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BACKGROUND: The increasing number of semi-invasive pain therapies in knee osteoarthritis poses challenges in decision-making. This review aimed to simultaneously compare established intra-articular therapies with newer peri-articular therapies and explore effect modifiers. METHODS: Randomized controlled trials were searched from five electronic databases without date or language restrictions. Study selection and data extraction of reports, retrieved up to May 2024, were performed independently by paired assessors. The primary outcome was 6-month pain score. Nine treatments were included. The effect size (ES) for each treatment, relative to placebo, was estimated using standardized means difference and expressed with 95% confidence intervals (CI). The rigor of results was evaluated with subgroup/sensitivity analyses. RESULTS: A total of 111 studies (14,695 participants) were included, with intra-articular hyaluronic acid having the greatest number of participants. Neuroablation demonstrated the greatest ES (1.08, 95% CI: 0.07, 2.10). While platelet-rich plasma (PRP) ranked second (ES: 0.75, 95% CI: 0.28, 1.22), it was the only intervention demonstrating statistically significant effect at 3, 6, and 12 months. However, this statistical significance was lost in some sensitivity analyses. Larger estimates for biologics and PRP compared with prolotherapy, steroid, and hyaluronic acid injections were consistently observed across different timepoints and in multiple sensitivity analyses. Generally, no statistically significant difference was found between the nine types of therapies. CONCLUSION: Although there is robust evidence suggesting greater efficacy of PRP, potentially including biologics, over other interventions, future research is needed to identify the phenotype or patient subgroup that would benefit most from PRP.

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Bioelectrochemical system (BES) is a unique biotechnology for wastewater treatment and energy recovery, and extracellular electron transfer (EET) between microbe and electrode is the key to optimize the performance of BESs. Resazurin is an effective artificial compound that can promote EET in BESs, but the way how it transports electrons is not fully understood. In this study differential pulse voltammetry revealed that the redox potential of resorufin (RR) (intermediate of resazurin reduction, actual electron mediator) within Geobacter sulfurreducens biofilm was positively shifted by 100 mV than that of free RR, and this shift was attenuated by the mutation of outer-membrane cytochrome gene omcE but not by omcS and omcZ mutation, indicating that RR specifically interacted with OmcE. By using heterologously expressed OmcE monomers in Escherichia coli, it was found that RR bonded with OmcE monomers with a moderate intensity (dissociation constant of 720 nM), and their interaction obviously increased the content of α helix in OmcE monomers. Biomolecular analysis indicated that heme II of OmcE monomer might be the binding site for RR (binding energy of -7.01 kJ/mol), which were favorable for electron transfer within OmcE-RR complex. Comparative transcriptomics showed that RZ addition significantly upregulated the expression of omcE, periplasmic cytochrome gene ppcB, and outer-membrane genes omaB, ombB and omcB, thus, it was hypothesized that OmcE-bound RR might serve as potential electron acceptor of OmbB-OmaB-OmcB porin complex which passes electrons across outer membrane. Our work demonstrated a new pathway of artificial electron mediators in facilitating EET in Geobacter species, which may guide the application of electron mediator in improving the performance of BESs.

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Background: Vascular invasion is a major risk factor for poor prognosis of liver transplantation (LT) for hepatocellular carcinoma (HCC), and this study aimed to evaluate the feasibility and efficacy of deceased donor LT (DDLT) for the treatment of microvascular invasion (MVI) and segmental portal vein tumor thrombus (PVTT). Methods: We retrospectively analyzed 141 patients who received DDLT for HCC combined with vascular invasion from January 2016 to December 2023 at Shulan (Hangzhou) Hospital. To assess the risk of vascular invasion associated with the LT prognosis, we evaluated various clinicopathologic variables. The recurrence-free survival (RFS) and overall survival (OS) based on different types of vascular invasion were also analyzed. Results: A total of 141 patients were enrolled in this study, including patients with MVI (MVI group, n=60), segmental PVTT with segmental branches of the portal vein or above (segmental PVTT group, n=13), and lobar PVTT involving the left and right branches of the portal vein or the main portal vein (lobar PVTT group, n=68). Between the tumor recurrence group and the no recurrence group, there were significant differences in alpha-fetoprotein (AFP) level, tumor total diameter, pretransplant treatment, histological grade, and types of vascular invasion. Subgroup analyses were performed according to the types of vascular invasion, the lobar PVTT group had a significantly higher recurrence rate (lobar vs. MVI: 88.2% vs. 35.0%, lobar vs. segmental: 88.2% vs. 30.8%, both P<0.001), but there was no difference in recurrence rate between the MVI group and the segmental PVTT group (35.0% vs. 30.8%, P>0.99). The 3-year RFS rate and OS rate were as low as 9.1% and 45.9% in the lobar PVTT group, compared with 65.5% and 76.0% in the MVI group, 58.3% and 75.0% in the segmental PVTT group. Multivariate analysis showed that Child-Pugh classification, tumor total diameter, histological grade, and lobar PVTT were the main risk factors affecting RFS, whereas Child-Pugh classification, tumor total diameter, and lobar PVTT were the main risk factors affecting OS. Finally, analysis of the segmental PVTT group revealed that RFS was significantly higher in well and moderately-differentiated patients than in poor-differentiated patients (P=0.01). Conclusions: Lobar PVTT remains a contraindication to LT, whereas segmental PVTT can still be considered for LT after careful screening.

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Objective: To evaluate the predictive performance of metagenomic next-generation sequencing (mNGS) in identifying and predicting pulmonary infections following liver transplantation and to investigate its association with patient outcomes within the initial four-week post-transplantation period. Methods: We retrospectively analyzed 41 liver transplant patients with suspected pulmonary infections from August 2022 to May 2023. Bronchoalveolar lavage fluid (BALF) samples were collected on the first postoperative day for metagenomic next generation sequencing (mNGS) and culture. The predictive capability of mNGS for subsequent infections was assessed by monitoring inflammatory biomarkers and comparing the detection rates with culture methods. Real-time Polymerase Chain Reaction (Rt-PCR) was used to monitor Human betaherpesvirus 5 (CMV) and Human parvovirus B19 (B19) weekly during a four-week postoperative period. Inflammatory biomarkers and blood coagulation function were evaluated on specific days throughout the first, third, fifth, and during four weeks following surgery. The study was conducted until August 2023 to evaluate the patients' prognostic survival outcome, classifying them into groups based on the mortality and survival. Results: The analysis included a total of 41 patients, comprising 32 males and 9 females, with an average age of 52 (47, 63) years. Within one week after liver transplantation, there were 7 cases of bacterial infections, 5 cases of fungal infections, 19 cases of mixed infections, 8 cases without any infection, and 2 cases with unidentified pathogen-associated infections. mNGS successfully predicted 39 (72 %) strains of pathogens, while culture-based methods only detected 28 (52 %) strains. Among the 8 patients diagnosed as non-infected, culture methods identified positive results in 4 cases (50 %), whereas mNGS yielded positive results in 7 cases (87.5 %). The detection rates of CMV and B19 by Rt-PCR within 4 weeks after liver transplantation were 61 % and 17 %, respectively (25/41, 7/41) among the patients. During the study period, a total of 9 patients succumbed while 32 patients survived. The death group and the survival group exhibited significant differences in CRP, HGB, and INR levels at specific monitoring time points. The proportion of CMV detection in blood was significantly higher in the death group compared to the surviving group. Elevated CRP level was identified as a prognostic risk factor. Conclusions: Despite the presence of false positives, mNGS still presents a potential advantage in predicting pulmonary infection pathogens following liver transplantation. Furthermore, the levels of CRP and CMV carrier status within four weeks post-surgery exhibit significant associations with patient survival and prognosis.

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This genetic association study examines the genetic aspects of necrobiotic xanthogranuloma in 3 patients in China.

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Pentatricopeptide repeat (PPR) gene family constitutes one of the largest gene families in plants, which mainly participate in RNA editing and RNA splicing of organellar RNAs, thereby affecting the organellar development. Recently, some evidence elucidated the important roles of PPR proteins in the albino process of plant leaves. However, the functions of PPR genes in the woody mangrove species have not been investigated. In this study, using a typical true mangrove Kandelia obovata, we systematically identified 298 PPR genes and characterized their general features and physicochemical properties, including evolutionary relationships, the subcellular localization, PPR motif type, the number of introns and PPR motifs, and isoelectric point, and so forth. Furthermore, we combined genome-wide association studies (GWAS) and transcriptome analysis to identify the genetic architecture and potential PPR genes associated with propagule leaves colour variations of K. obovata. As a result, we prioritized 16 PPR genes related to the albino phenotype using different strategies, including differentially expressed genes analysis and genetic diversity analysis. Further analysis discovered two genes of interest, namely Maker00002998 (PLS-type) and Maker00003187 (P-type), which were differentially expressed genes and causal genes detected by GWAS analysis. Moreover, we successfully predicted downstream target chloroplast genes (rps14, rpoC1 and rpoC2) bound by Maker00002998 PPR proteins. The experimental verification of RNA editing sites of rps14, rpoC1, and rpoC2 in our previous study and the verification of interaction between Maker00002998 and rps14 transcript using in vitro RNA pull-down assays revealed that Maker00002998 PPR protein might be involved in the post-transcriptional process of chloroplast genes. Our result provides new insights into the roles of PPR genes in the albinism mechanism of K. obovata propagule leaves.

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Tumor recurrence is a life-threatening complication after liver transplantation (LT) for hepatocellular carcinoma (HCC). Precise recurrence risk stratification before transplantation is essential for the management of recipients. Here, we aimed to establish an inflammation-related prediction model for posttransplant HCC recurrence based on pretransplant peripheral cytokine profiling. Two hundred and ninety-three patients who underwent LT in two independent medical centers were enrolled, and their pretransplant plasma samples were sent for cytokine profiling. We identified four independent risk factors, including alpha-fetoprotein, systemic immune-inflammation index, interleukin 6, and osteocalcin in the training cohort (n = 190) by COX regression analysis. A prediction model named inflammatory fingerprint (IFP) was established based on the above factors. The IFP effectively predicted posttransplant recurrence (area under the receiver operating characteristic curve [AUROC]: 0.792, C-index: 0.736). The high IFP group recipients had significantly worse 3-year recurrence-free survival rates (37.9 vs. 86.9%, p < 0.001). Simultaneous T-cell profiling revealed that recipients with high IFP were characterized by impaired T cell function. The IFP also performed well in the validation cohort (n = 103, AUROC: 0.807, C-index: 0.681). In conclusion, the IFP efficiently predicted posttransplant HCC recurrence and helped to refine pretransplant risk stratification. Impaired T cell function might be the intrinsic mechanism for the high recurrence risk of recipients in the high IFP group.

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OBJECTIVE: To investigate the effects of selinexor, a inhibitor of nuclear export protein 1 (XPO1) on the proliferation inhibition and apoptosis of Kasumi-1 cells in acute myeloid leukemia (AML). METHODS: MTS method was used to detect the inhibitory effect of different concentrations of selinexor on the proliferation of Kasumi-1 cells at different time points. The apoptosis rate and cell cycle changes after treatment with different concentration of selinexor were detected by flow cytometry. RESULTS: Selinexor inhibited the growth of Kasumi-1 cells at different time points in a concentration-dependent manner (r 24 h=0.7592, r 48 h=0.9456, and r 72 h=0.9425). Selinexor inhibited Kasumi-1 cells growth in a time-dependent manner (r =0.9057 in 2.5 µmol/L group, r =0.9897 in 5 µmol/L group and r =0.9994 in 10 µmol/L group). Selinexor could induce apoptosis of Kasumi-1 cells in a dose-dependent manner (r =0.9732), and the apoptosis of Kasumi-1 cells was more obvious with the increase of drug concentration. The proportion of G0/G1 phase was significantly increased and the proportion of S phase was significantly decreased after the treatment of Kasumi-1 cells by selinexor. With the increase of drug concentration, the proportion of Kasumi-1 cells cycle arrest in G0/G1 phase was increased and the cell synthesis was decreased. CONCLUSION: Selinexor can promote the death of tumor cells by inhibiting Kasumi-1 cells proliferation, inducing apoptosis and blocking cell cycle.

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Apoptosis , Proliferación Celular , Hidrazinas , Leucemia Mieloide Aguda , Triazoles , Hidrazinas/farmacología , Triazoles/farmacología , Apoptosis/efectos de los fármacos , Humanos , Proliferación Celular/efectos de los fármacos , Leucemia Mieloide Aguda/tratamiento farmacológico , Línea Celular Tumoral , Ciclo Celular/efectos de los fármacos , Proteína Exportina 1 , Carioferinas

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BACKGROUND: Sarcopenia is associated with unfavourable long-term survival in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). However, the impact of myosteatosis and muscle loss on patient prognosis has not been investigated. METHODS: Seven hundred fifty-six HCC patients who received LT at 3 transplant centres were included. Computed tomography (CT) images of recipients were collected to measure skeletal muscle index (SMI) and skeletal muscle radiodensity (SMRA). The impact of myosteatosis on the prognosis of sarcopenic and non-sarcopenic patients was studied separately. Muscle status was evaluated based on the presence of sarcopenia and myosteatosis. The muscle loss of 342 males was calculated as the relative change of SMI between pre- and post-LT evaluations. Cox regression models were used to identify predictors of overall survival (OS) and recurrence-free survival (RFS). RESULTS: The study comprised 673 males and 83 females. The median follow-up time was 31 months (interquartile range, 19-43 months). Prior to LT, 267 (39.7%) and 187 (27.8%) males were defined as sarcopenic (low-SMI) and myosteatotic (low-SMRA), respectively. For sarcopenic recipients, the presence of myosteatosis was followed by a 23.6% decrease in 5 year OS (P < 0.001) and a 15.0% decrease in 5 year RFS (P = 0.014). Univariate and multivariate analyses revealed that muscle status was an independent predictor of OS [hazard ratio (HR), 1.569; 95% confidence interval (CI), 1.317-1.869; P < 0.001] and RFS (HR, 1.369; 95% CI, 1.182-1.586; P < 0.001). Postoperatively, a muscle loss >14.2% was an independent risk factor for poor OS (HR, 2.286; 95% CI, 1.358-3.849; P = 0.002) and RFS (HR, 2.219; 95% CI, 1.418-3.471; P < 0.001) in non-sarcopenic recipients (N = 209). CONCLUSIONS: Pre-transplant myosteatosis aggravated the adverse impact of sarcopenia on liver transplant outcomes in male HCC patients. Post-transplant muscle loss might assist in prognostic stratification of recipients without pre-existing sarcopenia, intriguing new insights into individualized management.

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BACKGROUND: Chitinase-3 like-protein-1 (CHI3L1) is a member of the mammalian chitinase-like proteins and elevated serum CHI3L1 level has been proved to be associated with poor prognosis in hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between serum CHI3L1 levels and body composition parameters in patients with HCC after liver transplantation (LT). METHODS: This retrospective study enrolled 200 patients after LT for HCC. Blood samples were collected and serum concentrations of CHI3L1 were measured by enzyme-linked immunosorbent assay. Computer tomography (CT) were used to estimate skeletal muscle and adipose tissue mass. Spearman's rank correlation test was performed to assess associations between serum CHI3L1 levels and these body composition parameters. A Cox proportional-hazards regression model was performed to identify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) curves were constructed using the Kaplan-Meier method and compared by the log-rank test. RESULTS: Total 71 patients (35.5%) were diagnosed with myosteatosis according to skeletal muscle radiation attenuation (SMRA). The 5-year OS rates were 66.9% in non-myosteatosis group, significantly higher than 49.5% in myosteatosis group (p = 0.025), while the RFS of myosteatosis group (5-year RFS: 52.6%) or non-myosteatosis group (5-year RFS: 42.0%) shown no significant difference (p = 0.068). The serum CHI3L1 level were significantly negative correlated with SMRA (r = -0.3, p < 0.001). Interestingly, in patients with myosteatosis, Kaplan-Meier analysis revealed that elevated serum CHI3L1 levels were associated with worse OS (p < 0.001) and RFS (p = 0.047). However, in patients without myosteatosis, Kaplan-Meier analysis found elevated serum CHI3L1 levels were not associated with OS (p = 0.070) or RFS (p = 0.104). CONCLUSIONS: Elevated CHI3L1 was negatively correlated with SMRA, and predicted poorer prognosis in Chinese population after LT for HCC, especially in those patients with concomitant myosteatosis. Monitoring serum CHI3L1 can predict prognosis and effectively guide individual nutrition intervention.

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Biomarcadores de Tumor , Carcinoma Hepatocelular , Proteína 1 Similar a Quitinasa-3 , Neoplasias Hepáticas , Humanos , Proteína 1 Similar a Quitinasa-3/sangre , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Femenino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Biomarcadores de Tumor/sangre , Composición Corporal , Músculo Esquelético/patología , Músculo Esquelético/metabolismo , Músculo Esquelético/diagnóstico por imagen , Trasplante de Hígado , Adulto , Anciano , Tejido Adiposo/patología , Tejido Adiposo/metabolismo , Estimación de Kaplan-Meier , Tomografía Computarizada por Rayos X

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OBJECTIVE: To assess the role of Machine Learning (ML) in identification critical factors of dementia and mild cognitive impairment. METHODS: 371 elderly individuals were ultimately included in the ML analysis. Demographic information (including gender, age, parity, visual acuity, auditory function, mobility, and medication history) and 35 features from 10 assessment scales were used for modeling. Five machine learning classifiers were used for evaluation, employing a procedure involving feature extraction, selection, model training, and performance assessment to identify key indicative factors. RESULTS: The Random Forest model, after data preprocessing, Information Gain, and Meta-analysis, utilized three training features and four meta-features, achieving an area under the curve of 0.961 and a accuracy of 0.894, showcasing exceptional accuracy for the identification of dementia and mild cognitive impairment. CONCLUSIONS: ML serves as a identification tool for dementia and mild cognitive impairment. Using Information Gain and Meta-feature analysis, Clinical Dementia Rating (CDR) and Neuropsychiatric Inventory (NPI) scale information emerged as crucial for training the Random Forest model.

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Disfunción Cognitiva , Demencia , Aprendizaje Automático , Humanos , Disfunción Cognitiva/diagnóstico , Femenino , Anciano , Masculino , Demencia/diagnóstico , China , Anciano de 80 o más Años , Pruebas Neuropsicológicas/normas , Pruebas Neuropsicológicas/estadística & datos numéricos , Pueblos del Este de Asia

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Objective: To systematically evaluate the efficacy of hyperbaric oxygen therapy (HBOT) as an adjunct therapy for treating sleep disorders in patients with Parkinson's disease (PD). Methods: We conducted comprehensive searches in eight databases from inception through September 2023, including PubMed, Cochrane Library, Embase, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), China Science and Technology Periodical Database (VIP), and Wanfang Database. The objective was to identify randomized controlled trials (RCTs) evaluating HBOT's effectiveness in alleviating sleep disorder symptoms in PD patients as an adjunct therapy. Literature screening and data extraction were independently executed by the authors. Meta-analyses were performed using Review Manager 5.3 software, and publication bias and sensitivity analyses were assessed using Stata 17.0 software. Results: Seven RCTs involving 461 participants were included. The findings revealed that the addition of HBOT significantly enhanced sleep efficiency (MD = 15.26, 95% CI [10.89, 19.63], p < 0.00001), increased time in bed (MD = 69.65, 95% CI [43.01, 96.30], p < 0.00001), total sleep time (MD = 75.87, 95% CI [25.42, 126.31], p = 0.003), slow-wave sleep (SWS) time (MD = 6.14, 95% CI [3.95, 8.34], p < 0.00001), and rapid eye movement sleep (REM) time (MD = 4.07, 95% CI [2.05, 6.08], p < 0.0001), and reduced awakening frequency (MD = -11.55, 95% CI [-15.42, -7.68], p < 0.00001) and sleep latency (MD = -6.60, 95% CI [-9.43, -3.89], p < 0.00001). Additionally, significant improvements were observed in the Pittsburgh Sleep Quality Index (PSQI) (MD = -2.52, 95% CI [-2.85, -2.18], p < 0.00001), Epworth Sleepiness Scale (ESS) (MD = -2.90, 95% CI [-3.34, -2.47], p < 0.00001), Unified Parkinson's Disease Rating Scale Part III (UPDRS III) (MD = -1.32, 95% CI [-2.16, -0.47], p = 0.002), and Hoehn and Yahr grading (H-Y grading) (MD = -0.15, 95% CI [-0.28, -0.01], p = 0.03). Conclusion: The current meta-analysis supports the efficacy of HBOT as an adjunct therapy in managing sleep disorders in PD patients. It is recommended for PD patients experiencing sleep disturbances.Systematic review registration:https://www.crd.york.ac.uk/, identifier: CRD42023462201.

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Alzheimer's disease (AD) is recognized as the leading cause of dementia, imposing a significant economic toll on society. Despite the emergence of novel therapeutic approaches for AD, their efficacy and safety mandates further validation through rigorous clinical trials. In this context, hypertension (HTN) has garnered considerable attention as an amendable risk factor for AD. Research indicates that hypertension during midlife is associated with an elevated risk of AD in later years, influencing both the onset and progression of the disease. Nevertheless, the relationship between AD and hypertension in the later stages of life remains a subject of debate. Moreover, the consequences of blood pressure reduction on cognitive function, along with the optimal pharmacological interventions and therapeutic thresholds for hypertension, have emerged as pivotal areas of inquiry. This review synthesizes findings on epidemiology, neuroimaging, and biomarkers, and the effects of antihypertensive medications to elucidate the link between hypertension and cognitive performance. We particularly investigate how hypertension and AD are related by plasma sulfide dysregulation, offering possible indicators for future diagnosis and therapy.

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Enfermedad de Alzheimer , Hipertensión , Neuroimagen , Humanos , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Hipertensión/fisiopatología , Hipertensión/complicaciones , Neuroimagen/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Encéfalo/metabolismo

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Ferroptosis , Ferroptosis/efectos de los fármacos , Humanos , Neoplasias/patología , Neoplasias/metabolismo , Lípidos/química , Muerte Celular , Animales

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Asthma is a chronic respiratory disease characterized by airway inflammation and remodeling. Epithelial-mesenchymal transition (EMT) of bronchial epithelial cells is considered to be a crucial player in asthma. Methyltransferase-like 14 (METTL14), an RNA methyltransferase, is implicated in multiple pathological processes, including EMT, cell proliferation and migration. However, the role of METTL14 in asthma remains uncertain. This research aimed to explore the biological functions of METTL14 in asthma and its underlying upstream mechanisms. METTL14 expression was down-regulated in asthmatic from three GEO datasets (GSE104468, GSE165934, and GSE74986). Consistent with this trend, METTL14 was decreased in the lung tissues of OVA-induced asthmatic mice and transforming growth factor-ß1 (TGF-ß1)-stimulated human bronchial epithelial cells (Beas-2B) in this study. Overexpression of METTL14 caused reduction in mesenchymal markers (FN1, N-cad, Col-1 and α-SMA) in TGF-ß1-treated cells, but caused increase in epithelial markers (E-cad), thus inhibiting EMT. Also, METTL14 suppressed the proliferation and migration ability of TGF-ß1-treated Beas-2B cells. Two transcription factors, ETS1 and RBPJ, could both bind to the promoter region of METTL14 and drive its expression. Elevating METTL14 expression could reversed EMT, cell proliferation and migration promoted by ETS1 or RBPJ deficiency. These results indicate that the ETS1/METTL14 and RBPJ/METTL14 transcription axes exhibit anti-EMT, anti-proliferation and anti-migration functions in TGF-ß1-induced bronchial epithelial cells, implying that METTL14 may be considered an alternative candidate target for the treatment of asthma.

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Asma , Bronquios , Células Epiteliales , Transición Epitelial-Mesenquimal , Metiltransferasas , Proteína Proto-Oncogénica c-ets-1 , Factor de Crecimiento Transformador beta1 , Humanos , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Metiltransferasas/metabolismo , Metiltransferasas/genética , Animales , Bronquios/metabolismo , Bronquios/patología , Bronquios/citología , Células Epiteliales/metabolismo , Células Epiteliales/patología , Ratones , Proteína Proto-Oncogénica c-ets-1/metabolismo , Proteína Proto-Oncogénica c-ets-1/genética , Asma/patología , Asma/metabolismo , Asma/genética , Línea Celular , Proliferación Celular , Ratones Endogámicos BALB C , Movimiento Celular , Regulación de la Expresión Génica/efectos de los fármacos

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Condiloma Acuminado , Humanos , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/patología

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BACKGROUND: The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) as neoadjuvant therapy before liver transplantation (LT) for advanced-stage hepatocellular carcinoma (HCC) and to analyze the prognostic factors. AIM: To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC. METHODS: A total of 99 individuals diagnosed with advanced HCC were studied retrospectively. The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT: DEB-TACE group (n = 45) and control group (n = 54). The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus (PVTT). The DEB-TACE group consisted of two subgroups: Group A (n = 31) without PVTT and group B (n = 14) with PVTT. The control group also had two subgroups: Group C (n = 37) without PVTT and group D (n = 17) with PVTT. Data on patient demographics, disease characteristics, therapy response, and adverse events (AEs) were collected. The overall survival (OS) and recurrence-free survival (RFS) rates were assessed using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS. RESULTS: The DEB-TACE group exhibited an overall response rate of 86.6%. Following therapy, there was a significant decrease in the median alpha-fetoprotein (AFP) level (275.1 ng/mL vs 41.7 ng/mL, P < 0.001). The main AE was post-embolization syndrome. The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group (68.9% vs 38.9%, P = 0.003; 86.7% vs 63.0%, P = 0.008). Within the subgroups, group A had higher 2-year rates of RFS and OS compared to group C (71.0% vs 45.9%, P = 0.038; 83.8% vs 62.2%, P = 0.047). The 2-year RFS rate of group B was markedly superior to that of group D (64.3% vs 23.5%, P = 0.002). Results from multivariate analyses showed that pre-LT DEB-TACE [hazard ratio (HR) = 2.73, 95% confidence interval (CI): 1.44-5.14, P = 0.04], overall target tumor diameter ≤ 7 cm (HR = 1.98, 95%CI: 1.05-3.75, P = 0.035), and AFP level ≤ 400 ng/mL (HR = 2.34; 95%CI: 1.30-4.19, P = 0.009) were significant risk factors for RFS. Additionally, pre-LT DEB-TACE (HR = 3.15, 95%CI: 1.43-6.96, P = 0.004) was identified as a significant risk factor for OS. CONCLUSION: DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

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Melatonin (N-acetyl-5-methoxytryptamine) is reported to improve mood disorders in perimenopausal women and gut microbiome composition is altered during menopausal period. The possible role of microbiome in the treatment effect of melatonin on menopausal depression remains unknown. Here, it is shown that melatonin treatment reverses the gut microbiota dysbiosis and depressive-like behaviors in ovariectomy (OVX) operated mice. This effect of melatonin is prevented by antibiotic cocktails (ABX) treatment. Transferring microbiota harvested from adolescent female mice to OVX-operated mice is sufficient to ameliorate depressive-like behaviors. Conversely, microbiota transplantation from OVX-operated mice or melatonin-treated OVX-operated mice to naïve recipient mice exhibits similar phenotypes to donors. The colonization of Alistipes Inops, which is abundant in OVX-operated mice, confers the recipient with depressive-like behaviors. Further investigation indicates that the expansion of Alistipes Inops induced by OVX leads to the degradation of intestinal tryptophan, which destroys systemic tryptophan availability. Melatonin supplementation restores systemic tryptophan metabolic disorders by suppressing the growth of Alistipes Inops, which ameliorates depressive-like behaviors. These results highlight the previously unrecognized role of Alistipes Inops in the modulation of OVX-induced behavioral disorders and suggest that the application of melatonin to inhibit Alistipes Inops may serve as a potential strategy for preventing menopausal depressive symptoms.

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Propylparaben (PrPB) is a known endocrine disrupting chemicals that is widely applied as preservative in pharmaceuticals, food and cosmetics. PrPB has been detected in human urine samples and human serum and has been proven to cause functional decline in reproduction. However, the direct effects of PrPB on mammalian oocyte are still unknown. Here, we demonstrationed that exposure to PrPB disturbed mouse oocyte maturation in vitro, causing meiotic resumption arrest and first polar body extrusion failure. Our results indicated that 600 µM PrPB reduced the rate of oocyte germinal vesicle breakdown (GVBD). Further research revealed that PrPB caused mitochondrial dysfunction and oxidative stress, which led to oocyte DNA damage. This damage further disturbed the activity of the maturation promoting factor (MPF) complex Cyclin B1/ Cyclin-dependent kinase 1 (CDK1) and induced G2/M arrest. Subsequent experiments revealed that PrPB exposure can lead to spindle morphology disorder and chromosome misalignment due to unstable microtubules. In addition, PrPB adversely affected the attachment between microtubules and kinetochore, resulting in persistent activation of BUB3 amd BubR1, which are two spindle-assembly checkpoint (SAC) protein. Taken together, our studies indicated that PrPB damaged mouse oocyte maturation via disrupting MPF related G2/M transition and SAC depended metaphase-anaphase transition.

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Ciclo Celular , Exposición a Riesgos Ambientales , Oocitos , Parabenos , Parabenos/toxicidad , Ciclo Celular/efectos de los fármacos , Oocitos/efectos de los fármacos , Oocitos/crecimiento & desarrollo , Femenino , Animales , Ratones , Disruptores Endocrinos/toxicidad , Ratones Endogámicos ICR , Cuerpos Polares/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Huso Acromático/efectos de los fármacos , Cromosomas/efectos de los fármacos , Microtúbulos/efectos de los fármacos

RESUMEN

Rodents, such as those that feed on plants and nest in plant roots, can significantly affect the growth and development of desert plants. The aim of this study was to investigate the effects of Rhombomys opimus disturbance on the photosynthetic characteristics and nutrient status of Haloxylon ammodendron at different growth stages in the Gurbantunggut Desert. The effects of great gerbil disturbance on the photosynthetic characteristics of H. ammodendron at different growth stages were investigated by measuring the gas exchange parameters, instantaneous water use efficiency, and chlorophyll fluorescence parameters of H. ammodendron at different ages (young, middle, and adult) under the disturbance of great gerbils. The soil nutrients in the assimilated branches and rhizosphere of H. ammodendron at different growth stages were tracked to reveal the relationship between the H. ammodendron nutrient content and gerbil disturbance. The results showed that great gerbil disturbance decreased the organic carbon content in the rhizosphere soil of adult H. ammodendron and increased the total nitrogen content in the rhizosphere soil and the nitrogen and potassium contents in the assimilated branches at each growth stage. The net photosynthetic rate and instantaneous water use efficiency of H. ammodendron decreased at each growth stage, and the maximum photochemical efficiency and non-photochemical quenching parameters of the young H. ammodendron decreased. However, the actual photochemical efficiency and photochemical parameters of the middle H. ammodendron increased. It was concluded that the disturbance of great gerbils decreased the photosynthetic capacity of H. ammodendron and increased the content of total nitrogen in the soil and nitrogen and potassium in the plant. This study revealed that the Gurbantunggut Desert great gerbil and H. ammodendron do not have a simple predation relationship. It laid a foundation for the study of the moderate disturbance threshold and better use of the mutually beneficial relationship between the two.