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Purpose: Peak Expiratory Flow (PEF) is associated with a variety of adverse health outcomes in older adults; however, the relationship between PEF and frailty remains uncertain, and this study investigated the relationship between PEF and frailty within an olderly Asian demographic. Methods: Data were sourced from the Chinese Health and Retirement Longitudinal Study (CHARLS). Individuals in the study, all 60 years or older, underwent baseline PEF assessments quantified as standardized residual (SR) percentile values. The evaluation of frailty was conducted based on the criteria established by Fried. Participants without frailty at the outset were tracked over a four-year period, during which the relationships between PEF and frailty were examined through logistic regression and discrete-time Cox regression analyses. Results: Among 5,060 participants, cross-sectional analysis revealed that the prevalence of frailty was 2-3 times higher in the lower 10-49th and < 10th SR percentile groups compared to the 80-100th SR percentile group. The longitudinal study corroborated these results, showing an adjusted hazard ratio (HR) of 2.01 (95% CI, 1.15-3.51) for PEF SR percentiles below the 10th, in contrast to those between the 80th and 100th percentiles. Conclusion: PEF independently predicts and determines frailty in older adults. Declines in PEF greater than expected are associated with the development of frailty. Subsequent studies are encouraged to delve deeper into the connection between respiratory function and frailty in diverse contexts.
Subject(s)
Frailty , Humans , Longitudinal Studies , Male , Female , Aged , China/epidemiology , Peak Expiratory Flow Rate , Cross-Sectional Studies , Middle Aged , Aged, 80 and over , Frail Elderly/statistics & numerical data , Prevalence , Retirement/statistics & numerical dataABSTRACT
OBJECTIVE: Although several acupuncture and moxibustion therapies have been tested in managing breast cancer-related lymphedema (BCRL), there is little consensus regarding the best options for treating this condition. This systematic review and network meta-analysis compared the efficacy of various acupuncture and/or moxibustion therapies for BCRL. METHODS: Seven databases and two clinical registration centers were searched from their inception to December 1st, 2023. The Cochrane Collaboration risk-of-bias assessment tool evaluated the quality of included RCTs. A pairwise meta-analysis was performed in STATA 16.0, while a network meta-analysis was performed in R 4.2.2. RESULTS: 18 studies were included in this analysis. Our results showed that acupuncture and moxibustion methods had great advantages in improving BCRL of patients with breast cancer. In particular, needle-warming moxibustion (NWM) could be the optimal acupuncture and moxibustion method for improving clinical effectiveness and reducing the degree of swelling of affected limbs. CONCLUSION: Our findings suggest that NWM has great potential in treating BCRL. It may reduce arm circumference, lower swelling levels, and improve clinical effectiveness. Nevertheless, more multi-center, high-quality, and large sample RCTs will be needed in the future.
Subject(s)
Acupuncture Therapy , Breast Cancer Lymphedema , Moxibustion , Humans , Moxibustion/methods , Moxibustion/adverse effects , Female , Acupuncture Therapy/methods , Acupuncture Therapy/adverse effects , Breast Cancer Lymphedema/therapy , Network Meta-Analysis , Treatment Outcome , Breast Neoplasms/complications , Breast Neoplasms/therapyABSTRACT
Repairing damaged tissue caused by bacterial infection poses a significant challenge. Traditional antibacterial hydrogels typically incorporate various components such as metal antimicrobials, inorganic antimicrobials, organic antimicrobials, and more. However, drawbacks such as the emergence of multi-drug resistance to antibiotics, the low antibacterial efficacy of natural agents, and the potential cytotoxicity associated with metal antibacterial nanoparticles in hydrogels hindered their broader clinical application. In this study, we successfully developed imidazolium poly(ionic liquids) (PILs) polymer microspheres (APMs) through emulsion polymerization. These APMs exhibited notable antibacterial effectiveness and demonstrated minimal cell toxicity. Subsequently, we integrated the APMs into a gelatin methacryloyl (GelMA)-polyethylene glycol (PEG) hydrogel. This composite hydrogel not only showcased strong antibacterial and anti-inflammatory properties but also facilitated the migration of human skin fibroblasts (HSF) and human umbilical vein endothelial cells (HUVECs) and promoted osteogenic differentiation in vitro.
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Inbreeding depression refers to the reduced performance arising from increased homozygosity, a phenomenon that is the reverse of heterosis and exists among plants and animals. As a natural self-pollinated crop with strong heterosis, the mechanism of inbreeding depression in rice is largely unknown. To understand the genetic basis of inbreeding depression, we constructed a successive inbreeding population from the F2 to F4 generation and observed inbreeding depression of all heterotic traits in the progeny along with the decay of heterozygosity in each generation. The expected depression effect was largely explained by 13 QTLs showing dominant effects for spikelets per panicle, 11 for primary branches, and 12 for secondary branches, and these loci constitute the main correlation between heterosis and inbreeding depression. However, the genetic basis of inbreeding depression is also distinct from that of heterosis, such that a biased transmission ratio of alleles for QTLs with either dominant or additive effects in four segregation distortion regions would result in minor effects in expected depression. Noticeably, two-locus interactions may change the extent and direction of the depression effects of the target loci, and overall interactions would promote inbreeding depression among generations. Using an F2:3 variation population, the actual performance of the loci showing expected depression was evaluated considering the heterozygosity decay in the background after inbreeding. We found inconsistent or various degrees of background depression from the F2 to F3 generation assuming different genotypes of the target locus, which may affect the actual depression effect of the locus due to epistasis. The results suggest that the genetic architecture of inbreeding depression and heterosis is closely linked but also differs in their intrinsic mechanisms, which expand our understanding of the whole-genome architecture of inbreeding depression.
Subject(s)
Hybrid Vigor , Inbreeding Depression , Oryza , Quantitative Trait Loci , Oryza/genetics , Hybrid Vigor/genetics , Heterozygote , Inbreeding , Hybridization, Genetic , Crosses, Genetic , AllelesABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) patients complicated with portal vein tumor thrombus (PVTT) exhibit poor prognoses and treatment responses. AIM: To investigate efficacies and safety of the combination of PD-1 inhibitor, transcatheter arterial chemoembolization (TACE) and Lenvatinib in HCC subjects comorbid with PVTT. METHODS: From January 2019 to December 2020, HCC patients with PVTT types I-IV were retrospectively enrolled at Beijing Ditan Hospital. They were distributed to either the PTL or TACE/Lenvatinib (TL) group. The median progression-free survival (mPFS) was set as the primary endpoint, while parameters like median overall survival, objective response rate, disease control rate (DCR), and toxicity level served as secondary endpoints. RESULTS: Forty-one eligible patients were finally recruited for this study and divided into the PTL (n = 18) and TL (n = 23) groups. For a median follow-up of 21.8 months, the DCRs were 88.9% and 60.9% in the PTL and TL groups (P = 0.046), res-pectively. Moreover, mPFS indicated significant improvement (HR = 0.25; P < 0.001) in PTL-treated patients (5.4 months) compared to TL-treated (2.7 months) patients. There were no treatment-related deaths or differences in adverse events in either group. CONCLUSION: A triplet regimen of PTL was safe and well-tolerated as well as exhibited favorable efficacy over the TL regimen for advanced-stage HCC patients with PVTT types I-IV.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Phenylurea Compounds , Quinolines , Thrombosis , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Liver Neoplasms/therapy , Liver Neoplasms/drug therapy , Retrospective Studies , Portal Vein/pathology , Chemoembolization, Therapeutic/adverse effects , Treatment Outcome , Thrombosis/etiologyABSTRACT
Redox-responsive hydropersulfide prodrugs are designed to enable a more controllable and efficient hydropersulfide (RSSH) supply and to thoroughly explore their biological and therapeutic applications in oxidative damage. To obtain novel activation patterns triggered by redox signaling, we focused on NAD(P)H: quinone acceptor oxidoreductase 1 (NQO1), a canonical antioxidant enzyme, and designed NQO1-activated RSSH prodrugs. We also performed a head-to-head comparison of two mainstream structural scaffolds with solid quantitative analysis of prodrugs, RSSH, and metabolic by-products by LC-MS/MS, confirming that the perthiocarbamate scaffold was more effective in intracellular prodrug uptake and RSSH production. The prodrug was highly potent in oxidative stress management against cisplatin-induced nephrotoxicity. Strikingly, this prodrug possessed potential feedback activation properties by which the delivered RSSH can further escalate the prodrug activation via NQO1 upregulation. Our strategy pushed RSSH prodrugs one step further in the pursuit of efficient release in biological matrices and improved druggability against oxidative stress.
Subject(s)
NAD(P)H Dehydrogenase (Quinone) , Oxidation-Reduction , Oxidative Stress , Prodrugs , Sulfides , Prodrugs/pharmacology , Prodrugs/chemistry , Oxidative Stress/drug effects , NAD(P)H Dehydrogenase (Quinone)/metabolism , Oxidation-Reduction/drug effects , Sulfides/chemistry , Sulfides/pharmacology , Humans , Animals , Tandem Mass Spectrometry , Cisplatin/pharmacology , Antioxidants/pharmacology , Antioxidants/chemistry , MiceABSTRACT
MDMB-4F-BICA, also known as 4F-MDMB-BICA, is a new psychoactive substance that emerged in 2020. It is often illegally added to electronic cigarette oil for inhalation abuse, leading to serious adverse symptoms and even death. There are significant differences in pharmacokinetics between inhalation administration and conventional drug delivery methods. Inhalation administration can pass through the blood-brain barrier to enter the brain directly. However, the specific distribution of the drug in the brain following inhalation has not been well investigated. In order to scientifically compare the absorption and distribution of MDMB-4F-BICA after two administration methods (inhalation and subcutaneous injection), this study analyzed the drug concentration in mice blood and brain by LC-MS/MS after systemic exposure inhalation in the form of electronic cigarettes. The aim was to conduct the pharmacokinetics study of MDMB-4F-BICA after inhalation('vapor') administration. Pharmacokinetics and distribution of the compound revealed that the maximum concentrations in blood of this compound were reached at 0.5 min and 15 min, respectively, and the concentration in the brain reached the maximum at the same time after two modes of administration. The drug concentration in the brain was higher than that of subcutaneous injection, and the drug remained at a low concentration in the brain for a long period (20 ng/g brain tissue) with a significant distribution in several olfactory primary cortex brain regions. Taken together, the pharmacokinetics of the synthetic cannabinoid MDMB-4F-BICA after single systemic exposure inhalation were investigated for the first time in this study. A basis for subsequent evaluation research of inhalation-related harmfulness is provided by comparing the distribution of drugs in the brain after the two administration modes.
Subject(s)
Electronic Nicotine Delivery Systems , Illicit Drugs , Animals , Mice , Tandem Mass Spectrometry , Chromatography, Liquid , Administration, Inhalation , Injections, SubcutaneousABSTRACT
Microplastics (MPs) are known to cause liver toxicity as they can spread through the food chain. Most researches on their toxicity have focused on individual organs, neglecting the crucial "gut-liver axis"-a bidirectional communication pathway between the gut and liver. Probiotics have shown promise in modulating the effects of environmental pollutants. In this study, we exposed mice to Lactobacillus rhamnosus GG (LGG, 100 mg/kg b.w./d) and/or polystyrene microplastics (PS-MPs, 5 mg/kg b.w./d) for 28 d via gavage to investigate how probiotics influence live toxicity through the gut-liver axis. Our results demonstrated that PS-MPs induced liver inflammation (increased IL-6 and TNF-α) and disrupted lipid metabolism. However, when combined with LGG, these effects were alleviated. LGG also improved colon health, rectifying ciliary defects and abnormal mucus secretion caused by PS-MPs. Furthermore, LGG improved gut microbiota dysbiosis induced by PS-MPs. Metabolomics and gene expression analysis (Cyp7a1 and Cyp7b1) indicated that LGG modulated bile acid metabolism. In summary, LGG appears to protect the liver by maintaining gut homeostasis, enhancing gut barrier integrity, and reducing the liver inflammation. These findings confirm the potential of LGG to modulate liver toxicity caused by PS-MPs through the gut-liver axis, offering insights into probiotics' application for environmental pollutant detoxification.
Subject(s)
Gastrointestinal Microbiome , Lacticaseibacillus rhamnosus , Probiotics , Mice , Animals , Polystyrenes , Microplastics , Plastics , Liver , InflammationABSTRACT
Parent-Child Attachment (PCA) and Hostile Attribution Bias (HAB) are closely related to aggression, but findings regarding their relationships are inconsistent. There is a lack of understanding of the underlying mechanism between PCA and aggression. This review employed meta-analysis approaches to investigate the associations between PCA and aggression, as well as between HAB and aggression, and the mechanism for the PCA-aggression association. An article search was conducted in CNKI, PubMed, PsycINFO, Web of Science, ProQuest, and Google Scholar. Totally, 118 studies involving general populations and those at high risk for aggression were included. Results revealed negative associations between Parent-Child Attachment Security (PCAS) and aggression (ρ = -.267, p < .001) and positive associations between Parent-Child Attachment Insecurity (PCAI) and aggression (ρ = .240, p < .05). HAB and aggression were found to be positively associated (ρ = .303, p < .001). As for the PCAS-aggression association, a larger effect size was found in females than in males. The HAB-reactive aggression association was stronger than the HAB-proactive aggression association. In Eastern culture, the association between HAB and aggression was stronger than in Western culture. HAB mediated the association between PCAS and aggression. Our findings contribute to the understanding of the occurrence and development of aggression by establishing an association between attachment theory and the social information processing model. The practical implications include interventions targeting cultivating PCAS and alleviating HAB, which might serve as effective ways to reduce aggression, yet aggression type, gender, and cultural background should be taken into consideration.
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OBJECTIVES: This study aimed to investigate the potential correlations among serum 25-hydroxyvitamin D [25(OH)D] levels, white matter hyperintensity (WMH) and cognitive function in patients with non-disabling ischemic cerebrovascular events (NICE). METHODS: This was a prospective investigation of 160 NICE patients with age of 40 years or older. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA). White matter lesions were evaluated by WMH using Fazekas scores. Spearman correlation analysis and linear regression models were used to identify the associations between serum 25(OH)D levels and cognitive function. Binary logistic regression analysis models were used to evaluate the predictable value of serum 25(OH)D levels and WMH for cognitive impairment. RESULTS: Patients with inadequate 25(OH)D levels had lower MoCA score (P=0.008), and a higher proportion of severe WMH (P=0.043). Spearman correlation analysis demonstrated that serum 25(OH)D concentrations were positively associated with MoCA score (rs=0.185, P=0.019) while negatively related to the proportion of severe WMH (sWMH) (rs=-0.166, P=0.036).The association between 25(OH)D concentrations and MoCA score remained significant in linear regression (adjusted ß=0.012, 95%CI:0.001-0.203).Adjusted binary logistic regression analysis showed that the odds ratio of cognitive impairment with insufficient 25(OH)D concentration was 5.038 (95%CI:1.154-21.988) compared with the sufficient group and the sWMH (OR=2.728, 95%CI:1.230-6.051) was identified as an independent risk factor for cognitive decline in NICE patients. CONCLUSION: Serum 25(OH)D levels and white matter lesions were independently and significantly associated with cognitive impairment in NICE patients.
Subject(s)
Leukoaraiosis , Vitamin D , White Matter , Adult , Humans , Cognition , Prospective Studies , White Matter/diagnostic imagingABSTRACT
Objective: To identify whether intracranial hematoma (ICH) evacuation improves the prognosis of patients with ruptured anterior communicating artery (AcomA) aneurysms concomitant with small ICHs (≥10 mL and <25 mL). Methods: Data on patients diagnosed with small ICHs secondary to ruptured AcomA aneurysms who underwent surgery in our department between January 2010 and February 2018 was retrospectively analyzed. The patients were divided into two groups based on whether the hematoma was evacuated. The modified Rankin Scale (mRS) was used to assess prognosis six months after onset. Results: The study recruited 58 patients, 19 of whom underwent aneurysm clipping and ICH evacuation. While 33 patients underwent aneurysm clipping, 6 patients underwent coiling embolism without ICH evacuation. The average ICH volume was 15.27±4.07 mL. In the hematoma-evacuated group, 13 (68.4%) patients had unfavorable outcomes (mRS scores of 4 to 6). In the non-evacuated hematoma group, 13 (33.3%) patients had unfavorable outcomes (P = 0.001), postoperative infarction occurred in 11 (57.9%) patients in the hematoma evacuation group and 9 (23.1%) patients in the other group (P = 0.009). Conclusion: ICH evacuation was associated with unfavorable outcomes and postoperative infarction in ruptured AcomA aneurysms with concomitant small hematomas (<25 mL). Aneurysm clipping or coiling without ICH evacuation may be a safe and effective choice; however, further investigation is needed.
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In the situation of mass vaccination against COVID-19, few studies have reported on the early kinetics of specific antibodies (IgG/IgM/IgA) of vaccine breakthrough cases. There is still a lack of epidemiological evidence about the value of serological indicators in the auxiliary diagnosis of COVID-19 infection, especially when the nucleic acid results were undetectable. Omicron breakthrough cases post-inactivated vaccination (n = 456) and COVID-19-naive individuals with two doses of inactivated vaccination (n = 693) were enrolled. Blood samples were collected and tested for SARS-CoV-2 antibody levels based on the magnetic chemiluminescence enzyme immunoassay. Among Omicron breakthrough cases, the serum IgG antibody level was 36.34 Sample/CutOff (S/CO) (95% confidence interval [CI], 31.89 to 40.79) in the acute phase and 88.45 S/CO (95% CI, 82.79 to 94.12) in the recovery phase. Serum IgA can be detected in the first week post-symptom onset (PSO) and showed an almost linear increase within 5 weeks PSO. Compared with those of breakthrough cases, IgG and IgA titers of the postimmune group were much lower (4.70 S/CO and 0.46 S/CO, respectively). Multivariate regression showed that serum IgG and IgA levels in Omicron breakthrough cases were mainly affected by the weeks PSO (P < 0.001). Receiver operating characteristic ROC0 curve analysis showed that the area under the curve (AUC) was 0.744 and 0.806 when the cutoff values of IgA and IgG were 1 S/CO and 15 S/CO, respectively. Omicron breakthrough infection can lead to a further increase in IgG and IgA levels relative to those of the immunized population. When nucleic acid real-time PCR was negative, we would use the kinetics of IgG and IgA levels to distinguish the breakthrough cases from the immunized population. IMPORTANCE This study fills a gap in the epidemiological evidence by investigating the value of serological indicators, particularly IgG and IgA levels, in the auxiliary diagnosis of COVID-19 infections when nucleic acid results are undetectable. The findings reveal that among Omicron breakthrough cases, both IgG and IgA antibody levels exhibit significant changes. Serum IgG levels increase during the acute phase and rise further in the recovery phase. Serum IgA can be detected as early as the first week post-symptom onset (PSO), showing a consistent linear increase within 5 weeks PSO. Furthermore, receiver operating characteristic (ROC) curve analysis demonstrates the potential of IgG and IgA cutoff values as diagnostic markers. The study's conclusion underscores the importance of monitoring IgG and IgA kinetics in distinguishing Omicron breakthrough cases from vaccinated individuals. These findings contribute to the development of more accurate diagnostic approaches and help inform public health strategies during the ongoing COVID-19 pandemic.
Subject(s)
COVID-19 , Nucleic Acids , Humans , COVID-19/diagnosis , Pandemics , SARS-CoV-2 , Antibodies, Viral , Immunoglobulin G , Immunoglobulin AABSTRACT
Background and purpose: Corpus callosum (CC) infarction is an extremely rare subtype of cerebral ischemic stroke, however, the symptoms of cognitive impairment often fail to attract early attention of patients, which seriously affects the long-term prognosis, such as high mortality, personality changes, mood disorders, psychotic reactions, financial burden and so on. This study seeks to develop and validate models for early predicting the risk of subjective cognitive decline (SCD) after CC infarction by machine learning (ML) algorithms. Methods: This is a prospective study that enrolled 213 (only 3.7%) CC infarction patients from a nine-year cohort comprising 8,555 patients with acute ischemic stroke. Telephone follow-up surveys were carried out for the patients with definite diagnosis of CC infarction one-year after disease onset, and SCD was identified by Behavioral Risk Factor Surveillance System (BRFSS) questionnaire. Based on the significant features selected by the least absolute shrinkage and selection operator (LASSO), seven ML models including Extreme Gradient Boosting (XGBoost), Logistic Regression (LR), Light Gradient Boosting Machine (LightGBM), Adaptive Boosting (AdaBoost), Gaussian Naïve Bayes (GNB), Complement Naïve Bayes (CNB), and Support vector machine (SVM) were established and their predictive performances were compared by different metrics. Importantly, the SHapley Additive exPlanations (SHAP) was also utilized to examine internal behavior of the highest-performance ML classifier. Results: The Logistic Regression (LR)-model performed better than other six ML-models in SCD predictability after the CC infarction, with the area under the receiver characteristic operator curve (AUC) of 77.1% in the validation set. Using LASSO and SHAP analysis, we found that infarction subregions of CC infarction, female, 3-month modified Rankin Scale (mRS) score, age, homocysteine, location of angiostenosis, neutrophil to lymphocyte ratio, pure CC infarction, and number of angiostenosis were the top-nine significant predictors in the order of importance for the output of LR-model. Meanwhile, we identified that infarction subregion of CC, female, 3-month mRS score and pure CC infarction were the factors which independently associated with the cognitive outcome. Conclusion: Our study firstly demonstrated that the LR-model with 9 common variables has the best-performance to predict the risk of post-stroke SCD due to CC infarcton. Particularly, the combination of LR-model and SHAP-explainer could aid in achieving personalized risk prediction and be served as a decision-making tool for early intervention since its poor long-term outcome.
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Carex communities in most Yangtze-disconnected lakes have been degraded severely due to alterations in water level fluctuations. To explore the feasibility of restoring the lakeshore Carex communities through ecological regulation of water level, the present study selected the Yangtze-connected Qili Lake (the lakeshore was dominated by Carex) and the Yangtze-disconnected Wuchang Lake (the lakeshore was dominated by Zizania latifolia) as model systems, and analyzed the lakeshore seed bank characteristics and seed-related quantitative, morphological, and germination traits of three representative Carex species. According to the results, although Carex seed density in the Qili Lake seed bank was obviously higher than that in Wuchang Lake, their contribution to the total seed density in both lakes was extremely low, with no significant difference between the two lakes. The results indicate that restoration of the degraded Carex communities using existing seed bank in Yangtze-disconnected lakes exclusively through water level regulation is not feasible. In addition, the seed densities of aboveground parts of Carex cinerascens, Carex dimorpholepis, and Carex argyi in Qili Lake were 6.9 × 104, 45.1 × 104, and 3.6 × 104 seeds/m2, respectively, which can provide high numbers of seeds continuously for lakeshore Carex restoration. The results of seed germination experiments showed that light, burial depth, and their interaction had significant effects on seed germination of the three species, whereas water condition had a significant effect only on C. dimorpholepis seed germination. The average germination rates of the three Carex species were 16.63 %, 19.06 %, and 7.78 %, respectively. However, considering the high seed densities in the aboveground parts of the three species, there are considerable numbers of seeds that can be used for Carex restoration. Therefore, the restoration of Carex communities in lakeshore zones of Yangtze-disconnected lakes is still possible if water level regulation can be combined with natural or artificial seed supplementation.
Subject(s)
Carex Plant , Lakes , Water , Seeds/physiology , Dietary Supplements , China , EcosystemABSTRACT
BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) predicts a poor prognosis. The aim of the present study was to evaluate the efficacy and safety of using lenvatinib and camrelizumab combined with transarterial chemoembolization (TACE) to treat HCC with PVTT. METHODS: This was a single-arm, open-label, multicenter, and prospective study. Eligible patients with advanced HCC accompanied by PVTT were enrolled to receive TACE combined with lenvatinib and camrelizumab. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. RESULTS: Between April 2020 and April 2022, 69 patients were successfully enrolled. With a median follow-up time of 17.3 months, the median age of the patient cohort was 57 years (range: 49-64 years). According to modified Response Evaluation Criteria in Solid Tumors, the ORR was 26.1% (18 partial responses [PRs]) and the DCR was 78.3% (18 PRs, 36 stable diseases [SDs]). The median PFS (mPFS) and median OS (mOS) were 9.3 and 18.2 months, respectively. And tumor number >3 was identified as an adverse risk factor for both PFS and OS. The most common adverse events across all grades included fatigue (50.7%), hypertension (46.4%), and diarrhea (43.5%). Twenty-four patients (34.8%) experienced Grade 3 toxicity that was relieved by dose adjustment and symptomatic treatment. No treatment-related deaths occurred. CONCLUSIONS: TACE combined with lenvatinib and camrelizumab is a well-tolerated modality treatment with promising efficacy for advanced HCC with PVTT.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Thrombosis , Humans , Middle Aged , Carcinoma, Hepatocellular/pathology , Prospective Studies , Liver Neoplasms/pathology , Portal Vein/pathology , Chemoembolization, Therapeutic/adverse effects , Treatment Outcome , Thrombosis/pathology , Retrospective StudiesABSTRACT
OBJECTIVE: To retrospectively analyze clinical characteristics and survival time of patients with diffuse large B-cell lymphoma (DLBCL), detect prognosis-related markers, and establish a nomogram prognostic model of clinical factors combined with biomarkers. METHODS: One hundred and thirty-seven patients with DLBCL were included in this study from January 2014 to March 2019 in the First Affiliated Hospital of Nanchang University. The expression of GCET1, LMO2, BCL-6, BCL-2 and MYC protein were detected by immunohistochemistry (IHC), then the influences of these proteins on the survival and prognosis of the patients were analyzed. Univariate and multivariate Cox regression analysis were used to gradually screen the prognostic factors in nomogram model. Finally, nomogram model was established according to the result of multivariate analysis. RESULTS: The positive expression of GCET1 protein was more common in patients with Ann Arbor staging I/II (P =0.011). Compared with negative patients, patients with positive expression of LMO2 protein did not often show B symptoms (P =0.042), and could achieve better short-term curative effect (P =0.005). The overall survival (OS) time of patients with positive expression of LMO2 protein was significantly longer than those with negative expression of LMO2 protein (P =0.018), though the expression of LMO2 protein did not correlate with progression-free survival (PFS) (P >0.05). However, the expression of GCET1 protein had no significant correlation with OS and PFS. Multivariate Cox regression analysis showed that nomogram model consisted of 5 prognostic factors, including international prognostic index (IPI), LMO2 protein, BCL-2 protein, MYC protein and rituximab. The C-index applied to the nomogram model for predicting 4-year OS rate was 0.847. Moreover, the calibrated curve of 4-year OS showed that nomogram prediction had good agreement with actual prognosis. CONCLUSION: The nomogram model incorporating clinical characteristics and IHC biomarkers has good discrimination and calibration, which provides a useful tool for the risk stratification of DLBCL.
Subject(s)
Lymphoma, Large B-Cell, Diffuse , Nomograms , Humans , Prognosis , Immunohistochemistry , Retrospective Studies , Clinical Relevance , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Rituximab/therapeutic use , Proto-Oncogene Proteins c-bcl-2 , Transcription Factors , Antineoplastic Combined Chemotherapy ProtocolsABSTRACT
OBJECTIVE: Primary brainstem hemorrhage (PBSH) is a devastating acute neurological disorder with a poor prognosis. This study aimed to identify risk factors associated with poor outcomes in PBSH patients and develop a novel nomogram for predicting prognosis, with external validation. METHODS: A total of 379 patients with PBSH were included in the training cohort. The primary outcome of interest was a modified Rankin Scale score (mRS) of 4-6 at 90 days post-onset. Multivariable logistic regression was used to construct a nomogram based on relevant variables. Model performance was tested in the training cohort and externally validated for discriminatory ability, calibration, and clinical utility at a separate institution. The nomogram was also compared to the ICH score in terms of predictive ability. RESULTS: The poor outcome rate at 90 days was 57.26% (217/379) in the training cohort and 61.27% (106/173) in the validation cohort. Multivariable logistic regression analysis identified age, Glasgow Coma Scale (GCS) score, and hematoma size as significant risk factors for poor outcomes. Nomograms based on these variables demonstrated good discrimination, with an area under the curve (AUC) of 0.855 and 0.836 in the training and validation cohorts, respectively. Furthermore, the nomogram showed superior predictive value to the ICH score for the 90-day outcome in both cohorts. CONCLUSION: This study developed and externally validated a nomogram risk prediction model for predicting poor outcomes at 90 days in patients with PBSH, using age, GCS score, and hematoma size as predictors. The nomogram demonstrated good discrimination, calibration, and clinical validity, serving as a valuable assessment and decision-making tool.
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The majority of low-grade gliomas (LGGs) in adults invariably progress to glioblastoma over time. Spectrin ß non-erythrocytic 2 (SPTBN2) is detected in numerous tumors and is involved in tumor occurrence and metastasis. However, the specific roles and detailed mechanisms of SPTBN2 in LGG are largely unknown. The present study performed pan-cancer analysis for the expression and prognosis of SPTBN2 in LGG using The Cancer Genome Atlas and The Genotype-Tissue Expression. Western blotting was used to detect the amount of SPTBN2 between glioma tissues and normal brain tissues. Subsequently, based on expression, prognosis, correlation and immune infiltration, non-coding RNAs (ncRNAs) were identified that regulated SPTBN2 expression. Finally, tumor immune infiltrates associated with SPTBN2 and prognosis were performed. Lower expression of SPTBN2 was correlated with an unfavorable outcome in LGG. A significant correlation between the low SPTBN2 mRNA expression and poor clinicopathological features was observed, including wild-type isocitrate dehydrogenase status (P<0.001), 1p/19q non-codeletion (P<0.001) and elders (P=0.019). The western blotting results revealed that, compared with normal brain tissues, the amount of SPTBN2 was significantly lower in LGG tissues (P=0.0266). Higher expression of five microRNAs (miRs/miRNAs), including hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-16-5p, hsa-miR-34c-5p and hsa-miR-424-5p, correlated with poor prognosis by targeting SPTBN2 in LGG. Subsequently, four long ncRNAs (lncRNAs) [ARMCX5-GPRASP2, BASP1-antisense RNA 1 (AS1), EPB41L4A-AS1 and LINC00641] were observed in the regulation of SPTBN2 via five miRNAs. Moreover, the expression of SPTBN2 was significantly correlated with tumor immune infiltration, immune checkpoint expression and biomarkers of immune cells. In conclusion, SPTBN2 was lowly expressed and correlated with an unfavorable prognosis in LGG. A total of six miRNAs and four lncRNAs were identified as being able to modulate SPTBN2 in a lncRNA-miRNA-mRNA network of LGG. Furthermore, the current findings also indicated that SPTBN2 possessed anti-tumor roles by regulating tumor immune infiltration and immune checkpoint expression.
ABSTRACT
Long noncoding RNAs (LncRNAs) are very important in the way that docetaxel resistance (DR) happens in prostate cancer (PCa) patients. ImmuneScore and StromalScore were calculated using PCa-related expression data from TCGA and the ESTIMATE algorithm. We finally found the DEGs that were related to the immune system and the stroma of the patients by making profiles of the DEGs in ImmuneScore and StromalScore. The CancerSubtypes algorithm identified prognosis-related PCa subtypes, and the GSVA assessed their pathway activity. A UniCox regression analysis was used to identify a prognosis-related differential gene set. We then used intersection analysis to identify immunological and prognostic (IP)-related genes (IPGs). The coexpression of long noncoding RNAs (lncRNAs) and IPGs was used to identify IP-related lncRNAs (IPLs). Three methods (SVM-RFE, random forest, and LASSO) were used to find genes that overlap in the GEO database. A gene signature was then validated by building an ROC curve. CIBERSORT technology was used to look at the possibility of a link between the gene signature and immune cells. LncRNA-miRNA pairs and miRNA-mRNA pairs from the miRDB and TargetScan databases were used to construct the ERVH48-1-miR-4784-WNT2B ceRNA regulation network. The concentration of docetaxel elevated the expression of ERVH48-1. Overexpression of ERVH48-1 increased PCa-DR cell proliferation, invasion, and migration while inhibiting apoptosis. ERVH48-1 increased the tumorigenicity of PCa-DR cells in nude mice. ERVH48-1, acting as a ceRNA, targeted miR-4784 to increase WNT2B expression. ICG001 therapy increased Wnt/-catenin signaling activity in PCa-DR cells by inhibiting ERVH48-1. Finally, ERVH48-1 increased docetaxel resistance in a WNT2B-dependent manner via the miR-4784/Wnt/-catenin pathway.