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OBJECTIVE: Accumulating evidence indicates that oxidative stress and the disruption of antioxidant defenses play an important role in the neurobiology of bipolar disorder (BD). Studies have found that increased oxidative stress may be associated with cell apoptosis and neuronal damage in BD patients. Hence, this study explored the research field related to BD and oxidative stress from a bibliometrics perspective. METHODS: Literature search and relevant data retrieval based on the Web of Sciences Core Collection (WoSCC). R software (version 4.2.2), VOSviewer software (version 1.6.18), and CiteSpace (version 6.1.6) were used in this bibliometric analysis. RESULTS: A total of 2081 publications related to BD and oxidative stress were published between 1986 and 2024. Bipolar Disorders was the journal that had the most publications in this area (72; 3.46%; IF = 5.9), while the United States (1285; 61.7%) and the University of Toronto (377; 18.1%) were the most productive country and institution, respectively. Apart from "oxidative stress" and "bipolar disorder," the most frequently used keywords were "schizophrenia," "prefrontal cortex," and "nitric oxide." CONCLUSIONS: The growing number of publications related to BD and oxidative stress in recent years highlights the importance of this research field. Hot topics in research related to BD and oxidative stress included animal experiments and molecular mechanisms, psychiatric-related inflammation and biomarkers, neurodegenerative diseases, and metabolism. Furthermore, the biological mechanisms of BD, particularly biomarkers and inflammation, may be the emerging research priority area in the future.
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Bibliometría , Trastorno Bipolar , Estrés Oxidativo , Trastorno Bipolar/metabolismo , Estrés Oxidativo/fisiología , HumanosRESUMEN
BACKGROUND: Chemotherapeutic agents including cisplatin, gemcitabine, and pemetrexed, significantly enhance the efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) by increasing PD-L1 expression and potentiating T cell cytotoxicity. However, the low response rate and adverse effects limit the application of chemotherapy/ICI combinations in patients. METHODS: We screened for medicinal herbs that could perturb PD-L1 expression and enhance T cell cytotoxicity in the presence of anti-PD-L1 antibody, and investigated the underlying mechanisms. RESULTS: We found that the aqueous extracts of Centipeda minima (CM) significantly enhanced the cancer cell-killing activity and granzyme B expression level of CD8+ T cells, in the presence of anti-PD-L1 antibody. Both CM and its active component 6-O-angeloylplenolin (6-OAP) upregulated PD-L1 expression by suppressing GSK-3ß-ß-TRCP-mediated ubiquitination and degradation. CM and 6-OAP significantly enhanced ICI-induced reduction of tumor burden and prolongation of overall survival of mice bearing NSCLC cells, accompanied by upregulation of PD-L1 and increase of CD8+ T cell infiltration. CM also exhibited anti-NSCLC activity in cells and in a patient-derived xenograft mouse model. CONCLUSIONS: These data demonstrated that the induced expression of PD-L1 and enhancement of CD8+ T cell cytotoxicity underlay the beneficial effects of 6-OAP-rich CM in NSCLCs, providing a clinically available and safe medicinal herb for combined use with ICIs to treat this deadly disease.
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Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Animales , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/farmacología , Antígeno B7-H1/metabolismo , Línea Celular Tumoral , Linfocitos T CD8-positivos/efectos de los fármacos , Ratones , Extractos Vegetales/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , FemeninoRESUMEN
Programmed cell death ligand 2 (PD-L2), a ligand for the receptor programmed cell death 1 (PD-1), has an identity of 34% with its twin ligand PD-L1 and exhibits higher binding affinity with PD-1 than PD-L1. However, the role of PD-L2 in non-small cell lung cancer (NSCLC) progression, especially tobacco-induced cancer progression, has not been fully understood. Here, we found that PD-L2 promoted tumor growth in murine models with recruitment of regulatory T cells (Tregs). In patients with NSCLC, PD-L2 expression level in tumor samples was higher than in counterpart normal controls and was positively associated with patients' response to anti-PD-1 treatment. Mechanismly, PD-L2 bound its receptor Repulsive guidance molecule B (RGMB) on cancer cells and activated extracellular signal-regulated kinase (Erk) and nuclear factor κB (NFκB), leading to increased production of chemokine CCL20, which recruited Tregs and contributed to NSCLC progression. Consistently, knockdown of RGMB or NFκB p65 inhibited PD-L2-induced CCL20 production, and silencing of PD-L2 repressed Treg recruitment by NSCLC cells. Furthermore, cigarette smoke and carcinogen benzo(a)pyrene (BaP) upregulated PD-L2 in lung epithelial cells via aryl hydrocarbon receptor (AhR)-mediated transcription activation, whose deficiency markedly suppressed BaP-induced PD-L2 upregulation. These results suggest that PD-L2 mediates tobacco-induced recruitment of Tregs via the RGMB/NFκB/CCL20 cascade, and targeting this pathway might have therapeutic potentials in NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Quimiocina CCL20 , Neoplasias Pulmonares , FN-kappa B , Proteína 2 Ligando de Muerte Celular Programada 1 , Linfocitos T Reguladores , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Humanos , FN-kappa B/metabolismo , Animales , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Proteína 2 Ligando de Muerte Celular Programada 1/metabolismo , Proteína 2 Ligando de Muerte Celular Programada 1/genética , Quimiocina CCL20/metabolismo , Quimiocina CCL20/genética , Ratones , Fumar Tabaco/efectos adversos , Transducción de Señal , Línea Celular Tumoral , Masculino , FemeninoRESUMEN
BACKGROUND AND AIM: Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori. METHODS: A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14 days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4 weeks after treatment completion. RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P < 0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P < 0.001). CONCLUSION: Triple therapy comprising vonoprazan (20 mg), amoxicillin (750 mg), and bismuth potassium citrate (220 mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients.
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This study aims to investigate the mechanism of Huangqin Qingre Chubi Capsules(HQC) in delaying chondrocyte senescence of osteoarthritic(OA) rats by regulating the p53/p21 signaling pathway. Rheumatic fever paralysis models of OA rats were induced based on monosodiun iodoacetate(MIA) combined with external rheumatic fever environmental stimuli and divided into normal(Con) group, OA model(MIA) group, OA model+rheumatic fever stimulation model(MIA-M) group, MIA-M+HQC low-dose(MIA-M+HQC-L) group, medium-dose(MIA-M+HQC-M) group, and high-dose(MIA-M+HQC-H) group, and MIA-M+glucosamine(MIA-M+GS) group. The models were successfully prepared and administered by gavage for 30 d. The pathological changes of cartilage were observed by hematoxylin-eosin(HE) and Senna O solid green(SO) staining. The expression of interleukin(IL)-1ß and IL-6 was detected by enzyme-linked immunosorbent assay(ELISA). Flow cytometry(FCM) was used to detect apoptosis and cell cycle. The mRNA expression of MMP13, ADAMTS-5, COLâ ¡, and TGF-ß was detected by RT-qPCR. The protein expression of p53/p21, p16, Bax, and Bcl-2 was detected by Western blot. The articular cartilage surface of rats in the Con group was smooth, and the tide line was smooth. The cartilage layer of MIA and MIA-M groups was obviously damaged, and the cartilage matrix was reduced. The above conditions were more severe in the MIA-M group. The cartilage surface of the HQC high-dose group and MIA-M+GS group was basically intact with clear delamination. Compared with the MIA-M+HQC-H group, Mankin's score was higher in the HQC low-dose and medium-dose groups, and the change was not obvious in the MIA-M+GS group. Compared with the Con group, the proportion of chondrocytes G_1 was elevated in the MIA and MIA-M groups, and the proportion of the S phase and G_2 phase was significantly decreased. In addition, the apoptosis rate was increased. Compared with MIA-M, HQC groups inhibited apoptosis and promoted cell proliferation in a concentration-dependent manner. Compared with the MIA-M+HQC-H group, the effect was more significant in the HQC high-dose group than in the HQC medium-low dose, while it was not significant in the MIA-M+GS group. Compared with the Con group, IL-1ß and IL-6 were elevated in the MIA and MIA-M groups, and mRNA levels of MMP13 and ADAMTS-5 were elevated. p53, p21, p16, and Bax protein were elevated, and mRNA levels of COLâ ¡ and TGF-ß were decreased. Compared with the MIA-M group, IL-1ß and IL-6 decreased after drug interventions of HQC and GS, and mRNA levels of MMP13 and ADAMTS-5, as well as protein levels of p53, p21, Bax, and p16 decreased. In addition, Bcl-2 increased. The improvement of these indexes was significantly better in the MIA-M+HQC-H group than in the HQC low-dose and medium-dose groups, and the difference with the MIA-M+GS group was not significant. HQC delayed MIA-induced chondrocyte senescence in OA rats, inhibited inflammatory response and extracellular matrix(ECM) degradation, and its mechanism may be related to the inhibition of the p53/p21 pathway.
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Condrocitos , Medicamentos Herbarios Chinos , Osteoartritis , Ratas Sprague-Dawley , Transducción de Señal , Proteína p53 Supresora de Tumor , Animales , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Osteoartritis/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/genética , Ratas , Transducción de Señal/efectos de los fármacos , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Masculino , Senescencia Celular/efectos de los fármacos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Cápsulas , Humanos , Apoptosis/efectos de los fármacosRESUMEN
Background: Research on the mental health and quality of life (hereafter QOL) among fire service recruits after the end of the COVID-19 restrictions is lacking. This study explored the network structure of depression, anxiety and insomnia, and their interconnections with QOL among fire service recruits in the post-COVID-19 era. Methods: This cross-sectional study used a consecutive sampling of fire service recruits across China. We measured the severity of depression, anxiety and insomnia symptoms, and overall QOL using the nine-item Patient Health Questionnaire (PHQ-9), seven-item Generalized Anxiety Disorder scale (GAD-7), Insomnia Severity Index (ISI) questionnaire, and World Health Organization Quality of Life-brief version (WHOQOL-BREF), respectively. We estimated the most central symptoms using the centrality index of expected influence (EI), and the symptoms connecting depression, anxiety and insomnia symptoms using bridge EI. Results: In total, 1,560 fire service recruits participated in the study. The prevalence of depression (PHQ-9 ≥ 5) was 15.2% (95% CI: 13.5-17.1%), while the prevalence of anxiety (GAD-7 ≥ 5) was 11.2% (95% CI: 9.6-12.8%). GAD4 ("Trouble relaxing") had the highest EI in the whole network model, followed by ISI5 ("Interference with daytime functioning") and GAD6 ("Irritability"). In contrast, PHQ4 ("Fatigue") had the highest bridge EI values in the network, followed by GAD4 ("Trouble relaxing") and ISI5 ("Interference with daytime functioning"). Additionally, ISI4 "Sleep dissatisfaction" (average edge weight = -1.335), which was the central symptom with the highest intensity value, had the strongest negative correlation with QOL. Conclusion: Depression and anxiety were important mental health issues to address among fire service recruits in the post-COVID-19 era in China. Targeting central and bridge symptoms identified in network analysis could help address depression and anxiety among fire service recruits in the post-COVID-19 era.
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Ansiedad , COVID-19 , Depresión , Calidad de Vida , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Estudios Transversales , Masculino , China/epidemiología , Depresión/epidemiología , COVID-19/epidemiología , COVID-19/psicología , Ansiedad/epidemiología , Femenino , Adulto , Adulto Joven , Bomberos/psicología , Bomberos/estadística & datos numéricos , Encuestas y Cuestionarios , PrevalenciaRESUMEN
Small cell lung cancer (SCLC) is a recalcitrant cancer characterized by high frequency loss-of-function mutations in tumor suppressors with a lack of targeted therapy due to absence of high frequency gain-of-function abnormalities in oncogenes. SMARCAL1 is a member of the ATP-dependent chromatin remodeling protein SNF2 family that plays critical roles in DNA damage repair and genome stability maintenance. Here, we showed that SMARCAL1 was overexpressed in SCLC patient samples and was inversely associated with overall survival of the patients. SMARCAL1 was required for SCLC cell proliferation and genome integrity. Mass spectrometry revealed that PAR6B was a downstream SMARCAL1 signal molecule which rescued inhibitory effects caused by silencing of SMARCAL1. By screening of 36 FDA-approved clinically available agents related to DNA damage repair, we found that an aza-anthracenedione, pixantrone, was a potent SMARCAL1 inhibitor which suppressed the expression of SMARCAL1 and PAR6B at protein level. Pixantrone caused DNA damage and exhibited inhibitory effects on SCLC cells in vitro and in a patient-derived xenograft mouse model. These results indicated that SMARCAL1 functions as an oncogene in SCLC, and pixantrone as a SMARCAL1 inhibitor bears therapeutic potentials in this deadly disease.
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Proliferación Celular , ADN Helicasas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Animales , ADN Helicasas/genética , ADN Helicasas/metabolismo , Proliferación Celular/efectos de los fármacos , Ratones , Línea Celular Tumoral , Daño del ADN , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Reparación del ADN/efectos de los fármacosRESUMEN
Background: Lung cancer (LC) is a leading cause of cancer-associated mortality worldwide, with high incidence and mortality rates. Ly6/PLAUR domain containing 3 (LYPD3) is a tumorigenic and highly glycosylated cell surface protein that has been rarely reported in LC. This study aimed to explore the prognostic role and immune cell infiltration of LYPD3 in LC. Methods: We used ExoCarta, a database of exosomal proteins and RNA, to select exosomes in LC. The Tumor Immune Estimation Resource (TIMER) and Human Protein Atlas (HPA) databases were utilized to compare the expression of LYPD3 in LC. We applied Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Kaplan-Meier (KM) plotter to evaluate the prognostic prediction performance of LYPD3. Biological processes (BPs), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and gene set enrichment analysis (GSEA) analyses were performed to illustrate the possible role of LYPD3 in LC. The correlations between LYPD3 and immune cell infiltration were explored using Tumor and Immune System Interaction Database (TISIDB), GEPIA2, and TIMER. R software was used for statistical analysis and mapping. Results: A total of 904 exosome molecules were screened in LC. Further analysis showed that the up-regulation of LYPD3 in these 904 exosome molecules was associated with poor prognosis in LC. Pan-cancer analyses revealed that the expression of LYPD3 varied in many cancers, particularly in LC. Clinical correlation analysis indicated that LYPD3 was associated with stage and T classification in LC. We observed that LYPD3 co-expression genes were associated with cell cycle, DNA replication, proteasome, and regulation of the actin cytoskeleton by GSEA. Moreover, LYPD3 was associated with immune modulators. Immunophenoscores (IPS) and IPS-CTLA4 were significantly different between the high LYPD3 group and low LYPD3 group. Additionally, the median half maximal inhibitory concentration (IC50) of bexarotene, cyclopamine, etoposide, and paclitaxel in LYPD3 high group was significantly lower than that in LYPD3 low group. Conclusions: LYPD3 is involved in many BPs of LC, such as regulating immune cell infiltration and affecting prognosis. Therefore, LYPD3 may have potential value as a biomarker for prognosis and immunotherapy in LC.
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Estrogens and androgens are typical steroid hormones and often occur together in contaminated aquatic environments, but their mixed effects in aquatic organisms have been less well reported. In this study, the endocrine disrupting effects of binary mixtures of 17ß-estradiol (E2) and testosterone (T) in western mosquitofish (Gambusia affinis) were assessed by analyzing the sex ratio, secondary sex characteristics, gonadal histology, and transcriptional expression of target genes related to the hypothalamic-pituitary-gonadal (HPG) axis in G. affinis (from embryos) continuously exposed to E2 (50 ng/L), T (T1: 50 ng/L; T2: 200 ng/L), and mixtures of both (E2 + T1: 50 + 50 ng/L; E2 + T2: 50 + 200 ng/L) for 119 d. The results showed that exposure to E2 + T1 and E2 + T2 reduced the length ratio of ray 4/6 ratio in male G. affinis, suggesting feminized phenomenon in male G. affinis. Furthermore, 16.7-38.5 % of female G. affinis showed masculinized anal fins and hemal spines when exposed to T alone and in combination with E2. Importantly, the transcriptional levels of certain target genes related to the HPG axis were significantly altered in G. affinis following exposure to E2 and T alone and in combinations. Moreover, exposure to E2 and T in combinations can lead to combined effects (such as synergistic and antagonistic effects) on the transcriptional levels of some genes. These results collectively suggest that exposure to environmentally relevant concentrations of E2 and T alone and in mixtures can impact the endocrine system of G. affinis, and may pose potential risks in aquatic systems.
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Ciprinodontiformes , Contaminantes Químicos del Agua , Masculino , Femenino , Animales , Testosterona/metabolismo , Estradiol/metabolismo , Andrógenos/toxicidad , Sistema Endocrino , Ciprinodontiformes/genética , Ciprinodontiformes/metabolismo , Contaminantes Químicos del Agua/metabolismoRESUMEN
The interactions between estrogen and androgen in aquatic animals remain largely unknown. In this study, two generations (F0 and F1) of western mosquitofish (Gambusia affinis) were continuously exposed to 17α-ethinylestradiol (EE2, 10 ng/L), methyltestosterone (MT, 10 ng/L (MTL); 50 ng/L (MTH)), and mixtures (EE2+MTL and EE2+MTH). Various endpoints, including sex ratio (phenotypic and genetic), secondary sex characteristics, gonadal histology, and transcriptional profile of genes, were examined. The results showed that G. affinis exposed to MTH and EE2+MTH had a > 89.7 % of phenotypic males in F1 generation, with 34.5 and 50.0 % of these males originated from genetic females, respectively. Moreover, females from F0 and F1 generations exposed to MTH and EE2+MTH exhibited masculinized anal fins and skeletons. The combined effect of MT and EE2 on most endpoints was dependent on MT. Furthermore, significant transcriptional alterations in certain target genes were observed in both the F0 and F1 generations by EE2 and MT alone and by mixtures, showing some degree of interactions. These findings that the effects of EE2+MTH were primarily on the phenotypic sex of G. affinis in offspring generation suggest that G. affinis under chronic exposure to the binary mixture contaminated water could have sex-biased populations.
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Ciprinodontiformes , Contaminantes Químicos del Agua , Masculino , Femenino , Animales , Etinilestradiol/toxicidad , Metiltestosterona/toxicidad , Contaminantes Químicos del Agua/toxicidad , Estrógenos , Ciprinodontiformes/genéticaRESUMEN
AIMS: The lipid reference intervals (RIs) that are currently used for children in China are not based on studies of the local population and normally do not consider age or gender differences. This study aimed to establish age- and sex-specific RIs for the fasting serum lipid levels in the pediatric population aged 0 - 15 years in Nanjing, China. METHODS: 5,866 children aged 3 days to ï¼15 years were recruited to establish serum lipid RIs, and the triglyceride (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) levels were analyzed using the Roche cobas702 automatic biochemical analyzer. Low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (nHDL-C) levels were calculated (LDL-C=TC-HDL-C-TG/5, and nHDL-C=TC-HDL-C). Smoothed percentile curves for the boys and girls were generated using the LMS method. Age- and sex-specific RIs were the determined according to the methods recommended by the Clinical and Laboratory Standards Institute EP28-A3c guidelines. RESULTS: This study showed that the serum lipid levels varied considerably throughout childhood and adolescence, with sex differences, especially in infants aged less than 2 years and puberty. Based on the Harris-Boyd method, sex partitions were required for ages ï¼6 months in the TC indicator and for ages ≤ 28 days in LDL-C and nHDL-C. Age partitions were also required for all serum lipid parameters. CONCLUSIONS: We established age- and sex-specific RIs for TG, TC, HDL-C, LDL-C, and nHDL-C parameters in children aged 0 days to ï¼15 years in Nanjing, China. These data are thus considered to be useful for the screening of dyslipidemia in children and adolescents.
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Ayuno , Lípidos , Humanos , Masculino , Femenino , Lactante , Adolescente , Niño , Valores de Referencia , Preescolar , China/epidemiología , Lípidos/sangre , Recién Nacido , Ayuno/sangre , Factores Sexuales , Factores de Edad , Triglicéridos/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangreRESUMEN
Tumor cells are usually considered defective in mitochondrial respiration, but human non-small cell lung cancer (NSCLC) tumor tissues are shown to have enhanced glucose oxidation relative to adjacent benign lung. Here, we reported that oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) inhibited glycolysis and promoted oxidative metabolism in NSCLC cells. CIP2A bound to pyruvate kinase M2 (PKM2) and induced the formation of PKM2 tetramer, with serine 287 as a novel phosphorylation site essential for PKM2 dimer-tetramer switching. CIP2A redirected PKM2 to mitochondrion, leading to upregulation of Bcl2 via phosphorylating Bcl2 at threonine 69. Clinically, CIP2A level in tumor tissues was positively correlated with the level of phosphorylated PKM2 S287. CIP2A-targeting compounds synergized with glycolysis inhibitor in suppressing cell proliferation in vitro and in vivo. These results indicated that CIP2A facilitates oxidative phosphorylation by promoting tetrameric PKM2 formation, and targeting CIP2A and glycolysis exhibits therapeutic potentials in NSCLC.
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PURPOSE: This paper explores the causes of paediatric inguinal hernia (PIH) recurrence after single-port laparoscopic percutaneous extraperitoneal closure (SPLPEC). METHOD: From January 2015 to December 2020, the clinical data of 3480 children with PIHs who underwent SPLPEC were retrospectively reviewed, including 644 children who underwent SPLPEC with a homemade single-hook hernia needle from January 2015 to December 2016 and 2836 children who underwent the SPLPEC with a double-hook hernia needle and hydrodissection from January 2017 to December 2020. There were 39 recurrences (including communicating hydrocele) during the 2-5 years of follow-up. The findings of redo-laparoscopy were recorded and correlated with the revised video of the first operation to analyse the causes of recurrence. RESULT: Thirty-three males and 6 females experienced recurrence, and 8 patients had a unilateral communicating hydrocele. The median time to recurrence was 7.1 months (0-38). There were 20 cases (3.11%) in the single-hook group and 19 cases (0.67%) in the double-hook group. Based on laparoscopic findings, recurrence most probably resulted from multiple factors, including uneven tension of the ligation (10 cases), missing part of the peritoneum (14 cases), loose ligation (8 cases), broken knot (5 cases), and knot reaction (2 cases). All children who underwent repeat SPLPEC were cured by double ligations or reinforcement with medial umbilical ligament. CONCLUSION: The main cause of recurrence is improper ligation. Tension-free and complete PIH ligation are critical to the success of surgery, which requires avoiding the peritoneum skip area and the subcutaneous and muscular tissues. Redo-laparoscopic surgery was suitable for the treatment of recurrent inguinal hernia (RIH). For giant hernias, direct ligation of the internal ring incorporating the medial umbilical ligament (DIRIM) may be needed.
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Hernia Inguinal , Laparoscopía , Hidrocele Testicular , Masculino , Femenino , Niño , Humanos , Lactante , Hernia Inguinal/etiología , Hernia Inguinal/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Herniorrafia/métodos , Laparoscopía/métodos , Hidrocele Testicular/cirugía , RecurrenciaRESUMEN
Compiling evidence supports that selenium plays a vital role in glucose metabolism. Triglyceride-glucose index (TyG) and triglyceride-glucose-body mass index (TyG-BMI) are commonly used in epidemiologic studies to evaluate insulin resistance and cardiovascular disease (CVD) risks. This study is aimed to investigate the association between whole blood selenium concentration and TyG and TyG-BMI. A total of 6290 participants (age ≥ 20 years) from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 were included. Multiple linear regression models were used to examine the association between blood selenium quartiles and TyG and TyG-BMI. Subgroup analysis stratified by diabetes status was also performed. The adjusted model showed a positive association between TyG and blood selenium concentration (ß [95%CI] = 0.099 [0.063, 0.134], p < 0.001) and TyG-BMI (ß [95%CI] = 3.185 [2.102, 4.268], p < 0.001). The association persisted after stratification by diabetes status (p < 0.001). Participants were stratified into four quartiles based on selenium concentration (Q1: 1.08-2.24 µmol/L, Q2: 2.25-2.42 µmol/L, Q3: 2.43-2.62 µmol/L, Q4: 2.63-8.08). Compared with the Q1 group, TyG in the Q3 and Q4 groups was significantly higher (ß = 0.075 [95%CI 0.039 to 0.112] and ß = 0.140 [95%CI 0.103 to 0.176], respectively). Additionally, TyG-BMI in the Q2, Q3, and Q4 groups was higher than that in the Q1 group (ß = 1.189 [95%CI 0.065 to 2.314], ß = 2.325 [95%CI 1.204 to 3.446], and ß = 4.322 [95%CI 3.210 to 5.435], respectively). Blood level of selenium was positively associated with TyG and TyG-BMI, indicating that excessive blood selenium may be associated with impaired insulin sensitivity and increased risk of cardiovascular disease.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Resistencia a la Insulina , Selenio , Adulto , Humanos , Adulto Joven , Índice de Masa Corporal , Encuestas Nutricionales , Enfermedades Cardiovasculares/epidemiología , Glucosa , Triglicéridos , Glucemia , Factores de Riesgo , BiomarcadoresRESUMEN
Purpose: Immune checkpoint inhibitors (ICIs) have been developed for clinical application and proven effective for non-small cell lung cancer (NSCLC). Blockade of the programmed cell death 1 (PD-1) protein can partially reinvigorate circulating exhausted-phenotype CD8+ T cells (Tex cells) in preclinical models, however the clinical implication in anti-PD-1-based immunotherapy in NSCLC is unknown. Methods: Serum specimens were obtained before and during treatment from 145 patients with NSCLC patients who received anti-PD-1 treatment and their prognoses were followed-up. Indicators such as cell subpopulations, T cell invigoration were detected by clinical laboratory testing. Survival curves were estimated by the Kaplan-Meier method, Cox regression analysis was used to identify factors associated with prognoses of NSCLC patients. Results: The expressions of Ki-67 in PD-1+/CD8+ T cells in most NSCLC patients (97 of 145 cases) increased after treatment. The responding Ki-67+/CD8+ T cell population was mainly CD45RAlo CD27hi, containing cells with high expression of CTLA-4, PD-1, and 2B4 and low expression of NKG2-D (P < 0.0001). The maximum fold change of Ki-67+/PD-1+/CD8+T cells in treatment cycles and the tumor burden determined by imaging may be associated with survival. Patients with higher Ki-67 expression on PD-1+CD8+ T-cells (pretreatment) had statistically significant increased progression-free survival (PFS). A Ki-67 expression to tumor burden ratio greater than 0.6 at the 1st cycle of anti-PD-1 immunotherapy was associated with improvement of PFS and overall survival (P < 0.05). Conclusion: Activation of circulating Tex cells before or during therapy related to tumor burden may be associated with clinical efficacy of anti-PD-1 immune therapy in NSCLC.
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Ashi points play a significant role in the clinical localization and qualitative diagnosis of acupuncture, as well as in selecting acupoints along the meridians and applying tonifying or reducing techniques. This paper introduces the theoretical basis and existing technical methods of objectification of ashi point diagnosis and treatment. It proposes that using sensory quantitative testing to determine the temperature and tenderness thresholds of ashi points could help to identify the pathological characteristics of "cold" "heat" "deficiency" or "excess" of ashi points. In addition, the possibility of objectification of ashi point diagnosis-treatment plan is explored from three perspectives, precision of selection of ashi point therapy, objectification of effect evaluation of ashi point analgesia, and differentiation of the studies on ashi point analgesic mechanism, aiming to provide new research ideas for the modernization of traditional Chinese acupuncture.
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Terapia por Acupuntura , Acupuntura , Analgesia , Meridianos , Puntos de AcupunturaRESUMEN
Although chemoimmunotherapy is the current standard of care for initial treatment of mantle cell lymphoma (MCL), newer data suggest that there may be a role for a chemotherapy-free approach. We report the 9-year follow-up results of a multicenter, phase 2 study of lenalidomide plus rituximab (LR) as the initial treatment of MCL. The LR doublet is used as induction and maintenance until progression, with optional discontinuation after 3 years. We previously reported an overall response rate of 92% in evaluable patients, with 64% achieving a complete response. At a median follow-up of 103 months, 17 of 36 evaluable patients (47%) remain in remission. The 9-year progression-free survival and overall survival were 51% and 66%, respectively. During maintenance, hematologic adverse events included asymptomatic grade 3 or 4 cytopenia (42% neutropenia, 5% thrombocytopenia, and 3% anemia) and mostly grade 1 to 2 infections managed in the outpatient setting (50% upper respiratory infections, 21% urinary tract infections, 16% sinusitis, 16% cellulitis, and 13% pneumonia, with 5% requiring hospitalization). More patients developed grade 1 and 2 neuropathy during maintenance therapy (29%) than during induction therapy (8%). Twenty-one percent of patients developed secondary malignancies, including 5% with invasive malignancies, whereas the remainder were noninvasive skin cancers treated with local skin-directed therapy. Two patients permanently discontinued therapy because of concerns of immunosuppression during the COVID-19 pandemic. With long-term follow-up, LR continues to demonstrate prolonged, durable responses with manageable safety as initial induction therapy. This trial was registered at www.clinicaltrials.gov as #NCT01472562.
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Linfoma de Células del Manto , Adulto , Humanos , Rituximab/efectos adversos , Lenalidomida/uso terapéutico , Linfoma de Células del Manto/patología , Estudios de Seguimiento , Pandemias , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
WUSCHEL-related homeobox (WOX) is a plant-specific transcription factor (TF), which plays an essential role in the regulation of plant growth, development, and abiotic stress responses. However, little information is available on the specific roles of WOX TFs in sacred lotus (Nelumbo nucifera), which is a perennial aquatic plant with important edible, ornamental, and medicinal values. We identified 15 WOX TFs distributing on six chromosomes in the genome of N. nucifera. A total of 72 WOX genes from five species were divided into three clades and nine subclades based on the phylogenetic tree. NnWOXs in the same subclades had similar gene structures and conserved motifs. Cis-acting element analysis of the promoter regions of NnWOXs found many elements enriched in hormone induction, stress responses, and light responses, indicating their roles in growth and development. The Ka/Ks analysis showed that the WOX gene family had been intensely purified and selected in N. nucifera. The expression pattern analysis suggested that NnWOXs were involved in organ development and differentiation of N. nucifera. Furthermore, the protein-protein interaction analysis showed that NnWOXs might participate in the growth, development, and metabolic regulation of N. nucifera. Taken together, these findings laid a foundation for further analysis of NnWOX functions.
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Genes Homeobox , Nelumbo , Nelumbo/genética , Filogenia , Factores de Transcripción/genética , Desarrollo de la PlantaRESUMEN
Poor sleep quality is prevalent among members of the military but rates of poor sleep quality vary between studies. This study examined the global prevalence of poor sleep quality in military personnel and veterans as well as possible moderators of prevalence differences between studies. PubMed, EMBASE, Web of Science, and PsycINFO were systematically searched from their inception dates to September 1, 2022. Studies were included if they were conducted on military personnel and/or veterans and prevalence estimates of poor sleep quality could be generated from assessments with standardized tools. A random-effects model was used to calculate the pooled prevalence and its 95% confidence intervals (CIs). Fifty-nine studies (N = 28,100) were included for analysis with sample sizes ranging from 14 to 8481. Two studies were rated as "high quality" (3.39%), while 57 were rated as "moderate quality" (96.61%). The overall pooled prevalence of poor sleep quality in military personnel and veterans was 69.00% (95% CI: 62.33-75.30%); pooled rates were 57.79% (95% CI: 49.88-65.50%) and 82.88% (95% CI: 74.08-90.21%) for active duty personnel and veterans, respectively. Subgroup analyses indicated study region, study design, sampling method, Pittsburg Sleep Quality Index cut-off values, and service type moderated prevalence of poor sleep quality. Meta-regression analyses indicated sample size, mean age, depression and posttraumatic stress disorder (PTSD) were associated with prevalence differences between studies. Poor sleep quality was more common in both active duty military personnel and veterans who were older and those who reported PTSD or depression. Regular monitoring of sleep quality and sleep hygiene should be promoted in this population. More relevant studies in middle- and low-income countries should also be conducted.
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Arginase has shown promising potential in treating cancers by arginine deprivation therapy; however, low enzymatic activity and stability of arginase are impeding its development. This study was aimed to improve the enzymological properties of a marine bacterial arginase by carboxymethyl chitosan (CMCS) conjugation. An arginase producing marine bacterium Priestia megaterium strain P6 was isolated and identified. The novel arginase PMA from the strain was heterologously expressed, purified, and then conjugated to CMCS by ionic gelation with calcium chloride as the crosslinking agent. Enzymological properties of both PMA and CMCS-PMA conjugate were determined. The optimum temperature for PMA and CMCS-PMA at pH 7 were 60 °C and 55 °C, respectively. The optimum pH for PMA and CMCS-PMA at 37 °C were pH 10 and 9, respectively. CMCS-PMA showed higher thermostability than PMA over 55-70 °C and higher pH stability over pH 4-11 with the highest pH stability at pH 7. At 37 °C and pH of 7, i.e., around the human blood temperature and pH, CMCS-PMA was higher than the free PMA in enzymatic activity and stability by 24% and 21%, respectively. CMCS conjugation not only changed the optimum temperature, optimum pH, and enzymatic activity of PMA, but also improved its pH stability and temperature stability, and thus made it more favorable for medical application.