RESUMO
Objective: To estimate the impacts of different anesthetic protocols on the speed and quality of postoperative resuscitation in patients undergoing painless gastroscopy. Methods: This was a prospectively designed randomized control study that included 150 patients who underwent painless gastroscopy in Hainan Cancer Hospital affiliated to Hainan Medical College between April and December of 2023. All the patients, classified as American Society of Aneshesiologists (ASA) Grade â or â ¡, were randomly divided into three groups with different anesthetic protocols, including propofol group (group P), remimazolam group (group R) and remimazolam with flumazenil group (group RF). There were eventually 50 patients in each group. The three groups of patients were compared for their resuscitation time and the time that they stayed in the resuscitation room (addressed as"room time"below). At 10 min and 20 min after resuscitation, each patient was tested for recognition ability (orientation score), walking ability and fine motor skill (including reaction speed, quick-click ability and visual memory), respectively, with possible adverse reactions recorded spontaneously, such as hypotension, dizziness, nausea and vomitus. Results: There were 29 males and 21 females in group P with an average age of (34±6) years, 27 males and 23 females in group R with an average age of (36±8) years, and 26 males and 24 females in group RF with an average age of (33±7) years, respectively. All examinations for each patient were successfully completed with no interruptions. The resuscitation time and room time of group RF were (47±15) s and (26±5) min,respectively, which were both shorter than those in either group R [(489±92) s and (35±6) min] or group P [(196±61) s and (31±7) min] (all P<0.05). The orientation score of patients in group RF at 10 min after resuscitation was (79.0±10.5), which was significantly higher than that in group R (70.0±11.7) (P<0.05). The patients' walking ability score of group RF at 10 min and 20 min after resuscitation were [(23.6±10.8), (48.0±4.5)], which were better than those in group R[(15.4±11.1), (47.6±4.8)] (both P<0.05). The patients' reaction speed and quick-click scores of group RF were [(851.0±150.9), (547.0±114.0) ms] and [(758.0±73.2), (629.0±128.9) ms], which were better than those in either group R [(1 151.0±206.0), (732.0±135.1) ms], [(893.0±110.9), (765.8±125.8) ms] or group P [(985.0±225.3), (613.0±123.2) ms], [(831.0±87.7), (691.0±115.8) ms] (all P<0.05). The incidence rate of hypotension in group P was 18% (9/50), higher than that in either Group R [4% (2/50)] or group RF [2% (1/50)] (all P<0.05). The incidence rates of dizziness, nausea and vomitus were comparable among all the three groups with no statistical differences (all P>0.05). Conclusion: In patients undergoing anesthesia with remazolam, the use of flumazenil can not only shorten the resuscitation time and the time that the patients need to stay in the resuscitation room, but also speed up the recovery of the patients' recognition, walking and fine motor skill abilities.
Assuntos
Gastroscopia , Humanos , Feminino , Masculino , Adulto , Anestesia/métodos , Estudos Prospectivos , Período de Recuperação da Anestesia , Propofol/administração & dosagem , Período Pós-Operatório , Ressuscitação/métodos , Anestésicos/administração & dosagemRESUMO
Objective: To investugate the unique electrocardiogram (ECG) characteristics of fulminant myocarditis (FM) patients and provide important clues for the diagnosis of FM. Methods: This was a retrospective study. Patients diagnosed with acute myocarditis at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from February 2017 to April 2022 were enrolled and divided into fulminant myocarditis group (FM) and non-fulminant myocarditis group (NFM) according to clinical diagnosis. A total of 246 healthy people who underwent physical examination in the Health examination Center of Tongji Hospital at the same period were selected as the control group. The clinical data and ECG characteristics of the above 3 groups were analyzed and compared. Logistic regression model was used to analyze the influence of ECG parameters on left ventricular ejection fraction in FM patients. Receiver operating curves were constructed to evaluate the predictive value of different ECG parameters for FM. Results: A total of 180 patients were included in this study (FM group: n=123; NFM group: n=57), with an age of (35.0±16.2) years and 106 males (58.89%). Compared with NFM group, ECG was significantly abnormal in FM group, with a higher incidence of sinus tachycardia, ventricular tachycardia or ventricular fibrillation, escape rhythm, right bundle branch block, third degree atrioventricular block, ST-segment elevation, low voltage, prolonged QTc interval, and widened QRS wave in the FM group (all P<0.05). The ECG parameters showed that the amplitude of the full lead QRS wave in FM group was lower than that in NFM group (P<0.01). The average heart rate and QTc interval of FM group were significantly higher than those of NFM and control groups (all P<0.05). Although ST-segment elevation had a higher incidence in the FM group, ECG parameters showed that except for leads â ¢ and aVF, the ST segment levels in all leads in the FM group were lower than those in the control group (all P<0.05). There was a statistically significant difference in some ST segment changes between FM and NFM groups, while there was no statistical difference between the NFM and control groups. Multivariate regression analysis showed that widened QRS wave and increased heart rate were the influencing factors for left ventricular systolic dysfunction in FM patients (OR=16.914, 95%CI: 1.367-209.224, P=0.028; OR=1.026, 95%CI: 1.010-1.042, P=0.001). Receiver operating curve analysis showed that heart rate>86.90 beat/min, QTc>431.50 ms, and RV5+SV1<1.72 mV had certain predictive value for FM diagnosis. Conclusions: FM patients displayed marked and severe ECG abnormalities, and characteristic changes in ECG can provide important first clues for the diagnosis of FM.
Assuntos
Eletrocardiografia , Miocardite , Humanos , Miocardite/fisiopatologia , Miocardite/diagnóstico , Masculino , Eletrocardiografia/métodos , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Doença Aguda , Fibrilação Ventricular/fisiopatologia , Fibrilação Ventricular/diagnósticoRESUMO
The global diversity of fungi has been estimated between 2 to 11 million species, of which only about 155 000 have been named. Most fungi are invisible to the unaided eye, but they represent a major component of biodiversity on our planet, and play essential ecological roles, supporting life as we know it. Although approximately 20 000 fungal genera are presently recognised, the ecology of most remains undetermined. Despite all this diversity, the mycological community actively researches some fungal genera more commonly than others. This poses an interesting question: why have some fungal genera impacted mycology and related fields more than others? To address this issue, we conducted a bibliometric analysis to identify the top 100 most cited fungal genera. A thorough database search of the Web of Science, Google Scholar, and PubMed was performed to establish which genera are most cited. The most cited 10 genera are Saccharomyces, Candida, Aspergillus, Fusarium, Penicillium, Trichoderma, Botrytis, Pichia, Cryptococcus and Alternaria. Case studies are presented for the 100 most cited genera with general background, notes on their ecology and economic significance and important research advances. This paper provides a historic overview of scientific research of these genera and the prospect for further research. Citation: Bhunjun CS, Chen YJ, Phukhamsakda C, Boekhout T, Groenewald JZ, McKenzie EHC, Francisco EC, Frisvad JC, Groenewald M, Hurdeal VG, Luangsa-ard J, Perrone G, Visagie CM, Bai FY, Blaszkowski J, Braun U, de Souza FA, de Queiroz MB, Dutta AK, Gonkhom D, Goto BT, Guarnaccia V, Hagen F, Houbraken J, Lachance MA, Li JJ, Luo KY, Magurno F, Mongkolsamrit S, Robert V, Roy N, Tibpromma S, Wanasinghe DN, Wang DQ, Wei DP, Zhao CL, Aiphuk W, Ajayi-Oyetunde O, Arantes TD, Araujo JC, Begerow D, Bakhshi M, Barbosa RN, Behrens FH, Bensch K, Bezerra JDP, Bilanski P, Bradley CA, Bubner B, Burgess TI, Buyck B, Cadez N, Cai L, Calaça FJS, Campbell LJ, Chaverri P, Chen YY, Chethana KWT, Coetzee B, Costa MM, Chen Q, Custódio FA, Dai YC, Damm U, de Azevedo Santiago ALCM, De Miccolis Angelini RM, Dijksterhuis J, Dissanayake AJ, Doilom M, Dong W, Alvarez-Duarte E, Fischer M, Gajanayake AJ, Gené J, Gomdola D, Gomes AAM, Hausner G, He MQ, Hou L, Iturrieta-González I, Jami F, Jankowiak R, Jayawardena RS, Kandemir H, Kiss L, Kobmoo N, Kowalski T, Landi L, Lin CG, Liu JK, Liu XB, Loizides M, Luangharn T, Maharachchikumbura SSN, Makhathini Mkhwanazi GJ, Manawasinghe IS, Marin-Felix Y, McTaggart AR, Moreau PA, Morozova OV, Mostert L, Osiewacz HD, Pem D, Phookamsak R, Pollastro S, Pordel A, Poyntner C, Phillips AJL, Phonemany M, Promputtha I, Rathnayaka AR, Rodrigues AM, Romanazzi G, Rothmann L, Salgado-Salazar C, Sandoval-Denis M, Saupe SJ, Scholler M, Scott P, Shivas RG, Silar P, Souza-Motta CM, Silva-Filho AGS, Spies CFJ, Stchigel AM, Sterflinger K, Summerbell RC, Svetasheva TY, Takamatsu S, Theelen B, Theodoro RC, Thines M, Thongklang N, Torres R, Turchetti B, van den Brule T, Wang XW, Wartchow F, Welti S, Wijesinghe SN, Wu F, Xu R, Yang ZL, Yilmaz N, Yurkov A, Zhao L, Zhao RL, Zhou N, Hyde KD, Crous PW (2024). What are the 100 most cited fungal genera? Studies in Mycology 108: 1-411. doi: 10.3114/sim.2024.108.01.
Assuntos
Atrofia Muscular Espinal , Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Atrofia Muscular Espinal/terapia , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/tratamento farmacológico , Atrofias Musculares Espinais da Infância/terapia , Atrofias Musculares Espinais da Infância/genética , Atrofias Musculares Espinais da Infância/diagnóstico , Atrofias Musculares Espinais da Infância/tratamento farmacológico , Proteína 2 de Sobrevivência do Neurônio Motor/genética , Criança , Éxons , OligonucleotídeosRESUMO
Objective: To investigate the pathogenic mechanism and clinical characteristics of the novel splicing variant of ATP-binding cassette subfamily B member 4 (ABCB4) and provide a basis for subsequent genetic diagnosis. Methods: The clinical data of a 5-year-old child with cholestatic liver disease admitted to the Beijing Children's Hospital of Capital Medical University was retrospectively analyzed. The pathogenic variations were detected by whole exome sequencing and verified by Sanger sequencing, and bioinformatics was used to predict the pathogenicity of the mutation sites. Possible pathogenic variations were verified in vitro by Minigene assay. The clinical outcome was followed after discharge from hospital. Results: The 5-year-old boy had developed cholestasis at the age of 11 months. His physical examination showed obvious enlargement of the liver and spleen. Cholestatic cirrhosis was diagnosed by liver function tests, abdominal ultrasonography, liver biopsy and pathology. The results of genetic analysis showed that the patient was a complex heterozygote of the ABCB4 gene, with a pathogenic mutation c.2860G>A and a novel mutation c.2065-8T>G, derived from the mother and father respectively. The conservative prediction of the c.2065-8T>G site showed that this region was highly conserved and may affect splicing. Minigene assay results confirmed that the c.2065-8T>G mutation resulted in a 7 bp retention of intron 16 in the mature mRNA. In the absence of nonsense-mediated mRNA decay, the amino acid frameshift forms a truncated protein, which is represented by p.Glu689ValfsTer19. The patient was diagnosed as progressive familial intrahepatic cholestasis type 3 (PFIC3) and treated with ursodeoxycholic acid (UDCA). His clinical symptoms improved during 18 months of follow-up. Conclusions: The c.2065-8T>G variant is confirmed to affect the splicing process and exhibits complex heterozygosity with c.2860G>A, which is identified as the cause of the disease. PFIC3 children with this variant showed cholestatic liver disease as the main manifestation with a slow progression and was sensitive to treatment with UDCA.
Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP , Colestase Intra-Hepática , Mutação , Fenótipo , Humanos , Masculino , Colestase Intra-Hepática/genética , Colestase Intra-Hepática/diagnóstico , Pré-Escolar , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/deficiência , Sequenciamento do Exoma , Genótipo , Heterozigoto , Estudos Retrospectivos , Ácido Ursodesoxicólico/uso terapêutico , Fígado/patologiaRESUMO
Objective: To investigate the molecular mechanisms of chronic rhinosinusitis (CRS), to identify key cell subgroups and genes, to construct effective diagnostic models, and to screen for potential therapeutic drugs. Methods: Key cell subgroups in CRS were identified through single-cell transcriptomic sequencing data. Essential genes associated with CRS were selected and diagnostic models were constructed by hdWGCNA (high dimensional weighted gene co-expression network analysis) and various machine learning algorithms. Causal inference analysis was performed using Mendelian randomization and colocalization analysis. Potential therapeutic drugs were identified using molecular docking technology, and the results of bioinformatics analysis were validated by immunofluorescence staining. Graphpad Prism, R, Python, and Adobe Illustrator software were used for data and image processing. Results: An increased proportion of basal and suprabasal cells was observed in CRS, especially in eosinophilic CRS with nasal polyps (ECRSwNP), with P=0.001. hdWGCNA revealed that the "yellow module" was closely related to basal and suprabasal cells in CRS. Univariate logistic regression and LASSO algorithm selected 13 key genes (CTSC, LAMB3, CYP2S1, TRPV4, ARHGAP21, PTHLH, CDH26, MRPS6, TENM4, FAM110C, NCKAP5, SAMD3, and PTCHD4). Based on these 13 genes, an effective CRS diagnostic model was developed using various machine learning algorithms (AUC=0.958). Mendelian randomization analysis indicated a causal relationship between CTSC and CRS (inverse variance weighted: OR=1.06, P=0.006), and colocalization analysis confirmed shared genetic variants between CTSC and CRS (PPH4/PPH3>2). Molecular docking results showed that acetaminophen binded well with CTSC (binding energy:-5.638 kcal/mol). Immunofluorescence staining experiments indicated an increase in CTSC+cells in CRS. Conclusion: This study integrates various bioinformatics methods to identify key cell types and genes in CRS, constructs an effective diagnostic model, underscores the critical role of the CTSC gene in CRS pathogenesis, and provides new targets for the treatment of CRS.
Assuntos
Catepsina C , Rinossinusite , Transcriptoma , Humanos , Algoritmos , Doença Crônica , Biologia Computacional , Perfilação da Expressão Gênica , Aprendizado de Máquina , Análise da Randomização Mendeliana , Simulação de Acoplamento Molecular , Pólipos Nasais/genética , Rinossinusite/genética , Análise de Célula Única , Catepsina C/genéticaRESUMO
Objective: To assess the capability of seven reference medical laboratories to detect BCR::ABL1 p210 transcription levels and to compare the results among those laboratories. Methods: The interlaboratory comparison was carried out in two stages. The samples were prepared by the reference laboratory. The quantitative values of BCR::ABL1 p210 of the comparison samples covered 0.001%-0.01%, 0.01%-0.1%, 0.1%-1%, 1%-10% and>10% in each stage. Real-time quantitative PCR (RT-PCR) and dPCR (digital PCR) were used to examine the samples. The conversion factor (CF) was calculated and validated for each laboratory. Results: In the RT-PCR comparison, one laboratory was failed to detect BCR::ABL1 p210 in fourteen samples at the first stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.133-0.338) and 95% limits of agreement within ±5 folds (upper limit 0.147-0.785, lower limit -0.770--0.109), and the corresponding CF values were calculated and validated. In the dPCR comparison, one laboratory did not report results at the second stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.026-0.267) and 95% limits of agreement within±5 folds (upper limit 0.084-0.991, lower limit -0.669--0.135), and the corresponding CF values were calculated and validated. The samples with BCR::ABL1 p210 quantitative values of 0.01%-0.1%, 0.1%-1%, 1%-10% and >10% could be detected by both RT-PCR and qPCR. When the quantitative value of BCR::ABL1 p210 was 0.001%-0.01%, the detection rate of dPCR was higher than that of RT-PCR (85.56% vs. 68.00%). Conclusions: A good consistency is present among various laboratories. The quantitative value of BCR::ABL1 p210 is comparable among laboratories as shown by the CF value conversion. For quantitative detection of BCR::ABL1 p210 deep molecular reaction, dPCR has a higher positive detection rate and more advantages than RT-PCR. To ensure the accuracy and reproducibility of the BCR::ABL1 p210 test, it is imperative for every laboratory to enhance their daily quality control practices.
Assuntos
Proteínas de Fusão bcr-abl , Reação em Cadeia da Polimerase em Tempo Real , Humanos , Proteínas de Fusão bcr-abl/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Reprodutibilidade dos TestesRESUMO
Objective: To investigate the regulatory effect and mechanism of interleukin-22 (IL-22) on the gingival epithelial barrier in the context of periodontal inflammation. Methods: IL-22 knockout (IL-22 KO) mice were constructed, and periodontitis mice models were established through oral gavage with polymicrobial inoculation. DNAs were extracted from the oral plaques of IL-22 KO periodontitis mice group (n=7) and their wild-type littermates periodontitis group (n=7) to establish a periodontitis-related oral microbiota database"PD-RiskMicroDB", determining the relationship between changes in oral microbiota and microbial function in two groups using 16S rRNA sequencing results. Gingival epithelial cells (GEC) were cultured by modified trypsinization method, and were stimulated with 100 µg/L IL-22, Porphyromonas gingivalis (Pg) (multiplicity of infection:100), separately or together for 3 and 12 hours. The experimental groups were as follows: control group (no stimulation), IL-22 group, Pg group and Pg+IL-22 group. The expression of barrier protein E-cadherin in each group at 3 h was detected by immunofluorescence, real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting. Fluorescein isothiocyanate-dextran-mediated epithelial cell permeability experiment was conducted to clarify the changes in permeability of GEC in each group at 3 and 12 h. The mRNA expressions of E-cadherin in the gingival epithelium of wild-type littermates periodontitis group and IL-22 KO periodontitis group were detected by RT-qPCR. Fifteen C57BL/6 wild-type mice were randomly divided into control group (n=5), periodontitis group (n=5) and periodontitis+IL-22 treatment group (n=5). RT-qPCR and immunohistochemistry (IHC) staining were used to detect the expression level of E-cadherin in the gingival epithelium of each group. Results: 16S rRNA sequencing results showed that the composition of oral microbiota changed in IL-22 KO periodontitis group, of which the abundance of bacterial genera related to periodontal tissue invasion was significantly increased (linear discriminant analysis score: 2.22, P=0.009), compared with wild-type littermates periodontitis group. In vitro cell experiments showed that after Pg infection for 3 hours, the cell connections of GEC in Pg group were interrupted, and the fluorescence intensity of E-cadherin was reduced in Pg group compared with the control group. Meanwhile, the mRNA and protein expression levels of E-cadherin (mRNA: 0.69±0.12; protein: 0.60±0.12) were downregulated compared with the control group [mRNA: 1.00±0.00 (P=0.043); protein: 1.04±0.08 (P=0.003)], respectively. The fluorescence intensity of E-cadherin in the Pg+IL-22 group was enhanced compared with Pg group, and expression levels of E-cadherin mRNA (1.16±0.10) and protein (0.98±0.07) in Pg+IL-22 group showed a significant increase compared with Pg group [mRNA: 0.69±0.12 (P=0.005); protein: 0.60±0.12 (P=0.007)]. The result of epithelial permeability test showed that there was no statistical difference in epithelial permeability among control group, Pg group, IL-22 group and Pg+IL-22 group with treatment for 3 hours (F=0.20, P=0.893). While when the treatment time turned to be 12 hours, the epithelial barrier permeability showed a significant increase in Pg group (1.39±0.15) compared with control group (1.00±0.00, P=0.027), and a decrease in Pg+IL-22 group (1.02±0.18) compared with Pg group (1.39±0.15, P=0.034). In vivo, the mRNA expression of E-cadherin in the gingival epithelium of IL-22 KO periodontitis group decreased significantly (0.32±0.21) compared with wild-type littermates periodontitis group (1.01±0.01) (t=5.70, P=0.005). Moreover, RT-qPCR and IHC staining results showed that the mRNA expression level of E-cadherin (0.40±0.07) and absorbance value of E-cadherin positive expression (0.02±0.00) in gingival epithelial tissue of periodontitis group were both significantly down-regulated compared with control group [mRNA: 1.00±0.00 (P=0.005); absorbance value of E-cadherin positive expression: 0.04±0.01 (P=0.006)]. Meanwhile, the mRNA expression level of E-cadherin (1.06±0.24) and the absorbance value of E-cadherin positive expression (0.03±0.01) were both observed increase in periodontitis+IL-22 treatment group compared with periodontitis group (P=0.003, P=0.039). Conclusions: IL-22 may exert a protective effect on the gingival epithelial barrier in an inflammatory environment by regulating the invasiveness of oral microbiota and the expression of host barrier protein.
Assuntos
Caderinas , Gengiva , Interleucina 22 , Interleucinas , Camundongos Knockout , Microbiota , Periodontite , Porphyromonas gingivalis , Animais , Interleucinas/metabolismo , Caderinas/metabolismo , Gengiva/citologia , Gengiva/metabolismo , Gengiva/microbiologia , Camundongos , Periodontite/microbiologia , Periodontite/metabolismo , Células Epiteliais/metabolismo , RNA Ribossômico 16SRESUMO
Peripheral neuropathy is a well-described side effect of certain chemotherapeutic agents, including taxanes, and often improves in the weeks following treatment. The recurrence of motor and sensory neuropathies after anaesthesia has not yet been described to our knowledge. We present a case of transient recurrence of chemotherapy-induced peripheral neuropathy following general anaesthesia. Although an exact mechanism has not yet been described and is likely multifactorial in nature, anaesthetists should be prepared to address this phenomenon in the growing population of patients on chemotherapeutic agents.
RESUMO
The increasing incidence of myopia has become a global public health concern. Exploring the mechanisms underlying the onset and progression of myopia is crucial for prevention and control. This paper reviews the role of peripheral retinal defocus mechanisms in the development of myopia, with particular emphasis on the interaction between accommodation lag and peripheral retinal defocus, as well as the impact of optical intervention on myopia control effectiveness. In recent years, researchers have developed various optical tools for myopia prevention and control based on the peripheral retinal defocus theory, such as peripheral defocus spectacle lenses, orthokeratology lenses, and peripheral defocus soft contact lenses. This paper aims to provide clinicians with the latest research findings to deepen their understanding of the mechanisms involved in myopia development and to guide the future development and clinical application of myopia prevention and control products.
Assuntos
Progressão da Doença , Miopia , Retina , Humanos , Miopia/terapia , Miopia/fisiopatologia , Acomodação Ocular , Óculos , Lentes de Contato Hidrofílicas , Procedimentos Ortoceratológicos/métodos , Refração OcularRESUMO
Objective: To investigate the impact of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort study was performed to include 178 patients with â ¢-â £ NSCLC complicated with COPD who received at least 2 times of immunotherapy in Xinqiao Hospital of the Army Medical University from January 2019 to August 2021. Baseline peripheral blood inflammatory indicators such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were collected within 2 weeks before the first treatment, with the last one being on or before February 7, 2022. X-tile software was used to determine the optimal cut-off value of peripheral blood inflammatory indicators. The Cox multivariate regression models were used to analyze the factors affecting progression free survival (PFS) and overall survival (OS). Results: Among the 178 patients, there were 174 males (97.8%) and 4 females (2.2%); the age ranged from 42 to 86 (64.3±8.3) years old.There were 30 cases (16.9%) of immunotherapy monotherapy, 114 cases (64.0%) of immunotherapy combined with chemotherapy, 21 cases (11.8%) of immunotherapy combined with antivascular therapy, and 13 cases (7.3%) of immunotherapy combined with radiotherapy. The median follow-up period was 14.5 months (95%CI: 13.6-15.3 months). The objective response rate (ORR) and disease control rate (DCR) were 44.9% (80/178) and 90.4% (161/178) for the whole group, the median PFS was 14.6 months (95%CI: 11.6-17.6 months), and the median OS was 25.7 months (95%CI: 18.0-33.4 months). The results of Cox multivariate analysis showed that IL-6>9.9 ng/L (HR=5.885, 95%CI: 2.558-13.543, P<0.01), TNF-α>8.8 ng/L (HR=3.213, 95%CI: 1.468-7.032, P=0.003), IL-8>202 ng/L (HR=2.614, 95%CI: 1.054-6.482, P=0.038), systemic immune inflammatory index (SII)>2 003.95 (HR=2.976, 95%CI: 1.647-5.379, P<0.001) were risk factors for PFS, and advanced lung cancer inflammation index (ALI)>171.15 was protective factor for PFS (HR=0.545, 95%CI: 0.344-0.863, P=0.010). IL-6>9.9 ng/L(HR=6.124, 95%CI: 1.950-19.228, P<0.002), lactate dehydrogenase (LDH)>190.7 U/L (HR=2.776, 95%CI: 1.020-7.556, P=0.046), SII>2 003.95 (HR=4.521, 95%CI: 2.241-9.120, P<0.001) were risk factors for OS, and ALI>171.15 was a protective factor for OS (HR=0.434, 95%CI: 0.243-0.778, P=0.005). Conclusion: Baseline high levels of IL-6, TNF-α, IL-8, SII, LDH, and low levels of ALI are risk factors for poor prognosis in patients with advanced NSCLC-COPD receiving immunotherapy.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Interleucina-6 , Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Fator de Necrose Tumoral alfa , Humanos , Masculino , Feminino , Carcinoma Pulmonar de Células não Pequenas/terapia , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Pulmonar Obstrutiva Crônica/sangue , Pessoa de Meia-Idade , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/sangue , Idoso , Estudos Retrospectivos , Interleucina-6/sangue , Adulto , Fator de Necrose Tumoral alfa/sangue , Inflamação , Interleucina-8/sangue , Idoso de 80 Anos ou maisRESUMO
1. The accumulation of excessive fat plays a role in the development of non-alcoholic fatty liver disease (NAFLD) and phytogenic feed additives have the potential to ameliorate this. This study involved the isolation and culture of primary hepatocytes from chicken embryos to establish a model of hepatic steatosis induced by oleic acid/dexamethasone (OA/DEX). Lipid accumulation and cell viability were assessed using Nile Red staining, Oil Red O staining and cell count Kit -8 (CCK8) following treatment with varying concentrations of quercetin (Que). The potential mechanism by which Que exerts its effects was preliminarily investigated.2. The results indicated that OA effectively treated lipid accumulation in hepatocytes. There was no notable variance in cell proliferation between the normal and OA/DEX groups when subjected to Que treatment at concentrations of 1000 ng/ml and 10 000 ng/ml. Triglycerides and cholesterol (low and high density) decreased with Que treatment, with the most substantial reduction observed at 10 000 ng/ml.3. Gene expression levels decreased to levels similar to those in the control groups. Western blot data demonstrated that sterol regulatory element-binding protein 1 (SREBP-1) protein expression correlated with its mRNA expression level. Que mitigated lipid accumulation through the alpha serine/threonine protein kinase (AKT) and extracellular signal-regulated kinase (ERK) pathways. Expression levels of lipid-related genes (APOB, PPARα, CYP3A5 and SREBP-1) decreased to levels similar to the control groups. Western blot data demonstrated that the SREBP-1 protein expression correlated with its mRNA expression level.4. Supplementation with Que ameliorated lipid accumulation through AKT and ERK signalling pathway in OA/DEX-induced high-fat hepatocytes.
Assuntos
Hepatócitos , Metabolismo dos Lipídeos , Quercetina , Animais , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Quercetina/farmacologia , Quercetina/administração & dosagem , Embrião de Galinha , Metabolismo dos Lipídeos/efeitos dos fármacos , Ácido Oleico/farmacologia , Dexametasona/farmacologia , Galinhas , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Células CultivadasAssuntos
Hepatite B Crônica , Hepatite B , Complicações Infecciosas na Gravidez , Gravidez , Feminino , Humanos , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/tratamento farmacológico , Antivirais/uso terapêutico , Vírus da Hepatite B , Hepatite B/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológicoRESUMO
Systemic treatment, including molecular targeted therapy, immunotherapy, and chemotherapy, is an important means of achieving long-term survival in patients with intermediate-and advanced-stage liver cancer. However, some patients are insensitive to treatment and even develop drug resistance. Mitochondria are the center of cellular energy metabolism and, at the same time, are the priority targets for systemic therapy. Mitochondrial homeostasis plays an important role in the treatment of liver cancer. The relationship between the two advances is elucidated so as to provide better ideas for the clinical treatment of liver cancer.
Assuntos
Neoplasias Hepáticas , Mitocôndrias , Humanos , Imunoterapia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/metabolismo , HomeostaseRESUMO
Objectives: To investigate the efficacy of short-term substitution of recombinant humanized anti-CD25 monoclonal antibody (Basiliximab) as acute GVHD (aGVHD) prophylaxis in calcineurin inhibitors (CNI) intolerant patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: This study included 17 patients with refractory malignant hematological disorders who underwent salvage allo-HSCT at the Bone Marrow Transplantation Department of Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from August 2021 to August 2022 and were treated with Baliximab to prevent aGVHD due to severe adverse reactions to CNI. There were seven men and ten women, with a median age of 43 years (18-67). Following the discontinuation of CNI, Basiliximab was administered at a dose of 1 mg/kg once weekly until CNI or mTOR inhibitors were resumed. Results: Basiliximab was started at an average of 5 (1-32) days after HSCT. The median duration of substitution was 20 (7-120) days. All had neutrophil engraftment within a median of 12 (10-17) days. Thirteen patients had platelet engraftment after a median of 13 (11-20) days. Four patients did not develop stable platelet engraftment. Eight patients (47.1% ) developed Grade â ¡-â £ aGVHD, while four (23.6% ) developed Grade â ¢/â £ aGVHD. Only one patient died from aGVHD. Before the end of the followup period, seven of 17 patients died. The longest followup period of the survivors was 347 days, and the median survival rate was not met. The overall survival (OS) rate at six months was 62.6%. Among the 17 patients, 13 (76.4% ) experienced cytomegalovirus reactivation, 7 (41.2% ) experienced EB virus activation, and no cytomegalovirus disease was observed. Conclusions: When CNI intolerance occurs during allo-HSCT, short-term replacement with Baliximab can be used as an alternative to prevent aGVHD.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Monoclonais/uso terapêutico , Basiliximab/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , China , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversosAssuntos
Anticorpos Biespecíficos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Anticorpos Biespecíficos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Criança , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Antígenos CD19/imunologiaRESUMO
In recent years, with the development of artificial intelligence, deep learning has been gradually applied to clinical treatment and research. It has also found its way into the applications in radiotherapy, a crucial method for cancer treatment. This study summarizes the commonly used and latest deep learning algorithms (including transformer, and diffusion models), introduces the workflow of different radiotherapy, and illustrates the application of different algorithms in different radiotherapy modules, as well as the defects and challenges of deep learning in the field of radiotherapy, so as to provide some help for the development of automatic radiotherapy for cancer.