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Aim: To identify the optimal first-line treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC). Materials & methods: We conducted a network meta-analysis (CRD42023486863) to systematically evaluate the efficacy and safety of eight first-line treatment regimens for ES-SCLC, including 15 clinical trials. Results: Our analysis showed that the PD-1/PD-L1 + etoposide combined with platinum (EP) and PD-L1 + vascular endothelial growth factor (VEGF) + EP regimens significantly enhanced overall survival and progression-free survival, with subgroup analysis revealing that serplulimab ranked as the most promising option for improving overall survival. Integrating anti-angiogenesis drugs into immunochemotherapy presents potential benefits, with an increased incidence of adverse events necessitating further investigation. Conclusion: Our findings offer valuable insights for future research and for developing more effective treatment strategies for ES-SCLC, underscoring the critical need for continued innovation in this therapeutic area.
[Box: see text].
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Psoriasis is a common skin disease affecting 1-3% of the population (Gelfand et al., 2005; Ferrándiz et al., 2001). Approximately 30% of patients with psoriasis develop psoriatic arthritis (PsA), an inflammatory arthritis associated with psoriasis (Haroon et al., 2013; Prey et al., 2010). Generalized pustular psoriasis (GPP) affects about 1.3% of psoriasis patients. Recently, numerous novel susceptibility loci for psoriasis vulgaris (PsV) have been discovered thorough the application of genome-wide association studies (GWASs). Among them, the major histocompability complex is the locus with the strongest effect. Outside the major histocompability complex region, the novel susceptibility loci of PsV can be incorporated into an integrated pathogenic model comprising distinct signaling networks affecting skin barrier function, innate immune responses involving NF-κB signaling, and adaptive immune responses involving CD8 T cells and IL-23/IL-17-mediated lymphocyte signaling. Compared with PsV, only three GWASs were performed in PsA (Ellinghaus et al., 2012; Hüffmeier et al., 2010; Stuart et al., 2015), accompanied with other candidate gene studies, most of the PsA susceptibility loci have been proved to be associated with PsV. However, the genetic study of GPP is quite different. Up to now, IL36RN is the only associated gene of GPP that has been widely verified. The data are based on homozygosity mapping and direct sequencing in consanguineous Tunisian multiplex families with autosomal recessive GPP (Marrakchi et al., 2011). Some researchers suggested that GPP and PsV are etiologically distinct clinical entities (Capon, 2013), challenging the traditional understanding of psoriasis. The percentages of IL36RN-negative patients have been reported to range from 51% (Li et al., 2013) to 84% (Setta-Kaffetzi et al., 2013), implying that additional risk loci, genetic interactions, and other factors may account for the other GPP cases. Recently, more than 10 GWASs of PsV have identified a number of susceptibility loci, making PsV GWASs a rich source of potential risk loci for other subtypes of psoriasis. Here, we use information emerging form PsV GWASs to make inferences about the genetic etiology of PsA and GPP in a Chinese population.
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BACKGROUND: Significance of platelet distribution width (PDW) and mean platelet volume (MPV) in assessing disease activity of systemic lupus erythematosus (SLE) remains unclear. This study was aimed to evaluate PDW and MPV as potential disease activity markers in adult SLE patients. MATERIALS AND METHODS: A total of 204 study participants, including 91 SLE patients and 113 age- and gender-matched healthy controls, were selected in this cross-sectional study. They were classified into three groups: control group (n = 113), active SLE group (n = 54), and inactive SLE group (n = 37). Demographic, clinical, and laboratory data were analyzed. RESULTS: In patient group, PDW was statistically higher than that in control group (13.54 ± 2.67 vs. 12.65 ± 2.34, P = 0.012), and in active group, PDW was significantly increased compared to inactive group (14.31 ± 2.90 vs. 12.25 ± 1.55, P < 0.001). However, MPV was significantly lower in SLE group than in control group (10.74 ± 0.94 vs. 11.09 ± 1.14, P = 0.016). PDW was positively correlated with SLE disease activity index (P < 0.001, r = 0.529) and erythrocyte sedimentation rate (P = 0.002, r = 0.321) and negatively correlated with C3 (P < 0.001, r = -0.419). However, there was no significant association between MPV and these study variables. A PDW level of 11.85% was determined as a predictive cutoff value of SLE diagnosis (sensitivity 76.9%, specificity 42.5%) and 13.65% as cutoff of active stage (sensitivity 52.6%, specificity 85.3%). CONCLUSION: This study first associates a higher PDW level with an increased SLE activity, suggesting PDW as a novel indicator to monitor the activity of SLE.
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BACKGROUND: Cultured epithelial cells transplantation is a known surgical technique for vitiligo. OBJECTIVE: To evaluate the factors influencing efficacy and safety of cultured epithelial cells transplantation in 9-month follow-up. METHODS: Demographic, clinical, and repigmentation outcomes were reviewed for patients with facial segmental vitiligo who had undergone cultured epithelial cells transplantation from November 2013 to July 2015 at the clinic of the Department of Dermatology, Huashan Hospital, China. RESULTS: Twenty-eight patients who had undergone cultured epithelial cells transplantation were included. A satisfactory result (>50% repigmentation) was achieved in 79% patients with facial segmental vitiligo in 9 months. The treatment effect was significantly different in 6th month (Pâ=â0.032), 9th month (Pâ=â0.006) compared with 3rd month. Disease stability did significantly affect repigmentation outcome in 9th month (Zâ=â2.113, Pâ=â0.035). No significant difference was observed between single segmental type versus mixed type (Zâ=â1.081, Pâ=â0.280). Adverse effects were nearly absent. CONCLUSION: Cultured epithelial cells transplantation is a relatively safe and effective therapy for facial segmental stable vitiligo patients.
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Trasplante de Células/métodos , Células Cultivadas/trasplante , Células Epiteliales/trasplante , Cara/fisiopatología , Vitíligo , Humanos , Vitíligo/fisiopatología , Vitíligo/terapiaRESUMEN
BACKGROUND: Severe combined immunodeficiency (SCID) can be cured by using allogeneic hematopoietic stem cell transplantation, and the absence of host immunity often obviates the need for preconditioning. Depending on the underlying genetic defect and when blocks in differentiation occur during lymphocyte ontogeny, infants with SCID have absent or greatly reduced numbers of functional T cells. Natural killer (NK) cell populations are usually absent in the SCID-X1 and Janus kinase 3 forms of SCID and greatly reduced in adenosine deaminase deficiency SCID but often present in other forms of the disorder. OBJECTIVE: To determine if SCID phenotypes indicate host permissiveness to donor cell engraftment. METHODS: A retrospective data analysis considered whether host NK cells influenced donor T-cell engraftment, immune reconstitution, and long-term outcomes in children who had undergone nonconditioned allogeneic stem cell transplantation between 1990 and 2011 in the United Kingdom. Detailed analysis of T- and B-cell immune reconstitution and donor chimerism was compared between the NK(+) (n = 24) and NK(-) (n = 53) forms of SCID. RESULTS: Overall, 77 children underwent transplantation, with survival of 90% in matched sibling donor/matched family donor transplants compared with 60% when alternative donors were used. Infants with NK(-)SCID were more likely to survive than NK(+) recipients (87% vs 62%, P < .01) and had high-level donor T-cell chimerism with superior long-term recovery of CD4 T-cell immunity. Notably, 33% of children with NK(+)SCID required additional transplantation procedures compared with only 8% of children with NK(-)SCID (P < .005). CONCLUSIONS: NK(-)SCID disorders are highly permissive for donor T-cell engraftment without preconditioning, whereas the presence of NK cells is a strong indicator that preparative conditioning is required for engraftment of T-cell precursors capable of supporting robust T-cell reconstitution.
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Supervivencia de Injerto/inmunología , Células Asesinas Naturales/inmunología , Inmunodeficiencia Combinada Grave/inmunología , Linaje de la Célula/inmunología , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Lactante , Recién Nacido , Masculino , Inmunodeficiencia Combinada Grave/mortalidad , Inmunodeficiencia Combinada Grave/terapia , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Quimera por Trasplante , Acondicionamiento Pretrasplante , Trasplante HomólogoRESUMEN
AIM: Homocysteine (Hcy) can elicit neuronal cell death, and hyperhomocysteinemia is a strong independent risk factor for Alzheimer's disease. The aim of this study was to examine the effects of hydrogen sulfide (H2S) on Hcy-induced endoplasmic reticulum (ER) stress and neuronal apoptosis in rat hippocampus. METHODS: Adult male SD rats were intracerebroventricularly (icv) injected with Hcy (0.6 µmol/d) for 7 d. Before Hcy injection, the rats were treated with NaHS (30 or 100 µmol·kg(-1)·d(-1), ip) and/or k252a (1 µg/d, icv) for 2 d. The apoptotic neurons were detected in hippocampal coronal slices with TUNEL staining. The expression of glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), cleaved caspase-12, and BDNF in the hippocampus were examined using Western blotting assays. The generation of H2S in the hippocampus was measured with the NNDPD method. RESULTS: Hcy markedly inhibited the production of endogenous H2S and increased apoptotic neurons in the hippocampus. Furthermore, Hcy induced ER stress responses in the hippocampus, as indicated by the upregulation of GRP78, CHOP, and cleaved caspase-12. Treatment with the H2S donor NaHS increased the endogenous H2S production and BDNF expression in a dose-dependent manner, and significantly reduced Hcy-induced neuronal apoptosis and ER stress responses in the hippocampus. Treatment with k252a, a specific inhibitor of TrkB (the receptor of BDNF), abolished the protective effects of NaHS against Hcy-induced ER stress in the hippocampus. CONCLUSION: H2S attenuates ER stress and neuronal apoptosis in the hippocampus of Hcy-treated rats via upregulating the BDNF-TrkB pathway.
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Factor Neurotrófico Derivado del Encéfalo/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Sulfuro de Hidrógeno/farmacología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Receptor trkB/metabolismo , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Hipocampo/citología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Homocisteína/metabolismo , Hiperhomocisteinemia/metabolismo , Masculino , Neuronas/citología , Neuronas/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Regulación hacia ArribaRESUMEN
Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.
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BACKGROUND/OBJECTIVES: It seems that global DNA hypomethylation in CD4+T cells is linked to the pathogenesis of systemic lupus erythematosus (SLE). However, the underlying mechanism by which SLE patients show hypomethylated DNA remains unclear. This study explored the relationship between DNA methylation patterns and expression levels of DNA methyltransferases (DNMT1) and MBD2 in CD4+T cells of SLE patients. METHODS: CD4+T cells were obtained from 30 patients with SLE and 18 normal controls. The global DNA methylation levels in CD4+T cells were evaluated by the Methyflash DNA methylation quantification kit. The mRNA levels of DNMT1 and MBD2 were quantified by quantitative real-time polymerase chain reaction. RESULTS: SLE patients had significantly lower global DNA methylation levels than controls, and the global DNA methylation was inversely correlated with the SLE disease activity index (SLEDAI). The mRNA levels of DNMT1 in SLE patients were significantly lower than that of controls and there was no correlation between DNMT1 mRNA levels and SLEDAI but there was a positive correlation between DNMT1 mRNA levels and global DNA methylation. The mRNA levels of MBD2 in SLE patients were significantly higher than in controls, and there was positive correlation between MBD2 mRNA levels and SLEDAI and an inverse correlation between MBD2 mRNA levels and global DNA methylation. CONCLUSIONS: Global DNA hypomethylation may play a pivotal role in the pathogenesis of SLE. Abnormal expression levels of DNMT1 and MBD2 mRNA may be important causes of the global hypomethylation observed in CD4+T cells in SLE.
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ADN (Citosina-5-)-Metiltransferasas/genética , Metilación de ADN/genética , Proteínas de Unión al ADN/genética , Lupus Eritematoso Sistémico/genética , Adolescente , Adulto , Linfocitos T CD4-Positivos/metabolismo , Estudios de Casos y Controles , ADN (Citosina-5-)-Metiltransferasa 1 , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , Índice de Severidad de la Enfermedad , Transcripción Genética , Adulto JovenRESUMEN
OBJECTIVE: To explore the serum levels and significance of hypoxic inducible factor (HIF)-1α and HIF-2α in Tibetan and Han residents living at different altitudes. METHODS: A total of 100 healthy adults of Han in plain (altitude 5 m, group P) and Tibetan and Han at moderate altitude (2260 m, groups M1 & M2) and high altitude (4380 m, groups H1 & H2) (n = 20 each) were selected from June 2010 to August 2010. Venous blood samples were collected in the morning. The serum concentrations of HIF-1α and HIF-2α were measured with enzyme-linked immunosorbent assay (ELISA) to analyze the correlations of HIF-1α and HIF-2α with arterial partial pressure of oxygen (PaO2) and hemoglobin (Hb). RESULTS: The level of HIF-1α in group H2 ( (6.06 ± 1.85) µg/L) was higher than that in groups P ( (4.56 ± 0.85) µg/L, P < 0.05) , M1 ((4.41 ± 1.05) µg/L, P < 0.01) and M2 ( (4.59 ± 1.03) µg/L, P < 0.05) . The level of HIF-1α in group H1 ( (5.27 ± 0.98) µg/L) was higher than that in group M1 (P < 0.05) . The level of HIF-2α in group H2 ((0.83 ± 0.48) µg/L) was higher than that in groups P ((0.33 ± 0.11) µg/L, P < 0.01), M1 ((0.14 ± 0.06 )µg/L, P < 0.01) and M2( (0.24 ± 0.11) µg/L, P < 0.01) . The level of HIF-2α in group M1 was lower than that in groups P (P < 0.01) and M2 (P < 0.01). The level of HIF-2α in group H1((0.18 ± 0.16)µg/L) was lower than that in groups P (P < 0.05) and H2 (P < 0.01) . The levels of HIF-1α and HIF-2α were negatively correlated with PaO2 (r = -0.475, -0.551, both P < 0.01) and positively with Hb in Han groups (r = 0.433, 0.463, all P < 0.01). The levels of HIF-1α and HIF-2α had no correlation with PaO2 in Tibetan groups (r = -0.270, -0.198, both P > 0.05). No correlation existed between HIF-1α and Hb in Tibetan. A positive correlation existed between HIF-2α and Hb in Tibetan (r = 0.325, P < 0.01). CONCLUSIONS: The changes of HIF-1α and HIF-2α vary for Tibetan and Han residents at different altitudes. And the level of HIF-2α is consistent with the change of Hb. As compared with HIF-1α, HIF-2α may play a more important role in regulating Hb.
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Altitud , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/sangre , Subunidad alfa del Factor 1 Inducible por Hipoxia/sangre , Adulto , Pueblo Asiatico , Hemoglobinas/análisis , Humanos , Grupos Minoritarios , Características de la Residencia , Adulto JovenRESUMEN
Algal toxins are important metabolites of toxic harmful algal blooms (HABs), and their qualitative and qualitative detection can serve as early warning indicators for toxic HABs, complementing traditional HAB monitoring and improving the accuracy of early warning. Therefore, this work took the detection of domoic acid (DA) as an example and prepared zeolitic imidazolate framework-8 (ZIF-8) with high enrichment performance and high water stability and its core-shell composite material SiO2@ZIF-8 as an adsorbent filler. Density functional theory (DFT) calculations and interference experiments verified that Zn2+ on SiO2@ZIF-8 played a crucial role in enriching DA on SiO2@ZIF-8. By using it as a solid-phase extraction (SPE) filler, it showed excellent performance compared with other SPE columns (C18/HLB/SAX/ZIF-8). Therefore, the SiO2@ZIF-8 column was coupled to high-performance liquid chromatography-mass spectrometry (SPE-HPLC-MS/MS) to establish a highly sensitive detection method for algal toxins in seawater, which had a wide linear range (12.0-5000.0 ng L-1), good reproducibility (RSD) and low limit of detection (4.0 ng L-1), and realized the monitoring of trace DA in the Pingtan sea area of Fujian Province from 2021 to 2022. By comparing other HAB early warning indicators such as salinity and pH and combining them with the information released by the Fujian Provincial Ocean and Fisheries Bureau, the content of DA in seawater measured by the established SPE-HPLC-MS/MS method can provide reference information for HAB monitoring and early warning.
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Dióxido de Silicio , Zeolitas , Espectrometría de Masas en Tándem/métodos , Adsorción , Zeolitas/química , Reproducibilidad de los Resultados , Teoría Funcional de la Densidad , Agua de Mar/química , Toxinas Marinas/análisis , Extracción en Fase Sólida/métodosRESUMEN
1. Formaldehyde (FA) has been found to cause toxicity to neurons. However, its neurotoxic mechanisms have not yet been clarified. Increasing evidence has shown that oxidative damage is one of the most critical effects of formaldehyde exposure. Paraoxonase-1 (PON-1) is a pivotal endogenous anti-oxidant. Thus, we hypothesized that FA-mediated downregulation of PON1 is associated with its neurotoxicity. 2. In the present work, we used PC12 cells to study the neurotoxicity of FA and explore whether PON-1 is implicated in FA-induced neurotoxicity. 3. We found that FA has potent cytotoxic and apoptotic effects on PC12 cells. FA induces an accumulation of intracellular reactive oxygen species along with downregulation of Bcl-2 expression, as well as increased cytochrome c release. FA significantly suppressed the expression and activity of PON-1 in PC12 cells. Furthermore, H(2)S, an endogenous anti-oxidant gas, antagonizes FA-induced cytotoxicity as well as 2-hydroxyquinoline, a specific inhibitor of PON-1, which also induces cytotoxicity to PC12 cells. 4. The results of the present study provide, for the first time, evidence that the inhibitory effect on PON-1 expression and activity is involved in the neurotoxicity of FA, and suggest a promising role of PON-1 as a novel therapeutic strategy for FA-mediated toxicity.
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Arildialquilfosfatasa/metabolismo , Formaldehído/toxicidad , Neuronas/efectos de los fármacos , Síndromes de Neurotoxicidad/enzimología , Síndromes de Neurotoxicidad/etiología , Animales , Apoptosis/efectos de los fármacos , Arildialquilfosfatasa/antagonistas & inhibidores , Arildialquilfosfatasa/biosíntesis , Arildialquilfosfatasa/genética , Hidrolasas de Éster Carboxílico/metabolismo , Línea Celular Tumoral , Citocromos c/genética , Citocromos c/metabolismo , Regulación hacia Abajo/genética , Formaldehído/efectos adversos , Formaldehído/metabolismo , Sulfuro de Hidrógeno/farmacología , Hidroxiquinolinas/farmacología , Neuronas/enzimología , Síndromes de Neurotoxicidad/metabolismo , Estrés Oxidativo/efectos de los fármacos , Células PC12 , Ratas , Especies Reactivas de Oxígeno/metabolismo , Hipersensibilidad Respiratoria/enzimología , Hipersensibilidad Respiratoria/metabolismo , Proteína Letal Asociada a bcl/antagonistas & inhibidores , Proteína Letal Asociada a bcl/genética , Proteína Letal Asociada a bcl/metabolismoRESUMEN
BACKGROUND: Acne vulgaris and rosacea are common inflammatory complications of the skin, both characterized by abnormal infiltration of immune cells. The two diseases can be differentiated based on characteristic profile of the immune cell infiltrates at the periphery of disease lesions. In addition, dysregulated infiltration of immune cells not only occur in the acne lesions but also in non-lesional areas of patients with the disease, thus characterizing the immune infiltration in these sites can further enhance our understanding on the pathogenesis of acne. METHODS: Five microarray data-sets (GSE108110, GSE53795, GSE65914, GSE14905 and GSE78097) were downloaded from Gene Expression Omnibus. After removing the batch effects and normalizing the data, we applied the CIBERSORT algorithm combined with signature matrix LM22, to describe 22 types of immune cells' infiltration in acne less than 48 hour (H) old, in comparation with non-lesional skin of acne patients, healthy skin and rosacea (including erythematotelangiectatic rosacea, papulopustular rosacea and phymatous rosacea) and we compared gene expression of Th1 and Th17-related molecules in acne, rosacea and healthy control. RESULTS: Compared with the non-lesional skin of acne patients, healthy individuals and rosacea patients, there is a significant increase in infiltration of neutrophils, monocytes and activated mast cells around the acne lesions, less than 48 H after their development. Contrarily, few naive CD4+ T cells, plasma cells, memory B cells and resting mast cells infiltrate acne sites compared to the aforementioned groups of individuals. Moreover, the infiltration of Regulatory T cells (Tregs) in acne lesions is substantially lower, relative to non-lesional sites of acne patients and skin of healthy individuals. In addition, non-lesional sites of acne patients exhibit lower infiltration of activated memory CD4+ T cells, plasma cells, memory B cells, M0 macrophages, neutrophils, resting mast cells but higher infiltration of Tregs and resting dendritic cells relative to skin of healthy individuals. Intriguingly, we found that among the 3 rosacea subtypes, the immune infiltration profile of papulopustular rosacea is the closest to that of acne lesions. In addition, through gene expression analysis of acne, rosacea and skin tissues of healthy individuals, we found a higher infiltration of Th1 and Th17 cells in acne lesions, relative to non-lesional skin areas of acne patients. CONCLUSIONS: Our study provides new insights into the inflammatory pathogenesis of acne, and the difference between acne and rosacea, which helps in differentiating the two diseases. Our findings also guide on appropriate target therapy of the immune cell infiltrates in the two disease conditions.
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Biología Computacional/métodos , Rosácea/inmunología , Células TH1/inmunología , Células Th17/inmunología , Acné Vulgar/inmunología , Acné Vulgar/patología , Expresión Génica , Humanos , Rosácea/patología , Células TH1/citología , Células Th17/citologíaRESUMEN
Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening severe adverse drug reactions. The use of corticosteroids and intravenous immunoglobulin (IVIg) in SJS/TEN remains controversial. Methods: In this single-center, observational, propensity-matched, retrospective study, we collected a total of 224 patients with SJS/TEN who were hospitalized in our department from 2008 to 2019; according to treatment with IVIg combined with corticosteroids or with corticosteroids alone, patients were divided into combination therapeutic group (163 patients) and monotherapeutic group (61 patients). Patients from the two groups were matched by their propensity score in blocks of 2:1. Comparisons of the clinical characteristics and prognoses between propensity-matched SJS/TEN patients treated with IVIg combined with corticosteroids and corticosteroids alone were made. Results: After our propensity matching, a total of 145 patients were yielded, including 93 patients treated with IVIg and 52 patients not treated with IVIg. All of the 23 variables reflected good matching between patients treated with/without IVIg, and no significant difference was observed. Although there was no significant difference between the totally predicted and actual mortality in both of our groups, the actual mortality was lower than it was predicted in patients treated with IVIg [p > 0.250, the standardized mortality ratio (SMR) was 0.38, 95% CI 0.00-0.91] and patients treated without IVIg (p = 1.000, the SMR was 0.75, 95% CI 0.00-1.76). IVIg tended toward reducing the time to arrest of progression by 1.56 days (p = 0.000) and the length of hospital stay by 3.37 days (p = 0.000). The mortality rate was 45% lower for patients treated with IVIg combined with corticosteroids than those only treated with corticosteroid therapy, although it was not statistically significant (p = 0.555). The incidence of skin infections was significantly lower in the combined therapy group (p < 0.025), and the total infection rate of patients treated with combination therapy tended to decrease by 67% compared to patients treated with corticosteroids alone (p = 0.047). Conclusion: The actual mortality rate of patients treated with corticosteroids alone or IVIg combined with corticosteroids tended to be lower than those predicted by TEN-specific severity-of-illness score (SCORTEN), although there was no significance. Compared with those treated by corticosteroids alone, combination therapy was prone to bring a better prognosis for SJS/TEN patients.
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Breast cancer, as one of the most malignant tumors, poses a serious threat to the lives of females. Nucleotide exchange factor SIL1 is an important regulator of endoplasmic reticulum function that might have a specific role in tumor progression. In this study, we aimed to investigate the effect of SIL1 on the proliferation, apoptosis, and metastasis of human breast cancer. SIL1-specific small interfering RNA was transfected into two breast cancer cell lines, MCF7 and MDA-MB-231, to generate SIL1 knockdown cells. Clone formation and Cell Counting Kit-8 assays were performed to determine cell proliferation. Wound healing and transwell assays were used to detect the cell migration and invasion, respectively. Cell cycle and apoptosis were determined by flow cytometry. The messenger RNA and protein levels of target genes were analyzed using quantitative real-time PCR and western blot. According to the results of TCGA and GTEx database analysis, we determined that SIL1 was overexpressed in 1085 breast cancer samples compared with 291 normal samples. Knockdown of SIL1 inhibited the proliferation, migration, and invasion of MCF7 and MDA-MB-231 cells, accordingly. The cell cycle was blocked at the G1 phase following transfection of SIL1-specific small interfering RNA through the inhibition of Cyclin D1, CDK4, and CDK6. SIL1 knockdown induced apoptosis and also promoted the activity of Caspase9 and Bax. Furthermore, SIL1 was able to promote phosphorylation of ERK1/2. Based on these results, SIL1 might act as an oncogene and accelerate the progression of human breast cancer.
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Neoplasias de la Mama , Apoptosis/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Ciclo Celular/genética , Línea Celular Tumoral , Femenino , Factores de Intercambio de Guanina Nucleótido/farmacología , Humanos , Nucleótidos/farmacologíaRESUMEN
BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions with high mortality. The use of corticosteroids and the management of complications (e.g. infection) in SJS/TEN remains controversial. METHODS: A retrospective study was performed among 213 patients with SJS/TEN who were hospitalized in our department between 2008 and 2018, to investigate the causative agents, clinical characteristics, complications, and prognoses of SJS/TEN mainly treated by systemic corticosteroids combined with intravenous immunoglobulin (IVIG). RESULTS: The causative drugs of SJS/TEN in these patients mainly consisted of antibiotics (61/213, 28.6%), anticonvulsants (52/213, 24.4%), and nonsteroidal anti-inflammation drugs (24/213, 11.3%), among which carbamazepine was the most frequently administered drug (39/213, 18.3%). There were significant differences in the maximum dosage, time to corticosteroid tapering, and the total dosage of corticosteroid between the SJS group and the TEN group, as well as among the three groups (P = 0.000), whereas in the initial dose of corticosteroid was not statistically significant among the three groups (P = 0.277). In a series of 213 cases, 18.4 cases (8.6%) were expected to die based on the score for the toxic epidermal necrolysis (SCORTEN) system, whereas eight deaths (3.8%) were observed; the difference was not statistically significant (P = 0.067; SMR = 0.43, 95% CI: 0.06, 0.48). The most common complications were electrolyte disturbance (174/213, 81.7%), drug-induced liver injury (64/213, 30.0%), infection (53/213, 24.9%), and fasting blood sugar above 10 mmol/L (33/213, 15.5%). Respiratory system (22/213, 10.3%) and wound (11/213, 5.2%) were the most common sites of infection. Multivariate logistic regression analysis indicated that the maximum blood sugar (≥10 mmol/L), the time to corticosteroid tapering (≥12 d), the maximum dosage of corticosteroid (≥1.5 mg/kg/d), and the total body surface area (TBSA) (≥10%) were defined as the most relevant factors of the infection. CONCLUSION: The mortality of patients in this study was lower than that predicted by SCORTEN, although there was no significant difference between them. Hyperglycemia, high-dose corticosteroid, and the TBSA were closely related to the infections of patients with SJS/TEN.
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Glucocorticoides/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Neumonía/epidemiología , Síndrome de Stevens-Johnson/tratamiento farmacológico , Infección de Heridas/epidemiología , Lesión Renal Aguda/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Alopurinol/efectos adversos , Antibacterianos/efectos adversos , Antiinflamatorios no Esteroideos/efectos adversos , Anticonvulsivantes/efectos adversos , Glucemia/metabolismo , Superficie Corporal , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , China/epidemiología , Estudios de Cohortes , Medicamentos Herbarios Chinos/efectos adversos , Femenino , Hemorragia Gastrointestinal/epidemiología , Supresores de la Gota/efectos adversos , Humanos , Hiperglucemia/epidemiología , Hipertensión/epidemiología , Infecciones por Klebsiella/epidemiología , Masculino , Persona de Mediana Edad , Aspergilosis Pulmonar/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Síndrome de Stevens-Johnson/etiología , Síndrome de Stevens-Johnson/mortalidad , Tasa de Supervivencia , Desequilibrio Hidroelectrolítico/epidemiologíaRESUMEN
BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; Pâ<â0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; Pâ<â0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.
Asunto(s)
Anticuerpos Monoclonales , Psoriasis , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , China , Método Doble Ciego , Humanos , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Etanercept biosimilar recombinant human tumour necrosis factor-α receptor II: IgG Fc fusion protein (rhTNFR-Fc, trade name Yisaipu) has shown good efficacy in the treatment of moderate-to-severe plaque psoriasis. To compare the efficacy and safety of rhTNFR-Fc plus methotrexate (MTX) and rhTNFR-Fc plus placebo in Chinese patients with moderate-to-severe plaque psoriasis. In this multicentre, randomized, placebo-controlled trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned in a 1:1 ratio to receive rhTNFR-Fc plus MTX or rhTNFR-Fc plus placebo. The primary endpoint was the proportion of patients achieving Psoriasis Area and Severity Index improvement of at least 75% (PASI 75) from baseline at week 24. Adverse events (AEs) were recorded to evaluate safety. Efficacy analysis was performed using the intent-to-treat principle. A total of 466 patients were enrolled and randomly received rhTNFR-Fc plus MTX (combination group, n = 233) or rhTNFR-Fc plus placebo (monotherapy group, n = 233). PASI 75 at week 24 was significantly higher in the combination group than in the monotherapy group (81.86% vs. 65.50%, p < 0.001). Similar results were observed in other PASI improvement scores at week 12 [PASI 75, 62.39% vs. 44.54% (p < 0.001); PASI 50, 87.17% vs. 75.55% (p = 0.001); and PASI 90, 34.07% vs. 18.78% (p < 0.001)] and week 24 [PASI 50, 92.48% vs. 85.59% (p = 0.019); and PASI 90, 64.16% vs. 42.36% (p < 0.001)]. Significantly more patients had a static Physicians' Global Assessment of clear or almost clear in the combination group than in the monotherapy group at week 12 (26.46% vs. 12.50%, p < 0.001) and week 24 (62.38% vs. 40.83%, p < 0.001). The most common AEs in the two groups were upper respiratory tract infection and abnormal liver function. The combination therapy of rhTNFR-Fc plus MTX was an effective therapy for moderate-to-severe plaque psoriasis with an acceptable safety and tolerability profile, indicating that it was feasible and well tolerated for patients.
Asunto(s)
Etanercept/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/genética , Inmunoglobulina G/genética , Metotrexato/uso terapéutico , Psoriasis/tratamiento farmacológico , Receptores Tipo II del Factor de Necrosis Tumoral/genética , Proteínas Recombinantes de Fusión/genética , Adulto , Biosimilares Farmacéuticos , China , Método Doble Ciego , Quimioterapia Combinada , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placebos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis. METHODS: We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12. RESULTS: The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, Pâ<â0.05) and placebo (13.9%, Pâ<â0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, Pâ<â0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported. CONCLUSION: During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.
Asunto(s)
Psoriasis , Método Doble Ciego , Estudios de Seguimiento , Humanos , Pomadas , Psoriasis/tratamiento farmacológico , Resorcinoles , Índice de Severidad de la Enfermedad , Estilbenos , Resultado del TratamientoRESUMEN
The 2019 novel coronavirus infection has brought a great challenge in prevention and control of the national epidemic of coronavirus disease 2019 (COVID-19) in China. During the fight against the epidemic of COVID-19, properly carrying out pre-examination and triage for patients with skin lesions and fever has been a practical problem encountered in hospitals for skin diseases as well as clinics of dermatology in general hospitals. Considering that certain skin diseases may have symptom of fever, and some of the carriers of 2019 novel coronavirus and patients with COVID-19 at their early stage may do not present any symptoms of COVID-19, to properly deal with the visitors to clinics of dermatology, the Chinese Society of Dermatology organized experts to formulate the principles and procedures for pre-examination and triage of visitors to clinics of dermatology during the epidemic of COVID-19.