmus of the pedicle. The intersection of simulated screw and lumbar spine was marked as region of interest (ROI) and a mask was generated. The average CT value [Hounsfield unit (HU)] and the screw length of ROI were automatically measured by Mimics 16.0 software. In addition, the head inclination angle and head camber angle of the screw were measured respectively. Point F was the intersection of the level of the lowest edge of the transverse process and the lumbar isthmus periphery. The horizontal and vertical distance between point F and the starting point were measured, and the relationship between the three schemes and the position of the zygapophysial joint and spinous process was observed. RESULTS: Plan A has the highest ROI average HU, with the maximum value appearing in L 4; plan B has the longest screw length, with the maximum value appearing in L 5; plan C has the largest nail track head inclination angle, with the maximum value appearing in L 4; plan B has the largest nail track head camber angle, with the maximum value appearing in L 3. The screw length and head camber angle of the nail in group B were significantly greater than those in groups A and C ( P<0.05); the head inclination angle in groups A, B, and C was gradually increased, showing significant differences ( P<0.05); there was no significant difference in the average HU value of ROI between the 3 groups ( P>0.05). In plan A, 74.48% (143/192) screws had a horizontal distance of -2 to 4 mm from point F, a vertical distance of 6-14 mm from point F, a head inclination angle of (14.64±2.77)°, and a head camber angle of (6.55±2.09)°, respectively; in plan B, 84.58% (203/240) screws had a horizontal distance of 1-6 mm from point F, a vertical distance of 1-5 mm from point F, a head inclination angle of (26.93±2.21)°, and a head camber angle of (10.29±2.46)°, respectively; in plan C, 85.94% (165/192) screws had a horizontal distance of -2 to 3 mm from point F, a vertical distance of -2 to 4 mm from point F, a head inclination angle of (33.50±3.69)°, and a head camber angle of (6.47±2.48)°, respectively. CONCLUSION: Plan B should be selected as the starting point of the L 1-L 5 CBT implant. It is located at the intersection of the lowest horizontal line of the transverse process root and the lateral edge of the lumbar isthmus, which is 1-6 mm horizontally inward, 1-5 mm vertically upward, with a head inclination angle of (26.93±2.21)°, and a head camber angle of (10.29±2.46)°, respectively.

Correlation between replicative senescence of endometrial gland epithelial cells in shedding and non-shedding endometria and endometriosis cyst during menstruation.

To investigate correlation between abnormal replicative senescence of endometrial gland epithelial cells (EGECs) in shedding and non-shedding endometria and endometriosis cyst during menstruation. Musashi-1 expression, ß-catenin expression, and EGECs ultrastructure in shedding and non-shedding endometrium when menstruation were observed through real-time PCR and transmission electron microscopy technologies. (1) Musashi-1 and ß-catenin exhibited a high expression in shedding and non-shedding endometria in experimental group, showing a positive correlation between each other; and were significantly higher than that in control group. However; there was no correlation between these two in control group. (2) Transmission electron microscopy results: In experimental group, organelles in EGECs in shedding endometrium obtained were abundant on the first day of menstruation, nuclei were irregular, double nucleoli could be observed, and chromatin was rich. Furthermore, morphology of EGECs in non-shedding endometrium was irregular, organelles were abundant, basement membrane was irregular with abnormal curvature, and a large amount of collagenic fibers were found in intercellular spaces. On the fifth day of menstruation, the cilia and microvilli on secretory cells in endometrium increased and prolongated, and organelles became extremely rich. EGECs have potentials of division, proliferation, invasion and migration; and is associated with formation of endometriosis cysts.

The anti-cancer potency and mechanism of a novel tumor-activated fused toxin, DLM.

Melittin, which acts as a membrane-disrupting lytic peptide, is not only cytotoxic to tumors, but also vital to normal cells. Melittin had low toxicity when coupled with target peptides. Despite significant research development with the fused toxin, a new fused toxin is needed which has a cleavable linker such that the fused toxin can release melittin after protease cleavage on the tumor cell surface. We describe a novel fused toxin, composed of disintegrin, uPA (urokinase-type plasminogen activator)-cleavable linker, and melittin. Disintegrin is a single strand peptide (73 aa) isolated from Gloydius Ussuriensis venom. The RGD (Arg-Gly-Asp) site of disintegrin dominates its interaction with integrins on the surface of the tumor cells. uPA is over-expressed and plays an important role in tumor cell invasiveness and metastatic progression. The DLM (disintegrin-linker-melittin) linker is uPA-cleavable, enabling DLM to release melittin. We compared binding activity of our synthesized disintegrin with native disintegrin and report that DLM had less binding activity than the native form. uPA-cleavage was evaluated in vitro and the uPA-cleavable linker released melittin. Treating tumors expressing uPA with DLM enhanced tumor cell killing as well as reduced toxicity to erythrocytes and other non-cancerous normal cells. The mechanism behind DLM tumor cell killing was tested using a DNA ladder assay, fluorescent microscopy, flow cytometry, and transmission electron microscopy. Data revealed tumor cell necrosis as the mechanism of cell death, and the fused DLM toxin with an uPA-cleavable linker enhanced tumor selectivity and killing ability.

Elevated CO2 decreases the response of the ethylene signaling pathway in Medicago truncatula and increases the abundance of the pea aphid.

The performance of herbivorous insects is greatly affected by plant nutritional quality and resistance, which are likely to be altered by rising concentrations of atmospheric CO2 . We previously reported that elevated CO2 enhanced biological nitrogen (N) fixation of Medicago truncatula, which could result in an increased supply of amino acids to the pea aphid (Acyrthosiphon pisum). The current study examined the N nutritional quality and aphid resistance of sickle, an ethylene-insensitive mutant of M. truncatula with supernodulation, and its wild-type control A17 under elevated CO2 in open-top field chambers. Regardless of CO2 concentration, growth and amino acid content were greater and aphid resistance was lower in sickle than in A17. Elevated CO2 up-regulated N assimilation and transamination-related enzymes activities and increased phloem amino acids in both genotypes. Furthermore, elevated CO2 down-regulated expression of 1-amino-cyclopropane-carboxylic acid (ACC), sickle gene (SKL) and ethylene response transcription factors (ERF) genes in the ethylene signaling pathway of A17 when infested by aphids and decreased resistance against aphids in terms of lower activities of superoxide dismutase (SOD), peroxidase (POD), and polyphenol oxidase (PPO). Our results suggest that elevated CO2 suppresses the ethylene signaling pathway in M. truncatula, which results in an increase in plant nutritional quality for aphids and a decrease in plant resistance against aphids.

Transfection of colorectal cancer cells with chemokine MCP-3 (monocyte chemotactic protein-3) gene retards tumor growth and inhibits tumor metastasis.

AIM: To evaluate the possibility of the induction of anti-tumor immune response by transfecting the colorectal cancer cells with chemokine MCP-3 gene. METHODS: Mouse MCP-3 gene was transduced into mouse colorectal cancer cells CMT93 by using of Liposome. G418-resistant clones were selected and the MCP-3 mRNA expression was detected by RT-PCR. The chemotactic activity of MCP-3 in the cell culture supernatant was detected by Chemotaxis assay. The tumorigenicity of wild type CMT93 and CMT93 gene transfectants were detected by in vivo experiments. The immune cell infiltrations in tumor tissue and tumor metastasis were detected histopathologically. RESULTS: MCP-3 mRNA expression was detected by RT-PCR in gene-transfected cells (CMT93/MCP-3), but not in control groups. And MCP-3 secreted in the cell culture supernatant possessed chemotatic activity. The results from in vivo experiments showed that the tumorigenicity of CMT93/MCP-3 had not decreased, but the tumors derived from CMT93/MCP-3 cells grew more slowly than those from CMT93 cells (1.021+/-0.253) cm(2) vs (1.769+/-0.371) cm(2), P<0.05) or CMT93/mock cells (1.021+/-0.253) cm(2) vs (1.680 +/-0.643)cm(2), P<0.05). Histophathological results showed few immune cells infiltrating in the tumor tissue derived from the controls. In the tumor tissue derived from CMT93/MCP-3, infiltrating immune cells increased. In addition, no tumor metastasis was found in all mice inoculated with CMT93/MCP-3 tumor cells. But all mice had tumor metastasis in CMT93 controls and 4 in 5 mice had tumor metastasis in CMT93/mock controls. CONCLUSION: The results suggested that the transfection of chemokine MCP-3 gene could promote the induction of anti-colorectal cancer immunity, but the tumor growth could not be inhibited completely by merely MCP-3 gene transfection.