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Abstract Background The clinical features of cerebellar high-grade gliomas (cHGGs) in adults have not been thoroughly explored. This large-scale, population-based study aimed to comprehensively outline these traits and construct a predictive model. Methods Patient records diagnosed with gliomas were collected from various cohorts and analyzed to compare the features of cHGGs and supratentorial HGGs (sHGGs). Cox regression analyses were employed to identify prognostic factors for overall survival and to develop a nomogram for predicting survival probabilities in patients with cHGGs. Multiple machine learning methods were applied to evaluate the efficacy of the predictive model. Results There were significant differences in prognosis, with SEER-cHGGs showing a median survival of 7.5 months and sHGGs 14.9 months (p

Abstract Background Evidence has revealed a connection between cuproptosis and the inhibition of tumor angiogenesis. While the efficacy of a model based on cuproptosis-related genes (CRGs) in predicting the prognosis of peripheral organ tumors has been demonstrated, the impact of CRGs on the prognosis and the immunological landscape of gliomas remains unexplored. Methods We screened CRGs to construct a novel scoring tool and developed a prognostic model for gliomas within the various cohorts. Afterward, a comprehensive exploration of the relationship between the CRG risk signature and the immunological landscape of gliomas was undertaken from multiple perspectives. Results Five genes (NLRP3, ATP7B, SLC31A1, FDX1, and GCSH) were identified to build a CRG scoring system. The nomogram, based on CRG risk and other signatures, demonstrated a superior predictive performance (AUC of 0.89, 0.92, and 0.93 at 1, 2, and 3 years, respectively) in the training cohort. Furthermore, the CRG score was closely associated with various aspects of the immune landscape in gliomas, including immune cell infiltration, tumor mutations, tumor immune dysfunction and exclusion, immune checkpoints, cytotoxic T lymphocyte and immune exhaustion-related markers, as well as cancer signaling pathway biomarkers and cytokines. Conclusion The CRG risk signature may serve as a robust biomarker for predicting the prognosis and the potential viability of immunotherapy responses. Moreover, the key candidate CRGs might be promising targets to explore the underlying biological background and novel therapeutic interventions in gliomas.

Abstract Idiopathic normal pressure hydrocephalus (iNPH) affects mainly aged populations. The gradual shortening of telomere length (TL) is one of the hallmarks of aging. Whereas the genetic contribution of TL to the iNPH is incompletely understood. We aimed to investigate the causal relationship between TL and iNPH through the Mendelian randomization (MR) analysis. We respectively obtained 186 qualified single nucleotide polymorphisms (SNPs) of TL and 20 eligible SNPs of iNPH for MR analysis. The result of MR analysis showed that genetically predicted longer TL was significantly associated with a reduced odd of iNPH (odds ratio [OR] = 0.634 95% Confidence interval [CI] 0.447–0.899, p = 0.011). The causal association remained consistent in multivariable MR (OR = 0.530 95% CI 0.327–0.860, p = 0.010). However, there was no evidence that the iNPH was causally associated with the TL (OR = 1.000 95% CI 0.996–1.004, p = 0.955). Our study reveals a potential genetic contribution of TL to the etiology of iNPH, that is a genetically predicted increased TL might be associated with a reduced risk of iNPH.

Following ion-adsorption rare earth mining, the residual tailings experience considerable heavy metal contamination and gradually evolve into a pollution source. Therefore, the leaching characteristics and environmental impact of heavy metals in ion-adsorption rare earth tailings require immediate and thorough investigation. This study adopted batch and column experiments to investigate the leaching behaviour of heavy metals in tailings and assess the impact of tailings on paddy soil, thereby providing a scientific basis for environmental protection in mining areas. The results showed that Mn, Zn, and Pb contents were 431.67, 155.05, and 264.33 mg·kg−1, respectively, which were several times higher than their respective background values, thereby indicating significant heavy metal contamination in the tailings. The batch leaching experiment indicated that Mn and Pb were priority control heavy metals. Heavy metals were divided into fast and slow leaching stages. The Mn and Pb leaching concentrations far exceeded environmental limits. The DoseResp model perfectly fitted the leaching of all heavy metals from the tailings (R2 > 0.99). In conjunction with the findings of the column experiment and correlation analysis, the chemical form, rainfall pH, ammonia nitrogen, and mineral properties were identified as the primary factors controlling heavy metal release from tailings. Rainfall primarily caused heavy metal migration in the acid-extraction form from the tailings. The tailing leachate not only introduced heavy metals into the paddy soil but also caused the transformation of the chemical form of heavy metals in the paddy soil, further exacerbating the environmental risk posed by heavy metals. The study findings are significant for environmental conservation in mining areas and implementing environmentally friendly practices in rare earth mining.

Abstract 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.

Background: The purpose of this study was to compare the efficacy and safety of utidelone plus capecitabine for advanced first-line versus second-line or above therapy in metastatic breast cancer patients who had previously received anthracycline and taxane. At the same time, we compared the efficacy of utidelone plus capecitabine and vinorelbine plus cisplatin in advanced first-line treatment of metastatic breast cancer. Patients and methods: A retrospective cohort of 11 patients with metastatic breast cancer previously treated with anthracycline and taxane (including neoadjuvant and adjuvant therapies) for advanced first-line with utidelone plus capecitabine, 32 patients treated with second-line or above, and 60 patients with vinorelbine plus cisplatin between October 2011 and August 2022 was collected. The first and second groups were treated with utidelone plus capecitabine, and the third group was treated with vinorelbine plus cisplatin. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), objective response rate (ORR), and treatment safety. Results: By 03/31/2023, median PFS reached 11.70 months (95 % CI 0.093–0.141) in utidelone plus capecitabine group in the advanced first-line therapy, compared to 5.60 months (95 % CI 0.025–0.079) in the second-line or above therapy [HR 0.42, (95 % CI 0.226–0.787), P = 0.0077]. In utidelone plus capecitabine, the median OS was not reached in the advanced first-line therapy, with a mean overall survival of 23.16 months (95 % CI 0.198–0.265); whereas the median OS in the second-line or above therapy was 19.50 months (95 % CI 0.083–0.307), with a mean overall survival of 16.89 months (95 % CI 0.136–0.202) [HR 0.26, (95 % CI 0.098–0.678), P = 0.0495]. The ORR for advanced first-line therapy was 27.27 % (95%CI 0.060, 0.610) compared with 15.63 % (95%CI 0.053, 0.328) for second-line or above. In advanced first-line therapy, utidelone plus capecitabine was superior to vinorelbine plus cisplatin with a median PFS of 6.12 months (95 % CI 0.051–0.072) [HR 0.49, (95 % CI 0.286–0.839), P = 0.0291]. Compared with utidelone plus capecitabine, the median OS in vinorelbine plus cisplatin advanced first-line therapy group was 35.37 months (95 % CI 0.258–0.449), and the mean overall survival was 40.79 months (95 % CI 0.315–0.501) [HR 0.54, (95 % CI 0.188–1.568), P = 0.2587]. The ORR for vinorelbine plus cisplatin was 18.33 % (95 % CI 0.095, 0.304). The most common adverse events in our study were neurological toxicity, hand-foot syndrome, hematological toxicity, gastrointestinal toxicity, and hepatic and renal function abnormalities. There were no deaths due to adverse effects during the utidelone plus capecitabine treatment period. Conclusions: In MBC, advanced first-line therapy with utidelone plus capecitabine resulted in more favorable PFS, OS, and ORR than second-line or above therapy. In advanced first-line therapy, utidelone plus capecitabine had superior PFS, and ORR compared with vinorelbine plus cisplatin. This study concludes that utidelone plus capecitabine is a more valuable chemotherapy option in advanced first-line MBC.

Abstract An acute infectious disease of northern sheatfish (Silurus soldatovi) was found in a commercial aquaculture pond in Tianjin, China. Herein, two dominant bacterial strains were isolated from naturally diseased northern sheatfish and identified as Aeromonas veronii and Vibrio cholerae. Seven healthy and seven naturally diseased fish that were collected from the pond were used for the gut microbiota analysis by high‐throughput 16S rRNA gene sequencing. The α‐diversity indices (ACE, Chao 1, and Shannon) did not differ significantly between diseased and healthy fish (p > 0.05), but a significant separation was observed between them when β‐diversity analysis of the bacterial population was performed. The diseased fish demonstrated a significant elevation in the relative abundances of Aeromonas, Vibrio, Blautia, and Megamonas and a decrease in Cetobacterium, Bacteroides, Chryseolinea, Ralstonia, and Pseudomonas compared with healthy fish (p

Abstract Introduction A pan-genotypic and effective treatment regimen for patients with chronic hepatitis C virus (HCV) infection remains an unmet medical need in China. Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. We conducted a phase 3 study to evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV infection. Methods All patients received 600 mg alfosbuvir tablets plus 60 mg daclatasvir tablets once daily for 12 weeks. The primary endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). A follow-up visit was done at week 4 and 12, and those who achieved SVR12 were followed up at post-treatment week 24. Results Of the 326 patients who received at least one dose of the study drug, 320 (98.2% [95% confidence interval (CI): 96.5%–99.5%]) achieved sustained virological response at post-treatment week 12 (SVR12), which was superior to the historical SVR12 rate of 88% (p

Cytomegalovirus (CMV) infection involving the skin is relatively rare. We herein report a case involving a man in his late 70s with positive hepatitis B surface antigen who presented with multiform skin lesions, including a papuloid rash, papular urticaria, and purpura. The patient had taken no antiviral drugs for nearly 13 years but had recently developed severe liver injury. Laboratory examination revealed positive CMV immunoglobulin M, CMV polymerase chain reaction result of 1.09 × 10 2 copies/mL, and a slightly decreased CD4+ cell count; however, the CD8+ T-cell count was within the normal range. A skin biopsy was performed in the region of the papular eruption on the left inner thigh, and the pathologic findings were consistent with CMV infection. After admission, the patient began a combination of antiviral therapy for hepatitis B virus and CMV. After 3 weeks of treatment, the patient was discharged with skin lesions, and his liver function recovered.

Abstract 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.

In the context of carbon neutrality, the carbon capture, utilization and storage (CCUS) is a key technology to achieve energy conservation and emission reduction. In view of the high energy consumption and degradation of organic amine solutions in the carbon capture process, an electrochemically mediated amine regeneration (EMAR) is a promising carbon capture technology, which uses the complexation between Cu(II) and absorbent to achieve the release of CO2. The CO2 absorption and desorption performance of nine absorbents was measured using the absorption and desorption experimental device. It was found that the primary and secondary amine solutions have better absorption performance than tertiary amines, but the regeneration efficiency is not high under the traditional thermal desorption method, and there is great potential for improvement. The Cu(II) was added directly to the CO2-saturated amine solution, and the solution was found to exhibit excellent desorption properties. Under the same conditions, the cathodic and anode electrochemical parameters of different alcohol amine solutions were tested, and the electrochemical parameters such as polarization potential, current density and solution internal resistance, as well as absorption and desorption performance and raw material cost were comprehensively considered, and the DETA was selected as the research object to continue the exploration of subsequent experimental conditions. The electrochemical reaction device was used to study the 30% DETA aqueous solution saturated with CO2, and the influence of four influencing factors, i.e. electrolyte type, electrolyte concentration, Cu(II) concentration and temperature on the electrochemical reaction process, was explored. It was found that NaBr has a lower corrosion potential among the four selected electrolytes, and the advantage of potential at high concentrations is more obvious, which is more conducive to the reaction. The high electrolyte concentration can reduce the corrosion potential to 0.2 V relative to the absence of electrolyte, and both it and temperature can effectively reduce the charge transfer resistance and increase the reaction rate. In addition, the low Cu(II) load is conducive to the formation of Cu(II) and the desorption of CO2, and the increase of the concentration of Cu(II) in solution will inhibit the oxidation of anode copper to copper ions, which is conducive to the formation of elemental copper and the regeneration of DETA. The study results provide reference data for the engineering application of this technology.

Abstract 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.

BackgroundPostpartum depression (PPD) is a type of depressive episode related to parents after childbirth, which causes a variety of symptoms not only for parents but also affects the development of children. The causal relationship between potential risk factors and PPD remains comprehensively elucidated.MethodsLinkage disequilibrium score regression (LDSC) analysis was conducted to screen the heritability of each instrumental variant (IV) and to calculate the genetic correlations between effective causal factors and PPD. To search for the causal effect of multiple potential risk factors on the incidence of PPD, random effects of the inverse variance weighted (IVW) method were applied. Sensitivity analyses, including weighted median, MR-Egger regression, Cochrane’s Q test, and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), were performed to detect potential Mendelian randomization (MR) assumption violations. Multivariable MR (MVMR) was conducted to control potential multicollinearity.ResultsA total of 40 potential risk factors were investigated in this study. LDSC regression analysis reported a significant genetic correlation of potential traits with PPD. MR analysis showed that higher body mass index (BMI) (Benjamini and Hochberg (BH) corrected p = 0.05), major depression (MD) (BH corrected p = 5.04E-19), and schizophrenia (SCZ) (BH corrected p = 1.64E-05) were associated with the increased risk of PPD, whereas increased age at first birth (BH corrected p = 2.11E-04), older age at first sexual intercourse (BH corrected p = 3.02E-15), increased average total household income before tax (BH corrected p = 4.57E-02), and increased years of schooling (BH corrected p = 1.47E-11) led to a decreased probability of PPD. MVMR analysis suggested that MD (p = 3.25E-08) and older age at first birth (p = 8.18E-04) were still associated with an increased risk of PPD.ConclusionIn our MR study, we found multiple risk factors, including MD and younger age at first birth, to be deleterious causal risk factors for PPD.

Abstract Study design This is an observational retrospective cohort study. Objective The purpose of this study is to investigate the incidence rate of depression and anxiety and the changes in patients treated with percutaneous kyphoplasty (PKP) following ERAS protocol. Summary of background data The incidence of depression and anxiety is not uncommon in patients with osteoporotic vertebral compression fracture (OVCF), which affects the prognosis of surgery. Enhanced recovery after surgery (ERAS) protocols can improve the perioperative stress response of patients. Materials and methods Patients were treated conventionally in 2019 as the control group (CG) (n = 281), and patients were treated according to the ERAS protocol in 2020 as the intervention group (IG) (n = 251). All patients were evaluated for depression and anxiety using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 at admission, postoperative 1 week, 1 month and 3, 6, 12 months. Results The degree of depression statistically decreased in the IG at follow-up periods (p

Abstract Background The current molecular classifications cannot completely explain the polarized malignant biological behavior of low‐grade gliomas (LGGs), especially for tumor recurrence. Therefore, we tried to identify suspicious hub genes related to tumor recurrence in LGGs. Methods In this study, we constructed a gene‐miRNA‐lncRNA co‐expression network for LGGs by a weighted gene co‐expression network analysis (WGCNA). GDCRNATools and the WGCNA R package were mainly used in data analysis. Results Sequencing data from 502 LGG patients were analyzed in this study. Compared with recurrent glioma tissues, we identified 774 differentially expressed (DE) mRNAs, 49 DE miRNAs, and 129 DE lncRNAs in primary LGGs and ultimately determined that the expression of MKLN1 was related to tumor recurrence in LGG. Conclusion This study identified the potential biomarkers for the pathogenesis and recurrence of LGGs and proposed that MKLN1 could be a potential therapeutic target.

The spatial organisation of diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) remains to be investigated. Here, the authors integrate short-read and long-read spatial profiling of DMG and GBM to identify regulatory programs and cellular ecosystems in distinct glioma niches.

Elemene is a second-line broad-spectrum anti-tumour drug that has been used in China for more than two decades. However, its main anti-tumour ingredient, β-elemene, has disadvantages, including excessive lipophilicity and relatively weak anti-tumour efficacy. To improve the anti-tumour activity of β-elemene, based on its minor molecular weight character, we introduced furoxan nitric oxide (NO) donors into the β-elemene structure and designed six series of new generation β-elemene NO donor hybrids. The synthesised compounds could effectively release NO in vitro, displayed significant anti-proliferative effects on U87MG, NCI-H520, and SW620 cell lines. In the orthotopic glioma model, compound Id significantly and continuously suppressed the growth of gliomas in nude mice, and the brain glioma of the treatment group was markedly inhibited (>90%). In short, the structural fusion design of NO donor and β-elemene is a feasible strategy to improve the in vivo anti-tumour activity of β-elemene.

Abstract Excessive inflammatory responses contribute to the pathogenesis and lethality of highly pathogenic human coronaviruses, but the underlying mechanism remains unclear. In this study, the N proteins of highly pathogenic human coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), middle east respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were found to bind MASP-2, a key serine protease in the lectin pathway of complement activation, resulting in excessive complement activation by potentiating MBL-dependent MASP-2 activation, and the deposition of MASP-2, C4b, activated C3 and C5b-9. Aggravated inflammatory lung injury was observed in mice infected with adenovirus expressing the N protein. Complement hyperactivation was also observed in SARS-CoV-2-infected patients. Either blocking the N protein:MASP-2 interaction, MASP-2 depletion or suppressing complement activation can significantly alleviate N protein-induced complement hyperactivation and lung injury in vitro and in vivo. Altogether, these data suggested that complement suppression may represent a novel therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses.

While water splitting electrolysis offers an appealing means to produce H2 fuel, catalysts show sluggish reaction rate in neutral media. Here, authors utilize hydrogen spillover from oxygen-deficient tungsten oxides to Ru nanoparticles to boost the neutral-pH H2 evolution performances.

Abstract Background Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it’s role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. Methods In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. Results As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p

Background: The prognosis of diffuse midline glioma (DMG) patients with H3K27M (H3K27M-DMG) alterations is poor; however, a model that encourages accurate prediction of prognosis for such lesions on an individual basis remains elusive. We aimed to construct an H3K27M-DMG survival model based on DeepSurv to predict patient prognosis. Methods: Patients recruited from a single center were used for model training, and patients recruited from another center were used for external validation. Univariate and multivariate Cox regression analyses were used to select features. Four machine learning models were constructed, and the consistency index (C-index) and integrated Brier score (IBS) were calculated. We used the receiver operating characteristic curve (ROC) and area under the receiver operating characteristic (AUC) curve to assess the accuracy of predicting 6-month, 12-month, 18-month and 24-month survival rates. A heatmap of feature importance was used to explain the results of the four models. Results: We recruited 113 patients in the training set and 23 patients in the test set. We included tumor size, tumor location, Karnofsky Performance Scale (KPS) score, enhancement, radiotherapy, and chemotherapy for model training. The accuracy of DeepSurv prediction is highest among the four models, with C-indexes of 0.862 and 0.811 in the training and external test sets, respectively. The DeepSurv model had the highest AUC values at 6 months, 12 months, 18 months and 24 months, which were 0.970 (0.919–1), 0.950 (0.877–1), 0.939 (0.845–1), and 0.875 (0.690–1), respectively. We designed an interactive interface to more intuitively display the survival probability prediction results provided by the DeepSurv model. Conclusion: The DeepSurv model outperforms traditional machine learning models in terms of prediction accuracy and robustness, and it can also provide personalized treatment recommendations for patients. The DeepSurv model may provide decision-making assistance for patients in formulating treatment plans in the future.

The predicted leakage rate of piping circumferential through-wall cracks (CTWC) under various loading levels is a critical factor for the application of leak-before-break (LBB) technology. In current engineering approaches, the effect of welding residual stress has not been carefully taken into account. In this paper, both numerical analyses and comparative verification are adopted to examine the influence of typical welding residual stress field on the crack opening displacement for austenitic stainless steel piping with representative geometric dimensions and in situ measured material performance curves. An in-depth investigation is carried out to reveal the effect of the residual stress on morphological parameters of the CTWC flow channel. In the case where the residual internal stress of welding has the greatest effect, the Henry-Fauske model is employed to analyze the flow medium passing through the CTWC and the corresponding leak rate for a typical nuclear power plant. The results indicate that the welding residual stress leads to a substantial change in the crack opening displacement and crack morphology parameters. Both the current GE/EPRI method and the NUREG/CR-6837 modification recommended by the American Electric Power Research Institute underestimate the effect of this phenomenon, resulting in a higher prediction of the medium leakage rate. A similar situation is most likely to occur for the cases of short cracks in thin-walled piping and long cracks in thick-walled piping. Additionally, the obtained results reveal that the welding residual stress causes the whole crack surface to open negatively, and the axial line of the long crack on the thick-walled piping is close to a conic curve under specific conditions.

In order to expand the application scope of rabbit bone, the degreasing rabbit bone micro powder (DRBM) which was previously studied by the project group was added into wheat flour to study the effect of DRBM on the properties of dough and noodles. The results showed that, with the increasing of DRBM, the whiteness of the mixed dough decreased, and the blue yellow value increased significantly(P

For inter-basin water transfer (IBWT) projects, the conflict between social, economic, and ecological objectives makes water allocation processes more complex. Specific to the problem of water resource conflict in IBWT projects, we established an optimal allocation model of generalized (conventional) water resources (G (C) model) to demonstrate the advantages of the G model. The improved multi-objective cuckoo optimization algorithm (IMOCS) was applied to search the Pareto frontiers of the two models under normal, dry, and extremely dry conditions. The optimal allocation scheme set of generalized (conventional) water resources (G (C) scheme set) consists of ten Pareto optimal solutions with the minimum water shortage selected from the Pareto optimal solutions of the G (C) model. The analytic hierarchy process (AHP) combined with criteria importance using the inter-criteria correlation (CRITIC) method was used to assign weights of evaluation indexes in the evaluation index system. The non-negative matrix method was employed to evaluate the G (C) scheme set to determine the best G (C) scheme for the Jiangsu section of the South-to-North Water Transfer (J-SNWT) Project. The results show that (1) the Pareto frontier of the G model is better than that of the C model, and (2) the best G scheme shows better index values compared to the best C scheme. The total water shortages are reduced by 254.2 million m3 and 827.9 million m3 under the dry condition, respectively, and the water losses are reduced by 145.1 million m3 and 141.1 million m3 under the extremely dry condition, respectively. These findings could not only provide J-SNWT Project managers with guidelines for water allocation under normal, dry, and extremely dry conditions but also demonstrate that the G model could achieve better water-allocation benefits than the C model for inter-basin water transfer projects.

Abstract Alleviating odontoblast inflammation is crucial to control the progression of pulpitis. Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from mitochondria of inflamed odontoblasts into the cytosol. Bacteria-induced inflammation leads to a novel type of cell death named pyroptosis. The canonical pyroptosis is a gasdermin (GSDM)-dependent cytolytic programmed cell death characterized by cell swelling and pore formation in the plasma membrane. To date, whether odontoblast cytosolic mtDNA regulates dental pulp inflammation through the canonical pyroptosis pathway remains to be elucidated. In this study, high gasdermin D (GSDMD) expression was detected in human pulpitis. We found that LPS stimulation of mDPC6T cells promoted BAX translocation from the cytosol to the mitochondrial membrane, leading to mtDNA release. Moreover, overexpression of isolated mtDNA induced death in a large number of mDPC6T cells, which had the typical appearance of pyroptotic cells. Secretion of the inflammatory cytokines CXCL10 and IFN-β was also induced by mtDNA. These results suggest that cytosolic mtDNA participates in the regulation of odontoblast inflammation through GSDMD-mediated pyroptosis in vitro. Interestingly, after overexpression of mtDNA, the expression of inflammatory cytokines CXCL10 and IFN-β was increased and not decreased in GSDMD knockdown mDPC6T cells. We further proposed a novel model in which STING-dependent inflammation in odontoblast-like cell is a compensatory mechanism to control GSDMD-mediated pyroptosis, jointly promoting the immune inflammatory response of odontoblasts. Collectively, these findings provide the first demonstration of the role of the mtDNA-GSDMD-STING in controlling odontoblast inflammation and a detailed description of the underlying interconnected relationship.

Abstract Dried blood samples (DBSs) have many advantages; yet, impediments have limited the clinical utilization of DBSs. We developed a novel volumetric sampling device that collects a precise volume of blood, which overcomes the heterogeneity and hematocrit issues commonly encountered in a traditional DBS card collection as well as allowing for more efficient extraction and processing procedures and thus, more efficient quantitation, by using the entire sample. We also provided a thorough procedure validation using this volumetric DBS collection device with an established quantitative proteomics analysis method, and then analyzed 1000 proteins using this approach in DBSs concomitantly with serum for future consideration of utility in clinical applications. Our data provide a first step in the establishment of a DBS database for the broad application of this sample type for widespread use in clinical proteomic and other analyses applications.

Objective To compare rapid prototyping technology (RP tech) in revision total hip arthroplasty (RTHA) with traditional examination methods and to see how they are different in evaluating acetabular anatomy and designing surgical procedure. Methods From February 2014 to March 2018, 43 RTHA patients with complex acetabulum defects were enrolled in this prospective study regardless of age or gender. Incomplete and unclear data were excluded. Three types of radiographic examination were performed on each patient before the revision surgery. Four groups of evaluations were designed: (i) X‐ray; (ii) computed tomography (CT‐scan); (iii) RP tech; and (iv) CT‐aided RP tech. Discrepancies between preoperative radiographic analysis and intra‐operative findings were separately compared by a team of surgeons. Premade surgical plans based on each evaluation method were compared with the final surgical procedure. The compliance of anatomic evaluation and surgical plan‐design based on 3D RP tech and traditional radiographs were ranked manually by a of team surgeons into: (i) complete accordance; (ii) general accordance; and (iii) undetermined structure/procedure. The difference in ranks between RP tech and traditional radiographic methods were analyzed with a nonparametric Kruskal‐Wallis test. P

Background: T cells play critical roles in the progression of tuberculosis (TB); however, knowledge regarding these molecular mechanisms remains inadequate. This study constructed a critical ceRNA network was constructed to identify the potentially important role of TB activation via T-cell regulation.Methods: We performed integrated bioinformatics analysis in a randomly selected training set from the GSE37250 dataset. After estimating the abundance of 18 types of T cells using ImmuCellAI, critical T-cell subsets were determined by their diagnostic accuracy in distinguishing active from latent TB. We then identified the critical genes associated with T-cell subsets in TB activation through co-expression analysis and PPI network prediction. Then, the ceRNA network was constructed based on RNA complementarity detection on the DIANA-LncBase and mirDIP platform. The gene biomarkers included in the ceRNA network were lncRNA, miRNA, and targeting mRNA. We then applied an elastic net regression model to develop a diagnostic classifier to assess the significance of the gene biomarkers in clinical applications. Internal and external validations were performed to assess the repeatability and generalizability.Results: We identified CD4+ T, Tr1, nTreg, iTreg, and Tfh as T cells critical for TB activation. A ceRNA network mediated by the MIR600HG/hsa-mir-21-5p axis was constructed, in which the significant gene cluster regulated the critical T subsets in TB activation. MIR600HG, hsa-mir-21-5p, and five targeting mRNAs (BCL11B, ETS1, EPHA4, KLF12, and KMT2A) were identified as gene biomarkers. The elastic net diagnostic classifier accurately distinguished active TB from latent. The validation analysis confirmed that our findings had high generalizability in different host background cases.Conclusion: The findings of this study provided novel insight into the underlying mechanisms of TB activation and identifying prospective biomarkers for clinical applications.

Abstract Background Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from damaged mitochondria into the cytosol. mtDNA stress may contribute to cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway activation in infectious diseases. Odontoblasts are the first cells challenged by cariogenic bacteria and involved in maintenance of the pulp immune and inflammatory responses to dentine-invading pathogens. In this study, we investigated that mtDNA as an important inflammatory driver participated in defending against bacterial invasion via cGAS-STING pathway in odontoblasts. Methods The normal tissues, caries tissues and pulpitis tissues were measured by western blotting and immunohistochemical staining. Pulpitis model was built in vitro to evaluated the effect of the cGAS-STING pathway in odontoblast-like cell line (mDPC6T) under inflammation. Western blot and real-time PCR were performed to detect the expression of cGAS-STING pathway and pro-inflammatory cytokines. The mitochondrial function was evaluated reactive oxygen species (ROS) generated by mitochondria using MitoSOX Red dye staining. Cytosolic DNA was assessed by immunofluorescent staining and real-time PCR in mDPC6T cells after LPS stimulation. Furthermore, mDPC6T cells were treated with ethidium bromide (EtBr) to deplete mtDNA or transfected with isolated mtDNA. The expression of cGAS-STING pathway and pro-inflammatory cytokines were measured. Results The high expression of cGAS and STING in caries and pulpitis tissues in patients, which was associated with inflammatory progression. The cGAS-STING pathway was activated in inflamed mDPC6T. STING knockdown inhibited the nuclear import of p65 and IRF3 and restricted the secretion of the inflammatory cytokines CXCL10 and IL-6 induced by LPS. LPS caused mitochondrial damage in mDPC6T, which promoted mtDNA leakage into the cytosol. Depletion of mtDNA inhibited the cGAS-STING pathway and nuclear translocation of p65 and IRF3. Moreover, repletion of mtDNA rescued the inflammatory response, which was inhibited by STING knockdown. Conclusion Our study systematically identified a novel mechanism of LPS-induced odontoblast inflammation, which involved mtDNA leakage from damaged mitochondria into the cytosol stimulating the cGAS-STING pathway and the inflammatory cytokines IL-6 and CXCL10 secretion. The mtDNA-cGAS-STING axis could be a potent therapeutic target to prevent severe bacterial inflammation in pulpitis. Video Abstract Graphic abstract

An amendment to this paper has been published and can be accessed via the original article.

Abstract Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was −13.31%, 95% CI −29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: −15.45%; 95% CI −30.82%, −0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.

Abstract Background Breast cancer bone metastasis has become one of the most common complications; however, it may cause cancer recurrence and bone nonunion, as well as local bone defects. Methods Herein, In vitro, we verified the effect of bioscaffold materials on cell proliferation and apoptosis through a CCK8 trial, staining of live/dead cells, and flow cytometry. We used immunofluorescence technology and flow cytometry to verify whether bioscaffold materials regulate macrophage polarization, and we used ALP staining, alizarin red staining and PCR to verify whether bioscaffold material promotes bone regeneration. In vivo, we once again studied the effect of bioscaffold materials on tumors by measuring tumor volume in mice, Tunel staining, and caspase-3 immunofluorescence. We also constructed a mouse skull ultimate defect model to verify the effect on bone regeneration. Results Graphene oxide (GO) nanoparticles, hydrated CePO4 nanorods and bioactive chitosan (CS) are combined to form a bioactive multifunctional CePO4/CS/GO scaffold, with characteristics such as photothermal therapy to kill tumors, macrophage polarization to promote blood vessel formation, and induction of bone formation. CePO4/CS/GO scaffold activates the caspase-3 proteasein local tumor cells, thereby lysing the DNA between nucleosomes and causing apoptosis. On the one hand, the as-released Ce3+ ions promote M2 polarization of macrophages, which secretes vascular endothelial growth factor (VEGF) and Arginase-1 (Arg-1), which promotes angiogenesis. On the other hand, the as-released Ce3+ ions also activated the BMP-2/Smad signaling pathway which facilitated bone tissue regeneration. Conclusion The multifunctional CePO4/CS/GO scaffolds may become a promising platform for therapy of breast cancer bone metastases.

Objective To determine the predictive value of intraoperative motor⁃evoked potential (MEP) on the muscle strength of patients undergoing glioma close to motor area under general anesthesia. Methods A total of 49 patients were included in this study from October 2019 to March 2020. The transcranial electrical stimulation (TES), direct cortical stimulation (DCS) and subcortical stimulation (SCS) were used to locate the motor cortex and corticospinal tract (CST), and to assess the functional integrity of motor system. A decrease of ≥ 50% of the baseline amplitude of TES or DCS was regarded as an alarm criteria. Muscle strength was evaluated with "gold standard" the Medical Research Council (MRC) scale before and after operation. Results Combined application of TES⁃MEP, DCS⁃MEP and SCS⁃MEP had better results in judging the integrity of motor conduction pathway. The sensitivity and specificity of TES⁃MEP were 2/5 and 100% (44/44), the positive predictive value and negative predictive value were 2/2 and 93.62% (44/47), respectively. The sensitivity and specificity of DCS⁃MEP were 1/1 and 10/10, the positive predictive value and negative predictive value were 1/1 and 10/10, respectively. There were 5 cases (10.20%) with new dyskinesia after operation. After 3 months of follow⁃up, muscle strength of one case returned to normal. The sensitivity and specificity of TES⁃MEP were 2/4 and 100% (45/45), the positive predictive value and negative predictive value were 2/2 and 95.74% (45/47), respectively. The sensitivity and specificity of DCS⁃MEP were 1/1 and 10/10, the positive predictive value and negative predictive value were 1/1 and 10/10, respectively. Conclusions This study indicates a high false negative rate after TES⁃MEP, DCS⁃MEP results were more consistent with postoperative motor function results, but the utilization rate was low due to the lack of exposure to the precentral gyrus cortex. Combined application of TES⁃MEP, DCS⁃MEP and SCS⁃MEP are more effective in judging the integrity of motor conduction pathway. DOI:10.3969/j.issn.1672⁃6731.2020.11.006

Abstract Background To determine the safety and efficacy of different doses of tolvaptan for treating Chinese cirrhotic patients with or without hyponatraemia who still had ascites after routine therapy with diuretics. Methods In the present placebo-controlled, randomized, double-blinded, multicentre clinical trial, patients with cirrhotic ascites who failed to adequately respond to a combination of an aldosterone antagonist plus an orally administered loop diuretic were randomly placed at a 4:2:1 ratio into 3 groups [the 15 mg/day tolvaptan group (N = 301), 7.5 mg/day tolvaptan group (N = 153) and placebo group (N = 76)] for 7 days of treatment. The effects and safety were evaluated on days 4 and 7. A change in body weight from baseline on day 7 of treatment was the primary endpoint. Results The administration of 7.5 or 15 mg/day tolvaptan significantly decreased body weight from baseline on day 7 of treatment compared to that with placebo treatment (P = 0.026; P = 0.001). For the secondary endpoints, changes in abdominal circumference from baseline and improvements in ascites were markedly different in the treatment groups and the placebo group on day 7 (P 7.5 = 0.05, P 15.0 = 0.002 and P 7.5 = 0.037, P 15.0 = 0.003), but there was no difference between the 7.5 mg/day and 15 mg/day dosage groups. The 24-h cumulative urine volume was higher in the 7.5 mg/day and 15 mg/day tolvaptan groups than the placebo group (P = 0.002, P

Taking the anthracite coal in Fanzhuang and Zhengzhuang blocks as the research object, the occurrence, migration and output path of gas and water in coal reservoir and its model were analyzed based on the permeability and nuclear magnetic resonance imaging experiments. The results show that the coal seam water in macropore and microscopic fracture with the pore diameter 10 μm; micropore and mesopore are the main occurrence spaces of CBM, and mesopore, microfracture and endogenous fracture are the main channels for migration and output of CBM, which are very important for migration and production of CBM. Among them, the development of pore and microfracture with the pore diameter >0.5 μm in coal reservoir of Fanzhuang and Zhengzhuang blocks is relatively weak, which restricts the gas production effect.

IntroductionAt present, lots of studies have discussed the effects and outcomes of cranioplasty using polyetheretherketone (PEEK). However, interventions or management for PEEK cranioplasty got less attention. This article presented a perioperative paradigm for preventing postoperative complications.Materials and MethodsModified PEEK plates with certified safety were implanted in patients who received evolving perioperative paradigm. Serial perioperative managements were developed as a comprehensive paradigm to prevent correlated risk factors of postoperative complications, which mainly included managements of epidural collections and wound healing. The preparation of the surgical area and systemic state were essential before surgery. During the operation, the blood supply of the incision and the handling of dura and temporalis were highlighted in our paradigm. After cranioplasty, management of subcutaneous drainage and wound healing were stressed. Patients received conventional management from February 2017 to August 2018 in our center. After the evolving paradigm developed, patients received comprehensive perioperative management from September 2018 to August 2020.ResultsA total of 104 patients who underwent PEEK cranioplasty were consecutively enrolled; 38 (36.5%) received conventional perioperative management, and 66 (63.5%) received evolving perioperative paradigm. The general information of the two groups was comparable. Notably, patients who received the evolving paradigm presented a significantly decreased incidence of postoperative complications from 47.4 to 18.2% (P < 0.01), among which the incidences of subcutaneous effusion, epidural hematoma, and subcutaneous infection decreased significantly.ConclusionThe evolving perioperative paradigm could effectively prevent risk factors and reduce related complications. It was valuable to promote these comprehensive managements and inspire more clinical practice on improving patients' outcomes after PEEK cranioplasty.

ObjectiveTo establish the relationship between hematoma sites of involvement and hematoma expansion (HE) in patients with deep intracerebral hemorrhage (ICH).MethodsEligible patients with deep ICH admitted to hospital within 6 hours of onset between 2018 and 2020 were included in this retrospective multi-center study. Individuals with secondary ICH were excluded. The volume of HE was evaluated based on admission and follow-up computed tomography scans. Associations between deep ICH sites of involvement and HE were examined using multivariable logistic regression analysis while adjusting for confounding covariates of HE.ResultsWe enrolled 583 individuals from three stroke centers. Data from a final total of 460 patients were used in the analysis; of these patients, 159 (34.6%) had HE. In the crude model without adjustment, external capsule, anterior limb of the internal capsule, and posterior limb of the internal capsule (PLIC) involvement were correlated with HE. After fully adjusted models for sex, age, intraventricular hemorrhage, Glasgow Coma Scale admission score, baseline ICH volume, and time from onset to initial computed tomography, multivariable logistic regression revealed that the PLIC is a robust predictor of HE in patients with deep ICH (adjusted odds ratio = 2.73; 95% confidence interval = 1.75–4.26; p < 0.001).ConclusionInvolvement of the posterior limb of the internal capsule in deep hemorrhage could be a promising predictor of HE.

A new Cu(II) compound, that is {[Cu(L)(ClO4)(H2O)(CH3CN)](ClO4)}n (1, L is 4-(furan-2-yl)-2,6-bis(pyridin-2-yl)pyridine), was solvothermally synthesized and structurally characterized. It features a 0D isolated unit, and these 0D isolated units are further hydrogen-bonded into a 3D supramolecular framework. The framework of 1 can be stable up to 284°C, and the optical band gap of 1 is 3.71 eV. Under the irradiation of ultraviolet light, complex 1 as a photocatalyst exhibits high activity for methylene blue (MB) degradation in the water solution. The above compound’s inhibitory activity on the inflammatory cytokines releasing was tested through exploiting ELISA detection. The real time RT-PCR was conducted to assess the compound’s suppression on the expression of bacterial survival gene.