True metachronous multiple spinal dural arteriovenous fistulas: case report and review of the literature.

Spinal dural arteriovenous fistulas (DAVFs) are the most common type of spinal vascular disorders. Multiple spinal DAVFs are very rare, and the majority of them appear synchronously. True metachronous multiple spinal DAVFs occur even more rarely. We report a case of true metachronous multiple spinal DAVFs. A 61-year-old male presented with progressive paraparesis. Spinal MRI showed extensive edema of the spinal cord from T5 to the conus and prominent vascular flow voids. MR angiography showed a left T10 DAVF. The fistula was treated surgically and the clinical symptoms gradually resolved. Recurrence of symptoms occurred 4 months after surgery. A second angiography showed a new fistula located at the right L1. The second fistula was treated surgically and the symptoms again gradually improved. Metachronous multiple spinal DAVF may present within 4 months of each other.

Profiles of transcriptome and metabolic pathways after hypobaric hypoxia exposure.

BACKGROUND: Hypoxia is a risk factor for non-alcoholic fatty liver diseases, leading to permanent imbalance of liver lipid homeostasis and steatohepatitis. However, a detailed understanding of the metabolic genes and pathways involved remains elusive. METHODS: In vivo experiments were designed to analyze body weight and lipid metabolism changes of rats under hypoxia. After this, we combined microarray analysis and gene overexpression experiments to validate the core mechanisms involved in the response to hypoxia. RESULTS: The hypobaric hypoxia treated rats exhibited significantly increased serum triglycerides (TG) (p < 0.05), despite no significant changes in serum alanine aminotransferase (ALT) and blood glucose (BG) were observed. In addition, serum high-density lipoprotein cholesterol (HDL-C) greatly increased after 3 days and then returned to normal level at 30 days. Interestingly, serum low-density lipoprotein cholesterol (LDL-C) showed an opposite pattern. Transcriptome analysis, qRT-PCR, ICC revealed that the genes PPARA, ANGPTL4, CPT-I, ACC and LPL play a crucial role in response to hypobaric hypoxia. IPA pathway analysis further confirmed that PPARA-mediated regulation of ANGPTL4 participated in TG clearance and lipoprotein metabolism. Finally, the PPARA-ANGPTL4 pathway was validated in rats and HL 7702 cells treated with Fenofibrate, a PPARA specific agonist. CONCLUSIONS: Our study showed this pathway plays an important role on lipid metabolism caused by hypobaric hypoxia and the potential target genes associated with oxygen-dependent lipid homeostasis in the liver.

Does preoperative gamma knife treatment affect the result of microresection of vestibular schwannoma?

PURPOSE: We aimed to explore the influence of preoperative gamma knife treatment on the clinical effect of microsurgical resection of vestibular schwannoma. METHODS: The data of patients who underwent vestibular schwannoma resection in our hospital between November 2010 and December 2019 were retrospectively collected. According to the data collected retrospectively and the inclusion and exclusion criteria, we selected these patients and divided them into Group A (with preoperative gamma knife treatment) and Group B (without preoperative gamma knife treatment). The pre/postoperative clinical manifestations, neurological function grade, postoperative complications, tumor recurrence and increase were collected and compared between the two groups. RESULTS: There were 40 and 823 patients enrolled in Groups A and B, respectively. There were no significant differences in the general condition, tumor size and side, or neurological performance of the patients in those two groups before the operation. At the last follow-up, the number of patients with poor facial nerve function was 15 (39.5%) in Group A and 170 (20.7%) in Group B (P = 0.021 < 0.05). In Group A and Group B, disequilibrium occurred in 14 (36.8%) patients and 124 (15.1%) patients, respectively, after the operation (P = 0.012 < 0.05). Seven (17.5%) patients had pneumonia in Group A, and 21 (2.6%) patients had pneumonia in Group B (P = 0.04 < 0.05) after the operation. CONCLUSION: When a patient with vestibular schwannoma undergoes microsurgical surgery, the preoperative history with gamma knife treatment may make recovery from postoperative facial paralysis difficult for the patients, making them more prone to suffer from postoperative disequilibrium and postoperative pneumonia.

Comparison of Sleep Disturbances Between Older Nursing Home Residents in High- and Low-Altitude Areas.

BACKGROUND AND OBJECTIVE: This study compared sleep disturbances between older adults living in nursing home located in high- and low-altitude areas and explored the association between sleep disturbances and quality of life (QoL). METHOD: In total, 207 participants living in a high-altitude area and 437 participants in a low-altitude area were included. Sleep disturbances (ie, difficulty in initiating sleep, difficulty in maintaining sleep, and early morning awakening) were measured using standardized questions. The independent demographic and clinical correlates of sleep disturbances in high-altitude area were examined using multiple logistic regression analyses. Each type of sleep disturbance was entered as the dependent variable separately, while those with significant group differences in the univariate analyses (ie, male gender, married status, age and depressive symptoms) were entered as independent variables. RESULTS: The prevalence of any type of sleep disturbances in the whole sample was 26.09%, with 41.54% in the high-altitude area and 18.76% in the low-altitude area. Physical, psychological, social, and environmental QoL domains were negatively associated with sleep disturbances in high-altitude area. Multiple logistic regression analyses revealed that male gender and married status were less likely to have sleep disturbances, while those with more severe depressive symptoms were more likely to have sleep disturbances in high-altitude area. CONCLUSION: Sleep disturbance is common among older nursing home residents in high-altitude areas. Considering the negative impact of sleep disturbance on QoL, regular screening and treatment strategies need to be developed directly for this population.

Identification of RPL5 and RPL10 as novel diagnostic biomarkers of Atypical teratoid/rhabdoid tumors.

BACKGROUND: Rhabdoid tumors (RTs) are aggressive tumors that occur most frequently in children under 2 years old, which often invade kidney (KRTs) and Center Nervous System, named Atypical teratoid/rhabdoid tumors (AT/RTs). RTs often progress fast and lead to a high lethality. RTs have a low incidence, we can hardly accumulate enough samples to elicit the diagnosis. More importantly, histologically, RTs present a host of neural, epithelial, mesenchymal, or ependymal patterns, which makes them rather variable and difficult to diagnose. Molecularly, RTs are diagnosed mainly on the lack of SMARCB1/INI1 protein expression, which, on the one hand, accounts for 75% of RTs, on the other hand, loss of expression of SMARCB1 is not exclusive to RTs. So, there is a need to find more accurate diagnose markers of RTs. METHODS: In this study, we analyzed 109 samples including AT/RT, KRT and corresponding normal samples downloaded form NCBI GEO database. First, we identified the differentially expressed lncRNAs and PCGs in AT/RT, KRT and corresponding normal samples. Second, we evaluated the co-expression relationship between lncRNA and PCG, and defined four types of the dysregulated PCG-lncRNA pairs. Third, we compared the differentially expressed genes, the dysregulated PCG-lncRNA pairs and commonly known cancer genes, we get potential diagnostic markers. Then, the potential diagnostic markers were subjected to Receiver operating characteristic (ROC) analysis to assess the diagnostic accuracy. Importantly, differential expression of the marker genes in different tumors was shown to distinguish AT/RT and KRT from other pediatric tumors specifically. RESULTS: We compared the expression profiles between 47 AT/RTs, 31 KRTs, 8 normal brain samples, and 23 normal kidney samples. After applying a stringent set of criteria on the gene expression profiles, we identified 3667 PCGs and 81 lncRNAs differentially expressed in AT/RT, 3809 PCGs and 34 lncRNAs differentially expressed in KRT tissues. Next, we compared the three sets(AT/RT versus control brain samples, KRT versus control kidney samples, and AT/RT versus KRT) of differentially expressed lncRNAs and PCGs, 491 PCGs and 2 lncRNAs appeared in all three sets. We examined the correlation of the expression levels of these genes in the 'three-set overlap' group and identified four types of dysregulated lncRNAs and PCGs. By compared these genes to the well-known cancer driver genes, 19 PCGs were selected as potential candidates of diagnostic markers. Filtered with the number of the corresponding co-expressed lncRNA (namely "degree"), eight PCGs with more than five lncRNAs in the 'three-set overlap' group were selected as candidate diagnostic markers. Among them, RPL5 and RPL10 exhibited high sensitivity and specificity in diagnosis of AT/RT and KRT. However, when these two genes were used to distinguish AT/RT and KRT from other pediatric tumors, only AT/RT can be distinguished from medulloblastoma. CONCLUSIONS: Our study mined existing GEO datasets for novel diagnostic markers associated with Rhabdoid tumors, and identified RPL5 and RPL10 as potential diagnostic markers for AT/RT. These two biomarkers may be used as supplementary biomarkers to canonical diagnostic tools such as biopsy and immunohistochemistry.

Multimodal treatments combined with gamma knife surgery for primary atypical teratoid/rhabdoid tumor of the central nervous system: a single-institute experience of 18 patients.

OBJECTIVES: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly malignant tumor of the central nervous system with poor prognosis. Nowadays, multimodal management, including surgery, chemotherapy (CMT), and radiation therapy (RT), is advocated. However, AT/RT treatment with gamma knife surgery (GKS) was rarely reported. The aim of this study was to assess the efficacy and safety of GKS for the treatment of AT/RT. PATIENTS AND METHODS: Medical records of AT/RT patients who underwent surgery from 2007 to 2014 at the West China Hospital were retrospectively reviewed and statistically analyzed. RESULTS: Eighteen patients (12 males and 6 females) were presented with AT/RTs. Median age during presentation was 20.5 months (range, 4-179 months). Twelve patients were < 3 years and six patients were > 3 years. Tumor location was supratentorial in seven patients, infratentorial in ten patients, and center area of the brain in one patient. Treatments performed were as follows: surgery alone in two patients, surgery+RT in two patients, surgery+CMT in five patients, surgery+CMT+RT in two patients, and surgery+CMT+RT+GKS in seven patients. The 2-year overall survival (OS) rate and event-free survival (EFS) rate for all 18 consecutive patients were 33.3 and 27.8%, respectively. Cox regression analyses showed that multimodal management combined with GKS was an independent positive prognostic factor for OS. CONCLUSIONS: Although AT/RTs are lethal cancer types, the OS of the disease was improved by using multimodal therapeutic strategies, including surgery, CMT, and RT, combined with GKS.

Successful microsurgical treatment of intracranial aneurysms in infants: a retrospective study and literature review.

OBJECTIVE: Intracranial aneurysms are extremely rare in infants, especially less than 1 year old. This study aimed to analyze the frequency of infantile intracranial aneurysm in our department and investigate the clinical characteristics, treatment strategies, and outcomes of this disease. METHODS: Six infants under 1 year old in 4350 patients with intracranial aneurysms were retrospectively analyzed from January 2010 to December 2016. RESULTS: The patients (5 females and 1 male) ranged in age from 2 to 11 (mean age, 4.67) months. Four patients presented with generalized seizure and vomiting, 3 showed lethargy, 1 presented eye deviation, and 1 had right-sided hemiparesis. Radiographically, two aneurysms were localized in the middle cerebral artery (MCA) of the M2 segment, two were located in the M3 segment of MCA, one was located at left MCA bifurcation, and one was located at the nonbranching site of the left supraclinoid internal carotid artery. All these lesions were successfully managed with aneurysm clipping or resection, and the improvement of neurological deficits was achieved in all patients. CONCLUSION: Intracranial aneurysms should be considered in the differential diagnosis of infants who present with acute raised intracranial pressure. An improvement of neurological deficits is noted in infants who are managed promptly with microsurgical techniques of clipping during the long-term follow-up.

The cyclophilin D/Drp1 axis regulates mitochondrial fission contributing to oxidative stress-induced mitochondrial dysfunctions in SH-SY5Y cells.

Oxidative stress plays a central role in the pathogenesis of various neurodegenerative diseases. Increasing evidences have demonstrated that structural abnormalities in mitochondria are involved in oxidative stress related nerve cell damage. And Drp1 plays a critical role in mitochondrial dynamic imbalance insulted by oxidative stress-derived mitochondria. However, the status of mitochondrial fusion and fission pathway and its relationship with mitochondrial properties such as mitochondrial membrane permeability transition pore (mPTP) have not been fully elucidated. Here, we demonstrated for the first time the role of Cyclophilin D (CypD), a crucial component for mPTP formation, in the regulation of mitochondrial dynamics in oxidative stress treated nerve cell. We observed that CypD-mediated phosphorylation of Drp1 and subsequently augmented Drp1 recruitment to mitochondria and shifts mitochondrial dynamics toward excessive fission, which contributes to the mitochondrial structural and functional dysfunctions in oxidative stress-treated nerve cells. CypD depletion or over expression accompanies mitochondrial dynamics/functions recovery or aggravation separately. We also demonstrated first time the link between the CypD to mitochondrial dynamics. Our data offer new insights into the mechanism of mitochondrial dynamics which contribute to the mitochondrial dysfunctions, specifically the role of CypD in Drp1-mediated mitochondrial fission. The protective effect of CsA, or other molecules affecting the function of CypD hold promise as a potential novel therapeutic strategy for governing oxidative stress pathology via mitochondrial pathways.

Effect of hawthorn polyphenol extracts on the physicochemical properties and digestibility of corn starch.

To investigate the effect of hawthorn polyphenols on the physicochemical properties and digestibility of corn starch, different proportions (1%, 2%, 3%, and 4% [w/w]) of hawthorn polyphenol extracts (HPEs) were mixed with corn starch, and their physicochemical properties and digestive properties were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, Rapid Visco Analysis, differential scanning calorimetry, and in vitro/in vivo analysis. Results indicated that small V-type crystal starch tended to be formed in the samples, and the addition of HPEs reduced the viscosity, prolonged the gelatinization temperature of corn starch, and increased the proportion of slowly digestible starch and resistant starch of the corn starch, which accounted for 36.32% ± 1.05% and 33.32% ± 4.07%, respectively. Compared with the raw corn starch, the postprandial blood glucose of mice that were administered the hawthorn polyphenols decreased significantly: the blood glucose peak (30 min) decreased from 14.30 ± 1.52 to 11.77 ± 1.21 mmol/L. Our study might provide some basic theoretical support for the application of hawthorn polyphenols in healthy starchy food processing.

Enhance the resistance of probiotics by microencapsulation and biofilm construction based on rhamnogalacturonan I rich pectin.

Microcapsules were always used as functional material carriers for targeted delivery and meanwhile offering protection. However, microcapsule wall materials with specific properties were required, which makes the choice of wall material a key factor. In our previous study, a highly branched rhamnogalacturonan I rich (RG-I-rich) pectin was extracted from citrus canning processing water, which showed good gelling properties and binding ability, indicating it could be a potential microcapsule wall material. In the present study, Lactiplantibacillus plantarum GDMCC 1.140 and Lactobacillus rhamnosus were encapsulated by RG-I-rich pectin with embedding efficiencies of about 65 %. The environmental tolerance effect was evaluated under four different environmental stresses. Positive protection results were obtained under all four conditions, especially under H2O2 stress, the survival rate of probiotics embedded in microcapsules was about double that of free probiotics. The storage test showed that the total plate count of L. rhamnosus encapsulated in RG-I-rich pectin microcapsules could still reach 6.38 Log (CFU/mL) at 25 °C for 45 days. Moreover, probiotics embedded in microcapsules with additional incubation to form a biofilm layer inside could further improve the probiotics' activities significantly in the above experiments. In conclusion, RG-I-rich pectin may be a good microcapsule wall material for probiotics protection.

Tumor treating fields for newly diagnosed high-grade glioma based on the criteria of 2021 WHO CNS5: A retrospective analysis of Chinese patients in a single center.

BACKGROUND AND OBJECTIVE: High-grade glioma (HGG) is known to be characterized by a high degree of malignancy and a worse prognosis. The classical treatment is safe resection supplemented by radiotherapy and chemotherapy. Tumor treating fields (TTFields), an emerging physiotherapeutic modality that targets malignant solid tumors using medium-frequency, low-intensity, alternating electric fields to interfere with cell division, have been used for the treatment of new diagnosis of glioblastoma, however, their administration in HGG requires further clinical evidence. The efficacy and safety of TTFields in Chinese patients with HGG were retrospectively evaluated by us in a single center. METHODS: We enrolled and analyzed 52 patients with newly diagnosed HGG undergoing surgery and standard chemoradiotherapy regimens from December 2019 to June 2022, and followed them until June 2023. Based on whether they used TTFields, they were divided into a TTFields group and a non-TTFields group. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups. RESULTS: There were 26 cases in the TTFields group and 26 cases in the non-TTFields group. In the TTFields group, the median PFS was 14.2 months (95% CI: 9.50-18.90), the median OS was 19.7 months (95% CI: 14.95-24.25) , the median interval from surgery to the start of treatment with TTFields was 2.47 months (95% CI: 1.47-4.13), and the median duration of treatment with TTFields was 10.6 months (95% CI: 9.57-11.63). 15 (57.69%) patients experienced an adverse event and no serious adverse event was reported. In the non-TTFields group, the median PFS was 9.57 months (95% CI: 6.23-12.91) and the median OS was 16.07 months (95% CI: 12.90-19.24). There was a statistically significant difference in PFS (p = 0.005) and OS (p = 0.007) between the two groups. CONCLUSIONS: In this retrospective analysis, TTFields were observed to improve newly diagnosed HGG patients' median PFS and OS. Compliance was much higher than reported in clinical trials and safety remained good.

Development and characterization of pH responsive sodium alginate hydrogel containing metal-phenolic network for anthocyanin delivery.

Favorable hydrogels can be used as a material to deliver bioactive molecules and improve the stability of bioactive substances, while their safety needs to be improved. In this study, protocatechuic acid (PCA) and Fe3+ were rapidly self-assembled to form a metal-phenolic network under different pH conditions, and then sodium alginate (SA) was added to prepare the SA/PCA/Fe hydrogel without adding other chemical reagents. The structural characteristic of SA/PCA/Fe hydrogel was characterized by infrared spectroscopy, X-ray diffraction analysis and scanning electron microscopy. The results showed that the structures of SA/PCA/Fe hydrogels prepared at different pH values were significantly different. The texture analysis, water-holding measurement and rheological analysis indicated that the SA/PCA/Fe hydrogel showed higher gel strength, water holding capacity and storage modulus. Thermogravimetric analysis illuminated that the SA/PCA/Fe hydrogel enhanced the thermal stability of free anthocyanins through encapsulating anthocyanins. Moreover, in vitro simulated digestion experiment revealed that SA/PCA/Fe hydrogel could control the release of anthocyanins in the simulated gastrointestinal tract. To sum up, this present study might provide a safer and feasible way for the delivery of bioactive substances.

Regulating the physicochemical, structural characteristics and digestibility of potato starch by complexing with different phenolic acids.

The effects of ferulic acid (FA), protocatechuic acid (PA), and gallic acid (GA) on the physicochemical characteristics, structural properties, and in vitro digestion of gelatinized potato starch (PS) were investigated. Rapid viscosity analysis revealed that the gelatinized viscosity parameters of PS decreased after complexing with different phenolic acids. Dynamic rheology results showed that phenolic acids could reduce the values of G' and G″ of PS-phenolic acid complexes, demonstrating that the addition of phenolic acids weakened the viscoelasticity of starch gel. Fourier-transform infrared spectra and X-ray diffraction results elucidated that phenolic acids primarily reduced the degree of short-range ordered structure of starch through non-covalent interactions. The decrease in thermal stability and the more porous microstructure of the complexes confirmed that phenolic acids could interfere with the gel structure of the starch. The addition of different phenolic acids decreased the rapidly digestible starch (RDS) content and increased the resistant starch (RS) content, with GA exhibiting the best inhibitory capacity on starch in vitro digestibility, which might be associated with the number of hydroxy groups in phenolic acids. These results revealed that phenolic acids could affect the physicochemical characteristics of PS and regulate its digestion and might be a potential choice for producing slow digestibility starch foods.

Pectin from Citrus unshiu Marc. Alleviates Glucose and Lipid Metabolism by Regulating the Gut Microbiota and Metabolites.

The effects of pectin from Citrus unshiu Marc. on glycolipid metabolism, the morphologies of the pancreas and epididymal fat, the gut microbiota, and the metabolites of short-chain fatty acids (SCFAs) in db/db mice were investigated in this study. The results indicated that pectin reduced the levels of fasting blood glucose, glycated serum protein, triglycerides, total cholesterol, and low-density lipoprotein cholesterol while increasing the levels of high-density lipoprotein cholesterol. Meanwhile, pectin could improve the morphology of islet cells and inhibit the hypertrophy of adipocytes. Additionally, pectin not only regulated the intestinal flora dysbiosis in db/db mice, as shown by the increasing proportion of Firmicutes/Bacteroidetes and the relative abundance of Ligilactobacillus, Lactobacillus, and Limosilactobacillus, but also remedied the metabolic disorder of SCFAs in db/db mice. These results suggest that pectin could promote glucose and lipid metabolism by regulating the intestinal flora with changes in SCFA profile. This study proves that pectin might serve as a new prebiotic agent to prevent the disorder of glycolipid metabolism.

Deep learning-based prediction of H3K27M alteration in diffuse midline gliomas based on whole-brain MRI.

BACKGROUND: H3K27M mutation status significantly affects the prognosis of patients with diffuse midline gliomas (DMGs), but this tumor presents a high risk of pathological acquisition. We aimed to construct a fully automated model for predicting the H3K27M alteration status of DMGs based on deep learning using whole-brain MRI. METHODS: DMG patients from West China Hospital of Sichuan University (WCHSU; n = 200) and Chengdu Shangjin Nanfu Hospital (CSNH; n = 35) who met the inclusion and exclusion criteria from February 2016 to April 2022 were enrolled as the training and external test sets, respectively. To adapt the model to the human head MRI scene, we use normal human head MR images to pretrain the model. The classification and tumor segmentation tasks are naturally related, so we conducted cotraining for the two tasks to enable information interaction between them and improve the accuracy of the classification task. RESULTS: The average classification accuracies of our model on the training and external test sets was 90.5% and 85.1%, respectively. Ablation experiments showed that pretraining and cotraining could improve the prediction accuracy and generalization performance of the model. In the training and external test sets, the average areas under the receiver operating characteristic curve (AUROCs) were 94.18% and 87.64%, and the average areas under the precision-recall curve (AUPRC) were 93.26% and 85.4%. CONCLUSIONS: The developed model achieved excellent performance in predicting the H3K27M alteration status in DMGs, and its good reproducibility and generalization were verified in the external dataset.

Metabolomic profiling of early inactive hepatic alveolar and cystic echinococcosis.

Hepatic alveolar echinococcosis (AE) and cystic echinococcosis (CE) are severe helminthic zoonoses and leading causes of parasitic liver damage. They pose a high mortality risk due to invisible clinical signs, especially at the early inactive stage. However, the specific metabolic profiles induced by inactive AE and CE lesions remain largely unclear. Therefore, we used gas chromatography-mass spectrometry-based metabolomic profiling to identify the global metabolic variations in AE and CE patient sera to differentiate between the two diseases and reveal the mechanisms underlying their pathogenesis. In addition, specific serum biomarkers of inactive hepatic AE and CE were screened using receiver operating curves, which can contribute to the clinical diagnosis of both diseases, especially in the earlier phase. These differential metabolites are involved in glycine, serine, tyrosine, and phenylalanine metabolism. Further analysis of key metabolic pathways showed that inactive AE lesions strongly alter amino acid metabolism in the host. CE lesions have an altered metabolism of oxidative stress response. These changes suggest these metabolite-associated pathways can serve as biomarkers to distinguish individuals with inactive AE and CE from healthy populations. This study also investigated the differences in serum metabolic profiles in patients with CE and AE. The biomarkers identified belonged to different metabolic pathways, including lipid, carnitine, androgen, and bile acid metabolism. Taken together, by investigating the different phenotypes of CE and AE with metabolomic profiling, serum biomarkers facilitating early diagnosis were identified.

Clinical outcomes and prognostic factors in the surgical treatment of spinal dural arteriovenous fistulas: a retrospective study of 118 patients.

Spinal dural arteriovenous fistulas (SDAVFs) are the most common type of spinal vascular malformations (AVMs), constituting approximately 70% of all spinal AVMs. The impact of various clinical and radiologic features on the outcomes in patients with SDAVFs is still controversial. The purpose of the study is to investigate the clinical outcomes and prognostic factors in patients with surgically treated SDAVFs in a single center. A retrospective review was performed for all patients with SDAVFs from January 2013 to September 2021 who underwent surgery at our institution. Medical records and pre- and postoperative imaging data were analyzed. Neurological function status was evaluated by modified Aminoff-Logue Scale (mALS). Student's t-test, Wilcoxon rank sum test, χ2 test and logistic regression were used to find significant prognostic factors. P values < 0.05 were considered significant. One hundred and eighteen patients were ultimately included in the study. By comparing preoperative and postoperative mALS, 69 (58.5%) patients experienced improvement, and 49 (41.5%) patients showed no improvement (worse or unchanged). Wilcoxon rank sum test showed that there was a difference between the improvement group and the no improvement group in preoperative mALS Micturition score and preoperative mALS Defecation score. The logistic regression revealed that preoperative mALS Gait score was associated with clinical improvement after surgery in patients with SDAVFs. Surgical treatment of SDAVFs is a safe and effective procedure and can lead to symptom improvement or stabilization in most patients. Preoperative neurological function status was the only factor associated with clinical prognosis.

A validated prognostic nomogram for patients with H3 K27M-mutant diffuse midline glioma.

H3 K27M-mutant diffuse midline glioma (H3 K27M-mt DMG) is a rare, highly invasive tumor with a poor prognosis. The prognostic factors of H3 K27M-mt DMG have not been fully identified, and there is no clinical prediction model for it. This study aimed to develop and validate a prognostic model for predicting the probability of survival in patients with H3 K27M-mt DMG. Patients diagnosed with H3 K27M-mt DMG in the West China Hospital from January 2016 to August 2021 were included. Cox proportional hazard regression was used for survival assessment, with adjustment for known prognostic factors. The final model was established using the patient data of our center as the training cohort and data from other centers for external independent verification. One hundred and five patients were ultimately included in the training cohort, and 43 cases from another institution were used as the validation cohort. The factors influencing survival probability in the prediction model included age, preoperative KPS score, radiotherapy and Ki-67 expression level. The adjusted consistency indices of the Cox regression model in internal bootstrap validation at 6, 12, and 18 months were 0.776, 0.766, and 0.764, respectively. The calibration chart showed high consistency between the predicted and observed results. The discrimination in external verification was 0.785, and the calibration curve showed good calibration ability. We identified the risk factors that affect the prognosis of H3 K27M-mt DMG patients and then established and validated a diagnostic model for predicting the survival probability of these patients.

Preparation and physicochemical properties characterization of hesperetin-grafted pectin conjugate.

Different ratios of hesperetin (HT) were successfully grafted onto pectin from basic water (PB) molecules via free radical-induced reaction. The structure of PB-HT conjugates was characterized by ultraviolet spectroscopy, infrared spectroscopy, X-ray diffraction and scanning electron microscopy. Results indicated that HT was successfully grafted onto pectin molecules, and PB-HT-0.5 showed the highest HT content (103.18 ± 2.76 mg/g). Thermogravimetric analysis indicated that HT crystals showed good thermal resistance and could improve the thermal stability of PB-HT conjugates. Additionally, PB-HT conjugates showed good cytocompatibility and blood compatibility. This study provides a novel and efficient method to synthesize hesperetin-grafted pectin conjugate, which showed potential application in the fields of functional foods in the future.

Comparative Tandem Mass Tag-Based Quantitative Proteomics Analysis of Liver Against Chronic Hypoxia: Molecular Insights Into Metabolism in Rats.

Xu, Jin, Shenhan Gao, Mingyuan Xin, Wenjie Chen, Kaikun Wang, Wenjing Liu, Xinzong Yan, Sinan Peng, and Yanming Ren. Comparative tandem mass tag-based quantitative proteomics analysis of liver against chronic hypoxia: molecular insights into metabolism in rats. High Alt Med Biol. 24:49-58, 2023. Objective: Using a metabolomic approach, we uncovered key regulators in metabolism from tandem mass tag (TMT)-based proteomic analysis in animals chronically exposed to hypoxia. Methods: Sixteen Sprague-Dawley rats (n = 8 per group) were exposed to chronic normoxia or hypoxia (380 mmHg corresponding to a simulated altitude of 5,500 m) for 35 consecutive days. Hypoxia-induced alterations in metabolic pathways were analyzed from TMT-based proteomic analysis, complemented by western blot validation of key regulators. Results: We profiled biochemical parameters and serum lipids, found that serum alanine aminotransferase and blood glucose were not significantly changed due to chronic hypoxia. However, serum triglycerides, total cholesterol, high-density lipoprotein, and low-density lipoprotein (LDL) were significantly affected by chronic hypoxia. And the levels of LDL nearly doubled (p < 0.05) after hypoxia exposure for 35 days. Through Kyoto Encyclopedia of Genes and Genomes classification, we found several metabolic pathways were enriched, including lipid metabolism, cofactor and vitamin metabolism, amino acids metabolism, carbohydrate metabolism, and energy metabolism. To explore the potential functions of proteins in metabolic pathways that become a coordinated shift under chronic hypoxic conditions, Gene Ontology and pathway analysis were carried out on differentially expressed proteins. As the co-expression network shown in Figure, we identified the most significant differentially expressed proteins after chronic hypoxic changes in the livers of rats. Furthermore, we validated the gene expression profiles at the protein level using western blot. Results of western blot were in accordance with our quantitative polymerase chain reaction findings. The levels of fatty acid synthase and aquaporin 1 were significantly downregulated after 35 days and the levels of ATP citrate lyase, 2'-5'-oligoadenylate synthetase 1A, aldehyde dehydrogenase 2, and Ras-related protein Rap-1A were significantly upregulated after 35 days. Conclusions: Although this study cannot completely account for all the molecular mechanisms in rats, we provide a good analysis of protein expression and profiling of rats under chronic hypoxia conditions.