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Exploring ultrafast carrier dynamics is crucial for the materials' fundamental properties and device design. In this work, we employ time- and energy-resolved photoemission electron microscopy with tunable pump wavelengths from visible to near-infrared to reveal the ultrafast carrier dynamics of the elemental semiconductor tellurium. We find that two discrete sub-bands around the Γ point of the conduction band are involved in excited-state electron ultrafast relaxation and reveal that hot electrons first go through ultrafast intra sub-band cooling on a time scale of about 0.3 ps and then transfer from the higher sub-band to the lower one on a time scale of approximately 1 ps. Additionally, theoretical calculations reveal that the lower one has flat-band characteristics, possessing a large density of states and a long electron lifetime. Our work demonstrates that TR- and ER-PEEM with broad tunable pump wavelengths are powerful techniques in revealing the details of ultrafast carrier dynamics in time and energy domains.
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Objective: To explore the effect of Gegen Qinlian Decoction (GQD) combined with dietary management in the treatment of patients with Type-2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) (T2DM MetS). Methods: This is a retrospective analysis of 102 cases of T2DM in the Brain Hospital of Hunan Province, China from April 2020 to February 2023. Of them, 49 patients received conventional drug treatment (control group), and 53 patients received GQD combined with dietary management on the basis of conventional drugs (observation group). Treatment efficacy was calculated, and blood glucose levels before and after the treatment, blood lipid-related indicators, tumor necrosis factor-α (TNF-α) and adiponectin (ADP) levels, and incidence of adverse reactions were compared between the two groups. Results: The total efficacy of the observation group (92.45%) was significantly higher than that of the control group (75.51%) (P<0.05). After the treatment, blood glucose and lipid indicators in both groups were significantly improved compared to pretreatment levels, and were significantly better in the observation group than in the control group (P<0.05). After the treatment, TNF-α levels in both groups decreased compared to before the treatment, and were significantly lower in the observation group compared to the control group. Levels of ADP after the treatment increased, and were significantly higher in the observation group compared to the control group (P<0.05). Conclusions: When taken as an adjunct to the conventional drug regimen, GQD combined with dietary management can effectively regulate blood glucose and lipid metabolism in patients with T2DM and MetS (T2DM MetS), improve TNF-α and ADP levels, and enhance disease treatment effectiveness.
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Objective: To investigate the efficacy and safety of low-dose radiotherapy in treating eosinophilic lymphoid granuloma. Method: This study included a total of 20 patients diagnosed with eosinophilic lymphoid granuloma. All patients underwent low-dose three-dimensional conformal intensity-modulated radiotherapy for their lesions. We analyzed the control status of the lesions and any adverse reactions related to radiotherapy. Results: The overall effectiveness of low-dose radiotherapy in treating eosinophilic lymphoid granuloma was 90%. The incidence of grade I and grade II adverse reactions induced by radiotherapy was 70% and 30%, respectively. Over a median follow-up period of 23.6 months, all patients showed controlled lesions within the target delineation of radiotherapy. After radiotherapy, four patients experienced occasional pruritus, and one patient had a recurrence outside the target area three years later. No long-term severe adverse reactions related to radiotherapy were observed during the follow-up period. Conclusions: Low-dose radiotherapy demonstrates an apparent therapeutic effect on eosinophilic lymphoid granuloma with acceptable adverse reactions.
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PURPOSE: To determine the association between low molecular weight heparin (LMWH) use and mortality in hospitalized COVID-19 patients. METHODS: We conducted a retrospective study of patients consecutively enrolled from two major academic hospitals exclusively for COVID-19 in Wuhan, China, from January 26, 2020, to March 26, 2020. The primary outcome was adjusted in-hospital mortality in the LMWH group compared with the non-LMWH group using the propensity score. RESULTS: Overall, 525 patients with COVID-19 enrolled with a median age of 64 years (IQR 19), and 49.33% men. Among these, 120 (22.86%) were treated with LMWH. Compared with the non-LMWH group, the LMWH group was more likely to be older and male; had a history of hypertension, diabetes, coronary heart disease (CHD), or stroke; and had more severe COVID-19 parameters such as higher inflammatory cytokines or D-dimer. Compared with non-LMWH group, LMWH group had a higher unadjusted in-hospital mortality rate (21.70% vs. 11.10%; p = 0.004), but a lower adjusted mortality risk (adjusted odds ratio [OR], 0.20; 95% CI, 0.09-0.46). A propensity score-weighting analysis demonstrated similar findings (adjusted OR, 0.18; 95% CI, 0.10-0.30). Subgroup analysis showed a significant survival benefit among those who were severely (adjusted OR, 0.07; 95% CI, 0.02-0.23) and critically ill (adjusted OR, 0.32; 95% CI, 0.15-0.65), as well as among the elderly patients' age > 65, IL-6 > 10 times upper limit level, and D-dimer > 5 times upper limit level. CONCLUSIONS: Among hospitalized COVID-19 patients, LMWH use was associated with lower all-cause in-hospital mortality than non-LMWH users. The survival benefit was particularly significant among more severely ill patients.
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Anticoagulantes/uso terapêutico , Tratamento Farmacológico da COVID-19 , Heparina de Baixo Peso Molecular/uso terapêutico , Hospitalização , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , COVID-19/diagnóstico , COVID-19/mortalidade , China/epidemiologia , Comorbidade , Feminino , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/efeitos adversos , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
To explore the role of thymosin drugs in the prevention of novel coronavirus disease (COVID-19), we analyzed the preventive effects of different medication timings on health medical staff, and then provided recommendations for pharmaceutical monitoring of thymus drugs. The hospital-based retrospective study analyzed 435 medical staffers, treated with or without thymosin drugs as preventive medicines in our hospital of Wuhan City, from January 25 to March 25, 2020. For the prophylactics, the medical staff was prevented from pre-exposure prophylaxis (risk prevention of exposure to COVID-19 patients before using thymosin drugs) and postexposure prophylaxis (risk prevention of exposure to COVID-19 patients after using thymosin drugs). The effectiveness and safety of thymosin drugs were studied in the prevention and control of COVID-19 application, in real-world data research for the application of the drug for COVID- 19. In a similar exposure environment, compared to medical staffers who did not take preventive medicine, the use of thymosin drugs, before exposure and after exposure had an insignificant effect, and the adverse drug reaction (ADR) was increased, especially when thymosin drugs were used together with α-interferon.
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COVID-19/prevenção & controle , SARS-CoV-2/efeitos dos fármacos , Timosina/uso terapêutico , Adolescente , Adulto , Antivirais/uso terapêutico , Feminino , Hospitais , Humanos , Masculino , Corpo Clínico , Pessoa de Meia-Idade , Profilaxia Pré-Exposição/métodos , Estudos Retrospectivos , Adulto JovemRESUMO
To evaluate the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) vs calcium channel blockers (CCBs) on the progression of Corona Virus Disease 2019 (COVID-19) patients with hypertension in Wuhan. This retrospective single-center case series analyzed COVID-19 patients with hypertension, treated with ACEIs/ARBs or CCBs at the Tongji Hospital of Wuhan City, China from 25th January to 15th March 2020. After propensity score matching analysis, 76 patients were selected into two groups. Univariate and multivariable analyses were conducted to determine factors related to improvement measures and outcome measures by Cox proportional hazard regression models. Among 157 patients with confirmed COVID-19 combined hypertension, including 73 males and 84 females, a median age of 67.28 ± 9.11 vs 65.39 ± 10.85 years. A univariable analysis indicated that clinical classification, lymphocyte count, and interleukin-2 receptor were associated with a lengthened negative time of nucleic acid, with a significant difference between two groups (P = .036). Furthermore, we found no obvious difference in nucleic acid conversion time between ACEIs/ARBs and CCBs groups (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: [0.97, 3.38]; P = .18) in the multivariable analysis as well as chest computed tomography improved time (HR: 0.73; 95% CI [0.45, 1.2]; P = .87), and hospitalization time between ACEIs/ARBs and CCBs groups (HR: 1.06; 95% CI [0.44, 1.1]; P = .83). Our study provided additional evidence of no obvious difference in progress and prognosis between ACEIs/ACEIs and CCBs group, which may suggest ACEIs/ARBs may have scarcely influence on increasing the clinical severe situations of COVID-19 patients with hypertension.
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Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Tratamento Farmacológico da COVID-19 , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão/epidemiologia , Idoso , COVID-19/epidemiologia , China , Progressão da Doença , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hipertensão/virologia , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
Tocilizumab (TCZ), a monoclonal antibody against interleukin-6 (IL-6), emerged as an alternative treatment for COVID-19 patients with a risk of cytokine storms recently. In the present study, we aimed to discuss the treatment response of TCZ therapy in COVID-19 infected patients. The demographic, treatment, laboratory parameters of C-reactive protein (CRP) and IL-6 before and after TCZ therapy and clinical outcome in the 15 COVID-19 patients were retrospectively assessed. Totally 15 patients with COVID-19 were included in this study. Two of them were moderately ill, six were seriously ill and seven were critically ill. The TCZ was used in combination with methylprednisolone in eight patients. Five patients received the TCZ administration twice or more. Although TCZ treatment ameliorated the increased CRP in all patients rapidly, for the four critically ill patients who received an only single dose of TCZ, three of them (No. 1, 2, and 3) still dead and the CRP level in the rest one patient (No. 7) failed to return to normal range with a clinical outcome of disease aggravation. Serum IL-6 level tended to further spiked firstly and then decreased after TCZ therapy in 10 patients. A persistent and dramatic increase of IL-6 was observed in these four patients who failed treatment. TCZ appears to be an effective treatment option in COVID-19 patients with a risk of cytokine storms. And for these critically ill patients with elevated IL-6, the repeated dose of the TCZ is recommended.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Surtos de Doenças , Fatores Imunológicos/uso terapêutico , Metilprednisolona/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/efeitos dos fármacos , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , COVID-19 , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do TratamentoRESUMO
Hydroxychloroquine (HCQ) garnered scientific attention in early February following publication of reports showing in vitro activity of chloroquine (CQ) against coronavirus disease 2019 (COVID-19). While studies are mixed on this topic, the therapeutic effect of HCQ or CQ still need more valid clinical evidence. In this descriptive observational study, we aimed to discuss the treatment response of HCQ in COVID-19 infected patients and 30 cases were included. The demographic, treatment, laboratory parameters of C-reactive protein (CRP) and interleukin-6 (IL-6) before and after HCQ therapy and clinical outcome in the 30 patients with COVID-19 were assessed. To evaluate the effect of mediation time point, we also divided these cases into two groups, patients began administrated with HCQ within 7 days hospital (defined as early delivery group) and 7 days after hospital (defined as later delivery group). We found that, the elevated IL-6, a risk factor in severe patients were reduced to normal level after HCQ treatment. More importantly, patients treated with HCQ at the time of early hospital recovered faster than those who treated later or taken as second line choose for their obvious shorter hospitalization time. In summary, early use of HCQ was better than later use and the effect of IL-6 and CRP level cannot be ruled out.
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Tratamento Farmacológico da COVID-19 , Hidroxicloroquina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Aspartato Aminotransferases/sangue , Proteína C-Reativa/análise , China , Citocinas/sangue , Progressão da Doença , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Interleucina-6/sangue , Linfopenia/sangue , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores de Tempo , Adulto JovemRESUMO
The central purpose of this study was to investigate therapeutic effects of the botanical derivative, kinsenoside (KD), in experimental autoimmune hepatitis (AIH). Treatment with KD substantially reduced hepatic histopathological damage, induced by lymphocyte infiltration and proinflammatory cytokines, in concanavalin A-induced T-cell-mediated hepatitis, and in dendritic cells (DCs) loaded with hepatocellular carcinoma cells (DC/Hepa1-6) induced murine AIH. Interactions between immune cells after KD treatment in AIH were detected by anti-CD8 antibody blocking, CD8+ T cell sorting, and vaccinated mice with KD-pretreated DCs in a DC/Hepa1-6 model. These results showed that KD inhibited the elevated expressions of CD86 and major histocompatibility complex II, densities of chemokine receptor C-C chemokine receptor type 7, and extensive migration to lymph nodes, and increased the programmed death ligand 1 level of DCs, followed by suppressing CD8+ T cells, characterized as low differentiation and cytotoxicity, and eliciting cytokines balance. Furthermore, biochemical analysis, two-dimensional fingerprint screen and three-dimensional molecular docking results showed that KD bound to the vascular endothelial growth factor receptor 2 (VEGFR2) kinase domain, which inhibited the metabolism-related phosphatidylinositol 3 kinase/protein kinase B (PI3K-AKT) pathway in DCs and DC-modulated CD8+ T cells to lower the mitochondrial membrane potential and glucose/lipid utilization ratio in both cells. KD reversed activation of the PI3K-AKT pathway by 740 Y-P (PI3K agonist), thereby impeding the translocation and dimerization of signal transducer and activators of transcription (STAT) 3 and synergistically blocking the inflammation-related Janus kinase (JAK) 2/STAT3 pathway in DCs and DC-modulated T cells. CONCLUSION: KD treatment elicits immunosuppression against autoimmune liver injury by targeting VEGFR2, followed by diminishing the cross-talk of metabolism-related PI3K-AKT and inflammation-related JAK2-STAT3 pathways, and thereby disrupts DC-induced cross-priming of CD8+ T cell responses. (Hepatology 2016;64:2135-2150).
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4-Butirolactona/análogos & derivados , Linfócitos T CD8-Positivos/efeitos dos fármacos , Comunicação Celular/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Hepatite Autoimune/tratamento farmacológico , Imunossupressores/uso terapêutico , Monossacarídeos/uso terapêutico , 4-Butirolactona/uso terapêutico , Animais , Linfócitos T CD8-Positivos/fisiologia , Comunicação Celular/fisiologia , Células Dendríticas/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Mivacurium is the shortest acting nondepolarizing muscle relaxant currently available; however, the effect of different dosages and injection times of intravenous mivacurium administration in children of different ages has rarely been reported. This study was aimed to evaluate the muscle relaxant effects and safety of different mivacurium dosages administered over different injection times in pediatric patients. METHODS: Six hundred forty cases of pediatric patients, aged 2 m-14 years, ASA I or II, were divided into four groups (Groups A, B, C, D) according to the age class (2-12 m, 13-35 m, 3-6 years and 7-14 years) respectively, also each group were divided into four subgroups by induction dose (0.15, 0.2 mg/kg in 2-12 m age class; 0.2, 0.25 mg/kg in other three age classes), and mivacurium injection time (20 s, 40 s), totally 16 subgroups. Neuromuscular transmission was monitored with supramaximal train-of-four stimulation of the ulnar nerve. Radial artery blood (1 ml) was sampled to quantify plasma histamine concentrations before and 1, 4, and 7 min after mivacurium injection (P0, P1, P2 and P3). RESULTS: Five hundred sixty-two cases completed the study. There were no demographic differences within the four groups. The onset time of 0.2 mg/kg groups in 2-12 m aged patients were shorter than those of 0.15 mg/kg groups (189 ± 64 s vs. 220 ± 73 s, 181 ± 60 s vs. 213 ± 71 s, P <0.05), and the recovery times were no statistical differences. The T1 25% recovery time of 0.2 mg/kg in 3-6 years aged patients was shorter than that of 0.25 mg/kg group (693 ± 188 s vs. 800 ± 206 s, P <0.05). The onset and recovery times of mivacurium were not different in 13-35 m and 7-14 years aged patients. The plasma concentrations of histamine at P0, P1, P2 and P3 were not different within four groups. CONCLUSIONS: The induction dose and injection time of mivacurium had mostly insignificant effects on onset and recovery times. The main exception to this was that in 2-12 m aged patients, increasing the dose of mivacurium from 0.15 to 0.2 mg/kg accelerated the onset time by about 30 s. Mivacurium produced no significant release of histamine in any age group at the doses studied. TRIAL REGISTRATION: ClinicalTrials.gov Identifier- NCT02117401 , July 14, 2014. (Retrospectively registered).
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Isoquinolinas/efeitos adversos , Isoquinolinas/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Histamina/análogos & derivados , Histamina/sangue , Humanos , Lactente , Isoquinolinas/administração & dosagem , Masculino , Mivacúrio , Monitoração Neuromuscular , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/farmacologiaRESUMO
OBJECTIVE: To investigate the clinicpathologic features and diagnosis of plasmablastic lymphoma (PBL). METHODS: Eleven cases of PBL were collected and followed up, with review of the literature. HIV and EBV status and their relationships with the tumor were specially compared as well. RESULTS: In the current cohort, 10 patients were serologically HIV negative; the male to female ratio was 8 to 3, and the median age was 57 years. Ten cases showed extranodal involvement and one case was nodal based. At presentation, five patients had mid-facial involvement, including sinonasal area (3 cases) and oral cavity (2 cases). Histologically, six were PBL of oral mucosa type, and five were PBL with plasmacytic differentiation. In all cases, the neoplastic cells expressed CD138 and MUM-1, and were negative for CD20 and CD3ε; the median Ki-67 index was 80%. Five cases were EBER1/2 in situ hybridization positive. IgH or/and Igκ gene rearrangement was detected in all five cases examined. CONCLUSIONS: Most patients were no congenital or acquired immunodeficiency in the retrospective study. Of the died patients, EBER1/2 in situ hybridization were negative and their disease staging were â £, The neoplastic cells were immunoblastic or plasmablastic, sometimes the plasmacytoid cell can be seen and the neoplastic cell had mature plasma cell phenotype, the pathologic diagnosis of the lymphoma is still controversial now. Differentiate with plasma cell neoplasm is difficult, it is necessary to accumulate more cases for advanced study and observation in the future.
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Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/patologia , Feminino , Rearranjo Gênico , Humanos , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo , Plasmócitos , RNA Viral/metabolismo , Estudos RetrospectivosRESUMO
BACKGROUND: Regenerating islet-derived 3 (Reg3) is abnormally expressed in several human digestive system diseases, including chronic pancreatitis (CP) and pancreatic cancer (PC). AIM: The purpose of this study was to clarify the mechanism of the enhanced expression of Reg3 in inflammation-induced PC. METHODS: C57BL/6 mice were treated with caerulein for 6 weeks to induce CP and then injected with pReg3g--a lentivirus system encoding for murine Reg3g--accompanied by dimethylbenzanthracene to induce PC. We detected pancreatic histopathological characteristics, tumor-related gene expression, inflammation-associated pathway activation, serum biochemical indicators, and immunological cell activities. RESULTS: The mice that developed CP after caerulein treatment were marked by pronounced histologic lesions, elevated serum amylase levels, and activation of inflammation-related pathways. Mice given a high dose of pReg3g developed PC by 16 weeks, with recognizable tumors in the pancreas. While, both the low and high doses of pReg3g produced higher transcription of c-fos, k-ras, cytokeratin-19, and proliferating cell nuclear antigen, and a lower expression of caspase-3 compared to pNEG controls. Additionally, the higher dose of pReg3g increased the expressions of pSTAT3, NFκB (p65), and SOCS3 methylation during PC development. In addition, mice treated with pReg3g displayed higher levels of serum IL10 and TGFß and suppressed T lymphocyte proliferation and DC function. CONCLUSION: The comprehensive analysis suggests enhanced Reg3g expression exacerbates PC in inflammation-associated cancer progression. Reg3g appears to promote CP-related PC in mice through multiple mechanisms, involving enhanced transcription of pancreatic tumor markers, repression of anti-tumor immunity, and activation of STAT3/p65 signal transduction pathways.
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Carcinogênese/induzido quimicamente , Neoplasias Pancreáticas/metabolismo , Pancreatite Crônica/metabolismo , Proteínas/farmacologia , Células Acinares , Animais , Carcinogênese/metabolismo , Citocinas/genética , Citocinas/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Pancreáticas/induzido quimicamente , Neoplasias Pancreáticas/genética , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/patologia , Proteínas Associadas a Pancreatite , Proteínas/genética , Proteínas/metabolismo , Proto-Oncogenes/genética , Proto-Oncogenes/fisiologiaRESUMO
BACKGROUND: Previous studies have shown that a low dose of propofol IV bolus had a beneficial effect on intrathecal morphine-induced pruritus in humans. However, its exact mechanism has not been fully understood. In this study, we hypothesized that propofol relieved intrathecal morphine-induced pruritus in rats by upregulating the expression of cannabinoid-1 (CB[1]) receptors in anterior cingulate cortex (ACC). METHODS: Twenty-four Sprague-Dawley rats were divided into a control group and 20, 40, 80 µg/kg morphine groups to create an intrathecal morphine-induced scratching model. The effects of propofol on intrathecal 40 µg/kg morphine-induced scratching responses were then evaluated. Sixty rats were randomly assigned to control, normal saline, intralipid, and propofol groups, with pruritus behavior observation or killed 8 minutes after venous injection of normal saline, intralipid, or propofol, and brain tissues were then collected for assay. Immunohistochemistry was then performed to identify the expression of CB (1) receptor in ACC, and the concentration of CB(1) receptor in ACC was determined by Western blot analysis. RESULTS: Compared with the control group, rats in the 20, 40, 80 µg/kg morphine groups had higher mean scratching response rates after intrathecal morphine injection (P =0.020, 0.005, and 0.002, respectively). There was a statistical difference between 20 and 40 µg/kg morphine groups at 10 to 15 and 15 to 20 timepoints after intrathecal morphine injection (P = 0.049 and 0.017, respectively). Propofol almost abolished the scratching response that was induced by 40 µg/kg intrathecal morphine injection (F[2, 15] = 46.87, P < 0.001; F[22, 165] = 2.37, P = 0.001). Compared with the intralipid and normal saline groups, the scratching behavior was significantly attenuated in the propofol group (P < 0.001). Compared with control, normal saline, and intralipid groups, the protein expression of CB(1) receptor in ACC (Western blot) in the propofol group increased (0.86 ± 0.21, 0.94 ± 0.18, 0.86 ± 0.13, and 1.34 ± 0.32, respectively, P < 0.001). There was no significant difference among control, normal saline, and intralipid groups. Compared with the control, normal saline, and intralipid groups, the average number of neurons of CB(1) receptor in the ACC area were higher in the propofol group (21.0 ± 1.4, 19.3 ± 1.8, 24.8 ± 7.7, and 37.2 ± 3.3, respectively, P < 0.001). CONCLUSIONS: Morphine elicits dose-independent scratching responses after intrathecal injection in rats. Morphine 40 µg/kg intrathecal injection-induced scratching responses can be prevented by propofol. Increased protein expression of CB(1) receptors in ACC may contribute to the reversal of intrathecal morphine-induced scratching.
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Giro do Cíngulo/efeitos dos fármacos , Injeções Espinhais , Morfina/administração & dosagem , Propofol/uso terapêutico , Prurido/tratamento farmacológico , Regulação para Cima , Analgésicos Opioides/administração & dosagem , Anestésicos Intravenosos/uso terapêutico , Animais , Cateterismo Venoso Central , Relação Dose-Resposta a Droga , Veias Jugulares/patologia , Masculino , Complicações Pós-Operatórias/tratamento farmacológico , Prurido/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Receptor CB1 de Canabinoide/metabolismoRESUMO
Purpose: The prognosis of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) that are refractory to programmed cell death protein 1 (PD-1) immunotherapy is relatively poor. The salvage therapy was rarely investigated and urgently needed. Methods: We conducted a single center retrospective real-world study to explore the efficacy of cetuximab plus PD-1 inhibitors as salvage therapy in patients progressed from first-line immunotherapy. Results: In the present study, 28 eligible patients were included between October 2020 and May 2023. By the cut-off date (Sep 24th, 2023), the objective response rate (ORR) was 46.4% (95% CI, 29.5%-64.2%). Kaplan-Meier survival analysis revealed the median progression free survival (mPFS) in the study was 6.87 months (95% CI, 4.77-8.97 months), and median overall survival (mOS) was 9.67 months (95% CI, 4.79-14.55 months). Multivariate Cox regression analysis indicated that ECOG performance status and best response to salvage therapy was found to be the prognosis factor of salvage therapy. For the safety, the most common treatment related adverse events (TRAEs) were rash (72.1%), anemia (64.3%) and fatigue (46.5%) during the salvage therapy. The most common potential irAEs were hypothyroidism (25%), and pneumonitis (14.3%). Only 3 patients (10.7%) experienced grade 3 TRAEs, and no treatment-related deaths occurred. Conclusions: Our study showed the combination of cetuximab with PD-1 inhibitors might be a potential efficacy and safety choice in PD-1 refractory patients with R/M HNSCC which need further investigation.
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Cistanche deserticola, known for its extensive history in Traditional Chinese Medicine (TCM), is valued for its therapeutic properties. Recent studies have identified its anticancer capabilities, yet the mechanisms underlying these properties remain to be fully elucidated. In this study, we determined that a mixture of four cistanche-derived phenylethanoid glycosides (CPhGs), echinacoside, acteoside, 2-acetylacteoside, and cistanoside A, which are among the main bioactive compounds in C. deserticola, eliminated T-cell lymphoma (TCL) cells by inducing apoptosis and pyroptosis in vitro and attenuated tumor growth in vivo in a xenograft mouse model. At the molecular level, these CPhGs elevated P53 by inhibiting the SIRT2-MDM2/P300 and PI3K/AKT carcinogenic axes and activating PTEN-Bax tumor-suppressing signaling. Moreover, CPhGs activated noncanonical and alternative pathways to trigger pyroptosis. Interestingly, CPhGs did not activate canonical NLRP3-caspase-1 pyroptotic signaling pathway; instead, CPhGs suppressed the inflammasome factor NLRP3 and the maturation of IL-1ß. Treatment with a caspase-1/4 inhibitor and silencing of Gasdermin D (GSDMD) or Gasdermin E (GSDME) partially rescued CPhG-induced cell death. Conversely, forced expression of NLRP3 restored cell proliferation. In summary, our results indicate that CPhGs modulate multiple signaling pathways to achieve their anticancer properties and perform dual roles in pyroptosis and NLRP3-driven proliferation. This study offers experimental support for the potential application of CPhGs in the treatment of TCL.
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High-order harmonic generation (HHG) in condensed matter is highly important for potential applications in various fields, such as materials characterization, all-optical switches, and coherent light source generation. Linking HHG to the properties or dynamic processes of materials is essential for realizing these applications. Here, a bridge has been built between HHG and the transient properties of materials through the engineering of interband polarization in a photoexcited three-dimensional Dirac semimetal (3D-DSM). It has been found that HHG can be efficiently manipulated by the electronic relaxation dynamics of 3D-DSM on an ultrafast time scale of several hundred femtoseconds. Furthermore, time-resolved HHG (tr-HHG) has been demonstrated to be a powerful spectroscopy method for tracking electron relaxation dynamics, enabling the identification of electron thermalization and electron-phonon coupling processes and the quantitative extraction of electron-phonon coupling strength. This demonstration provides insights into the active control of HHG and measurements of the electron dynamics.
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OBJECTIVE: To develop and compare various preoperative cervical stromal invasion (CSI) prediction models, including radiomics, three-dimensional (3D) deep transfer learning (DTL), and integrated models, using single-sequence and multiparametric MRI. METHODS: Data from 466 early-stage endometrial carcinoma (EC) patients from three centers were collected. Radiomics models were constructed based on T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) mapping, contrast-enhanced T1-weighted imaging (CE-T1WI), and four combined sequences as well as 3D DTL models. Two integrated models were created using ensemble and stacking algorithms based on optimal radiomics and DTL models. Model performance and clinical benefits were assessed using area under the curve (AUC), decision curve analysis (DCA), net reclassification index (NRI), integrated discrimination index (IDI), and the Delong test for model comparisons. RESULTS: Multiparametric MRI models were superior to single-sequence models for radiomics or DTL models. Ensemble and stacking integrated models displayed excellent performance. The stacking model had the highest average AUC (0.908) and accuracy (0.883) in external validation groups 1 and 2 (AUC = 0.965 and 0.851, respectively) and emerged as the best predictive model for CSI. All models significantly outperformed the radiologist (P < 0.05). In terms of net benefits, all models demonstrated favorable outcomes in DCA, NRI, and IDI, with the stacking model yielding the highest net benefit. CONCLUSION: Multiparametric MRI-based radiomics combined with 3D DTL can be used to noninvasively predict CSI in EC patients with greater diagnostic accuracy than the radiologist. Stacking integrated models showed significant potential utility in predicting CSI. Which helps to provide new treatment strategy for clinicians to treat early-stage EC patients.
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For atomically thin two-dimensional materials, variations in layer thickness can result in significant changes in the electronic energy band structure and physicochemical properties, thereby influencing the carrier dynamics and device performance. In this work, we employ time- and energy-resolved photoemission electron microscopy to reveal the ultrafast carrier dynamics of PdSe2 with different layer thicknesses. We find that for few-layer PdSe2 with a semiconductor phase, an ultrafast hot carrier cooling on a timescale of approximately 0.3 ps and an ultrafast defect trapping on a timescale of approximately 1.3 ps are unveiled, followed by a slower decay of approximately tens of picoseconds. However, for bulk PdSe2 with a semimetal phase, only an ultrafast hot carrier cooling and a slower decay of approximately tens of picoseconds are observed, while the contribution of defect trapping is suppressed with the increase of layer number. Theoretical calculations of the electronic energy band structure further confirm the transition from a semiconductor to a semimetal. Our work demonstrates that TR- and ER-PEEM with ultrahigh spatiotemporal resolution and wide-field imaging capability has great advantages in revealing the intricate details of ultrafast carrier dynamics of nanomaterials.
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RATIONALE AND OBJECTIVES: Evaluating the capability of CT nomograms and CT-based radiomics nomograms to differentiate between Bronchiolar Adenoma (BA) and Early-stage Lung Adenocarcinoma (LUAD). MATERIALS AND METHODS: In this retrospective study; we analyzed data from 226 patients who were treated at our institution and pathologically confirmed to have either BA or Early-stage LUAD. Patients were randomly divided into a training cohort (n=158) and a testing cohort (n=68). All CT images were independently analyzed and measured by two radiologists using conventional computed tomography. Clinical predictive factors were identified using logistic regression. Multivariable logistic regression analysis was used to construct differential diagnostic models for BA and early-stage LUAD, including traditional CT and radiomics models. The performance of the models was determined based on the area under the receiver operating characteristic curve, discrimination ability, and decision curve analysis (DCA). RESULTS: Lesion shape, tumor-lung interface, and pleural retraction signs were identified as independent clinical predictors. The areas under the curve for the CT nomogram, radiomic features, and radiomics nomogram were 0.854, 0.769, and 0.901, respectively. Both the CT nomogram and the radiomics nomogram demonstrated good generalizability in distinguishing between the two entities. DCA indicated that the nomograms achieved a higher net benefit compared to the use of radiomic features alone. CONCLUSION: The two preoperative nomograms hold significant value in differentiating between patients with BA and those with Early-stage LUAD, and they contribute to informed clinical treatment decision-making.
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BACKGROUND: The presence of diabetes and plasma glucose concentration on admission are associated with adverse outcomes after an acute myocardial infarction (AMI), as high glucose can induce vascular endothelial cell apoptosis. This study explored the relative associations among admission plasma glucose level, soluble Fas (sFas) concentration, and long-term survival in patients with acute ST-elevation myocardial infarction (STEMI). METHODS: This prospective cohort study include 83 patients with acute STEMI. Based on their admission plasma glucose levels (7.8 and 11.1 mmol/L as the limits for low and high levels, respectively), patients were allocated into one of three groups: normal glucose (n = 33), median glucose (n = 24), and high glucose (n = 26). The admission plasma level of sFas was measured with a sandwich enzyme-linked immunosorbent assay (ELISA). Patients were followed up for an average of 89 ± 20 months for all causes of death and cardiovascular death. RESULTS: sFas levels were significantly higher in the high glucose group compared to the normal glucose group (5.87 ± 1.70 mmol/L vs. 3.07 ± 0.93 mmol/L, respectively, P < 0.05). The sFas level was positively associated with the admission plasma glucose level. The correlation coefficient (R) was 0.747, and R2 was 0.559. Mortality was significantly higher in the high glucose group compared to the normal glucose group (19.2% vs. 3.0%, respectively, P < 0.05). CONCLUSIONS: In patients with acute STEMI, plasma glucose level was high on admission, and sFas apoptosis levels were increased. Long-term follow-up revealed that a high admission plasma glucose level was associated with higher mortality compared to a normal admission glucose level.