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BACKGROUND: Immune checkpoints negatively regulate immune response, thereby playing an important role in maintaining immune homeostasis. Substantial studies have confirmed that blockade or deficiency of immune checkpoint pathways contributes to the deterioration of autoimmune diseases. In this context, focusing on immune checkpoints might provide alternative strategies for the treatment of autoimmunity. Lymphocyte activation gene 3 (LAG3), as a member of immune checkpoint, is critical in regulating immune responses as manifested in multiple preclinical studies and clinical trials. Recent success of dual-blockade of LAG3 and programmed death-1 in melanoma also supports the notion that LAG3 is a crucial regulator in immune tolerance. METHODS: We wrote this review article by searching the PubMed, Web of Science and Google Scholar databases. CONCLUSION: In this review, we summarize the molecular structure and the action mechanisms of LAG3. Additionally, we highlight its roles in diverse autoimmune diseases and discuss how the manipulation of the LAG3 pathway can serve as a promising therapeutic strategy as well as its specific mechanism with the aim of filling the gaps from bench to bedside.
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Doenças Autoimunes , Neoplasias , Humanos , Ativação Linfocitária , Proteína do Gene 3 de Ativação de Linfócitos , Antígenos CD/genética , Doenças Autoimunes/terapiaRESUMO
Viridicatin alkaloids as natural products have attracted great interest due to their unique core scaffold. To fully exploit their potential application in DNA-encoded chemical libraries that would facilitate drug discovery, we here describe an efficient on-DNA synthesis of viridicatin alkaloid-like scaffolds from isatins and DNA-tagged aldehydes. Promoted by benzenesulfonyl hydrazide, this reaction provided the corresponding DNA-conjugated viridicatin alkaloid-like products in moderate-to-excellent conversion yields, and DNA compatibility validated by enzymatic ligation and qPCR evaluation exhibited the feasible utility of this methodology in DEL synthesis. Cross substrate scope study, together with subsequent on-DNA chemical diversification, further showed the competence of this approach in focused natural product-like encoded library construction.
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Alcaloides , Hidroxiquinolinas , Bibliotecas de Moléculas Pequenas , DNARESUMO
BACKGROUND: Exogenous lipoid pneumonia (ELP) is a rare disease and its diagnosis is often mistaken or delayed. Secondary infection with rapidly growing non-tuberculous mycobacteria is a rare complication of lipoid pneumonia. CASE PRESENTATION: A 38-year-old man presented with fever, cough, sputum, chest tightness, and shortness of breath. He had a 2-year history of allergic rhinitis and used liquid paraffin-containing menthol nasal drops daily. A chest CT scan showed multiple patchy ground glass opacities with blurred borders in both lungs, which were located in the inner pulmonary field and distributed along the bronchi. His ambient air PO2 was 63 mmHg. The patient was diagnosed with ELP by CT-guided lung biopsy. The nasal drops were discontinued, and systemic glucocorticoids were administered. During treatment, the pulmonary lesions deteriorated, and bronchoalveolar lavage was performed during bronchoscopy. Additionally, Mycobacterium abscessus was detected in the lavage fluid. Upon detection of a secondary M. abscessus infection, glucocorticoids were gradually discontinued, and anti-M. abscessus treatment was implemented. The patient's symptoms rapidly ameliorated. After 11 months of anti-M. abscessus treatment, a repeat CT scan showed clear regression of the lung lesions. CONCLUSION: Routine microbiological examination of samples, including sputum or alveolar lavage fluid, is necessary for patients with diagnosed or suspected ELP.
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Coinfecção , Infecções por Mycobacterium , Pneumonia Lipoide , Masculino , Humanos , Adulto , Pneumonia Lipoide/induzido quimicamente , Pneumonia Lipoide/diagnóstico por imagem , Micobactérias não Tuberculosas , Brônquios , Líquido da Lavagem Broncoalveolar , Glucocorticoides/uso terapêuticoRESUMO
Peroxisome is one of the important organelles for intracellular lipid metabolism in plant cells and ß-oxidation of fatty acids in peroxisomes provides the energy for oil-containing seed germination. In this study, we identified an ATP-binding cassette (ABC) transporter gene, GmABCA7 from soybean, which is highly expressed in the different developmental stages of seeds. Transient expression of GmABCA7 in tobacco epidermal cells showed that GmABCA7 was specifically localized at the peroxisomes. Overexpression of GmABCA7 in Arabidopsis does not change seed phenotypes, or the overall levels of lipid, protein and sugar stored in the seeds; however, the transgenic seeds produced more gluconeogenic pathway precursors such as succinate and malate and germinated earlier compared to the wild type seeds. These results suggest that GmABCA7 may affect the ß-oxidation of fatty acids and play an important role in seed germination.
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Transportadores de Cassetes de Ligação de ATP/genética , Proteínas de Arabidopsis/genética , Arabidopsis/genética , Germinação/genética , Peroxissomos/genética , Sementes/genética , Arabidopsis/fisiologia , Regulação da Expressão Gênica de Plantas/genética , Genes de Plantas/genéticaRESUMO
OBJECTIVE: To explore the pathological characteristics and significance of RET proto-oncogene screening in multiple endocrine neoplasia type 2A (MEN2A) with cutaneous lichen amyloidosis (CLA). METHODS: Clinical data of 51 members from 7 unrelated pedigrees of MEN2A-CLA were collected. Systemic clinical investigations including biochemical testing, imaging examination, germline RET variant screening and histopathological examination were carried out. RESULTS: RET gene variants were detected in 28 patients with MEN2A (C634G/F/R/S/W and C611Y) including 12 males and 16 females, with the mean age of diagnosis being (41.1 ± 18.3) years old, which were consistent with their clinical manifestations. The incidence of medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), hyperparathyroidism (HPTH) and CLA among 28 MEN2A patients were 89.3%, 28.6%, 7.1% and 28.6%, respectively. Comparison of the incidence of MTC/PHEO/HPTH and CLA between C611Y and C634G/F/R/S/W, only PHEO and CLA in C611Y were lower than those in C634G/F/R/S/W (P < 0.05; P < 0.05). Among 8 patients with CLA, the male to female ratio was 2 : 6. The clinical features included pruritus in the interscapular region and presence of dry, thickened, scaly, brown pigment, clustered or desquamate-like plaques. The mean onset age of CLA [(18.4 ± 4.6) years] versus the mean age at diagnosis of CLA or MEN2A were significantly different (P < 0.001; P < 0.001). CONCLUSION: MEN2A-CLA may be the early clinical manifestation of MEN2A and most frequently occurred along with RET-C634 variant. To facilitate the recognition of MEN2A-CLA, to combine family investigation and screening of RET variant are helpful for early diagnosis and standardized treatment, which can improve the long-term outcome of MEN2A-specific tumors.
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Neoplasias das Glândulas Suprarrenais , Amiloidose Familiar , Líquens , Neoplasia Endócrina Múltipla Tipo 2a , Feocromocitoma , Neoplasias da Glândula Tireoide , Adolescente , Adulto , Carcinoma Neuroendócrino , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2a/genética , Proteínas Proto-Oncogênicas c-ret/genética , Dermatopatias Genéticas , Neoplasias da Glândula Tireoide/genética , Adulto JovemRESUMO
BACKGROUND: Germline RET mutations and variants are involved in development of multiple endocrine neoplasia type 2 (MEN2). The present study investigated a spectrum of RET variants, analyzed genotype-phenotype relationships, and evaluated their effect on the MEN2 phenotype in Han Chinese patients. METHODS: Targeted sequencing detected germline RET variants in 697 individuals, including 245 MEN2, 120 sporadic medullary thyroid cancer (MTC), and 15 pheochromocytoma (PHEO) patients and their 493 relatives. In silico analyses and classifications following ACMG-2015 were performed. Demographic, clinical variant types, and endocrine neoplasia molecular diagnosis records were also analyzed. RESULTS: Nineteen different RET mutations (18 point and 1 del/ins mutations) in 214 patients with MEN2A (97.7%) or MEN2B (2.3%) were found, of which exon 11/10 mutations accounted for 79% (169/214). Nineteen compound mutations were found in 31 patients with MEN2A. Twenty-three variants (18 single and 5 double base substitution/compound variants) non-classification were also found. Of these, 17 (3 of pathogenic, 10 of uncertain significance, 2 of likely benign and 2 as benign) were found in 31 patients with MTC/PHEO. The remaining 6 variants (4 of uncertain significance and 2 of likely benign) found in 8 carriers had no evidence of MEN2. The entire cohort showed MEN2A-related PHEO, all occurring in exons 11/10, particularly at C634. Kaplan-Meier curves showed age-dependent penetration rates of MTC and PHEO, and occurrence rates of PHEO in patients with exon 11 mutations were all higher than those within exon 10; these bilateral PHEO were always associated with exon 11 mutations (all P < 0.05). While patient offspring had PHEO, parents with MEN2A had none, the frequency was approximately 10%. Interestingly, at least 6.8% of families were adoptive. Also, 3 non-hotspot RET variants (R114H, T278N, and D489N) appeared with high frequency. Conversely, polymorphism S836S was absent. CONCLUSIONS: These data are largely consistent with current evidence-based recommendations in the clinical practice guidelines. Diversity of RET variants or carriers may involve a different natural disease course. Further large-scale targeted sequencing studies will serve as an accurate and cost-effective approach to investigating MEN2 genotype-phenotype correlations for discovery of rare or unknown variants of RET.
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Mutação em Linhagem Germinativa , Neoplasia Endócrina Múltipla Tipo 2a/genética , Proteínas Proto-Oncogênicas c-ret/genética , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proto-Oncogene MasRESUMO
BACKGROUND AND AIM: The relationship between the Helicobacter pylori (H. pylori) infection and homocysteine is unclear. We evaluated the effect of H. pylori on serum homocysteine in a healthy Chinese population. METHODS: A total of 21 184 individuals aged over 18 years underwent 13 C/14 C urease breath test (13 C/14 C-UBT) and blood tests and 5042 individuals with follow-up intervals greater than 6 months. Homocysteine levels are classified according to the Chinese expert consensus. RESULTS: The rates of H. pylori infection of normal level, mild level, moderate level, and severe level were 40.9%, 43.8%, 45.8%, and 46.6%, respectively (P = 0.000). H. pylori infection increased the risk of higher homocysteine concentration (OR = 1.406, P = 0.000). In the case-control study, the rates of persistent negative, new infection, persistent infection, and eradication infection were 43.6%, 11.2%, 22.9%, and 22.3%, respectively. The percentage of changes in serum homocysteine levels varied significantly among the different H. pylori infection statuses only in mild level (P = 0.024). Mean changed homocysteine values were higher in the subgroup of persistent infection than in the persistent negative subgroup (P = 0.004) and the eradication infection subgroup (P = 0.034). Serum homocysteine values were elevated only in the subgroup with over 3 years interval time and persistent infection (n = 107, mean paired differences = 1.1 ± 4.6 µmol/L, P = 0.014). CONCLUSIONS: There is a relationship between H. pylori and serum homocysteine, and persistent infection leads to elevation of the latter.
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Infecções por Helicobacter , Helicobacter pylori , Homocisteína/sangue , Infecção Persistente/sangue , Adolescente , Adulto , Idoso , Testes Respiratórios , Estudos de Casos e Controles , China/epidemiologia , Feminino , Infecções por Helicobacter/sangue , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infecção Persistente/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
Sulfur-containing scaffold, as a ubiquitous structural motif, has been frequently used in natural products, bioactive chemicals and pharmaceuticals, particularly C-S/N-S bonds are indispensable in many biological important compounds and pharmaceuticals. Development of mild and general methods for C-S/N-S bonds formation has great significance in modern research. Iodine and its derivatives have been recognized as inexpensive, environmentally benign and easy-handled catalysts or reagents to promote the construction of C-S/N-S bonds under mild reaction conditions, with good regioselectivities and broad substrate scope. Especially based on this, several new strategies, such as oxidation relay strategy, have been greatly developed and accelerated the advancement of this field. This review focuses on recent advances in iodine and its derivatives promoted hybridized C-S/N-S bonds formation. The features and mechanisms of corresponding reactions are summarized and the results of some cases are compared with those of previous reports. In addition, the future of this domain is discussed.
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BACKGROUND: The relationship between Helicobacter pylori (H pylori) and body mass index (BMI) is still inconclusive. Not only the high rate of H pylori infection but also the increasing higher BMI levels are endangering Chinese today. METHODS: The aim of this research was to evaluate the association between different situations of H pylori infection and BMI values or levels in Chinese healthy population. A total of 39 091 individuals aged from 18 years to 80 years, performed healthy examination including a 13 C/14 C urease breath test (13 C/14 C-UBT), were included. Among them, 30 224 individuals only had one time of health examination, and 8867 had two or more times. A case-cohort data of 8752 with an interval time more than 6 months, collected by the first and the last time, were established from the latter. BMI groups are classified according to the China recommendation: low weight (<18.5 kg/m2 ), normal weight (18.5 ~ 23.9 kg/m2 ), overweight (24.0 ~ 27.9 kg/m2 ), and obesity (≥28.0 kg/m2 ). RESULTS: The rate of H pylori infection among low weight, normal weight, overweight, and obesity was 43.2%, 44.7%, 46.4%, and 48.0%, respectively (P = .000). H pylori infection increased the risk of higher level of BMI (OR = 1.077, 95% confidence interval = 1.036-1.119, χ2 = 14.048, P = .000) with adjustments for sex and age. In the case-control study, the rate of persistent negative, persistent infection, new infection, and eradicated infection was 39.5%, 25.8%, 15.8%, and 18.9%, respectively, with a median interval time of 13 months. The mean obesity BMI descend values in the persistent negative subgroup were lower than those in the persistent infection subgroup (-0.21 ± 1.19 kg/m2 vs -0.003 ± 1.01 kg/m2 , P = .021). But the change of BMI classifications had no difference between the subgroups of H pylori infection in different BMI levels. CONCLUSIONS: H pylori infection was positively correlated with higher BMI levels. And H pylori persistent infection had a negative effect on the fall of BMI values in Chinese obese population.
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Povo Asiático/estatística & dados numéricos , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Obesidade/patologia , Adulto , Idoso , Índice de Massa Corporal , Testes Respiratórios , Estudos de Casos e Controles , China/epidemiologia , Estudos de Coortes , Feminino , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/epidemiologia , Risco , Redução de PesoRESUMO
Cadmium (Cd) is one of the most toxic heavy metals for plant growth in soil. ATP-binding cassette (ABC) transporters play important roles in biotic and abiotic stresses. However, few ABC transporters have been characterized in poplar. In this study, we isolated an ABC transporter gene PtoABCG36 from Populus tomentosa. The PtoABCG36 transcript can be detected in leaves, stems and roots, and the expression in the root was 3.8 and 2 times that in stems and leaves, respectively. The PtoABCG36 expression was induced and peaked at 12 h after exposure to Cd stress. Transient expression of PtoABCG36 in tobacco showed that PtoABCG36 is localized at the plasma membrane. When overexpressed in yeast and Arabidopsis, PtoABCG36 could decrease Cd accumulation and confer higher Cd tolerance in transgenic lines than in wild-type (WT) lines. Net Cd2+ efflux measurements showed a decreasing Cd uptake in transgenic Arabidopsis roots than WT. These results demonstrated that PtoABCG36 functions as a cadmium extrusion pump participating in enhancing tolerance to Cd through decreasing Cd content in plants, which provides a promising way for making heavy metal tolerant poplar by manipulating ABC transporters in cadmium polluted areas.
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Transportadores de Cassetes de Ligação de ATP/genética , Adaptação Fisiológica , Cádmio/toxicidade , Expressão Ectópica do Gene , Proteínas de Plantas/genética , Populus/metabolismo , Transportadores de Cassetes de Ligação de ATP/química , Transportadores de Cassetes de Ligação de ATP/metabolismo , Sequência de Aminoácidos , Arabidopsis/genética , Arabidopsis/fisiologia , Cádmio/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas , Saccharomyces cerevisiae/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genéticaRESUMO
Mercury (Hg) is a highly biotoxic heavy metal that contaminates the environment. Phytoremediation is a green technology for environmental remediation and is used to clean up Hg contaminated soil in recent years. In this study, we isolated an ATP-binding cassette (ABC) transporter gene PtABCC1 from Populus trichocarpa and overexpressed it in Arabidopsis and poplar. The transgenic plants conferred higher Hg tolerance than wild type (WT) plants, and overexpression of PtABCC1 could lead to 26-72% or 7-160% increase of Hg accumulation in Arabidopsis or poplar plants, respectively. These results demonstrated that PtABCC1 plays a crucial role in enhancing tolerance and accumulation to Hg in plants, which provides a promising way for phytoremediation of Hg contamination.
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Adaptação Biológica/genética , Biodegradação Ambiental/efeitos dos fármacos , Mercúrio/farmacologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/fisiologia , Plantas Geneticamente Modificadas/fisiologia , Arabidopsis/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Populus/genéticaRESUMO
A novel compound, [Ni(DCPTP)] n (termed Ni-DCPTP), based on the 4'-(3,5-dicarboxyphenyl)-2,2',6',2â³-terpyridine (DCPTP2-) ligand was presented here. Ni-DCPTP has a three-dimensional structure with a ths topology featuring one-dimensional (1D) helical channels. Ni-DCPTP shows an efficient removal of a trace amount of C2H2 from a C2H2/C2H4 (1/99) mixture with an excellent C2H4 productivity as demonstrated by both the transient breakthrough simulations and breakthrough experiments, generating the polymer-grade C2H4 gas (C2H2 < 40 ppm). The carboxylate oxygen atoms on the surface of 1D channels are the preferential binding sites for C2H2 molecules. This work demonstrates an elegant example with carboxylate oxygen-functionalized pore channels for effective C2H2/C2H4 separation.
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A simple and practical ring-closure procedure to prepare a range of diverse heterocycles has been developed. In this transformation, a variety of substituted (thio)salicylamides and thiosalicylic acids undergo a double 1,4-addition reaction with propiolate derivatives in the presence of an inorganic base (K3PO4), as a result benzothiazinones, benzoxazinones and benzoxathiinones were prepared in good to excellent yields, respectively, even in gram scales. In addition, further transformation towards more complex structures and oxicam drug analogues has also been successfully carried out.
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The versatile reactivity of isothiocyanate intermediates enabled the diversity-oriented synthesis (DOS) of N-heterocycles in a DNA-compatible manner. We first reported a mild in situ conversion of DNA-conjugated amines to isothiocyanates. Subsequently, a set of diverse transformations was successfully developed to construct 2-thioxo-quinazolinones, 1,2,4-thiadiazoles, and 2-imino thiazolines. Finally, the feasibility of these approaches in constructing DELs was further demonstrated through enzymatic ligation and mock pool preparation. This study demonstrated the advantages of combining in situ conversion strategies with DOS, which effectively broadened the chemical and structural diversity of DELs.
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DNA , Compostos Heterocíclicos , Isotiocianatos , Isotiocianatos/química , DNA/química , Compostos Heterocíclicos/química , Compostos Heterocíclicos/síntese química , Estrutura Molecular , Aminas/química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/síntese químicaRESUMO
OBJECTIVE: WeChat-based nursing interventions alleviate mental distress. This study intended to investigate the effect of WeChat online education and care (WOEC) on the mental health of caregivers and the satisfaction of elderly postoperative colorectal cancer (CRC) patients. METHODS: In total, 92 elderly postoperative CRC patients and 92 caregivers were randomly separated into the WOEC group (46 patients and 46 caregivers) and the control care group (46 patients and 46 caregivers). Caregivers received corresponding intervention for 8 weeks. Beck depression inventory (BDI) and beck anxiety inventory (BAI) of caregivers, and self-report satisfaction (SRS) of patients were assessed. RESULTS: In caregivers, BDI scores at 8 weeks after enrollment (W8) (P = 0.024) and BAI score at W8 (P = 0.009), depression severity at W8 (P = 0.036), as well as anxiety severity at 4 weeks after enrollment (W4) (P = 0.028) and W8 (P = 0.047) were declined in the WOEC group versus the control care group. Regarding patients, SRS scores at W4 (P = 0.044) and W8 (P = 0.025), the satisfaction degree at W4 (P = 0.033) and W8 (P = 0.034), as well as the satisfied and very satisfied rates at W4 (P = 0.031) and W8 (P = 0.029) were elevated in the WOEC group versus the control care group. By subgroup analyses, WOEC exhibited favorable effects on reducing mental stress in caregivers of patients with eastern cooperative oncology group performance status at enrollment <3, and in caregivers with an education level of high school & university and above. CONCLUSION: WOEC effectively relieves mental stress in caregivers of elderly postoperative CRC patients, and also elevates satisfaction in these patients.
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Cuidadores , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/psicologia , Cuidadores/educação , Cuidadores/psicologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Satisfação do Paciente , Angústia Psicológica , Depressão/etiologia , Estresse Psicológico/etiologia , Ansiedade/prevenção & controle , Ansiedade/etiologia , Educação a Distância , Satisfação PessoalRESUMO
OBJECTIVES: To investigate relationships between various symptoms occurring 1-2 and 5-6 days following days after thoracoscopic surgery, to identify core symptoms, and to monitor changes in core symptoms over time following lung cancer thoracoscopic surgery. METHODS: We evaluated symptoms using the Anderson Symptom Scale (Chinese version) and the Lung Cancer-Specific Symptoms Template in 214 lung cancer patients hospitalized in the Department of Thoracic Surgery of a provincial hospital in Jiangsu Province from March 2023 to September 2023. Data was collected at 1-2 days and 5-6 days postoperatively. Symptom networks were constructed for each time point, and centrality indicators were analyzed to identify core symptoms while controlling for influencing factors. RESULTS: According to the network analysis, fatigue (rs = 26.00ãrc = 0.05ãrb = 1.02) had the highest strength, closeness, and betweenness in the symptom network 1-2 days after lung cancer surgery. At 5-6 days after surgery, shortness of breath (rs = 27.00) emerged as the symptom with the highest strength, fatigue (rc = 0.04) had the highest closeness, and cough (rb = 1.08) ranked highest in betweenness within the symptom network. CONCLUSION: Fatigue stands out as the most core symptom in the network 1-2 days after lung cancer surgery. Shortness of breath, fatigue and cough are the most core symptoms in the symptom network 5-6 days after surgery. Therefore, clinical staff can improve the postoperative symptom experience of lung cancer patients by developing symptom management programmes tailored to these core symptoms.
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Fadiga , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fadiga/etiologia , Complicações Pós-Operatórias/epidemiologia , Toracoscopia/efeitos adversos , Toracoscopia/métodos , Dispneia/etiologia , Adulto , ChinaRESUMO
Objective: To evaluate the reliability and validity of the Chinese-translated Geriatric Locomotive Function Scale (GLFS-25) for the assessment of locomotive syndrome (LS) in individuals surviving malignancies. Methods: 393 tumor survivors at a general hospital in China were recruited. The Chinese version of GLFS-25 was utilized to conduct a cross-sectional survey to ascertain the tool's efficacy in measuring LS in this cohort. The scale's validity was examined through content, structural and discriminant validity assessments, while its reliability was investigated by determining the internal consistency (via Cronbach's α coefficient) and test-retest reliability (via intragroup correlation coefficient, ICC). Results: The Chinese-adapted GLFS-25 demonstrated a robust scale-level content validity index of 0.94, while item-level content validity indices ranged from 0.83 to 1.00 across individual items. The suitability of the scale for structural validity assessment was confirmed via exploratory factor analysis, yielding a Kaiser-Meyer-Olkin measure of 0.930 and a significant Bartlett's test of sphericity (χ2 = 3217.714, df = 300, P < 0.001). Subsequent confirmatory factor analysis (CFA) extracted four distinct factors: Social Activity Engagement, Daily Living Ability, Pain Experience and Physical Mobility. These factors accounted for 72.668 % of the variance, indicating substantial construct validity for measuring LS among this population. CFA supported the model's fit with the following indices: χ2/df = 1.559, RMSEA = 0.077, GFI = 0.924, CFI = 0.941, NFI = 0.919, and TLI = 0.933. The factor loadings for the four factors ranged from 0.771 to 0.931, indicating the items corresponding to the four factors effectively represented the constructs they were designed to measure. The correlation coefficients among the four factors were between 0.306 and 0.469, all lower than the square roots of the respective AVEs (0.838-0.867). This suggests a moderate correlation among the four factors and a distinct differentiation between them, indicating the Chinese version of the GLFS-25 exhibits strong discriminant validity in Chinese tumor survivors. Reliability testing revealed a high Cronbach's α coefficient for the overall scale at 0.961, with the subscales yielding coefficients of 0.751, 0.836, 0.930, and 0.952. The overall ICC was determined to be 0.935, with subscale ICCs ranging from 0.857 to 0.941, reinforcing the scale's reliability in this context. Conclusions: The Chinese version of the GLFS-25 exhibits strong reliability and validity for the assessment of LS in tumor survivors. It may serve as a diagnostic tool for LS, contributing to the prevention and management of musculoskeletal disorders and enhancing the prognosis for this patient population.
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Annelated benzodiazepines are attractive drug-like scaffolds with a broad spectrum of biological activities. Incorporation of this heterocyclic core into DNA-encoded chemical libraries (DELs) via multicomponent assembly is highly demanded. Herein, we developed a DNA-compatible method to generate the tricyclic benzodiazepine scaffold via catalyst-free three-component condensation using a broad range of aldehyde, o-phenylenediamine, and diketone sources. With either aldehyde or o-phenylenediamine conjugated with DNA tags, functionalized 1,5-benzodiazepine scaffolds were efficiently forged, expanding the chemical space of the diazepine-centered drug-like DEL.
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Benzodiazepinas , Bibliotecas de Moléculas Pequenas , DNA , CatáliseRESUMO
OBJECTIVE: To investigate the possible association between the SNP in the 5' untranslated region (5' UTR) of the human beta defensin 1 (DEFB1) gene and the susceptibility to pulmonary tuberculosis (PTB) in Chinese Han population. METHODS: In this case-control study, venous blood was collected from 102 patients with PTB and 148 healthful persons. Genomic DNA was extracted using whole blood DNA extraction kit. The -52A/G, -44C/G and -20A/G SNP were genotyped by PCR-directed sequencing. The genotypes and allele frequency were analyzed using the χ(2) test. The linkage disequilibrium and haplotype were analyzed by SHEsis software. RESULTS: A total of 102 patients with PTB (69 males and 33 females, (53.42 ± 20.22) years old) and 148 healthy control cases (95 males and 53 females, (50.67 ± 14.53) years old) were enrolled, with no difference in gender and age (all P values > 0.05). DEFB1 -44 CC genotype was significantly more frequently found in PTB patients than in control group (81.4% (83/102) vs 66.9% (99/148), χ(2) = 5.114, P < 0.05, OR = 2.096, 95%CI: 1.095 - 4.011), so was -44C allele (89.2% (182/204) vs 80.4% (238/296), χ(2) = 6.975, P < 0.05, OR = 1.576, 95%CI: 1.086 - 2.286). No difference in -52 A/G and -20 A/G SNP was observed between the two groups. The proportion of the GGG (-52/-44/-20) haplotype was lower in PTB patients than in the control group (0.030 vs 0.081, χ(2) = 5.629, P < 0.05, OR = 0.348, 95%CI: 0.140 - 0.863). No linkage disequilibrium was found among the SNP of the three sites (D' values were 0.132, 0.064, 0.088; r(2) values were 0.003, 0.002, 0.003; all P values > 0.05). CONCLUSION: These results suggest that the SNP of DEFB1 5' UTR is associated with susceptibility to PTB in Chinese Han population. -44 CâG SNP and the related haplotype (GGG) might play a protective role in the pathogenesis of PTB.
Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Tuberculose Pulmonar/genética , beta-Defensinas/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Multiple endocrine neoplasia type 2A (MEN 2A) is mainly caused by germline RET codon C634 mutation and is characterized by Medullary Thyroid Carcinoma (MTC), pheochromocytoma (PHEO), and hyperparathyroidism (HPTH). The early diagnosis and initial normative treatment are helpful for the long-term outcome of MEN2A. METHODS: Three index cases and their 29 relatives from three families with MEN2A were included in this study. Genetic screening was performed on all participants. Demographic, clinical profiles, tumor histopathologic features, and follow-up records were systematically analyzed. RESULTS: In total, RET C634Y mutation was identified in 10 individuals (10/32, 31.3%). Among them, 5 presented with MTC symptoms, whereas the other 5 did not show apparent clinical manifestation, and all were subjected to thyroidectomy with varying neck dissection. Compared to individuals in the former, the latter benefited greatly from RET screening with significantly younger age at diagnosis of MTC and surgery (18.1 ± 13.8 years vs. 39.0 ± 14.1 years, P =0.045), and lessaggressive MTC behavior (size: 0.74 vs. 2.82 cm, P =0.026; LN+/resected: 20.0% vs. 100.0%, P =0.048) and also lower recurrence rate of MTC (20.0% vs. 100.0%, P =0.048). The PHEO was identified in 6 of the 10 carriers (60.0%), and all had undergone adrenal-sparing surgery. During the 10 years of follow-up, one (16.7%) developed recurrence of PHEO. CONCLUSION: Integrated RET screening, serum calcitonin, and plasma metanephrine/ normetanephrine levels can facilitate the early diagnosis and standardized MTC/PHEO surgery to improve the prognosis of MEN2A. Laparoscopic adrenal-sparing surgery prior to the bilateral total thyroidectomy is a preferred surgical approach for PHEO.