BLM helicase unwinds lagging strand substrates to assemble the ALT telomere damage response.

The Bloom syndrome (BLM) helicase is critical for alternative lengthening of telomeres (ALT), a homology-directed repair (HDR)-mediated telomere maintenance mechanism that is prevalent in cancers of mesenchymal origin. The DNA substrates that BLM engages to direct telomere recombination during ALT remain unknown. Here, we determine that BLM helicase acts on lagging strand telomere intermediates that occur specifically in ALT-positive cells to assemble a replication-associated DNA damage response. Loss of ATRX was permissive for BLM localization to ALT telomeres in S and G2, commensurate with the appearance of telomere C-strand-specific single-stranded DNA (ssDNA). DNA2 nuclease deficiency increased 5'-flap formation in a BLM-dependent manner, while telomere C-strand, but not G-strand, nicks promoted ALT. These findings define the seminal events in the ALT DNA damage response, linking aberrant telomeric lagging strand DNA replication with a BLM-directed HDR mechanism that sustains telomere length in a subset of human cancers.

Synergistic Effect of Asphaltene, Resin, and Wax Improving the Emulsification and Interfacial Properties of a High-Phase-Inversion Thin Oil.

Nowadays, high-phase-inversion in situ emulsification technology has shown great potential in enhancing oil recovery from high-water-cut thin-oil reservoirs. However, emulsification characteristics, interfacial properties, and the mechanism of high phase inversion have not been systematically described. In this study, an emulsification experiment was conducted to investigate the effects of shear time, shear rate, and temperature on the phase inversion of thin oil. Furthermore, the influence of resin and wax on the dispersion of asphaltene was studied through microscopic morphology analysis. Interfacial tension measurement and interfacial viscoelasticity analysis were carried out to determine the interaction characteristics of asphaltene, resin, and wax at the interface. The results showed that, at 50 °C, the phase-inversion point of thin oil reached as high as 75%, and even at 60 °C, it remained at 70%. The shear time and shear rate did not affect the phase-inversion point of thin oil, while an increase in temperature led to a decrease in the phase-inversion point. Moreover, compared to the 20% phase-inversion point of base oil, the phase-inversion point increased with different proportions of asphaltene, resin, and wax. Particularly, at the ratio of asphaltene/resin/wax = 1:5:9, the phase-inversion point reached as high as 80%, indicating the optimal state. In this proportion, asphaltene aggregates exhibited the smallest and most uniform size, best dispersion, lower interfacial tension, and higher interfacial modulus. These findings provide reference and guidance for further enhancing oil recovery in medium-to-high-water-cut thin-oil reservoirs.

Targeting PCSK9 to upregulate MHC-II on the surface of tumor cells in tumor immunotherapy.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), the last member of the proprotein convertase family, functions as a classic regulator of low-density lipoprotein (LDL) by interacting with low-density lipoprotein receptor (LDLR). Recent studies have shown that PCSK9 can affect the occurrence and development of tumors and can be used as a novel therapeutic target. However, a comprehensive pan-cancer analysis of PCSK9 has yet to be conducted. METHODS: The potential oncogenic effects of PCSK9 in 33 types of tumors were explored based on the datasets of The Cancer Genome Atlas (TCGA) dataset. In addition, the immune regulatory role of PCSK9 inhibition was evaluated via in vitro cell coculture and the tumor-bearing mouse model. Finally, the antitumor efficacy of targeted PCSK9 combined with OVA-II vaccines was verified. RESULTS: Our results indicated that PCSK9 was highly expressed in most tumor types and was significantly correlated with late disease stage and poor prognosis. Additionally, PCSK9 may regulate the tumor immune matrix score, immune cell infiltration, immune checkpoint expression, and major histocompatibility complex expression. Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Combining PCSK9 inhibitors could enhance the efficacies of OVA-II tumor vaccine monotherapy. CONCLUSIONS: Conclusively, our pan-cancer analysis provided a more comprehensive understanding of the oncogenic and immunoregulatory roles of PCSK9 and demonstrated that targeting PCSK9 could increase the efficacy of long peptide vaccines by upregulating DC infiltration and MHC-II expression on the surface of tumor cells. This study reveals the critical oncogenic and immunoregulatory roles of PCSK9 in various tumors and shows the promise of PCSK9 as a potent immunotherapy target.

Long-term safety of lanthanum carbonate in the real word: a 19-year disproportionality analysis from the FDA Adverse Event Reporting System.

BACKGROUND: Lanthanum carbonate is widely used to manage serum phosphate and calcium levels in end-stage kidney disease (ESKD) patients, yet comprehensive long-term safety data are lacking. This study leverages the FDA Adverse Event Reporting System (FAERS) to assess the extended safety profile of lanthanum carbonate. RESEARCH DESIGN AND METHODS: We analyzed FAERS data (2004-2022) to study the association between lanthanum carbonate and adverse events (AEs). Using MedDRA v25.0, we identified risk signals through System Organ Classes (SOCs) and Preferred Terms (PTs). Disproportionality analyzes quantified lanthanum carbonate-associated AE signals. RESULTS: Among 3,284 reports, 2,466 were primary suspected AEs linked to lanthanum carbonate. Males reported AEs more frequently than females. Patients aged over 64 represented the majority. Median onset time for lanthanum carbonate-related AEs was 146 days. Gastrointestinal disorders were prevalent. We identified 16 new signals, including stress, abnormal hepatic function, cholelithiasis, bile duct stone, gastric cancer, and adenocarcinoma gastric. Stress was notable, particularly in male patients over 65 and those with lower weight. CONCLUSIONS: This study affirms lanthanum carbonate's long-term safety for reducing elevated blood phosphorus levels. While gastrointestinal disorders were common, attention must focus on emerging AEs, particularly stress, especially in elderly patients.

Effects of anti-osteoporosis treatment in elderly patients with osteoporosis and lumbar discectomy and fusion.

BACKGROUND: The effect of anti-osteoporosis treatment in elderly patients with osteoporosis and lumbar discectomy and fusion (LIF) for lumbar degenerative diseases is not well known. OBJECTIVE: This study aimed to evaluate the effect of perioperative anti-osteoporosis treatment in the patients with osteoporosis and LIF. METHODS: From January to December 2022, patients were divided into three groups according to the inclusive criteria: the normal group (Group A), the osteopenia group (Group B) and the osteoporosis group (Group C). Quantitative computed tomography (QCT), height of the intervertebral space (HIS), segmental sagittal angle (SSA), visual analogue scale (VAS) score and Oswestry Disability Index (ODI) were compared between the groups at the follow-up time. The serum Ca2 + , osteocalcin (OC), propeptide of type I procollagen (PINP) C-terminal cross-linking telopeptide of type I collagen (ß-CTX) and 25-OH vitamin D (25-OH VD) levels were compared between the groups at the time of follow-up. Interbody fusion was graded on the X-ray and CT images at the follow-up time. RESULTS: There were 165 patients in this study. There were significant differences in the mean age, mean score, HIS and SSA between the groups at the different follow-up times. There were significant differences in the concentrations of serum Ca2 + , OC, ß-CTX, 25-OH VD and PINP at the sixth month after surgery between the groups. There were significant differences in the concentrations of serum Ca2 + , ß-CTX and 25-OH VD between the pre-surgery and at six months after surgery in Group B and ß-CTX and 25-OH VD in Group C. There was a significant difference in the degree of fusion between Group B and C (χ2= 5.6243, P< 0.05). CONCLUSION: In elderly patients with LIF and osteoporosis, anti-osteoporosis therapy could reduce bone resorption and thus facilitate fusion. Anti-osteoporosis medication tends to enhance radiological, functional, and fusion short-term outcomes.

Identification of allograft inflammatory factor-1 suppressing the progression and indicating good prognosis of osteosarcoma.

BACKGROUND: Osteosarcoma is one of the most common cancers worldwide. Intense efforts have been made to elucidate the pathogeny, but the mechanisms of osteosarcoma are still not well understood. We aimed to investigate the potential biomarker, allograft inflammatory factor-1 (AIF1), affecting the progression and prognosis of osteosarcoma. METHODS: Three microarray datasets were downloaded from GEO datasets and one was obtained from the TCGA dataset. The differentially expressed genes (DEGs) were identified. GO and KEGG functional enrichment analyses of overlapped DEGs were performed. The PPI network of overlapped DEGs was constructed by STRING and visualized with Cytoscape. Overall survival (OS) and Metastasis free survival (MFS) were analyzed from GSE21257. Finally, the effect of the most relevant core gene affecting the progression of osteosarcoma was examined in vitro. RESULTS: One hundred twenty six DEGs were identified, consisting of 65 upregulated and 61 downregulated genes. Only AIF1 was significantly associated with OS and MFS. It was found that AIF1 could be enriched into the NF-κB signaling pathway. GSEA and ssGSEA analyses showed that AIF1 was associated with the immune invasion of tumors. Cell experiments showed that AIF1 was underexpressed in osteosarcoma cell lines, while the malignant propriety was attenuated after overexpressing the expression of AIF1. Moreover, AIF1 also affects the expression of the NF-κB pathway. CONCLUSION: In conclusion, DEGs and hub genes identified in the present study help us understand the molecular mechanisms underlying the carcinogenesis and progression of osteosarcoma, and provide candidate targets for diagnosis and treatment of osteosarcoma.

Postoperative Prognostic Nutritional Index and Fibrinogen Could Well Predict Poor Prognosis of Acute Type A Aortic Dissection Patients After Surgery.

INTRODUCTION: Inflammatory and immunological factors play pivotal roles in the prognosis of acute type A aortic dissection. We aimed to evaluate the prognostic values of immune-inflammatory parameters in acute type A aortic dissection patients after surgery. METHODS: A total of 127 acute type A aortic dissection patients were included. Perioperative clinical data were collected through the hospital's information system. The outcomes studied were delayed extubation, reintubation, and 30-day mortality. Multivariate logistic regression analysis and receiver operating characteristic analysis were used to screen the risk factors of poor prognosis. RESULTS: Of all participants, 94 were male, and mean age was 51.95±11.89 years. The postoperative prognostic nutritional indexes were lower in delayed extubation patients, reintubation patients, and patients who died within 30 days. After multivariate regression analysis, the postoperative prognostic nutritional index was a protective parameter of poor prognosis. The odds ratios (95% confidence interval) of postoperative prognostic nutritional index were 0.898 (0.815, 0.989) for delayed extubation and 0.792 (0.696, 0.901) for 30-day mortality. Low postoperative fibrinogen could also well predict poor clinical outcomes. The odds ratios (95% confidence interval) of postoperative fibrinogen were 0.487 (0.291, 0.813) for delayed extubation, 0.292 (0.124, 0.687) for reintubation, and 0.249 (0.093, 0.669) for 30-day mortality. CONCLUSION: Postoperative prognostic nutritional index and postoperative fibrinogen could be two promising markers to identify poor prognosis of acute type A aortic dissection patients after surgery.

Unidirectionally Structured Magnetic Phase-Change Composite Based on Carbonized Polyimide/Kevlar Nanofiber Complex Aerogel for Boosting Solar-Thermo-Electric Energy Conversion.

To realize highly efficient solar-thermo-electric energy conversion for clean electricity power generation, we have developed a new type of unidirectionally structured magnetic phase-change composite comprising a carbonized polyimide (C-PI)/Kevlar nanofiber (KNF) complex aerogel as a 3D carbon skeleton porous supporting material, CoFe2O4 nanoparticles as a magnetic additive, polyethylene glycol (PEG) as a phase-change material, and polypyrrole as a photothermal absorption coating layer. The as-fabricated C-PI/KNF complex aerogel exhibits a unidirectional microstructure, high porosity, robust skeleton frame, ultralight weight, and high thermal conductance. Featured with such unique structure and characteristics, the complex aerogel can offer an effective heat and electron transfer method to ensure highly efficient solar-thermal conversion and photothermal energy storage of the developed composite. The developed composite exhibits a high latent heat capacity of over 150 J g-1, outstanding shape stability along with a low leakage of 0.2 wt %, good thermal cycling stability, and high photothermal conversion efficiency of 84.8%. Based on the Seebeck effect, a solar thermoelectric generation system (STEGS) was constructed with the hot side coupled with the developed composite and the cold side immersed in air and ice water. Under 2.0 kW m-2 solar irradiation, the developed STEGS in ice water obtained maximum output voltage and current of 259.7 mV and 27.1 mA, respectively, which are significantly higher than those in air. The output power of the developed STEGS in an ice water environment is 50.6% higher than that in air under 4.0 kW m-2 solar irradiation. More importantly, the developed STEGS in ice water continuously generated output voltage and current for about 810 s without solar irradiation thanks to the latent heat release by the PEG component within the developed composite. In addition, the introduction of magnetic CoFe2O4 can accelerate solar-thermal conversion through periodic electron motion by the Néel relaxation or Brownian relaxation. This resulted in an increase in the maximum output voltage and current by 13.7 and 11.5%, respectively, under an alternating magnetic field as a result of the magnetism-accelerated solar-thermo-electric conversion. This study offers an innovative approach for developing PCM-based advanced functional materials for solar energy utilization in clean and sustainable electricity generation.

Worldwide research trends on tumor burden and immunotherapy: a bibliometric analysis.

Various immunotherapy has been greatly applied to comprehensive treatment of malignant cancer under different degrees of tumor burden. Scientific researchers have gained considerable progress in the relationship between immunotherapy and tumor burden in recent years. This review aimed to explore the prospect and developing trends in the field of tumor burden and immunotherapy from a bibliometric perspective. Articles about tumor burden and immunotherapy were collected from the Web of Science Core Collection (WoSCC) (retrieved on 3 January 2023). The R package 'Bibliometrix' analyzed the primary bibliometric features and created a three-filed plot to display the relationship between institutions, countries, and keywords. VOSviewer was used for co-authorship analysis, co-occurrence analysis, and their visualization. And CiteSpace calculated the citation burst references and keywords. A total of 1030 publications were retrieved from 35 years of scientific researches. The United States (US) and China published the most articles. The most productive journals were Cancer Immunology Immunotherapy and Journal for ImmunoTherapy of Cancer . The top one institution of the highest output was University of Texas MD Anderson Cancer Center. The hot keywords of strong citation burst strength in recent years were 'nivolumab', 'tumor microenvironment', and 'immune checkpoint inhibitor'. The most popular tumor type is melanoma. This bibliometric analysis mapped a basic knowledge structure. The field of tumor burden and immunotherapy is entering a rapid growing stage and keeping it value for future research.

Macrophages reprogramming improves immunotherapy of IL-33 in peritoneal metastasis of gastric cancer.

Peritoneal metastasis (PM) has a suppressive tumor immune microenvironment (TIME) that limits the effects of immunotherapy. This study aimed to investigate the immunomodulatory effects of intraperitoneal administration of IL-33, a cytokine that is reported to potentiate antitumor immunity and inhibit metastasis. We found survival was significantly prolonged in patients with high IL-33 mRNA expression. In immunocompetent mice, intraperitoneal administration of IL-33 could induce a celiac inflammatory environment, activate immunologic effector cells, and reverse the immunosuppressive tumor microenvironment, which effectively delayed tumor progression and PM of gastric cancer. Mechanistically, IL-33 could induce M2 polarization by activating p38-GATA-binding protein 3 signaling. IL-33 combined with anti-CSF1R or p38 inhibitor to regulate tumor-associated macrophages (TAMs) had a synergistic antitumor effect. Inducing a local inflammatory milieu by IL-33 administration provided a novel approach for treating peritoneal metastasis, which, when combined with TAM reprogramming to reshape TIME, can achieve better treatment efficacy.

Development and validation of web-based nomograms for predicting survival status in patients with intrahepatic cholangiocarcinoma depending on the surgical status: a SEER database analysis.

This study aimed to develop and validate prognostic nomograms that can estimate the probability of 1-, 3- and 5-year overall survival (OS) as well as cancer-specific survival (CSS) for Intrahepatic cholangiocarcinoma (ICCA) patients. Clinical data of 1446 patients diagnosed with ICCA between 2010 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. In both the OS and the CSS group, the training cohort and validation cohort were divided into a 7:3 ratio. Age, sex, AJCC T stage, AJCC N stage, AJCC M stage, surgical status, and tumor grade were selected as independent prognostic risk factors to build the nomograms. To compare the efficacy of predicting 1-, 3-, and 5-year OS and CSS rates of the nomogram with the 8th edition of the American Joint Committee on Cancer (AJCC) staging system, we evaluated the Harrell's index of concordance (C-index), area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) in both cohorts. The results showed the nomogram for 1-, 3-, and 5-year OS and CSS prediction performed better than the AJCC staging system. In the subgroup analysis for patients could not receive surgery as the primary treatment. We developed two nomograms for predicting the 1-, and 2-year OS and CSS rates following the same analysis procedure. Results indicate that the performance of both nomograms, which contained sex, AJCC T stage, AJCC M stage, chemotherapy, and tumor grade and prognostic factors, was also superior to the AJCC staging system. Meanwhile, four dynamic network-based nomograms were published. The survival analysis showed the survival rate of patients classified as high-risk based on the nomogram score was significantly lower compared to those categorized as low-risk (P < 0.0001). Finally, accurate and convenient nomograms were established to assist clinicians in making more personalized prognosis predictions for ICCA patients.

Whole-protein enteral nutrition formula supplementation reduces Escherichia and improves intestinal barrier function in HIV-infected immunological nonresponders.

People living with human immunodeficiency virus (PLWH) have persistent malnutrition, intestinal barrier dysfunction, and gut microbial imbalance. The interplay between gut microbiota and nutrients is involved in the immune reconstitution of PLWH. To evaluate the effects of whole-protein enteral nutrition formula supplementation on T-cell levels, intestinal barrier function, nutritional status, and gut microbiota composition in human immunodeficiency virus (HIV)-infected immunological nonresponders (INRs) who failed to normalize CD4+ T-cell counts, with a number <350 cells/µL, a pilot study was carried out in 13 HIV-infected INRs undergoing antiretroviral therapy who received a 3-month phase supplementation of 200 mL/200 kcal/45 g whole-protein enteral nutrition formula once daily. Our primary endpoint was increased CD4+ T-cell counts. Secondary outcome parameters were changes in intestinal barrier function, nutritional status, and gut microbiota composition. We showed that CD4+ T-cell counts of HIV-infected INRs increased significantly after the 3-month supplementation. Dietary supplementation for 3 months improved the intestinal barrier function and nutritional status of HIV-infected INRs. Furthermore, the enteral nutrition formula significantly decreased the relative abundance of Escherichia at the genus level and increased the alpha diversity of gut microbiota in HIV-infected INRs. The findings demonstrated that the whole-protein enteral nutrition formula aids in reducing Escherichia and improving intestinal barrier function in HIV-infected INRs. This study provides insight into the role of nutrients in the improvement of immune reconstitution in HIV-infected INRs. This study is registered in the Chinese Clinical Trial Registry (Document No. ChiCTR2000037839; http://www.chictr.org.cn/index.aspx).

Postoperative Prognostic Nutritional Index and Fibrinogen Could Well Predict Poor Prognosis of Acute Type A Aortic Dissection Patients After Surgery

ABSTRACT Introduction: Inflammatory and immunological factors play pivotal roles in the prognosis of acute type A aortic dissection. We aimed to evaluate the prognostic values of immune-inflammatory parameters in acute type A aortic dissection patients after surgery. Methods: A total of 127 acute type A aortic dissection patients were included. Perioperative clinical data were collected through the hospital's information system. The outcomes studied were delayed extubation, reintubation, and 30-day mortality. Multivariate logistic regression analysis and receiver operating characteristic analysis were used to screen the risk factors of poor prognosis. Results: Of all participants, 94 were male, and mean age was 51.95±11.89 years. The postoperative prognostic nutritional indexes were lower in delayed extubation patients, reintubation patients, and patients who died within 30 days. After multivariate regression analysis, the postoperative prognostic nutritional index was a protective parameter of poor prognosis. The odds ratios (95% confidence interval) of postoperative prognostic nutritional index were 0.898 (0.815, 0.989) for delayed extubation and 0.792 (0.696, 0.901) for 30-day mortality. Low postoperative fibrinogen could also well predict poor clinical outcomes. The odds ratios (95% confidence interval) of postoperative fibrinogen were 0.487 (0.291, 0.813) for delayed extubation, 0.292 (0.124, 0.687) for reintubation, and 0.249 (0.093, 0.669) for 30-day mortality. Conclusion: Postoperative prognostic nutritional index and postoperative fibrinogen could be two promising markers to identify poor prognosis of acute type A aortic dissection patients after surgery.

Comparison of Short-Term Surgery Outcomes and Clinical Characteristics Between Elderly and Non-Elderly Patients with Middle Third Parasagittal and Parafalcine Meningiomas.

Purpose: This study aims to compare the short-term surgery outcomes of the resection of meningiomas and clinical characteristics between elderly and non-elderly patients. Patients and Methods: This retrospective study included patients who underwent a resection of middle third parasagittal and parafalcine meningiomas between January 2011 and December 2020. All lesions arise from the middle third of the parafalcine or infiltrate superior sagittal sinus (SSS). The clinical characteristics studied included neurological deficit, peritumoral brain edema (PTBE), SSS invasion, tumor size, and symptoms; perioperative complications, and short-term surgery outcomes including neurological deficit, operative blood loss, postoperative hospitalization duration, and WHO classification were compared. Results: A total of 43 elderly patients and 63 non-elderly patients were included. Compared with non-elderly patients, elderly patients had larger lesions (P = 0.013) and presented with a larger PTBE (P = 0.019). SSS blockage was identified in 28.57% of elderly patients and 19.57% of non-elderly patients. Compared with non-elderly patients, elderly patients tended to suffer from more aggressive lesions (WHO II/III meningioma 6 vs 3, P = 0.154) and presented with longer postoperative hospital stays (17.25 ± 5.8 vs 13.50 ± 3.8, P = 0.009); conversely, while the non-elderly patients experienced more blood loss (P = 0.022) and had more perioperative reoperations (3 vs 1). No significant difference in neurological deficit was detected between the two groups (P = 0.97). After total tumor resection, patients with neurological deficits in both groups can recover during the follow-up period. Conclusion: Among the 106 patients with middle third parasagittal and falx meningiomas in our hospital, elderly patients had larger lesions, presented with more severe PTBE, and had longer postoperative hospital stays than younger patients. Conversely, younger patients had more blood loss and serious complications than elderly patients. Postoperative neurological dysfunction in elderly patients was similar to that in middle-aged and young patients.

Advanced lung cancer inflammation index combined with geriatric nutritional risk index predict all-cause mortality in heart failure patients.

BACKGROUND: This study was undertaken to explore the predictive value of the advanced lung cancer inflammation index (ALI) combined with the geriatric nutritional risk index (GNRI) for all-cause mortality in patients with heart failure (HF). METHODS AND RESULTS: We enrolled 1123 patients with HF admitted to our cardiology department from January 2017 to October 2021. Patients were divided into four groups, according to the median ALI and GNRI. From the analysis of the relationship between the ALI and GNRI, we concluded that there was a mild positive linear correlation (r = 0.348, p < 0.001) and no interaction (p = 0.140) between the ALI and GNRI. Kaplan‒Meier analysis showed that the cumulative incidence of all-cause mortality in patients with HF was highest in Group 1 (log-rank χ2 126.244, p < 0.001). Multivariate Cox proportional hazards analysis revealed that ALI and GNRI were independent predictors of all-cause mortality in HF patients (ALI: HR 0.407, 95% CI 0.296-0.560, p < 0.001; GNRI: HR 0.967, 95% CI 0.954-0.980, p < 0.001). The area under the curve (AUC) for ALI combined with GNRI was 0.711 (p < 0.001), according to the time-dependent ROC curve. CONCLUSION: ALI and GNRI were independent predictors of all-cause mortality in HF patients. Patients with HF had the highest risk of all-cause mortality when the ALI was < 24.60 and the GNRI was < 94.41. ALI combined with the GNRI has good predictive value for the prognosis of HF patients.

Association between three-territory sign and prognosis of acute ischemic stroke patients with malignancy.

Background: Multiple cerebral infarcts are usually secondary to cardiogenic embolism, particularly through atrial fibrillation (AF). The three-territory sign (TTS) is an imaging marker that reflects multiple cerebral lesions involving three vascular territories measured by diffusion-weighted imaging (DWI), and the most common etiology is an underlying malignancy. Recent studies have shown that TTS is six times more frequently observed in acute ischemic stroke (AIS) patients with malignancy than in those with AF-related AIS. However, the relevance of TTS to the prognosis of IS patients with malignancy remains unclear. Methods: Over a 5-year period (May 2016 to 31 June 2021), AIS admissions with DWI were identified from the First Affiliated Hospital of Xi'an Jiaotong University. Patients were divided into two groups according to whether they had malignancy or AF, resulting in a total of 80 patients with known malignancy (malignancy group) and 92 patients with AF (AF group). All DWI images were reviewed to determine the territory lesion count. Demographic, clinical, and laboratory data, together with radiographic examination data and modified Rankin Scale (mRS) score within a year, were collected. The main outcome was the association between TTS and the prognosis of AIS patients with malignancy, analyzed by a multivariate logistic regression model. Results: A total of 172 patients met the selection criteria, including 17 (21.3%) patients in the malignancy group and 8 (8.7%) patients in the AF group with TTS. Age and sex distributions were similar for AIS patients of malignancy and AF. The TTS was 2.4 times more likely to be observed in AIS patients with malignancy compared to AF-related IS patients. The univariate analysis showed that hypertension (OR = 1.137, 95%CI: 1.002-1.291), D-dimer (OR = 1.328, 95%CI: 1.022-1.726), fibrin degradation product (OR = 1.117, 95%CI: 1.010-1.236), and lactate dehydrogenase (LDH; OR = 1.007, 95%CI: 1.000-1.015) were the risk factors for the high mortality rate. Multivariate analysis showed that TTS was the independent risk factor for mortality in AIS patients with malignancy (adjusted OR: 6.866, 95% CI: 1.371-34.395). Conclusion: TTS was more frequently observed in AIS patients with malignancy than AF-related AIS and substantially related to high poor outcome (mRS > 2) in AIS patients with malignancy, indicating diagnostic and prognostic value in malignancy-associated hypercoagulation stroke.

Periodontopathogens Porphyromonas gingivalis and Fusobacterium nucleatum and Their Roles in the Progression of Respiratory Diseases.

The intricate interplay between oral microbiota and the human host extends beyond the confines of the oral cavity, profoundly impacting the general health status. Both periodontal diseases and respiratory diseases show high prevalence worldwide and have a marked influence on the quality of life for the patients. Accumulating studies are establishing a compelling association between periodontal diseases and respiratory diseases. Here, in this review, we specifically focus on the key periodontal pathogenic bacteria Porphyromonas gingivalis and Fusobacterium nucleatum and dissect their roles in the onset and course of respiratory diseases, mainly pneumonia, chronic obstructive pulmonary disease, lung cancer, and asthma. The mechanistic underpinnings and molecular processes on how P. gingivalis and F. nucleatum contribute to the progression of related respiratory diseases are further summarized and analyzed, including: induction of mucus hypersecretion and chronic airway inflammation; cytotoxic effects to disrupt the morphology and function of respiratory epithelial cells; synergistic pathogenic effects with respiratory pathogens like Streptococcus pneumoniae and Pseudomonas aeruginosa. By delving into the complex relationship to periodontal diseases and periodontopathogens, this review helps unearth novel insights into the etiopathogenesis of respiratory diseases and inspires the development of potential therapeutic avenues and preventive strategies.

Elastic stable intramedullary nail fixation versus submuscular plate fixation of pediatric femur shaft fractures in school age patients: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Studies of clinical outcomes that compare the elastic stable intramedullary nail (ESIN) with the submuscular plate (SMP) were controversial. The meta-analysis was performed to summarize existing evidence, aiming to determine whether ESIN was superior to SMP in pediatric femur shaft fractures. METHODS: Search strategies followed the recommendations of the Cochrane collaboration. Electronic searches such as PubMed, Embase, Web of Science, Cochrane were systematically searched for publications concerning ESIN and SMP from the inception date to March 2023. Two investigators independently searched, screened, and reviewed the full text of the article. Disagreements generated throughout the process were resolved by consensus, and if divergences remain, they were arbitrated by a third author. RESULTS: This study included 8 articles, comprising a total of 561 patients with a similar baseline. Compared to the SMP, the ESIN had shorter operation time (mean difference = -16.16; 95% CI = -22.83 to -9.48, P < .00001), and less intraoperative blood loss (mean difference = -53.62; 95% CI = -58.89 to -48.36, P < .00001), but had a higher incidence of implant irritation (odds ratio [OR] = 6.49; 95% CI = 3.01 to 13.98, P < .0001), lower limb malalignment (OR = 2.60; 95% CI = 1.12 to 6.04, P = .96) and overall complications(OR = 4.14; 95% CI = 2.51 to 6.84, P < .0001). And there was no significant difference in radiation time, length of hospital stay, limb length discrepancy, infection rate, delayed union rate and unplanned revised surgery rate (P > .05). CONCLUSIONS: Compared to the SMP, the ESIN offers shorter operative time, and less blood loss. However, the SMP is superior to ESINs in complication rates, especially regarding implant irritation and malalignment. Both methods could achieve excellent satisfactory functional outcomes. Thus, the SMP is an alternative choice in the pediatric femur shaft fracture.

An alternative extension of telomeres related prognostic model to predict survival in lower grade glioma.

OBJECTIVE: The alternative extension of the telomeres (ALT) mechanism is activated in lower grade glioma (LGG), but the role of the ALT mechanism has not been well discussed. The primary purpose was to demonstrate the significance of the ALT mechanism in prognosis estimation for LGG patients. METHOD: Gene expression and clinical data of LGG patients were collected from the Chinese Glioma Genome Atlas (CGGA) and the Cancer Genome Atlas (TCGA) cohort, respectively. ALT-related genes obtained from the TelNet database and potential prognostic genes related to ALT were selected by LASSO regression to calculate an ALT-related risk score. Multivariate Cox regression analysis was performed to construct a prognosis signature, and a nomogram was used to represent this signature. Possible pathways of the ALT-related risk score are explored by enrichment analysis. RESULT: The ALT-related risk score was calculated based on the LASSO regression coefficients of 22 genes and then divided into high-risk and low-risk groups according to the median. The ALT-related risk score is an independent predictor of LGG (HR and 95% CI in CGGA cohort: 5.70 (3.79, 8.58); in TCGA cohort: 1.96 (1.09, 3.54)). ROC analysis indicated that the model contained ALT-related risk score was superior to conventional clinical features (AUC: 0.818 vs 0.729) in CGGA cohorts. The results in the TCGA cohort also shown a powerful ability of ALT-related risk score (AUC: 0.766 vs 0.691). The predicted probability and actual probability of the nomogram are consistent. Enrichment analysis demonstrated that the ALT mechanism was involved in the cell cycle, DNA repair, immune processes, and others. CONCLUSION: ALT-related risk score based on the 22-gene is an important factor in predicting the prognosis of LGG patients.

Worldwide productivity and research trend of publications concerning tumor immune microenvironment (TIME): a bibliometric study.

BACKGROUND: As the complexity and diversity of the tumor immune microenvironment (TIME) are becoming better understood, burgeoning research has progressed in this field. However, there is a scarcity of literature specifically focused on the bibliometric analysis of this topic. This study sought to investigate the development pattern of TIME-related research from 2006 to September 14, 2022, from a bibliometric perspective. METHODS: We acquired both articles and reviews related to TIME from the Web of Science Core Collection (WoSCC) (retrieved on September 14, 2022). R package "Bibliometrix" was used to calculate the basic bibliometric features, present the collaborative conditions of countries and authors, and generate a three-field plot to show the relationships among authors, affiliations, and keywords. VOSviewer was utilized for co-authorship analysis of country and institution and keyword co-occurrence analysis. CiteSpace was used for citation burst analysis of keywords and cited references. In addition, Microsoft Office Excel 2019 was used to develop an exponential model to fit the cumulative publication numbers. RESULTS: A total of 2545 publications on TIME were included, and the annual publication trend exhibited a significant increase over time. China and Fudan University were the most productive country and institution, with the highest number of publications of 1495 and 396, respectively. Frontiers in Oncology held the highest number of publications. A number of authors were recognized as the main contributors in this field. The clustering analysis revealed six clusters of keywords that highlighted the research hot spots in the fields of basic medical research, immunotherapy, and various cancer types separately. CONCLUSIONS: This research analyzed 16 years of TIME-related research and sketched out a basic knowledge framework that includes publications, countries, journals, authors, institutions, and keywords. The finding revealed that the current research hot spots of the TIME domain lie in "TIME and cancer prognosis", "cancer immunotherapy", and "immune checkpoint". Our researchers identified the following areas: "immune checkpoint-based immunotherapy", "precise immunotherapy" and "immunocyte pattern", which may emerge as frontiers and focal points in the upcoming years, offering valuable avenues for further exploration.