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When searching over associations between congenital ear abnormalities, especially microtia and affiliated deformities like cleft lip or palate and congenital heart diseases, some clinical analysis and genetic theories are found. A 10-year-old boy sent to the plastic surgery hospital was puzzled by a congenital anterior auricular fistula with fluid trace for more than 9 years. The preoperative diagnoses were branchial cleft fistula and congenital left ear deformity with postoperation of TOF. By browsing over studies on genetic concerns and clinical performance, it may be attributed to a possible association between microtia, branchial cleft fistula, and tetralogy of Fallot, though whose fundamental mechanisms remain concerned.
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Região Branquial , Microtia Congênita , Tetralogia de Fallot , Humanos , Masculino , Tetralogia de Fallot/cirurgia , Região Branquial/anormalidades , Região Branquial/cirurgia , Criança , Microtia Congênita/cirurgia , Fístula/cirurgia , Fístula/congênito , Doenças Faríngeas , Anormalidades CraniofaciaisRESUMO
Due to rapid expansion in the global economy and industrialization, PM2.5 (particles smaller than 2.5 µm in aerodynamic diameter) pollution has become a key environmental issue. The public health and social development directly affected by high PM2.5 levels. In this paper, ambient PM2.5 concentrations along with meteorological data are forecasted using time series models, including random forest (RF), prophet forecasting model (PFM), and autoregressive integrated moving average (ARIMA) in Anhui province, China. The results indicate that the RF model outperformed the PFM and ARIMA in the prediction of PM2.5 concentrations, with cross-validation coefficients of determination R2, RMSE, and MAE values of 0.83, 10.39 µg/m3, and 6.83 µg/m3, respectively. PFM achieved the average results (R2 = 0.71, RMSE = 13.90 µg/m3, and MAE = 9.05 µg/m3), while the predicted results by ARIMA are comparatively poorer (R2 = 0.64, RMSE = 15.85 µg/m3, and MAE = 10.59 µg/m3) than RF and PFM. These findings reveal that the RF model is the most effective method for predicting PM2.5 and can be applied to other regions for new findings.
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Poluentes Atmosféricos , Poluição do Ar , Monitoramento Ambiental , Material Particulado , Material Particulado/análise , China , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Poluição do Ar/estatística & dados numéricos , Previsões , Tamanho da Partícula , Modelos TeóricosRESUMO
Background BRCA1 and BRCA2 (BRCA) mutation carriers face a high lifetime risk of developing ovarian cancer. Oral contraceptives are protective in this population; however, the impact of other types of contraception (e.g. intrauterine devices, implants, injections) is unknown. We undertook a matched case-control study to evaluate the relationship between type of contraception and risk of ovarian cancer among women with BRCA mutations. Methods A total of 1733 matched pairs were included in this analysis. Women were matched according to year of birth, date of study entry, country of residence, BRCA mutation type and history of breast cancer. Detailed information on hormonal, reproductive and lifestyle exposures were collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) associated with each contraceptive exposure. Results Ever use of any contraceptive was significantly associated with reduced risk of ovarian cancer (OR = 0.62; 95% CI 0.52-0.75; P < 0.0001), which was driven by significant inverse associations with oral contraceptives (OR = 0.66; 95% CI 0.54-0.79; P < 0.0001) and contraceptive implants (OR = 0.30; 95% CI 0.12-0.73; P = 0.008). We observed a similar effect with use of injections (OR = 0.37; 95% CI 0.10-1.38; P = 0.14), but this did not achieve significance. No significant associations were observed between patterns of intrauterine device use and risk of ovarian cancer. Conclusions These findings support a protective effect of oral contraceptives and implants on risk of ovarian cancer among women with BRCA mutations. The possible protective effect of injections requires further evaluation.
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Neoplasias da Mama , Neoplasias Ovarianas , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Carcinoma Epitelial do Ovário , Estudos de Casos e Controles , Anticoncepcionais Orais/uso terapêutico , Feminino , Heterozigoto , Humanos , Mutação , Neoplasias Ovarianas/etiologia , Neoplasias Ovarianas/genética , Fatores de RiscoRESUMO
BRCA1 and BRCA2 mutation carriers face an elevated lifetime risk of developing ovarian cancer. Oral contraceptives have been shown to significantly decrease the risk of ovarian cancer by approximately 50% in this high-risk population. Changes in contraceptive formulations and patterns of use over time have introduced lower hormonal dosages, different steroid types and non-oral routes of administration. Specifically, there has been a considerable shift in patterns of contraceptive use and the increase in the uptake of non-oral, long-acting, reversible contraception (e.g., intrauterine devices, implants, injections) has corresponded to a decline in oral contraceptive pill use. Whether or not these other methods confer a protective effect against ovarian cancer in the general population is not clear. To our knowledge, there have been no such studies conducted among BRCA mutation carriers. Furthermore, the impact of these changes on the risk of developing ovarian cancer is not known. In this article, we will review the existing epidemiologic evidence regarding the role of contraceptives and the risk of ovarian cancer with a focus on women with a BRCA1 or BRCA2 mutation. We will discuss recent findings and gaps in the knowledge while extrapolating from studies conducted among women from the noncarrier population.
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OBJECTIVES: To evaluate the impact of autoantibodies against the M2-muscarinic receptor (anti-M2-R) on the clinical outcomes of patients receiving the standard treatment for peripartum cardiomyopathy (PPCM). METHODS: A total of 107 PPCM patients who received standard heart failure (HF) treatment between January 1998 and June 2020 were enrolled in this study. According to anti-M2-R reactivity, they were classified into negative (n = 59) and positive (n = 48) groups, denoted as the anti-M2-R (-) and anti-M2-R (+) groups. Echocardiography, 6-min walk distance, serum digoxin concentration (SDC), and routine laboratory tests were performed regularly for 2 years. The all-cause mortality, cardiovascular mortality, and rehospitalisation rate for HF were compared between the two groups. RESULTS: A total of 103 patients were included in the final data analysis, with 46 in the anti-M2-R (+) group and 57 in the anti-M2-R (-) group. Heart rate was lower in the anti-M2-R (+) group than in the anti-M2-R (-) group at the baseline (102.7 ± 6.1 bpm vs. 96.0 ± 6.4 bpm, p < 0.001). The initial SDC was higher in the anti-M2-R (+) group than in the anti-M2-R (-) group with the same dosage of digoxin (1.25 ± 0.45 vs. 0.78 ± 0.24 ng/mL, p < 0.001). The dosages of metoprolol and digoxin were higher in the anti-M2-R (-) patients than in the anti-M2-R (+) patients (38.8 ± 4.6 mg b.i.d. vs. 27.8 ± 5.3 mg b.i.d., p < 0.0001, respectively, for metoprolol; 0.12 ± 0.02 mg/day vs. 0.08 ± 0.04 mg/day, p < 0.0001, respectively, for digoxin). Furthermore, there was a greater improvement in cardiac function in the anti-M2-R (-) patients than in the anti-M2-R (+) patients. Multivariate analysis identified negativity for anti-M2-R as the independent predictor for the improvement of cardiac function. Rehospitalisation for HF was lower in the anti-M2-R (-) group, but all-cause mortality and cardiovascular mortality were the same. CONCLUSIONS: There were no differences in all-cause mortality or cardiovascular mortality between the two groups. Rehospitalisation rate for HF decreased in the anti-M2-R (-) group. This difference may be related to the regulation of the autonomic nervous system by anti-M2-R.
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Autoanticorpos/sangue , Sistema Nervoso Autônomo/efeitos dos fármacos , Cardiomiopatias/tratamento farmacológico , Fármacos Cardiovasculares/uso terapêutico , Coração/inervação , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Transtornos Puerperais/tratamento farmacológico , Receptor Muscarínico M2/imunologia , Adulto , Autoimunidade , Sistema Nervoso Autônomo/fisiopatologia , Cardiomiopatias/imunologia , Cardiomiopatias/mortalidade , Cardiomiopatias/fisiopatologia , Feminino , Humanos , Readmissão do Paciente , Período Periparto , Gravidez , Complicações Cardiovasculares na Gravidez/imunologia , Complicações Cardiovasculares na Gravidez/mortalidade , Complicações Cardiovasculares na Gravidez/fisiopatologia , Estudos Prospectivos , Transtornos Puerperais/imunologia , Transtornos Puerperais/mortalidade , Transtornos Puerperais/fisiopatologia , Recuperação de Função Fisiológica , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
Exploring a combined phototherapeutic strategy to overcome the limitations of a single mode therapy and inducing high anticancer efficiency is highly promising for precision cancer nanomedicine. However, a single-wavelength laser activates dual photothermal/photodynamic therapy (PTT/PDT) treatment is still a formidable challenge. Herein, we strategically design and fabricate a multifunctional theranostic nanosystem based on chlorin e6-functionalized polydopamine (PDA) coated prussian blue/manganese dioxide nanoparticles (PB-MnO2@PDA-Ce6 NPs). Interestingly, the obtained PB-MnO2@PDA NPs not only offer an effective delivery system for Ce6 but also provide strong optical absorption in the near-infrared range, endowing high antitumor efficacy of PTT. More importantly, the as-prepared PB-MnO2@PDA-Ce6 nanoagents exhibit an effective oxygen generation, superior reactive oxygen species (ROS), and outstanding photothermal conversion ability to greatly improve PTT and PDT treatments. As a result, both in vitro and in vivo treatments guided by MR imaging on liver cancer cells reveal the complete cell/tumor eradication under a single wavelength of 660 nm laser irradiation, implying the simultaneous synergistic PDT/PTT effects triggered by PB-MnO2@PDA-Ce6 nanoplatform, which are much higher than individual treatment. Taken together, our phototherapeutic nanoagents exhibit an excellent therapeutic performance, which may act as a nanoplatform to find safe and clinically translatable routes to accelerate cancer therapeutics.
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Ferrocianetos/química , Indóis/química , Raios Infravermelhos , Compostos de Manganês/química , Nanopartículas/química , Óxidos/química , Oxigênio/metabolismo , Fotoquimioterapia/métodos , Polímeros/química , Linhagem Celular Tumoral , Desenho de Fármacos , Humanos , Indóis/farmacologia , Lasers , Polímeros/farmacologiaRESUMO
Systematic examination of the inputs and outputs of the nonlemniscal auditory thalamus will facilitate the functional elucidation of this complex structure in the central auditory system. In mice, comprehensive tracing studies that reveal the long-range connectivity of the nonlemniscal auditory thalamus are lacking. To this end, we used Cre-inducible anterograde and monosynaptic retrograde viruses in Calbindin-2A-dgCre-D and Calretinin-IRES-Cre mice, focusing on the differences across subdivisions of the nonlemniscal auditory thalamus. We found that, 1) the dorsal and medial parts of the auditory thalamus were predominantly connected to sensory processing centers, whereas the posterior intralaminar (PIN) and peripeduncular nucleus (PP) were additionally connected to emotion and motivation modulation centers; 2) ventral auditory cortical areas were the major source of cortical inputs for all subdivisions, and the PIN/PP received more inputs from cortical layer 5 than other subdivisions did; 3) deep layers of the superior colliculus and rostral part of the nonlemniscal inferior colliculus preferentially projected to the PIN/PP; and 4) compared with the dorsal auditory thalamus, the PIN/PP mainly innervated association cortices. In addition, new brain areas connected to the nonlemniscal auditory thalamus, mostly the PIN/PP, were identified. Our results suggested subdivision-specific function of the nonlemniscal auditory thalamus in sound processing.
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Vias Auditivas/anatomia & histologia , Tálamo/anatomia & histologia , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The protracted maturational process of temporal processing in layer 4 (L4) of primary auditory cortex (A1) has been extensively studied. Accumulating evidences show that layer 5 (L5) receives direct thalamic inputs as well. How the temporal responses in L5 may developmentally emerge remains unclear. Using in vivo loose-patch recordings in rat A1, we found that putative pyramidal (Pyr) neurons in developing L5 exhibited adult-like stimulus-following ability but less bursting shortly after hearing onset. L5 Pyr neurons in adult A1 exhibited phase-locking similar to L4 neurons, while L5 fast-spiking (FS) neurons showed greater phase-locking at 7 and 12.5 pps. In developing L5, whole-cell recordings revealed inhibition with decay constant comparable to that in adult L5, thereby avoiding the summation of inhibition that contributed to the strong adaptation in L4. Given the targets of L5 outputs, the relatively precocious temporal processing in L5 might contribute to temporal response maturation in connected cortical and subcortical areas. Our findings were in agreement with the idea that L5 may be a "hub" for processing cortical inputs and outputs that can operate independently of L4.
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Córtex Auditivo/crescimento & desenvolvimento , Inibição Neural , Células Piramidais/fisiologia , Estimulação Acústica , Adaptação Fisiológica , Animais , Potenciais Evocados Auditivos , Feminino , Ratos Sprague-Dawley , Fatores de TempoRESUMO
Faithful representation of sound envelopes in primary auditory cortex (A1) is vital for temporal processing and perception of natural sounds. However, the emergence of cortical temporal processing mechanisms during development remains poorly understood. Although cortical inhibition has been proposed to play an important role in this process, direct in-vivo evidence has been lacking. Using loose-patch recordings in rat A1 immediately after hearing onset, we found that stimulus-following ability in fast-spiking neurons was significantly better than in regular-spiking (RS) neurons. In-vivo whole-cell recordings of RS neurons revealed that inhibition in the developing A1 demonstrated much weaker adaptation to repetitive stimuli than in adult A1. Furthermore, inhibitory synaptic inputs were of longer duration than observed in vitro and in adults. Early in development, overlap of the prolonged inhibition evoked by 2 closely following stimuli disrupted the classical temporal sequence between excitation and inhibition, resulting in slower following capacity. During maturation, inhibitory duration gradually shortened accompanied by an improving temporal following ability of RS neurons. Both inhibitory duration and stimulus-following ability demonstrated exposure-based plasticity. These results demonstrate the role of inhibition in setting the pace for experience-dependent maturation of temporal processing in the auditory cortex.
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Potenciais de Ação/fisiologia , Córtex Auditivo/citologia , Córtex Auditivo/crescimento & desenvolvimento , Inibição Neural/fisiologia , Neurônios/fisiologia , Estimulação Acústica , Fatores Etários , Animais , Animais Recém-Nascidos , Impedância Elétrica , Neurônios/classificação , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
BACKGROUND The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a prognostic factor in patients who have some types of malignant tumors. The aim of this study was to investigate the prognostic significance of the HALP score in patients with small cell lung cancer (SCLC) before first-line treatment with etoposide. MATERIAL AND METHODS A retrospective study included 178 patients with SCLC who received first-line chemotherapy with etoposide between September 2015 and May 2019. The baseline clinical characteristics and blood parameters were recorded. Univariate and multivariate analysis and Kaplan-Meier plots were used to identify the factors associated with progression-free survival (PFS). RESULTS The optimal cut-off values of the HALP score was determined by X-tile software to be 25.8. Univariate and multivariate analysis showed that in 178 patients, the HALP score, body mass index (BMI), and serum albumin levels had no prognostic significance. In the patient age group <65 years, a BMI ≥24 kg/m² was an independent prognostic factor (HR, 1.943; 95% CI, 1.251-3.018) (P=0.003). In the patient age group ≥65 years, a HALP score >25.8 was an independent positive prognostic factor for outcome following first-line treatment with etoposide (HR, 0.483; 95% CI, 0.270-0.865) (P=0.014). CONCLUSIONS In patients <65 years with SCLC who underwent first-line treatment with etoposide, a BMI ≥24 kg/m² an independent prognostic factor, and in patients ≥65 years, a HALP score >25.8 was an independent predictor of improved outcome, associated with increased PFS.
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Biomarcadores Tumorais/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/sangue , Plaquetas/metabolismo , Índice de Massa Corporal , Etoposídeo/farmacologia , Etoposídeo/uso terapêutico , Feminino , Hemoglobinas/metabolismo , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Contagem de Linfócitos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Albumina Sérica Humana/metabolismo , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND: PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. RESULTS: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). CONCLUSIONS: PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama Masculina/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/mortalidade , Neoplasias da Mama Masculina/patologia , Neutropenia Febril Induzida por Quimioterapia/etiologia , Neutropenia Febril Induzida por Quimioterapia/prevenção & controle , China/epidemiologia , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Intervalo Livre de Progressão , Estudos Prospectivos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Adulto JovemRESUMO
Four custom fiber Bragg grating (FBG)-based sensors are developed to monitor an artificial landslide located in Nanjing, China. The sensors are composed of a rod and two FBGs. Based on the strength of the rods, two sensors are referred to as "hard sensors" (Sensor 1 and Sensor 2), the other two are referred to as "soft sensors" (Sensor 3 and Sensor 4). The two FBGs are fixed on each sensor rod at distances of 50 cm and 100 cm from the top of the rod (an upper FBG and a lower FBG). In the experiment presented in this paper, the sensors are installed on a slope on which an artificial landslide is generated through both machine-based and manual excavation. The fiber sensing system consists of the four custom FBG-based sensors, optical fiber, a static fiber grating demodulation instrument (SM125), and a PC with the necessary software. Experimental data was collected in the presence of an artificial landslide, and the results show that the lower FBGs are more sensitive than the upper FBGs for all four of the custom sensors. It was also found that Sensor 2 and Sensor 4 are more capable of monitoring small-scale landslides than Sensor 1 and Sensor 3, and this is mainly due to their placement location with respect to the landslide. The stronger rods used in the hard sensors make them more adaptable to the harsh environments of large landslides. Thus, hard sensors should be fixed near the landslide, while soft sensors should be placed farther away from the landslide. In addition, a clear tendency of strain variation can be detected by the soft sensors, which can be used to predict landslides and raise a hazard alarm.
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BACKGROUND: Platinum chemotherapy has a role in the treatment of metastatic triple-negative breast cancer but its full potential has probably not yet been reached. We assessed whether a cisplatin plus gemcitabine regimen was non-inferior to or superior to paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer. METHODS: For this open-label, randomised, phase 3, hybrid-designed trial undertaken at 12 institutions or hospitals in China, we included Chinese patients aged 18-70 years with previously untreated, histologically confirmed metastatic triple-negative breast cancer, and an ECOG performance status of 0-1. These patients were randomly assigned (1:1) to receive either cisplatin plus gemcitabine (cisplatin 75 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1 and 8) or paclitaxel plus gemcitabine (paclitaxel 175 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1 and 8) given intravenously every 3 weeks for a maximum of eight cycles. Randomisation was done centrally via an interactive web response system using block randomisation with a size of eight, with no stratification factors. Patients and investigator were aware of group assignments. The primary endpoint was progression-free survival and analyses were based on all patients who received at least one dose of assigned treatment. The margin used to establish non-inferiority was 1·2. If non-inferiority of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine was achieved, we would then test for superiority. The trial is registered with ClinicalTrials.gov, number NCT01287624. FINDINGS: From Jan 14, 2011, to Nov 14, 2013, 240 patients were assessed for eligibility and randomly assigned to treatment (120 in the cisplatin plus gemcitabine group and 120 in the paclitaxel plus gemcitabine group). 236 patients received at least one dose of assigned chemotherapy and were included in the modified intention-to-treat analysis (118 per group). After a median follow-up of 16·3 months (IQR 14·4-26·8) in the cisplatin plus gemcitabine group and 15·9 months (10·7-25·4) in the paclitaxel plus gemcitabine group, the hazard ratio for progression-free survival was 0·692 (95% CI 0·523-0·915; pnon-inferiority<0·0001, psuperiority=0·009, thus cisplatin plus gemcitabine was both non-inferior to and superior to paclitaxel plus gemcitabine. Median progression-free survival was 7·73 months (95% CI 6·16-9·30) in the cisplatin plus gemcitabine group and 6·47 months (5·76-7·18) in the paclitaxel plus gemcitabine group. Grade 3 or 4 adverse events that differed significantly between the two groups included nausea (eight [7%] vs one [<1%]), vomiting (13 [11%] vs one [<1%]), musculoskeletal pain (none vs ten [8%]), anaemia (39 [33%] vs six [5%]), and thrombocytopenia (38 [32%] vs three [3%]), for the cisplatin plus gemcitabine compared with the paclitaxel plus gemcitabine groups, respectively. In addition, patients in the cisplatin plus gemcitabine group had significantly fewer events of grade 1-4 alopecia (12 [10%] vs 42 [36%]) and peripheral neuropathy (27 [23%] vs 60 [51%]), but more grade 1-4 anorexia (33 [28%] vs 10 [8%]), constipation (29 [25%] vs 11 [9%]), hypomagnesaemia (27 [23%] vs five [4%]), and hypokalaemia (10 [8%] vs two [2%]). Serious drug-related adverse events were seen in three patients in the paclitaxel plus gemcitabine group (interstitial pneumonia, anaphylaxis, and severe neutropenia) and four in the cisplatin plus gemcitabine group (pathological bone fracture, thrombocytopenia with subcutaneous haemorrhage, severe anaemia, and cardiogenic syncope). There were no treatment-related deaths. INTERPRETATION: Cisplatin plus gemcitabine could be an alternative or even the preferred first-line chemotherapy strategy for patients with metastatic triple-negative breast cancer. FUNDING: Shanghai Natural Science Foundation.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Paclitaxel/administração & dosagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , China , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/efeitos adversos , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/patologia , GencitabinaRESUMO
We present a pilot study that aims to examine the possibility to easily and noninvasively detect and discriminate females with ovarian cancer (OC) from females that have no tumor(s) and from females that have benign genital tract neoplasia, using exhaled breath samples. The study is based on clinical samples and data from 182 females, as follows: 48 females with OC, 48 tumor-free controls and 86 females with benign gynecological neoplasia. Analysis of the breath samples with gas chromatography linked with mass spectrometry shows that decanal, nonanal, styrene, 2-butanone and hexadecane could serve as potential volatile markers for OC. Analysis of the same samples with tailor-made nanoarrays shows good discrimination between females with OC and females that have either no tumor or benign genital tract neoplasia (71% for accuracy, sensitivity and specificity). Conversely, the nanoarray output shows excellent discrimination between the OC patients and the tumor-free controls (79% sensitivity, 100% specificity and 89% accuracy). These results suggest that the nanoarray approach might be useful to avoid unnecessary complicated or expensive tests for tumor-free females in case of a negative result. In the case of positive result, the test will indicate with high probability the presence of OC.
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Testes Respiratórios , Neoplasias Ovarianas/metabolismo , Adulto , Fatores Etários , Idoso , Álcool Desidrogenase/análise , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Pessoa de Meia-Idade , Curva ROC , Compostos Orgânicos Voláteis/análiseRESUMO
AIM: We aimed to evaluate the preventive effect of the ligustrazine nanoparticles nano spray (LNNS) for postoperative peritoneal adhesions in female rat models. MATERIAL AND METHODS: Fifty Wistar female rats weighting 250-300 g were randomly assigned to seven equal groups. All animals in the seven groups underwent midline laparotomy and ceca were abraded with sterile rasp. Group 1 underwent sham operations without treatment. In group 2, a postoperative peritoneal adhesion model was created, but no medication was given. In group 3, a postoperative peritoneal adhesion model was treated with LNNS, 2.5 mg/kg. In group 4, a postoperative peritoneal adhesion model was treated with LNNS, 5 mg/kg. In group 5, a postoperative peritoneal adhesion model was treated with LNNS, 10 mg/kg. In group 6, a postoperative peritoneal adhesion model was treated with polylactic acid (PLA) nanoparticle. In group 7, a postoperative peritoneal adhesion model was treated with ligustrazine, 2.5 mg/kg. Ten days after surgery, macroscopic and pathologic assessments were performed, and peritoneal fluid samples were collected in each group. The levels of tumor necrosis factor-α, tissue plasminogen activator and plasminogen activator inhibitor-1 in peritoneal fluid were determined by enzyme-linked immunosorbent assay. RESULTS: The adhesion score and extent of groups 4 and 5 was lower than that of group 2 in macroscopic assessment (P < 0.05). A comparison of tumor necrosis factor-α and tissue plasminogen activator level in the peritoneal fluid also demonstrated significant differences among groups 2, 4 and 5 (P < 0.05). The levels of plasminogen activator inhibitor-1 in peritoneal fluid in the LNNS groups were decreased compared to group 1. CONCLUSION: We suggest that LNNS could reduce peritoneal adhesion formation and it could be applied as a novel intervention for postoperative peritoneal adhesion.
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Nanopartículas/administração & dosagem , Doenças Peritoneais/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Pirazinas/administração & dosagem , Aderências Teciduais/prevenção & controle , Animais , Líquido Ascítico/química , Ensaio de Imunoadsorção Enzimática , Feminino , Doenças Peritoneais/patologia , Inibidor 1 de Ativador de Plasminogênio/análise , Ratos , Ratos Wistar , Aderências Teciduais/patologia , Fator de Necrose Tumoral alfa/análiseRESUMO
Using spatial analysis function of Arcgis software, the present study investigated the building environment impact evaluation index system of coastal development in Liaoning Province. The factors of it included of current state of environmental quality, environmental impact of marine development and marine environmental disaster. Weighted factor analysis and comprehensive index method were utilized. At the end, comprehensive environment effect of coastal development in Liaoning Province were evaluated successfully. The result showed that the environmental effect of development activity were most serious, along the Zhao Jiatun coast in north of Zhimao bay and coast of Mianhua island in Dalian bay.
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Meio Ambiente , Análise Espacial , ChinaRESUMO
Adhesion-related complications after abdominal surgery bring out momentous morbidity and costs. Outcomes from animal experiments investigating prevention of adhesions are limited due to lack of consistency in existing animal models. Different intraperitoneal adhesion models were compared the inter observer variability was evaluated to seek for best model. Forty male SD rats weighting 250-300g were included and assigned randomly to four groups with diverse techniques, (A) postoperative adhesion cecum rat model abraded with sterile rasp; (B) postoperative adhesion cecum rat model abraded with sterile dry gauze; (C) postoperative adhesion cecum rat model abraded with sterile blade; (D) postoperative adhesion cecum rat model abraded with vascular clamp. Macroscopic adhesion scores were evaluated by Bigatti scoring system, and the incidence of adhesion were surveyed on the 7th day after the surgery. The results showed that four techniques currently used Bigatti adhesion scoring system are subjective, the sterile rasp is the most consistent and reproducible tool to establish an intraperitoneal adhesion model which is helpful for related studies and the development of new substances for adhesion prevention in the future.
Assuntos
Ceco/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Doenças Peritoneais/etiologia , Animais , Modelos Animais de Doenças , Masculino , Doenças Peritoneais/patologia , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Fatores de Tempo , Aderências TeciduaisRESUMO
BACKGROUND: Despite the use of modern immunochemotherapy regimens, a significant proportion of diffuse large B-cell lymphoma (DLBCL) patients will relapse. We proposed absolute lymphocyte count/absolute monocyte count ratio (ALC/AMC ratio) as a new prognostic factor in relapsed or primary refractory DLBCL. METHODS: We retrospectively analyzed 163 patients who have been diagnosed with relapsed or primary refractory DLBCL. The overall survival (OS) and progression-free survival (PFS) were measured from the time of first relapse. The Cox proportional hazards model was used to evaluate ALC/AMC ratio as prognostic factors for OS and PFS. RESULTS: On univariate and multivariate analysis performed with factors included in the saaIPI, early relapse, prior exposure to rituximab and autologous stem-cell transplantation (ASCT), the ALC/AMC ratio at the time of first relapse remained an independent predictor of PFS and OS (PFS: P < 0.001; OS: P < 0.001). Patients with lower ALC/AMC ratio (<2.0) had lower overall response rate, 1-year PFS and 2-year OS rate compared with those with higher ALC/AMC ratio (≥2.0). Moreover, the ALC/AMC ratio can provide additional prognostic information when superimposed on the saaIPI. CONCLUSIONS: Lower ALC/AMC ratio at the time of first relapse is a adverse prognostic factor for OS and PFS in relapsed or primary refractory DLBCL, and leads to the identification of high-risk patients otherwise classified as low/intermediate risk by the saaIPI alone.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos/imunologia , Linfoma Difuso de Grandes Células B/terapia , Monócitos/imunologia , Transplante de Células-Tronco , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Fatores de Tempo , Resultado do TratamentoRESUMO
To determine whether peripheral blood absolute lymphocyte/absolute monocyte counts ratio (ALC/AMC ratio) at diagnosis predicts survival of diffuse large B cell lymphoma (DLBCL) patients treated with standard first-line regimens, we retrospectively analyzed 244 patients with DLBCL who were treated with standard cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, or rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone. Progression-free survival and overall survival (PFS and OS) were estimated using the Kaplan-Meier method and two-tailed log-rank; The Cox proportional hazards model was used to evaluate ALC/AMC ratio as prognostic factors when adjusting for the International Prognostic Index (IPI). On univariate and multivariate analyses performed with factors included in the IPI, the ALC/AMC ratio at diagnosis remained an independent predictor of OS and PFS (OS: P < 0.001; PFS: P < 0.001). Patients with lower ALC/AMC ratio (<3.8) seemed to have lower complete remission rate, 2-year PFS and 3-year OS when compared to patients with ALC/AMC ratio ≥3.8, respectively (26 versus 90 %, P < 0.001; 18 versus 82 %, P < 0.001; 24 versus 86 %; P < 0.001, respectively). Moreover, the ALC/AMC ratio was able to further risk-stratify IPI 0-2 and three-five risk patient groups, respectively. The ALC/AMC ratio at the time of diagnosis may provide additional prognostic information beyond that of the IPI for patients with DLBCL who receive standard first-line regimens.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfócitos/metabolismo , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Monócitos/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prednisona/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento , Vincristina/administração & dosagem , Adulto JovemRESUMO
BACKGROUND: The visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score was correlated with the increase of left ventricular filling pressure (LVFP). HYPOTHESIS: We suspected that the VMT score might be a valuable prognostic biomarker for heart failure with mildly reduced ejection fraction (HFmrEF) patients. This study was to evaluate the predictive value of VMT score for 1-year all-cause and cardiovascular disease (CVD)-cause mortality in HFmrEF patients. METHODS: This cohort study enrolled 379 patients aged ≥18 years old with HFmrEF. Univariable and multivariable Cox regression analysis was employed to assess the association between VMT score and all-cause or CVD-cause mortality in HFmrEF patients. Hazards ratio (HR), and 95% confidence interval (CI) were effect sizes. Kaplan-Meier curves showed the survival probability of patients. The area under the curve (AUC) evaluated the prognostic value of the VMT score. RESULTS: The risk of all-cause mortality was increased in HFmrEF patients in the VMT score of 2 (HR = 2.80, 95%CI: 1.04-7.52) and 3 (HR = 4.29, 95%CI: 1.58-11.66). The VMT score of 3 was associated with an increased risk of 1-year CVD-cause mortality in patients with HFmrEF (HR = 7.63, 95%CI: 1.70-34.33). The AUC of VMT score for predicting 1-year all-cause mortality of HFmrEF patients was 0.724, and for predicting 1-year CVD-cause mortality of HFmrEF patients was 0.748. The survival probability of patients with the VMT score < 2 was higher than those with the VMT score of 2 and 3. CONCLUSION: The VMT score might be a reliable prognostic index for 1-year all-cause or CVD-cause mortality of HFmrEF patients.