Polyphenols as Potential Antioxidants for the Treatment of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is a common musculoskeletal system disease, which is one of the most important causes of low back pain. Despite the high prevalence of IDD, current treatments are limited to relieving symptoms, and there are no effective therapeutic agents that can block or reverse the progression of IDD. Oxidative stress, the result of an imbalance between the production of reactive oxygen species (ROS) and clearance by the antioxidant defense system, plays an important role in the progression of IDD. Polyphenols are antioxidant compounds that can inhibit ROS production, which can scavenge free radicals, reduce hydrogen peroxide production, and inhibit lipid oxidation in nucleus pulposus (NP) cells and IDD animal models. In this review, we discussed the antioxidant effects of polyphenols and their regulatory role in different molecular pathways associated with the pathogenesis of IDD, as well as the limitations and future prospects of polyphenols as a potential treatment of IDD.

Identification and quantification of nanoplastics in different crops using pyrolysis gas chromatography-mass spectrometry.

Quantitative studies of nanoplastics (NPs) abundance on agricultural crops are crucial for understanding the environmental impact and potential health risks of NPs. However, the actual extent of NP contamination in different crops remains unclear, and therefore insufficient quantitative data are available for adequate exposure assessments. Herein, a method with nitric acid digestion, multiple organic extraction combined with pyrolysis gas chromatography-mass spectrometry (Py-GC/MS) quantification was used to determine the chemical composition and mass concentration of NPs in different crops (cowpea, flowering cabbage, rutabagas, and chieh-qua). Recoveries of 74.2-109.3% were obtained for different NPs in standard products (N = 6, RSD <9.6%). The limit of detection (LOD) and the limit of quantitation (LOQ) were 0.02-0.5 µg and 0.06-1.5 µg, respectively. The detection method for NPs exhibited good external calibration curves and linearity with 0.99. The results showed that poly (vinylchloride) (PVC), poly (ethylene terephthalate) (PET), polyethylene (PE), and polyadiohexylenediamine (PA66) NPs could be detected in crop samples, although the accumulation levels associated with the various crops varied significantly. PVC (N.D.-954.3 mg kg-1, dry weight (DW)) and PE (101.3-462.9 mg kg-1, DW) NPs were the dominant components in the samples of all four crop species, while high levels of PET (414.3-1430.1 mg kg-1, DW) NPs were detected in cowpea samples. Furthermore, there were notable differences in the accumulation levels of various edible crop parts, such as stems (60.2%) > leaves (39.8%) in flowering cabbage samples and peas (58.8%) > pods (41.2%) in cowpea samples. This study revealed the actual extent of NP contamination in different types of crops and provided crucial reference data for future research.

Automated machine learning-based model for the prediction of pedicle screw loosening after degenerative lumbar fusion surgery.

The adequacy of screw anchorage is a critical factor in achieving successful spinal fusion. This study aimed to use machine learning algorithms to identify critical variables and predict pedicle screw loosening after degenerative lumbar fusion surgery. A total of 552 patients who underwent primary transpedicular lumbar fixation for lumbar degenerative disease were included. The LASSO method identified key features associated with pedicle screw loosening. Patient clinical characteristics, intraoperative variables, and radiographic parameters were collected and used to construct eight machine learning models, including a training set (80% of participants) and a test set (20% of participants). The XGBoost model exhibited the best performance, with an AUC of 0.884 (95% CI: 0.825-0.944) in the test set, along with the lowest Brier score. Ten crucial variables, including age, disease diagnosis: degenerative scoliosis, number of fused levels, fixation to S1, HU value, preoperative PT, preoperative PI-LL, postoperative LL, postoperative PT, and postoperative PI-LL were selected. In the prospective cohort, the XGBoost model demonstrated substantial performance with an accuracy of 83.32%. This study identified crucial variables associated with pedicle screw loosening after degenerative lumbar fusion surgery and successfully developed a machine learning model to predict pedicle screw loosening. The findings of this study may provide valuable information for clinical decision-making.

Quantifying anthropogenic emission of iron in marine aerosol in the Northwest Pacific with shipborne online measurements.

Anthropogenic emissions are recognized as significant contributors to atmospheric soluble iron (Fe) in recent years, which may affect marine primary productivity, especially in Fe-limited areas. However, the contribution of different emission sources to Fe in marine aerosol has been primarily estimated by modeling approaches. Quantifying anthropogenic Fe based on field measurements remains a great challenge. In this study, online multi-element measurements and Positive Matrix Factorization (PMF) were combined for the first time to quantify sources of atmospheric Fe and soluble Fe in the Northwest Pacific during a cruise in spring 2015. Fe concentration in 624 atmospheric PM2.5 samples measured online was 74.58 ± 90.87 ng/m3. The PMF results showed anthropogenic activities, including industrial coal combustion, biomass burning, and maritime transport, were important in this region, contributing 31.4 % of atmospheric Fe on average. In addition, anthropogenic Fe concentration resolved by PMF was comparable to the simulation results of the CMAQ (Community Multiscale Air Quality) and GEOS-Chem (Goddard Earth Observing System-Chemical transport) models, with better correlation to CMAQ (r = 0.76) than GEOS-Chem (r = 0.26). This study developed a new method to estimate atmospheric soluble Fe, which integrates Fe source apportionment results and Fe solubility from different sources. Soluble Fe concentration was estimated as 3.93 ± 5.14 ng/m3, of which 87.0 % was attributed to anthropogenic emissions. Notably, ship emission alone contributed 27.5 % of soluble Fe, though its contribution to total Fe was only 2.2 %. Finally, the total deposition fluxes of atmospheric Fe (37.11 ± 38.43 µg/m2/day) and soluble Fe (1.85 ± 2.13 µg/m2/day) were estimated. This study developed a new methodology for quantifying contribution of anthropogenic emissions to Fe in marine aerosol, which could greatly help the assessment of impacts of human activities on marine environment.

[Accumulation Characteristics, Sources, and Health Risks of Soil Lead of Urban Parks in Beijing].

Urban parks have multiple functions such as social culture, economy, and environmental services during urban development. The rapid development of cities and economy may lead to the accumulation of heavy metals in the soil of urban parks, which may threaten human health. A total of 140 soil samples were collected in 32 typical parks in Beijing. The accumulation characteristics of Pb in the soil of urban parks were analyzed using the single-factor pollution and geo-accumulation indices. The sources of Pb pollution in soils were quantitatively analyzed using the stable isotope of Pb, and the health risk was assessed using the probabilistic risk assessment method based on Monte Carlo simulation. The results showed that the geometric mean of Pb in soils of urban parks in Beijing was 38.63 mg·kg-1, which was 1.48 times the background value. However, it did not exceed the risk screening value(GB 36600-2018). The accumulation of soil Pb in urban parks increased with the increase in the proximity between the park and the central urban area and the increase in the establishment time. The soil Pb pollution index of 2 ring, 2-4 ring, and 4-6 ring parks were 0.16, 0.10, and 0.09, which did not reach the pollution level, and the geo-accumulation indices were 0.80, 0.07, and -0.31, respectively. Except for the no-moderate pollution level in ring 2 and ring 2 to ring 4, the other rings did not reach the pollution level. The sources of Pb pollution in urban parks were coal combustion, road dust, and paint, with the contributions of 45.4%, 19.6%, and 13.9%, respectively. The 95% quantiles of hazard index(HI) of soil Pb in the park for different age groups were 1.11E-01, 8.57E-02, 6.39E-02, 1.64E-02, 1.36E-02, 1.26E-02, 1.64E-02, and 1.78E-02, respectively, which indicated that there was no potential non-carcinogenic risk(HI<1). Exposure duration was the most sensitive to non-carcinogenic risks in people aged 0-18 years, and soil Pb concentration was the most sensitive to non-carcinogenic risks in people aged 18-80 years. The increase in body weight often reduced the non-carcinogenic risks. These results can provide theoretical basis for soil environmental risk control in urban parks.

[Clinical research progress of spinal epidural lipomatosis].

Objective: To review the clinical research progress of spinal epidural lipomatosis (SEL). Methods: The clinical studies on SEL at home and abroad in recent years were extensively reviewed, and the pathogenesis, clinical and imaging manifestations, and treatment status of SEL were summarized and analyzed. Results: SEL is a disease characterized by compression of the spinal cord and nerve roots due to abnormal accumulation of epidural adipose tissue in the spinal canal. Its prevalence and diagnosis rate are low and the pathogenesis is not fully understood. MRI is the most sensitive and specific diagnostic test for SEL. Surgical decompression and removal of excess adipose tissue are the only options for patients with acute SEL or those who have failed conservative management, and conservative management should be considered for other patients. Conclusion: SEL is a rare disease and related research still needs to be improved. In the future, high-quality, multi-center and large-sample studies will be of great significance for evaluating the choice of treatment methods and effectiveness of SEL patients.

Natural ocean iron fertilization and climate variability over geological periods.

Marine primary producers are largely dependent on and shape the Earth's climate, although their relationship with climate varies over space and time. The growth of phytoplankton and associated marine primary productivity in most of the modern global ocean is limited by the supply of nutrients, including the micronutrient iron. The addition of iron via episodic and frequent events drives the biological carbon pump and promotes the sequestration of atmospheric carbon dioxide (CO2 ) into the ocean. However, the dependence between iron and marine primary producers adaptively changes over different geological periods due to the variation in global climate and environment. In this review, we examined the role and importance of iron in modulating marine primary production during some specific geological periods, that is, the Great Oxidation Event (GOE) during the Huronian glaciation, the Snowball Earth Event during the Cryogenian, the glacial-interglacial cycles during the Pleistocene, and the period from the last glacial maximum to the late Holocene. Only the change trend of iron bioavailability and climate in the glacial-interglacial cycles is consistent with the Iron Hypothesis. During the GOE and the Snowball Earth periods, although the bioavailability of iron in the ocean and the climate changed dramatically, the changing trend of many factors contradicted the Iron Hypothesis. By detangling the relationship among marine primary productivity, iron availability and oceanic environments in different geological periods, this review can offer some new insights for evaluating the impact of ocean iron fertilization on removing CO2 from the atmosphere and regulating the climate.

Novel perspective in transplantation therapy of mesenchymal stem cells: targeting the ferroptosis pathway. / 间å 质干细胞移植治疗的新视角：靶向铁死亡通路.

Ex vivo culture-amplified mesenchymal stem cells (MSCs) have been studied because of their capacity for healing tissue injury. MSC transplantation is a valid approach for promoting the repair of damaged tissues and replacement of lost cells or to safeguard surviving cells, but currently the efficiency of MSC transplantation is constrained by the extensive loss of MSCs during the short post-transplantation period. Hence, strategies to increase the efficacy of MSC treatment are urgently needed. Iron overload, reactive oxygen species deposition, and decreased antioxidant capacity suppress the proliferation and regeneration of MSCs, thereby hastening cell death. Notably, oxidative stress (OS) and deficient antioxidant defense induced by iron overload can result in ferroptosis. Ferroptosis may inhibit cell survival after MSC transplantation, thereby reducing clinical efficacy. In this review, we explore the role of ferroptosis in MSC performance. Given that little research has focused on ferroptosis in transplanted MSCs, further study is urgently needed to enhance the in vivo implantation, function, and duration of MSCs.

Human health risk apportionment from potential sources of heavy metals in agricultural soils and associated uncertainty analysis.

Evaluating heavy metal pollution level in the soils and apportioning the source-specific health risk of heavy metals are critical for proposing environmental protection and remediation strategies to protection human health. This study explored heavy metal pollution and associated source-specific health risks in a typical rural industrial area, southwestern China. A total of 105 topsoil samples were collected and the concentrations of heavy metals, including As, Cd, Cr, Cu, Ni, Pb and Zn, were determined. Pollution load index and enrichment factors were used to evaluate the pollution level of heavy metals. Positive matrix factorization (PMF) model was applied to apportion the heavy metals and the associated source-specific health risks to adults and children were estimated via combining the PMF model with the health risk assessment. The results indicated that the soils were highly polluted by multiple heavy metals, especially for Cd, with the EF values of 24.94 and 22.55 in the upstream and downstream areas, respectively. Source apportionment results showed that atmospheric deposition, smelting activities, fertilizer and sewage application, and agrochemical utilization were the main anthropogenic sources, with the contributions of 37.11%, 23.69%, 19.69%, and 19.51%, respectively. Source-specific risk assessment identified atmospheric deposition as the priority source for the non-carcinogenic (NCR) and carcinogenic risks (CR) in the study area, with the contribution of 43.71% and 52.52% for adults, and 44.29% and 52.58% for children, respectively. Moreover, non-carcinogenic and carcinogenic risks posed to children (NCR: 2.84; CR: 1.31 × 10-4) from four sources was higher than those posed to adults (NCR: 0.29; CR: 5.86 × 10-5). The results of source-specific health risk assessment provided the valuable information on the priority sources for pollution preventing and risk controlling.

A nomogram for accurately predicting the surgical site infection following transforaminal lumbar interbody fusion in type 2 diabetes patients, based on glycemic variability.

Surgical site infection (SSI) is a common and serious complication of transforaminal lumbar interbody fusion (TLIF), and the occurrence of SSI usually leads to prolonged hospitalisation, increased medical costs, poor prognosis, and even death. The objectives of this study were to compare the incidence of SSI in patients with type 2 diabetes, investigate the correlation between perioperative glycemic variability and postoperative SSI, and develop a nomogram model to predict the risk of SSI. This study retrospectively analysed 339 patients with type 2 diabetes who underwent TLIF in the spinal surgery department of the Affiliated Zhongda Hospital of Southeast University from January 2018 to September 2021. The medical records of all patients were collected, and postoperative infection cases were determined according to the diagnostic criteria of surgical site infection. The risk factors for postoperative SSI were analysed by univariate and multivariate logistic regression. And Nomogram prediction model was established and validated. The nomogram incorporated seven independent predictors. Preoperative FPG-CV was the most important independent risk predictor of SSI, followed by preoperative MFBG, duration of drain placement, postoperative FPG-CV, preoperative blood glucose control scheme, duration of diabetes >5 years, and the number of fused vertebrae ≥2. The nomogram showed good diagnostic accuracy for the SS of both the training cohort and the validation cohort (AUC = 0.915 and AUC = 0.890). The calibration curves for the two cohorts both showed optimal agreement between nomogram prediction and actual observation. In conclusion, preoperative and postoperative glycemic variability is closely related to the occurrence of SSI. We developed and validated a nomogram to accurately predict the risk of SSI after TLIF surgery. It's helpful for spinal surgeons to formulate reasonable treatment plans and prevention strategies for type 2 diabetes patients.

18F-FDG PET/CT and MR imaging features of liver metastases in gastrointestinal stromal tumors: a cross-sectional analysis.

Background: Early detection of gastrointestinal stromal tumor (GIST) liver metastases is crucial for the management and prognosis. In our experience, GIST liver metastases can display hypermetabolism on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and marked enhancement on magnetic resonance imaging (MRI), which are uncommon in other tumors before treatment. Most literature focus on the imaging evaluation, prognosis after treatment and less is known about imaging features on both imaging methods before treatment. This study analyzes the imaging features of newly diagnosed GIST liver metastases on 18F-FDG PET/CT and MRI, with goal of improving diagnostic accuracy. Methods: This retrospective study included 55 patients with pathological or radiographical confirmed GIST liver metastases who underwent PET/CT (n=29), MRI (n=22), or both methods (n=4). PET/CT and MRI interpretation including lesion's morphologic features, number, density or signal intensity, hemorrhage, cystic changes or necrosis, maximum standardized uptake value (SUVmax) of liver metastases and liver background on PET imaging, degree and pattern of enhancement on MRI were obtained by two experienced nuclear medicine physicians and two radiologists respectively. Data are presented as numbers, percentages, means ± standard deviations or median (interquartile range). The correlation between diameter and SUVmax of metastases, and primary tumor SUVmax and synchronous liver metastases SUVmax were analyzed by Spearman's rank test. Results: On PET/CT visual analysis, 38.9%, 23.9%, and 37.2% of lesions showed significant hypermetabolism, slightly higher metabolism, and equal or lower metabolism than liver, respectively. There was a weak correlation between the diameter and SUVmax of liver metastases (rs =0.370, P<0.001), and a moderate correlation between SUVmax of synchronous liver metastases and the primary tumors (rs =0.492, P<0.001). On contrast-enhanced MRI, 90.8% of lesions showed heterogeneous enhancement in the arterial phase with the variable presentation, and 74.3% had different enhancement patterns between margins and intratumoral parenchyma. Conclusions: Liver lesions in GIST displaying significant, slight hypermetabolism on 18F-FDG PET/CT, marked or heterogeneous gradual enhancement within the intratumoral parenchyma with ring-like enhancement on MRI may denote the diagnosis of liver metastasis. However, GIST liver metastases may also display equal or lower metabolism than liver parenchyma on PET, making small lesions more difficult to diagnose.

A Privacy-Preserving Distributed Medical Data Integration Security System for Accuracy Assessment of Cancer Screening: Development Study of Novel Data Integration System.

BACKGROUND: Big data useful for epidemiological research can be obtained by integrating data corresponding to individuals between databases managed by different institutions. Privacy information must be protected while performing efficient, high-level data matching. OBJECTIVE: Privacy-preserving distributed data integration (PDDI) enables data matching between multiple databases without moving privacy information; however, its actual implementation requires matching security, accuracy, and performance. Moreover, identifying the optimal data item in the absence of a unique matching key is necessary. We aimed to conduct a basic matching experiment using a model to assess the accuracy of cancer screening. METHODS: To experiment with actual data, we created a data set mimicking the cancer screening and registration data in Japan and conducted a matching experiment using a PDDI system between geographically distant institutions. Errors similar to those found empirically in data sets recorded in Japanese were artificially introduced into the data set. The matching-key error rate of the data common to both data sets was set sufficiently higher than expected in the actual database: 85.0% and 59.0% for the data simulating colorectal and breast cancers, respectively. Various combinations of name, gender, date of birth, and address were used for the matching key. To evaluate the matching accuracy, the matching sensitivity and specificity were calculated based on the number of cancer-screening data points, and the effect of matching accuracy on the sensitivity and specificity of cancer screening was estimated based on the obtained values. To evaluate the performance, we measured central processing unit use, memory use, and network traffic. RESULTS: For combinations with a specificity ≥99% and high sensitivity, the date of birth and first name were used in the data simulating colorectal cancer, and the matching sensitivity and specificity were 55.00% and 99.85%, respectively. In the data simulating breast cancer, the date of birth and family name were used, and the matching sensitivity and specificity were 88.71% and 99.98%, respectively. Assuming the sensitivity and specificity of cancer screening at 90%, the apparent values decreased to 74.90% and 89.93%, respectively. A trial calculation was performed using a combination with the same data set and 100% specificity. When the matching sensitivity was 82.26%, the apparent screening sensitivity was maintained at 90%, and the screening specificity decreased to 89.89%. For 214 data points, the execution time was 82 minutes and 26 seconds without parallelization and 11 minutes and 38 seconds with parallelization; 19.33% of the calculation time was for the data-holding institutions. Memory use was 3.4 GB for the PDDI server and 2.7 GB for the data-holding institutions. CONCLUSIONS: We demonstrated the rudimentary feasibility of introducing a PDDI system for cancer-screening accuracy assessment. We plan to conduct matching experiments based on actual data and compare them with the existing methods.

N 6-methyladenosine RNA methylation: From regulatory mechanisms to potential clinical applications.

Epitranscriptomics has emerged as another level of epigenetic regulation similar to DNA and histone modifications. N 6-methyladenosine (m6A) is one of the most prevalent and abundant posttranscriptional modifications, widely distributed in many biological species. The level of N 6-methyladenosine RNA methylation is dynamically and reversibly regulated by distinct effectors including methyltransferases, demethylases, histone modification and metabolites. In addition, N 6-methyladenosine RNA methylation is involved in multiple RNA metabolism pathways, such as splicing, localization, translation efficiency, stability and degradation, ultimately affecting various pathological processes, especially the oncogenic and tumor-suppressing activities. Recent studies also reveal that N 6-methyladenosine modification exerts the function in immune cells and tumor immunity. In this review, we mainly focus on the regulatory mechanisms of N 6-methyladenosine RNA methylation, the techniques for detecting N 6-methyladenosine methylation, the role of N 6-methyladenosine modification in cancer and other diseases, and the potential clinical applications.

Primary vaginal malignant melanoma successfully treated with combination therapy: A case report.

Primary vaginal melanoma is rare compared to cutaneous melanoma, and it has a high rate of invasion and metastasis. The prognosis of tumors is poor and the quality of life of patients is low. In addition to traditional surgical and non-surgical treatment, combined treatments are more effective for patients with distant metastatic melanoma. Due to the high immunogenicity of vaginal malignant melanoma, immunotherapy has become an effective treatment strategy for distant metastatic vaginal melanoma, and with the application of immune checkpoint inhibitors (ICIs), outstanding achievements have been made in the treatment of the disease. Studies have shown that ICIs combined with radiotherapy (RT) or anti-angiogenic therapy can have a synergistic effect in certain tumor treatments, normalizing blood vessels and enhancing immune responses. However, whether ICIs combined with RT and anti-angiogenic therapy can benefit patients with distant metastatic vaginal melanoma remains unclear. The present study reports the clinical case of a patient with distant metastatic vaginal melanoma treated with combined RT, anti-angiogenic therapy and ICIs. The patient's primary tumor and distant metastases improved after combination therapy. The combination therapy successfully improved the patient's prognosis and prolonged the patient's overall survival. This provides a reference for combining all three treatment modalities in the treatment of distant metastatic vaginal melanoma.

Surgical Efficacy and Prognostic Factors for Acute Traumatic Central Cord Syndrome Without Fracture and Dislocation.

This study was undertaken to evaluate the effectiveness of surgical treatment of acute traumatic central cord syndrome (ATCCS) without fracture and dislocation and explore surgical timing and factors influencing postoperative recovery of spinal cord function. We retrospectively collected the general and clinical data of 112 patients with ATCCS (American Spinal Injury Association impairment scale grade C or D) without fracture and dislocation who underwent surgical treatment in our hospital from January 2013 to August 2019. We used statistical methods to evaluate the safety of the operation and explore the timing of surgery and the factors influencing postoperative recovery of spinal cord function. The mean age of the 112 patients was 60.64±12.91 years. The Japanese Orthopaedic Association score and the American Spinal Injury Association motor score (AMS) of the 112 patients were significantly higher at final follow-up than at admission. No significant difference in recovery of spinal cord function was seen between the early operation group (≤4 days) and the late operation group (>4 days). Comparison of patients with a good prognosis vs a poor prognosis showed that age, intrahand muscle strength at admission, maximum spinal cord compression, maximum canal compromise, length of high-intensity signal in the spinal cord on sagittal T2-weighted magnetic resonance imaging, AMS, and American Spinal Injury Association injury grade D/C at admission had a significant effect on recovery of spinal cord function. Surgical treatment of ATCCS without fracture and dislocation is safe and effective. Age, admission AMS and American Spinal Injury Association impairment scale score, intrinsic hand muscle strength, maximum canal compromise, maximum spinal cord compression, and length of high-intensity signal in the spinal cord can be used to predict postoperative recovery of spinal cord function. [Orthopedics. 2022;45(6):325-332.].

The Mini-Open Wiltse Approach with Pedicle Screw Fixation Versus Percutaneous Pedicle Screw Fixation for Treatment of Neurologically Intact Thoracolumbar Fractures: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of the present study was to compare the clinical outcomes and complications between the mini-open Wiltse approach with pedicle screw fixation (MWPSF) and percutaneous pedicle screw fixation (PPSF) in treating neurologically intact thoracolumbar fractures. METHODS: We comprehensively searched PubMed, Web of Science, Embase, and the Cochrane Library and performed a systematic review and meta-analysis of all randomized controlled trials and retrospective comparative studies assessing these important indexes of the 2 methods using Review Manager, version 5.4. The clinical outcomes are presented as the risk difference for dichotomous outcomes and the mean difference for continuous outcomes with the 95% confidence intervals. Heterogeneity was assessed using the χ2 test and I2 statistics. The study was registered with PROSPERO (CRD 42021290078). RESULTS: Two randomized controlled trials and six retrospective cohort studies were included in the present analysis. The percutaneous approach was associated with less intraoperative blood loss compared with the mini-open Wiltse approach. No significant differences were found in the total length of the incisions, hospitalization time, postoperative visual analog scale scores, postoperative Oswestry disability index, postoperative Cobb angle, postoperative Cobb angle correction, postoperative Cobb angle correction loss, accuracy rate of pedicle screw placement, and postoperative complications between MWPSF and PPSF. However, the incidence of facet joint violation was significantly higher in the PPSF group. In addition, MWPSF was associated with a shorter operative time, shorter intraoperative fluoroscopy time, lower hospitalization costs, better postoperative vertebral body angle and percentage of vertebral body height compared with PPSF. CONCLUSIONS: Both MWPSF and PPSF are safe and effective treatments of neurologically intact thoracolumbar fractures. Nevertheless, our results have indicated that MWPSF might be the better choice, because it has a shorter learning curve and decreased facet joint violation, operative time, hospitalization costs, and radiation exposure. In addition, MWPSF was associated with better improvement of the postoperative vertebral body angle and percentage of vertebral body height.

TCR Coexpression Signature Predicts Immunotherapy Resistance in NSCLC.

Background: Lung cancer has the highest morbidity and mortality rate among types of malignant tumors, and as such, research into prolonging the survival time of patients is vital. The emergence of immune checkpoint inhibitors (ICIs) has greatly improved the survival of patients with non-small cell lung cancer (NSCLC), however, the lack of effective biomarkers to predict the prognosis of immunotherapy has made it difficult to maximize the benefits. T cell receptor (TCR) is one of the most important components for recognizing tumor cells, and with this study we aim to clarify the relationship between TCR coexpression and the prognosis of NSCLC patients receiving immunotherapy. Methods: Univariate COX regression, logistics regression, and KM survival analysis were used to evaluate the relationship between TCR coexpression and the prognosis of immunotherapy. Additionally, CIBERSORT, Gene Set Enrichment Analysis (GSEA), and single-sample GSEA (ssGSEA) algorithms were used to evaluate the tumor immune microenvironment (TIME) of NSCLC patients. Results: Univariate Cox regression analysis showed that the TCR coexpression signature can be used as a clinical prognostic indicator for NSCLC patients receiving immunotherapy (p = 0.0205). In addition, those in the NSCLC group with a high TCR coexpression signature had significantly improved progression-free survival (PFS) (p = 0.014). In the ICI treatment cohort (GSE35640). In addition, there was a high infiltration of CD8+T cells, activated memory CD4+T cells, and M1 macrophages in the TIME of those with a high TCR coexpression signature. The results of pathway enrichment analysis showed that patients with a high TCR coexpression signature had significantly activated signal pathways such as lymphocyte proliferation and activation, chemokine binding, and inflammatory cytokine production. Also, we found that patients with a high TCR coexpression signature had an elevated T cell inflammation gene expression profile (GEP). Conclusion: We show that the TCR coexpression signature may be useful as a new biomarker for the prognosis of NSCLC patients undergoing immunotherapy, with high signatures indicating better treatment response. Additionally, we found that patients with a high TCR coexpression signature had tumor immune microenvironments with beneficial anti-tumor characteristics.

Parkin-mediated mitophagy protects against TNF-α-induced stress in bone marrow mesenchymal stem cells.

Bone marrow mesenchymal stem cells (BMSCs) have been investigated as cellular therapeutics for intervertebral disc degeneration. However, transplanted BMSCs are prone to be damaged. TNF-α is reported to extensively promote degeneration process. Nevertheless, the relationship between BMSCs senescence and TNF-α-induced stress has not been elucidated. Previous studies showed that mitophagy is a crucial factor in maintaining cellular homeostasis. Hence, we sought to clarify the role and mechanism of mitophagy in TNF-α-induced biological changes of BMSCs. Here, we found that TNF-α caused transient senescent damage in the early stage. Meanwhile, Parkin-mediated mitophagy was initiated and weakened the damage through maintaining mitochondria homeostasis. After inhibiting mitophagy by knockdown of Parkin, TNF-α irreversibly caused cellular senescence. These results suggested that Parkin-mediated mitophagy played protective role in BMSCs in response to TNF-α, which could be a crucial therapeutic target in the future.

Chemotherapy Can Synergize With Adoptive Immunotherapy to Inhibit Medulloblastoma Growth.

BACKGROUND/AIM: In the age of ever-increasing developments in targeted cancer treatments, new immune-based approaches for brain tumor therapy represent an attractive avenue. Despite encouraging pre-clinical data, results in patients have been sub-optimal, likely due to tumor-induced immune suppression and intrinsic resistance to immune attack. Chemotherapy and biologic agents may be able to disrupt these mechanisms and restore tumor sensitivity to immune attack. In this study, we explore whether a combination of gemcitabine and rapamycin can sensitize medulloblastoma cells to immunotherapy in vitro and in vivo. MATERIALS AND METHODS: With the commercial medulloblastoma cell line, Daoy, we explored the concentrations of combinations of Gemcitabine with rapamycin needed to induce cytotoxicity. Next, we used flow cytometry to assess the cytotoxicity of chemotherapy-treated Daoy cells with the addition of anti-tumor T-cells, generated from naive T-cells stimulated in the presence of Daoy lysate-pulsed dendritic cells. Then, we examined the efficacy of chemotherapy alone versus chemotherapy plus immunotherapy in tumor growth inhibition of subcutaneous medulloblastoma xenografts. RESULTS: Rapamycin alone at <1,000 nM had moderate activity against Daoy cells in vitro and IC50 was >1,000 nM. Gemcitabine had a 3-day IC50 alone of 10 nM but in combination with 100 nM rapamycin, it decreased to 1 nM, suggesting increased cytotoxicity with combined therapy. Stimulated T-cells mediated in-vitro cytotoxicity, although background cytotoxicity of unstimulated "naïve" T-cells was also significant. Finally, established subcutaneous Daoy cell xenografts in SCID mice were treated with chemotherapy alone or chemotherapy plus adoptive immunotherapy (stimulated and non-stimulated). Gemcitabine and rapamycin alone significantly slowed tumor growth, but the addition of immunotherapy further augmented inhibition. CONCLUSION: Combining immunotherapy and chemo-biologic therapy inhibit medulloblastoma cell and xenograft growth, and may offer an effective treatment for patients with medulloblastoma.

Eutrophication and watershed characteristics shape changes in dissolved organic matter chemistry along two river-estuarine transects.

Dissolved organic matter (DOM) plays a crucial role in the coastal carbon cycle. However, eutrophication-induced algal blooms and lateral transport from connected tidal marshes may significantly affect DOM cycling, which remains poorly understood. By combining a suite of bulk and optical techniques, and the Fourier transform ion cyclotron resonance mass spectrometry and ion mobility quadrupole time-of-flight mass spectrometry, we determined DOM concentration and composition along two typical river-estuary transects (namely Liao and Daliao rivers), Northeast China, with contrasting eutrophic state and distribution of tidal marshes. The Daliao River is characterized by a higher eutrophication degree and is surrounded with lower reed coverage than the Liao River. Compared to the Liao River, significantly higher dissolved organic carbon concentrations were observed in the Daliao River, where higher stable carbon isotope (δ13C) values and protein-like fluorescent components, characterized relatively higher autochthonous DOM. Further molecular analysis revealed higher peptide and sugar-like compounds but lower isomeric percentages of several molecular formulas in the Daliao River, suggesting higher molecular lability but lower isomeric complexity than the Liao River. Associations between optical and molecular signatures among all DOM samples revealed that a red-shifted humic-like C3 component was significantly correlated with molecular formulas with lower molecular weight and aromaticity, and higher H/C, indicating that C3 was likely a result of phytoplankton production coupled with further heterotrophic processing. Moreover, we found that reed marshes could introduce to both rivers a series of carboxylic-rich alicyclic compounds, highly unsaturated compounds, and polyphenols with high molecular weight and low H/C. This study suggests that eutrophication and reed marsh affect the DOM quality and can be a potential source of recalcitrant DOM compounds to coastal rivers and estuaries, which warrants further investigations considering the increasing worldwide eutrophication and sea-level rise in coastal delta environments.