Design, synthesis, biological evaluation of novel piperidine-based derivatives as potent poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a crucial member of DNA repair enzymes responsible for repairing DNA single-strand breaks. Developing PARP inhibitors based on synthetic lethality strategies is an effective approach for treating breast cancer and other diseases. In this study, a series of novel piperidine-based benzamide derivatives were designed and synthesized using structure-based drug design principles. The anticancer activities of these compounds were evaluated against five human cancer cell lines (MDA-MB-436, CAPAN-1, SW-620, HepG2, SKOV3, and PC3) and the preliminary structure-activity relationships were delineated. Among the compounds, 6a and 15d demonstrated potent antiproliferative effects against MDA-MB-436 cells with IC50 values of 8.56 ± 1.07 µM and 6.99 ± 2.62 µM, respectively. Furthermore, both compounds exhibited excellent inhibitory activity against PARP-1, with IC50 values of 8.33 nM and 12.02 nM, respectively. Mechanistic investigations revealed that 6a and 15d effectively inhibited colony formation and cell migration of HCT116 cells. Moreover, they induced apoptosis by upregulating the expression of Bax and cleaved Caspase-3, while downregulating the expression of Caspase-3 and Bcl-2 in HCT116 cells. Based on its impressive pharmacodynamic data in vitro, we conducted a study to evaluate the efficacy of 15d in a xenograft tumor model in mice when used in combination with cytotoxic agents. Collectively, these findings suggest that 15d could be promising drug candidates worthy of further investigation.

A pig model of symptomatic spinal epidural hematoma.

PURPOSE: The purpose of this study was to establish an animal model capable of simulating the development and decompression process of symptomatic spinal epidural hematoma (SSEH). METHODS: A total of 16 male Bama miniature pigs were included in this study and randomly allocated into four groups: Group A (4 h 20 mmHg hematoma compression), Group B (4 h 24 mmHg hematoma compression), Group C (4 h 28 mmHg hematoma compression), and Group Sham (control). Real-time intra-wound hematoma compression values were obtained using the principle of connectors. Electrophysiological analyses, including the latency and amplitude of somatosensory evoked potentials (SSEP) and motor evoked potentials (MEP), along with behavioral observations (Tarlov score), were performed to assess this model. RESULTS: ANOVA tests demonstrated significant differences in the latency and relative amplitude of SSEP and MEP between Groups C and Sham after 4 h of hematoma compression and one month after surgery (P < 0.01). Behavioral assessments 8 h after surgery indicated that animals subjected to 28 mmHg hematoma compression suffered the most severe spinal cord injury. Pearson correlation coefficient test suggested a negative correlation between the epidural pressure and Tarlov score (r = -0.700, p < 0.001). With the progression of compression and the escalation of epidural pressure, the latency of SSEP and MEP gradually increased, while the relative amplitude gradually decreased. CONCLUSIONS: When the epidural pressure reaches approximately 24 mmHg, the spinal cord function occurs progressive dysfunction. Monitoring epidural pressure would be an effective approach to assist to identify the occurrence of postoperative SSEH.

Complications and local recurrence of chondrosarcoma and chordoma treated by total tumor resection in thoracic and lumbar spine.

BACKGROUND: En bloc resection of spinal tumors is challenging and associated with a high incidence of complications; however, it offers the potential to reduce the risk of recurrence when a wide margin is achieved. This research aims to investigate the safety and efficacy of en bloc resection in treating thoracic and lumbar chondrosarcoma/chordoma. METHODS: Data from patients diagnosed with chondrosarcoma and chordoma in the thoracic or lumbar region, who underwent total en bloc or piecemeal resection at our institution over a 7-year period, were collected and regularly followed up. The study analyzed overall perioperative complications and compared differences in complications and local tumor recurrence between the two surgical methods. RESULTS: Seventeen patients were included, comprising 12 with chondrosarcoma and 5 with chordoma. Among them, 5 cases underwent intralesional piecemeal resection, while the remaining 12 underwent planned en bloc resection. The average surgical time was 684 min (sd = 287), and the mean estimated blood loss was 2300 ml (sd = 1599). Thirty-five complications were recorded, with an average of 2.06 perioperative complications per patient. 82% of patients (14/17) experienced at least one perioperative complication, and major complications occurred in 64.7% (11/17). Five patients had local recurrence during the follow-up, with a mean recurrence time of 16.2 months (sd = 7.2) and a median recurrence time of 20 months (IQR = 12.5). Hospital stays, operation time, blood loss, and complication rates did not significantly differ between the two surgical methods. The local recurrence rate after en bloc resection was lower than piecemeal resection, although not statistically significant (P = 0.067). CONCLUSIONS: The complication rates between the two surgical procedures were similar. Considering safety and local tumor control, en bloc resection is recommended as the primary choice for patients with chondrosarcoma/chordoma in the thoracic and lumbar regions who are eligible for this treatment.

MicroRNA-451a is a candidate biomarker and therapeutic target for major depressive disorder.

Background: Increasing evidence supports the role of microRNAs (miRNAs) in major depressive disorder (MDD), but the pathophysiological mechanism remains elusive. Aims: To explore the mechanism of microRNA-451a (miR-451a) in the pathology and behaviours of depression. Methods: Abnormal miRNAs such as miR-451a reported previously in the serum of patients with MDD were screened and then confirmed in a mouse model of depression induced by chronic restraint stress (CRS). Eight-week-old male C57BL/6 mice had miR-451a overexpression in the medial prefrontal cortex (mPFC) via adeno-associated virus serotype 9 vectors encoding a pri-mmu-miR-451a-GFP fusion protein followed by behavioural and pathological analyses. Finally, molecular biological experiments were conducted to investigate the potential mechanism of miR-451a against depression. Results: The serum levels of miRNA-451a were significantly lower in patients with MDD, with a negative correlation with the Hamilton Depression Scale scores. Additionally, a negative association between serum miR-451a and behavioural despair or anhedonia was observed in CRS mice. Notably, miR-451a expression was significantly downregulated in the mPFC of CRS-susceptible mice. Overexpressing miR-451a in the mPFC reversed the loss of dendritic spines and the depression-like phenotype of CRS mice. Mechanistically, miR-451a could inhibit CRS-induced corticotropin-releasing factor receptor 1 expression via targeting transcription factor 2, subsequently protecting dendritic spine plasticity. Conclusions: Together, these results highlighted miR-451a as a candidate biomarker and therapeutic target for MDD.

Comparison of En Bloc Resection and Intralesional Excision for Re-resection of Giant Cell Tumors of the Spine.

OBJECTIVE: Re-resection of spinal giant cell tumors is an exceedingly difficult procedure. Moreover, the prognosis of patients with en bloc resection or intralesional excision for re-resection has rarely been reported. This study aimed to compare the prognostic value of en bloc resection with that of intralesional excision in patients undergoing re-resection for giant cell tumors of the spine. METHODS: This retrospective analysis evaluated patients who underwent revision surgeries for relapse of giant cell tumors of the spine at our center between January 2005 and January 2021. Local progression-free survival represents the duration between en bloc resection or intralesional excision and tumor recurrence. Neurological recovery, survival rates, local control, and complications were evaluated. The Kaplan-Meier estimator was used for survival analysis. RESULTS: A total of 22 patients (nine men and 13 women) with a mean age of 34.1 (range 19-63) years were included. Significant statistical differences were found in the local tumor recurrence rate between patients treated with en bloc resection and those treated with intralesional excision (p < 0.05). The 5- and 10-year local progression-free survival rates were both 90% in the en bloc resection group, while in the intralesional excision group, the 5-year local progression-free survival rate was 80% with a 10-year rate of 45.7%. The en bloc resection group had a lower local tumor recurrence rate than that of the intralesional excision group (p < 0.05), but the former had a higher rate of complications (p = 0.015). CONCLUSIONS: This study revealed a low local recurrence rate in patients who underwent en bloc resection for giant cell tumors, while the perioperative complication rate was high.

Identification and validation of feature genes associated with M1 macrophages in preeclampsia.

Preeclampsia (PE) is a pregnancy-specific cardiovascular complication that is the leading cause of maternal and neonatal morbidity and mortality. Previous studies have indicated the importance of immune cells, such as M1 and M2 macrophages, in the pathogenesis of PE. However, the mechanisms leading to immune dysregulation are unclear. Data-independent acquisition proteomic analysis was performed on placental tissues collected from patients with PE and healthy controls. Transcriptome data for placenta samples from patients with PE and their corresponding controls were obtained from the Gene Expression Omnibus database. Differential analysis of transcriptome and proteome data between PE and control groups was performed using R software. Immunocytic infiltration scoring was performed using the quantiseq algorithm. Weighted gene co-expression network analysis (WGCNA) screened for feature genes associated with M1 cell infiltration. Protein-protein interaction (PPI) analysis identified hub genes. We confirm that the infiltration score of M1 macrophages was significantly increased in the placental tissues of patients with PE. Differential analysis, WGCNA, and PPI analysis identified four hub molecules associated with M1 cell infiltration (HTRA4, POGK, MFAP5, and INHBA). The hub molecules displayed dysregulated expression in PE tissues. The qPCR, Western blots, and immunohistochemistry analyses confirmed that Inhibin, beta A (INHBA) was highly expressed in placental tissues of patients with PE. Immunofluorescence revealed the extensive infiltration of M1 macrophages in the placental tissues of patients with PE and their co-localization with INHBA. The collective results identified hub genes associated with M1 macrophage infiltration, providing potential targets for the pathogenesis and treatment of PE.

Dosimetry impact of distinct gating strategies in cine MR image-guided breath-hold pancreatic cancer radiotherapy.

PURPOSE: To investigate the dosimetry effects of different gating strategies in cine magnetic resonance imaging (MRI)-guided breath-hold pancreatic cancer radiotherapy. METHODS: Two cine MRI-based gating strategies were investigated： a tumor contour-based gating strategy at a gating threshold of 0-5% and a tumor displacement-based gating strategy at a gating threshold of 3-5 mm. The cine MRI videos were obtained from 17 pancreatic cancer patients who received MRI-guided radiation therapy. We calculated the tumor displacement in each cine MR frame that satisfied the gating threshold and obtained the proportion of frames with different displacements. We generated IMRT and VMAT plans using a 33 Gy prescription, and motion plans were generated by adding up all isocenter-shift plans corresponding to different tumor displacements. The dose parameters of GTV, PTV, and organs at risk (OAR) were compared between the original and motion plans. RESULTS: In both gating strategies, the difference was significant in PTV coverage but not in GTV coverage between the original and motion plans. OAR dose parameters deteriorate with increasing gating threshold. The beam duty cycle increased from 19.5±14.3% (median 18.0%) to 60.8±15.6% (61.1%) for gating thresholds from 0% to 5% in tumor contour-based gating and from 51.7±11.5% (49.7%) to 67.3±12.4% (67.1%) for gating thresholds from 3 to 5 mm in tumor displacement-based gating. CONCLUSION: In tumor contour-based gating strategy, the dose delivery accuracy deteriorates while the dose delivery efficiency improves with increasing gating thresholds. To ensure treatment efficiency, the gating threshold might be no less than 3%. A threshold up to 5% may be acceptable in terms of the GTV coverage. The displacement-based gating strategy may serve as a potential alternative to the tumor contour based gating strategy, in which the gating threshold of approximately 4 mm might be a good choice for reasonably balancing the dose delivery accuracy and efficiency.

Surgery for metastatic spinal differentiated thyroid cancer: feasibility, outcome, and prognostic factors.

Study design: A retrospective cohort study. Objectives: This study aims to report the surgical outcome of metastatic spinal differentiated thyroid cancer (MSDTC) and analyze the factors affecting the prognosis. Methods: Thirty-five patients were recruited in our single institution who underwent spinal surgery and adjuvant therapies from 2009 to 2019. Two surgical procedures, total en-bloc spondylectomy and debulking surgery, were undertaken. Their clinical data, postoperative events, and survival data were collected and analyzed. Survival time and associated factors were further analyzed. Results: The cohort had a median survival time of 60 months. The mean visual analog scale scores and the Karnofsky performance score improved postoperatively (p < 0.05). The patients' Frankel grade was elevated for cases with preoperative neurological deficits (p < 0.05). In 31 patients who underwent debulking surgery, 41.9% (n = 13) had local recurrences, and radiotherapy reduced the risk of local relapse (p < 0.05). Preoperative and postoperative Frankel grades and radioactive iodine (RAI) therapy were associated with the patients' survival in the univariate analysis (p < 0.05). Furthermore, a multivariate regression analysis showed the postoperative Frankel grade as an independent prognostic factor. Conclusion: Pain, quality of life, and neurological status of patients can be effectively improved after surgery. Radiotherapy can reduce the risk of local recurrences, whereas RAI therapy has a limited effect on local and extraspinal tumor control. Neurological status was independently associated with the patients' survival.

Complications and prognosis of primary thoracic and lumbar giant cell tumors treated by total tumor resection.

BACKGROUND: Spinal giant cell tumor (SGCT) is a relatively rare primary tumor. En bloc resection is the preferred surgical procedure for it due to its aggressiveness, meanwhile leading to more complications. We reported the characteristics of perioperative complications and local control of total tumor resection including en bloc resection and piecemeal resection for primary thoracic and lumbar spinal giant cell tumors in a single center over 10 years. METHODS: This is a retrospective cross-sectional and cohort study. Forty-one consecutive patients with SGCTs who underwent total tumor resection from 2010 to 2020 at our institution and were followed up for at least 24 months were reviewed. Surgery data, complication characteristics and local tumor control were collected and compared by different surgical procedure. RESULTS: Forty-one patients were included, consisting of 18 males and 23 females, with a mean age of 34.2 years. Thirty-one had thoracic vertebra lesions, and 10 had lumbar vertebra lesions. Thirty-five patients were primary cases, and 6 patients were recurrent cases. Eighteen patients were treated by total en bloc spondylectomy (TES), 12 patients underwent en bloc resection according to WBB surgical system, and 11 patients underwent piecemeal resection. The average surgical time was 498 min, and the mean estimated blood loss was 2145 ml. A total of 58 complications were recorded, and 30 patients (73.2%) had at least one perioperative complication. All patients were followed up after surgery for at least 2 years. A total of 6 cases had postoperative internal fixation failure, and 4 cases presented local tumor recurrence (9.8%). CONCLUSIONS: Although the surgical technique is difficult and accompanied by a high rate of perioperative complications, en bloc resection can achieve favorable local control in SGCT. When it is too difficult to complete en bloc resection, thoroughly piecemeal resection without residual is also acceptable, given the relatively low recurrence rate.

Implant Materials for Anterior Column Reconstruction of Cervical Spine Tumor.

The spine is the most common site of bone metastases. Many cancer patients will ultimately develop spinal metastatic disease with symptomatic epidural spinal cord compression. At present, the main treatment for cervical spine tumors is surgical resection combined with postoperative radiotherapy. Implant materials for cervical spine anterior column reconstruction need to meet amounts of different properties, such as biocompatibility, bioactivity and the ability to maintain long-term mechanical strength. The selection of different materials determines the surgical efficacy and prognosis of patients to a certain extent. This article provides an overview of a variety of implant materials used for anterior column reconstruction after cervical spine tumor resection, introduces and analyzes their properties, advantages, disadvantages, derivatives, and applications in clinical practice, and looks forward to the future development of implant materials.

Treatment of spinal rhabdomyosarcoma in adults: A case report and literature review of current evidence.

Spinal rhabdomyosarcoma (RMS) is a rare yet highly malignant tumor in adults. Literature on this entity is lacking and no mature treatment guideline is currently available. The treatment arsenals include surgery, radiotherapy and chemotherapy, being used singly or jointly. However, the prognosis is dismal, with a mean overall survival period of 10 months. Thus, any case of this disease with encouraging outcomes shall be shared. A case of a middle-aged female patient with spinal RMS was presented in the current report. The patient suffered from back pain but was neurologically intact. The patient underwent a total en-bloc spondylectomy of the T11-L2 vertebrae and spinal reconstruction with 3D-printed prosthetic vertebrae. Afterwards, the patient received a rigid schedule of stereotactic body radiotherapy (SBRT) and chemotherapy. To date, the patient has survived for 40 months, with the preservation of neurological function and sustained mitigation of local pain after the operation. The patient suffered subcutaneous colonization of tumor cells and pulmonary metastasis 10 months postoperatively, but obtained a long locoregional control of 19 months. In conclusion, total en-bloc lesion resection is indicated for the treatment of isolated, primary spinal RMS in adults. Some authors reported that the usage of new surgical tools and instruments has facilitated surgery, which was previously invasive and technically challenging. Advanced radiotherapy techniques, such as SBRT, which were proven effective for local lesion control, should be implemented early after the operation. Chemotherapy remains the mainstay of treatment, but further research and evidence for the efficacy of regimens specifically for adults are required.

Abnormal resting-state function within language network and its improvement among post-stroke aphasia.

Several studies with resting-state magnetic resonance imaging (rs-fMRI) have examined functional impairments and plasticity within language network in patients with post-stroke aphasia (PSA). However, there is still ubiquitous inconsistency across these studies, partly due to restricted to very small sample size and the absence of validation with follow-up data. In the current study, we aimed at providing relatively strong evidence to support functional impairments and its reorganization in PSA. Here, the amplitude of low frequency fluctuations (ALFF) and functional connectivity were used to assess functional alterations of PSA with moderate sample size at baseline (thirty-five PSA patients and thirty-five healthy controls). Functional abnormalities at baseline were observed whether improved among sixteen follow-up patients. Compared with controls, PSA at baseline presented decreased ALFF in the left inferior frontal gyrus (IFG) and decreased functional connectivity of the left IFG with the bilateral supplementary motor area (SMA) and right superior temporal gyrus (STG). The decreased ALFF in IFG, decreased IFG-SMA and IFG-STG connectivity were enhanced among follow-up patients and was synchronized with language-performance improvement. Our results revealed reduced intrinsic neural activity and inter-connections within language network in PSA, which would be normalized synchronously as the improvement of language performance.

The Outcomes of Surgical and Nonsurgical Treatment in Patients With Spinal Metastases of Lung Cancer: Protocol for a Prospective Cohort Study.

BACKGROUND: Spinal metastases of lung cancer (SMLC) usually have a high degree of malignancy and require multimodality treatment. Patients with SMLC who experience clinical symptoms (eg, local pain, emerging or potential spinal instability, and progressive neurological dysfunction) require surgical treatment. However, there are discrepancies in the comparison of outcomes between surgical treatment and nonsurgical treatment. OBJECTIVE: This paper presents the protocol for a study that aims to compare the clinical outcomes of surgical treatment and nonsurgical treatment for SMLC, explore the prognostic factors of SMLC, and establish a survival prediction model based on these prognostic factors. METHODS: This is a prospective cohort study, with an anticipated sample size of 240 patients (120 patients in the surgical group and 120 patients in the nonsurgical group). We will collect baseline data, including demographic, clinical, and radiological information, as well as data from patient-reported questionnaires. Patients will be followed up at 3, 6, 12, and 24 months after treatment, and survival status will be assessed every 3 months. The primary outcome is the overall survival period. Prognostic factors associated with overall survival will be analyzed by univariate and multivariate Cox proportional hazards regression. Odds ratios with 95% CIs will be presented. Statistical significance is set at P<.05. RESULTS: This study has been approved by our institute's Medical Science Research Ethics Committee (IRB00006761-M2021085) after a careful audit of the design and content. Patient enrollment began in June 2022 at our hospital. Data collection is expected to be completed by early 2026, and the study results will be published by mid-2027. CONCLUSIONS: In this study, we propose to set up a prospective cohort of patients with SMLC to investigate the outcomes between surgical treatment and nonsurgical treatment. We will explore the role of surgical treatment in SMLC and provide guidance to peer surgeons. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100048151; http://www.chictr.org.cn/showproj.aspx?proj=129450. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38273.

Clinical Application of the Roussouly Classification in the Sagittal Balance Reconstruction of 101 Adolescent Idiopathic Scoliosis Patients.

PURPOSE: Although Roussouly classification has been widely used in spinal surgery, it was mainly applied to degenerative scoliosis patients and correlational studies concerning adolescent idiopathic scoliosis (AIS) are still insufficient. This retrospective study explored the clinical application of Roussouly classification in surgeries and prognosis prediction for AIS. METHODS: This clinical research selected 101 AIS patients who received surgeries between August 2005 and November 2019. Whole spine standing radiographs were obtained for each patient preoperatively, postoperatively, and at the last follow-up (>24 months). All patients were classified into "theoretical types" and "current types." Patients were further divided into mismatch or match groups based on the consistency of their current type and theoretical type. The main parameters include: proximal junctional angle (PJA), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), fixed thoracic kyphosis (TK), global TK, fixed lumbar lordosis (LL), global LL, thoracic tilt, proximal thoracic alignment (PTA), lumbar tilt, spino-sacral angle (SSA), and spinal tilt (ST). RESULTS: A total of 47.5% of AIS patients were subject to a preoperative mismatch of Roussouly classification. There was a significant difference in PI-LL between the preoperative mismatch and match groups (p = 0.008). There was a significant difference in the rate of PI-LL deformity between the match and mismatch groups with a preoperative mismatch (p = 0.037). A significant difference in thoracic tilt was observed between the postoperative mismatch and match groups (p = 0.019). The preoperative mismatch group has a higher risk of postoperative PI-LL malformation than match group (OR = 2.303, 95% CI: 1.026, 5.165). When mismatch occurred postoperatively, there were significant differences between groups in the rate of pelvic deformity (p = 0.002) and PI-LL deformity (p = 0.025) at the last follow-up. Compared with the postoperative match group, mismatch group had an increased risk of pelvic deformity (OR = 5.029, 95% CI: 1.618, 15.629) and PJK deformity (OR = 3.017, 95% CI: 1.709, 11.375) at the last follow-up. Short Form-36 and Scoliosis Research Society 22 score of the match group was significantly higher than that of the mismatch group at the last follow-up. CONCLUSION: The Roussouly classification mismatch before or after operation leads to increased risks of PI-LL deformity and pelvis deformity postoperatively or at the follow-up, which seriously worsens the clinical symptoms and prognosis of patients. Therefore, recovering to the theoretical type in Roussouly classification may effectively improve patients' prognosis.

Surgical Treatment of Spinal Metastatic Pheochromocytoma and Paraganglioma: A Single Institutional Cohort of 18 Patients.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: To describe surgeries and treatment outcomes of metastatic pheochromocytomas and paragangliomas (PPGLs) on the spine. METHODS: We reviewed a cohort of 18 patients with spinal PPGLs who were consecutively treated in our spinal center. Their clinical data was reviewed. The survival period and its relevant factors was then analyzed. RESULTS: The cohort included ten cases of pheochromocytomas and eight paragangliomas. The local pain and neurological deficits were the two most common symptoms. One third of the spinal PPGLs were diagnosed as functional tumors, arousing secondary hypertension. The imaging features were consistent with those of osteolytic lesions. The surgical strategies for the cohort included percutaneous vertebroplasty, neurological decompression and partial tumor resection, and total en-bloc resection. The postoperative courses were uneventful except 1 patient developed heart failure. The adjuvant therapies were implemented in 6 patients with 131I-MIBG, five with radiotherapy, two with chemotherapy, and 1 with target therapy. The median survival period was 39 months, and the overall survival rate of 1 year was 77.8% (14/18). The patients' Karnofsky performance scores were positively correlated with the survival period (P < .05). CONCLUSION: Surgery is indicated for intractable local pain and neurological impairment in the patients with spinal PPGLs. Palliative surgical strategies, including neurological decompression and partial tumor resection, could bring fair outcomes, especially for the patients in poor physical conditions.

Prognostic Analysis of Spinal Metastasis Secondary to Lung Cancer after Surgeries: A Unicentric, Large-Cohort, Retrospective Study.

PURPOSE: Spinal metastases of lung cancer (SMLC) usually have high degree of malignancy and require surgical treatment. However, there are several controversies about the efficacy of surgery. This study aimed to investigate factors predicting prognosis of SMLC after surgery-based comprehensive treatment. METHODS: A cohort of 112 cases of SMLC who underwent surgical treatment between 2009 and 2020 were retrospectively reviewed and analyzed. The surgical strategies included total en-bloc spondylectomy, debulking surgery, palliative decompression, and vertebral augmentation procedures. The patients were regularly followed-up. Survival analysis was performed, as well as analysis of the patients' neurological recovery, pain relief, and improvement of Karnosky performance score (KPS). Cox regression was used to analyze influencing factors of survival time, and Kaplan-Meier method was performed in survival analysis. RESULTS: The cohort included 63 males and 49 females, with an average age of 60.6 ± 10.6 years. Median survival time was 16 months. A total of 86.7% of paralysis patients' neurological function recovered and 83.9% of patients with low KPS score (10-40) improved. Surgical method was significantly correlated with improvement of neurological function (p < 0.001) and KPS (p < 0.001). The mean bleeding volume was 502 ml and operative time was 170 min. The survival rates at 3, 6, 12, 24, and 36 months were 92.0%, 80.4%, 63.4%, 63.4%, and 22.6%, respectively. Postoperative Frankel grade (p < 0.001), postoperative KPS score (p = 0.001), and application of molecular targeted drugs (p < 0.001) were significantly correlated with survival time in univariate analysis, while application of molecular targeted drugs was an independent predictor for a longer survival by a multivariate analysis. CONCLUSION: Surgery-based comprehensive treatment brought a fair outcome, with elongated survival time. Surgery can significantly improve patients' neurological function and physical performance status. Adjuvant targeted therapy is an independent positive factor for patients' survival.

The mechanism of the imbalance between proliferation and ferroptosis in pulmonary artery smooth muscle cells based on the activation of SLC7A11.

Pulmonary arterial hypertension (PAH) is a chronic, progressive pulmonary vascular disease. Pulmonary vascular remodelling (PVR) is one of the main pathological features of PAH. The main cause of PVR is cell death inhibition and excessive proliferation in pulmonary artery smooth muscle cells (PASMCs), which are also affected by oxidative stress. Ferroptosis is a newly identified form of cell death, which is associated with oxidative damage. It depends on the excessive accumulation of lipid peroxides and reactive oxygen species (ROS) in cells. Solute carrier family 7 member 11 (SLC7A11) is a subunit of the cystine/glutamate antiporter system Xc-, which inhibits ferroptosis by eliminating ROS through the promotion of GSH synthesis in cancer cells. However, very few studies exist on the relationship between ferroptosis and SLC7A11 in PAH. In this study, SLC7A11 was up-regulated in Sugen5416/hypoxia-induced PAH rats and patients with PAH. Moreover, SLC7A11 inhibited ferroptosis and promoted proliferation by overexpressing SLC7A11 in PASMCs. Additionally, ubiquitin aldehyde binding 1 (OTUB1), the main regulator of SLC7A11 stability, was involved in the ferroptosis and proliferation of PASMCs. Furthermore, erastin induced ferroptosis by inhibiting SLC7A11 and glutathione peroxidase 4 (GPX4) expressions in vivo and in vitro, suggesting that the continuous proliferation in hypoxic PASMCs could be reversed by erastin. Therefore, this study identifies novel targets and new research directions regarding PAH pathogenesis and treatment.

Automatic treatment planning for cervical cancer radiation therapy using direct three-dimensional patient anatomy match.

PURPOSE: Current knowledge-based planning methods for radiation therapy mainly use low-dimensional features extracted from contoured structures to identify geometrically similar patients. Here, we propose a knowledge-based treatment planning method where the anatomical similarity is quantified by the rigid registration of the three-dimensional (3D) planning target volume (PTV) and organs at risks (OARs) between an incoming patient and database patients. METHODS: A database that contains PTV and OARs contours from 81 cervical cancer radiation therapy patients was established. To identify the anatomically similar patients, the PTV of the new patient was registered to each PTV in the database and the Dice similarity coefficients were calculated for the PTV, rectum, and bladder between the new patient and database patients. Then the top 20 patients in the PTV match and top 3 patients in the subsequent bladder or rectum match were selected. The best dose-volume histogram parameters from the top three patients were applied as the dose constraints to the automatic plan optimization. A fast Fourier transform algorithm was developed to accelerate the 3D PTV registration process run through the database. The entire treatment planning process was automated using in-house customized Pinnacle scripts. The automatic plans were generated for 20 patients using leave-one-out scheme and were evaluated against the corresponding clinical plans. RESULTS: The automatic plans significantly reduced rectum and bladder V 50 Gy ${V_{50\,\,{\rm{Gy}}}}$ by 11.79% ± 5.2% (p < 0.01) and 2.85% ± 3.16% (p < 0.01), respectively. The dose parameters achieved for the PTV and other OARs were comparable to those in the clinical plans. The entire planning process, including both dose prediction and inverse optimization, costs about 6 min. CONCLUSIONS: The direct 3D contour match method utilizes the full spatial information of the PTV and OARs of interest and provides an intuitive measurement for patient plan anatomy similarity. The proposed automatic planning method can generate plans with better quality and higher efficiency.

3D-printed vertebral body for anterior spinal reconstruction in patients with thoracolumbar spinal tumors.

OBJECTIVE: A 3D-printed vertebral prosthesis can be used to reconstruct a bone defect more precisely because of its tailored shape, with its innermost porous structure inducing bone ingrowth. The aim of this study was to evaluate the clinical outcomes of using a 3D-printed artificial vertebral body for spinal reconstruction after en bloc resection of thoracolumbar tumors. METHODS: This was a retrospective analysis of 23 consecutive patients who underwent surgical treatment for thoracolumbar tumors at our hospital. En bloc resection was performed in all cases, based on the Weinstein-Boriani-Biagini surgical staging system, and anterior reconstruction was performed using a 3D-printed artificial vertebral body. Prosthesis subsidence, fusion status, and instrumentation-related complications were evaluated. Stability of the anterior reconstruction method was evaluated by CT, and CT Hounsfield unit (HU) values were measured to evaluate fusion status. RESULTS: The median follow-up was 37 (range 24-58) months. A customized 3D-printed artificial vertebral body was used in 10 patients, with an off-the-shelf 3D-printed artificial vertebral body used in the other 13 patients. The artificial vertebral body was implanted anteriorly in 5 patients and posteriorly in 18 patients. The overall fusion rate was 87.0%. The average prosthesis subsidence at the final follow-up was 1.60 ± 1.79 mm. Instrument failure occurred in 2 patients, both of whom had substantial subsidence (8.47 and 3.69 mm, respectively). At 3 months, 6 months, and 1 year postoperatively, the mean CT HU values within the artificial vertebral body were 1930 ± 294, 1997 ± 336, and 1994 ± 257, respectively, with each of these values being significantly higher than the immediate postoperative value of 1744 ± 321 (p < 0.05). CONCLUSIONS: The use of a 3D-printed artificial vertebral body for anterior reconstruction after en bloc resection of the thoracolumbar spinal tumor may be a feasible and reliable option. The low incidence of prosthesis subsidence of 3D-printed endoprostheses can provide good stability instantly. Measurement of HU values with CT is a valuable method to evaluate the osseointegration at the bone-metal interface of a 3D-printed vertebral prosthesis.