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1.
World J Diabetes ; 15(9): 1862-1873, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39280188

RESUMO

The increasing prevalence of diabetes has led to a growing population of end-stage kidney disease (ESKD) patients with diabetes. Currently, kidney transplantation is the best treatment option for ESKD patients; however, it is limited by the lack of donors. Therefore, dialysis has become the standard treatment for ESKD patients. However, the optimal dialysis method for diabetic ESKD patients remains controversial. ESKD patients with diabetes often present with complex conditions and numerous complications. Furthermore, these patients face a high risk of infection and technical failure, are more susceptible to malnutrition, have difficulty establishing vascular access, and experience more frequent blood sugar fluctuations than the general population. Therefore, this article reviews nine critical aspects: Survival rate, glucose metabolism disorder, infectious complications, cardiovascular events, residual renal function, quality of life, economic benefits, malnutrition, and volume load. This study aims to assist clinicians in selecting individualized treatment methods by comparing the advantages and disadvantages of hemodialysis and peritoneal dialysis, thereby improving patients' quality of life and survival rates.

3.
Eur J Med Chem ; 277: 116773, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39163779

RESUMO

Due to the emerging global epidemic of obesity, developing safe and effective agents for anti-obesity is urgently needed. Our previous study found that 2-pyrimidinylindole derivative Wd3d exhibited potential anti-obesity activity. Herein, to further optimize the potential moiety, structural modifications were proceeded for two rounds in this study. Firstly, we designed, synthesized, and evaluated 36 new derivatives of 2-pyrimidinylindole scaffold with different substituents on the indole ring and pyrimidine ring to investigate their structure-activity relationship (SAR). Then, analogs with potent activity had the aldehyde group replaced with the acylhydrazone group to reduce cytotoxicity and improve metabolic stability. Detailed SAR studies and animal evaluation experiments led to the discovery of the compound 9ga, which significantly reduced TG accumulation with an EC50 value of 0.07 µM and showed relatively low cytotoxicity with an IC50 value of around 24 µM. Oral administration of 9ga effectively prevented the excessive growth of body weight and lessened fat mass as well as liver mass, decreased lipid accumulation in the liver and blood, and improved the heart injury parameter in the diet-induced obesity mouse model significantly better than Wd3d. A mechanism study showed that 9ga regulated the lipid metabolism during early adipogenesis by inhibiting PPARγ pathway. In conclusion, our study further highlights the anti-obesity potential of 2-pyrimidinylindole derivatives in diet-induced obesity.


Assuntos
Fármacos Antiobesidade , Desenho de Fármacos , Indóis , Obesidade , Relação Estrutura-Atividade , Animais , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/síntese química , Fármacos Antiobesidade/química , Camundongos , Indóis/química , Indóis/farmacologia , Indóis/síntese química , Obesidade/tratamento farmacológico , Administração Oral , Estrutura Molecular , Masculino , Pirimidinas/química , Pirimidinas/farmacologia , Pirimidinas/síntese química , Relação Dose-Resposta a Droga , Camundongos Endogâmicos C57BL , Humanos , Células 3T3-L1
4.
Hortic Res ; 11(8): uhae166, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39108585

RESUMO

Sinojackia Hu represents the first woody genus described by Chinese botanists, with all species classified as endangered ornamental plants endemic to China. Their characteristic spindle-shaped fruits confer high ornamental value to the plants, making them favored in gardens and parks. Nevertheless, the fruits likely pose a germination obstacle, contributing to the endangered status of this lineage. Here we report the chromosome-scale genome of S. xylocarpa, and explore the mechanisms underlying its endangered status, as well as its population dynamics throughout evolution. Population genomic analysis has indicated that S. xylocarpa experienced a bottleneck effect following the recent glacial period, leading to a continuous population reduction. Examination of the pericarp composition across six stages of fruit development revealed a consistent increase in the accumulation of lignin and fiber content, responsible for the sturdiness of mature fruits' pericarps. At molecular level, enhanced gene expression in the biosynthesis of lignin, cellulose and hemicellulose was detected in pericarps. Therefore, we conclude that the highly lignified and fibrotic pericarps of S. xylocarpa, which inhibit its seed germination, should be its threatening mechanism, thus proposing corresponding strategies for improved conservation and restoration. This study serves as a seminal contribution to conservation biology, offering valuable insights for the study of other endangered ornamental plants.

5.
BMC Urol ; 24(1): 165, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39090582

RESUMO

BACKGROUND: We investigated the feasibility of the tertiary lymphoid structure (TLS) as a prognostic marker for penile squamous cell carcinoma(SCC). METHODS: We retrospectively collected data from 83 patients with penile squamous cell carcinoma. H&E-stained slides were reviewed for TLS density. In addition, clinical parameters were analyzed, the prognostic value of these parameters on overall survival (OS) was evaluated using ‒ Kaplan-Meier survival curves, and the prognostic value of influencing factors was evaluated using Cox multifactor design nomogram analysis. RESULT: BMI, T, N, and M are significant in the survival curve with or without tertiary lymphoid structure. BMI, T, N, M and TLS were used to construct a prognostic model for penile squamous cell carcinoma, and the prediction accuracy reached a consensus of 0.884(0.835-0.932), and the decision consensus reached 0.581(0.508-0.655). CONCLUSION: TLS may be a positive prognostic factor for penile squamous cell carcinoma, and the combination of BMI, T, N and M can better evaluate the prognosis of patients.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Penianas , Estruturas Linfoides Terciárias , Masculino , Neoplasias Penianas/patologia , Neoplasias Penianas/mortalidade , Humanos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Prognóstico , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Estruturas Linfoides Terciárias/patologia , Adulto , Taxa de Sobrevida
6.
Clin Respir J ; 18(8): e70006, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39188060

RESUMO

INTRODUCTION: Lung adenocarcinoma (LUAD) is one of the major histopathological types of non-small cell lung cancer (NSCLC), including solid, acinar, lepidic, papillary and micropapillary subtypes. Increasing evidence has shown that micropapillary LUAD is positively associated with a higher percentage of driver gene mutations, a higher incidence of metastasis and a poorer prognosis, while lepidic LUAD has a relatively better prognosis. However, the novel genetic change and its underlying mechanism in the progression of micropapillary LUAD have not been exactly determined. METHODS: A total of 181 patients with LUAD who underwent surgery at the First Affiliated Hospital of Huzhou University from January 2020 to December 2022 were enrolled. Three predominant lepidic and three predominant micropapillary LUAD tissue samples were carried out using whole-exome sequencing. Comprehensive analysis of genomic variations and the difference between lepidic and micropapillary LUAD was performed. In addition, the TMEM229A Q200del mutation was verified using our cohort and TCGA-LUAD datasets. The correlations between the TMEM229A Q200del mutation and the clinicopathological characteristics of patients with LUAD were further analyzed. The functions and mechanisms of TMEM229A Q200del on NSCLC cell proliferation and migration were also determined. RESULTS: The frequency of genomic changes in patients with micropapillary LUAD was higher than that in patients with lepidic LUAD. Mutations in EGFR, ATXN2, C14orf180, MUC12, NOTCH1, and PKD1L2 were concomitantly detected in three predominant micropapillary and three predominant lepidic LUAD cases. The TMEM229A Q200del mutation was only mutated in lepidic LUAD. Additionally, the TMEM229A Q200del mutation had occurred in 16 (8.8%) patients, and not found TMEM229A R76H and M346T mutations in our cohort, while TMEM229A mutations (R76H, M346T, and Q200del) occurred only in 1.0% of the TCGA-LUAD cohort. Further correlation analysis between the TMEM229A Q200del mutation and clinicopathological characteristics suggested that a lower frequency of the Q200del mutation was significantly associated with positive lymph node metastasis, advanced TNM stage, positive cancer thrombus, and pathological features. Finally, overexpression of TMEM229A Q200del suppressed NSCLC cell proliferation and migration in vitro. Mechanistically, overexpression of TMEM229A and TMEM229A Q200del both reduced the expression level of phosphorylated (p)-ERK and p-AKT (Ser473), and the reduced protein level of p-ERK in the TMEM229A Q200del group was more pronounced compared to the TMEM229A group. CONCLUSION: Our results demonstrated that the TMEM229A Q200del mutant may play a protective role in the progression of LUAD via inactivating ERK pathway, providing a potential therapeutic target in LUAD.


Assuntos
Adenocarcinoma de Pulmão , Sequenciamento do Exoma , Neoplasias Pulmonares , Proteínas de Membrana , Mutação , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Feminino , Sequenciamento do Exoma/métodos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Proliferação de Células/genética , Prognóstico , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular/genética
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(4): 1186-1190, 2024 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-39192417

RESUMO

OBJECTIVE: To observe the genetic variation of SH2B3 in patients with myeloid neoplasms. METHODS: The results of targeted DNA sequencing associated with myeloid neoplasms in the Department of Hematology, Xuanwu Hospital, Capital Medical University from November 2017 to November 2022 were retrospectively analyzed, and the patients with SH2B3 gene mutations were identified. The demographic and clinical data of these patients were collected, and characteristics of SH2B3 gene mutation, co-mutated genes and their correlations with diseases were analyzed. RESULTS: The sequencing results were obtained from 1 005 patients, in which 19 patients were detected with SH2B3 gene mutation, including 18 missense mutations (94.74%), 1 nonsense mutation (5.26%), and 10 patients with co-mutated genes (52.63%). Variant allele frequency (VAF) ranged from 0.03 to 0.66. The highest frequency mutation was p.Ile568Thr (5/19, 26.32%), with an average VAF of 0.49, involving 1 case of MDS/MPN-RS (with SF3B1 mutation), 1 case of MDS-U (with SF3B1 mutation), 1 case of aplastic anemia with PNH clone (with PIGA and KMT2A mutations), 2 cases of MDS-MLD (1 case with SETBP1 mutation). The other mutations included p.Ala567Thr in 2 cases (10.53%), p.Arg566Trp, p.Glu533Lys, p.Met437Arg, p.Arg425Cys, p.Glu314Lys, p.Arg308*, p.Gln294Glu, p.Arg282Gln, p.Arg175Gln, p.Gly86Cys, p.His55Asn and p.Gln54Pro in 1 case each. CONCLUSION: A wide distribution of genetic mutation sites and low recurrence of SH2B3 is observed in myeloid neoplasms, among of them, p.Ile568Thr mutation is detected with a higher incidence and often coexists with characteristic mutations of other diseases.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Peptídeos e Proteínas de Sinalização Intracelular , Mutação , Humanos , Proteínas Adaptadoras de Transdução de Sinal/genética , Estudos Retrospectivos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Variação Genética , Frequência do Gene , Mutação de Sentido Incorreto , Transtornos Mieloproliferativos/genética , Masculino , Neoplasias Hematológicas/genética
8.
J Med Chem ; 67(14): 12439-12458, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38996004

RESUMO

The discovery of effective and safe antiobesity agents remains a challenging yet promising field. Our previous studies identified Bouchardatine derivatives as potential antiobesity agents. However, the 8a-aldehyde moiety rendered them unsuitable for drug development. In this study, we designed two series of novel derivatives to modify this structural feature. Through a structure-activity relationship study, we elucidated the role of the 8a-aldehyde group in toxicity induction. We identified compound 14d, featuring an 8a-N-acylhydrazone moiety, which exhibited significant lipid-lowering activity and reduced toxicity. Compound 14d shares a similar lipid-lowering mechanism with our lead compound 3, but demonstrates improved pharmacokinetic properties and safety profile. Both oral and injectable administration of 14d significantly reduced body weight gain and ameliorated metabolic syndrome in diet-induced obese mice. Our findings identify 14d as a promising antiobesity agent and highlight the potential of substituting the aldehyde group with an N-acylhydrazone to enhance drug-like properties.


Assuntos
Aldeídos , Fármacos Antiobesidade , Hidrazonas , Obesidade , Animais , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/síntese química , Fármacos Antiobesidade/farmacocinética , Fármacos Antiobesidade/uso terapêutico , Fármacos Antiobesidade/química , Hidrazonas/farmacologia , Hidrazonas/química , Hidrazonas/síntese química , Hidrazonas/farmacocinética , Hidrazonas/uso terapêutico , Camundongos , Relação Estrutura-Atividade , Aldeídos/química , Masculino , Obesidade/tratamento farmacológico , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos , Humanos , Camundongos Obesos , Estrutura Molecular
9.
Eur J Med Chem ; 275: 116570, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38878517

RESUMO

Broussonetine S (9), its C-1' and C-10' stereoisomers, and their corresponding enantiomers have been synthesized from enantiomeric arabinose-derived cyclic nitrones, with cross metathesis (CM), epoxidation and Keck asymmetric allylation as key steps. Glycosidase inhibition assays showed that broussonetine S (9) and its C-10' epimer (10'-epi-9) were nanomolar inhibitors of bovine liver ß-galactosidase and ß-glucosidase; while their C-1' stereoisomers were 10-fold less potent towards these enzymes. The glycosidase inhibition results and molecular docking calculations revealed the importance of the configurations of pyrrolidine core and C-1' hydroxyl for inhibition potency and spectra. Together with the docking calculations we previously reported for α-1-C-alkyl-DAB derivatives, we designed and synthesized a series of 6-C-alkyl-DMDP derivatives with very simple alkyl chains. The inhibition potency of these derivatives was enhanced by increasing the length of the side chain, and maintained at nanomolar scale inhibitions of bovine liver ß-glucosidase and ß-galactosidase after the alkyl groups are longer than eight or ten carbons for the (6R)-C-alkyl-DMDP derivatives and their 6S epimers, respectively. Molecular docking calculations indicated that each series of 6-C-alkyl-DMDP derivatives resides in the same active site of ß-glucosidase or ß-galactosidase with basically similar binding conformations, and their C-6 long alkyl chains extend outwards along the hydrophobic groove with similar orientations. The increasing inhibitions of ß-glucosidase and ß-galactosidase with the number of carbon atoms in the side chains may be explained by improved adaptability of longer alkyl chains in the hydrophobic grooves. In addition, the lower ß-glucosidase and ß-galactosidase inhibitions of (6S)-C-alkyl-DMDP derivatives than their C-6 R stereoisomers can be attributed to the misfolding of their alkyl chains and resulted decreased adaptability in the hydrophobic groove. The work reported herein is valuable for design and development of more potent and selective inhibitors of ß-galactosidase and ß-glucosidase, which have potential in treatment of lysosomal storage diseases. Furthermore, part of the 6-C-alkyl-DMDP derivatives and their enantiomers were also tested as potential anti-cancer agents; all the compounds tested were found with moderate cytotoxic effects on MKN45 cells, which would indicate potential applications of these iminosugars in development of novel anticancer agents.


Assuntos
Desenho de Fármacos , Inibidores Enzimáticos , Simulação de Acoplamento Molecular , beta-Galactosidase , beta-Glucosidase , beta-Galactosidase/antagonistas & inibidores , beta-Galactosidase/metabolismo , Bovinos , Animais , Relação Estrutura-Atividade , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , beta-Glucosidase/antagonistas & inibidores , beta-Glucosidase/metabolismo , Estrutura Molecular , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química
10.
Front Surg ; 11: 1344269, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872725

RESUMO

Objective: To assess the feasibility, safety, and efficiency of simultaneous anterograde video laparoscopic inguinal and pelvic lymphadenectomy for penile cancer. Materials and methods: We reviewed retrospectively the records of 22 patients (44 lateral) who underwent inguinal lymph nodes dissection for penile cancer. The procedure was standardized as two planes, three holes, and six steps. Two Separate-planes: superior plane of eternal oblique aponeurosis/ / fascia lata; inferior plane of superficial camper fascia. Three holes: two artificial lateral boundary holes, the internal and external boundary holes, and the hole of oval fossa. Six steps: separate the first separate-plane; separate the second layer; separate two artificial lateral boundary holes; free great saphenous vein; separate the third hole and clean up the deep inguinal lymph nodes; pelvic lymphadenectomy. Results: A total of 22 cases were included and 9 patients underwent simultaneous pelvic lymphadenectomy. The average operation time on both sides was 7.52 ± 3.29 h, which was 0.5-1 h/side after skilled. The average amount of bleeding was 93.18 ± 50.84 ml. A total of 8 patients had postoperative complications, accounting for 36.36%, and no complications great than Clavien-Dindo class III occurred. Conclusion: This study demonstrated that the video laparoscopic simultaneous anterograde inguinal and pelvic lymphadenectomy is a feasible and safe technique. Indocyanine Green was helpful for lymph node identify.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38824095

RESUMO

BACKGROUND: In patients with hilar cholangiocarcinoma (HCCA), radical resection can be achieved by resection and reconstruction of the vasculature. However, whether vascular reconstruction (VR) improves long-term and short-term prognosis has not been demonstrated comprehensively. METHODS: This was a retrospective multicenter study of patients who received surgery for HCCA with or without VR. Variables associated with overall survival (OS) and recurrence-free survival (RFS) were identified based on Cox regression. Kaplan-Meier curves were used to explore the impact of VR. Restricted mean survival time (RMST) was used for comparisons of short-term survival between the groups. Patients' intraoperative and postoperative characteristics were compared. RESULTS: Totally 447 patients were enrolled. We divided these patients into 3 groups: VR with radical resections (n = 84); non-VR radical resections (n = 309) and non-radical resection (we pooled VR-nonradical and non-VR nonradical together, n = 54). Cox regression revealed that carbohydrate antigen 242 (CA242), vascular invasion, lymph node metastasis and poor differentiation were independent risk factors for OS and RFS. There was no significant difference of RMST between the VR and non-VR radical groups within 12 months after surgery (10.18 vs. 10.76 mon, P = 0.179), although the 5-year OS (P < 0.001) and RFS (P < 0.001) were worse in the VR radical group. The incidences of most complications were not significantly different, but those of bile leakage (P < 0.001) and postoperative infection (P = 0.009) were higher in the VR radical group than in the non-VR radical group. Additionally, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) up to 7 days after surgery tended to decrease in all groups. There was no significant difference in the incidence of postoperative liver failure between the VR and non-VR radical groups. CONCLUSIONS: Radical resection can be achieved with VR to improve the survival rate without worsening short-term survival compared with resection with non-VR. After adequate assessment of the patient's general condition, VR can be considered in the resection.

12.
Small ; 20(34): e2400985, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38693073

RESUMO

Ionic liquids have been widely used to improve the efficiency and stability of perovskite solar cells (PSCs), and are generally believed to passivate defects on the grain boundaries of perovskites. However, few studies have focused on the relevant effects of ionic liquids on intragrain defects in perovskites which have been shown to be critical for the performance of PSCs. In this work, the effect of ionic liquid 1-hexyl-3-methylimidazolium iodide (HMII) on intragrain defects of formamidinium lead iodide (FAPbI3) perovskite is investigated. Abundant {111}c intragrain planar defects in pure FAPbI3 grains are found to be significantly reduced by the addition of the ionic liquid HMII, shown by using ultra-low-dose selected area electron diffraction. As a result, longer charge carrier lifetimes, higher photoluminescence quantum yield, better charge carrier transport properties, lower Urbach energy, and current-voltage hysteresis are achieved, and the champion power conversion efficiency of 24.09% is demonstrated. These observations suggest that ionic liquids significantly improve device performance resulting from the elimination of {111}c intragrain planar defects.

13.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2345-2354, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812135

RESUMO

To investigate the effects of plumbagin on the proliferation and apoptosis of human hepatoma Huh-7 cells and its mechanism based on the creatine kinase B(CKB)/p53 signaling pathway. Huh-7 cells were treated with plumbagin from 1 to 12 µmol·L~(-1) for cell counting kit-8(CCK-8) assay, and 1, 3, and 6 µmol·L~(-1) were determined as low, medium, and high concentrations of plumbagin for subsequent experiments. CKB gene was knocked out in Huh-7 cells by clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated proteins(Cas)-9 gene editing technology. CKB overexpression lentivirus was transfected into Huh-7 cells to up-regulate the expression of CKB. Cell proliferation and apoptosis were detected by plate cloning assay and flow cytometry. The mRNA expression of CKB was detected by quantitative real-time PCR(qRT-PCR). CKB, p53, mouse double minute 2 homolog(MDM2), B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), and caspase-3 protein were detected by Western blot(WB). The results showed that plumbagin significantly inhibited the proliferation of Huh-7 cells and induced cell apoptosis. Compared with the control group, the apoptosis level was significantly increased in the plumbagin group, while the apoptosis level was significantly decreased in the plumbagin combined with the apoptosis inhibitor group. Plumbagin significantly down-regulated the protein expression levels of CKB, Bcl-2, and MDM2 and up-regulated the protein expression levels of p53, Bax, and caspase-3. Knockdown of the CKB gene decreased the proliferative ability of Huh-7 cells, increased the apoptotic rate, decreased the expression levels of Bcl-2 and MDM2 proteins, and increased the expression levels of p53, Bax, and caspase-3 proteins. After up-regulation of CKB expression, the proliferation ability of Huh-7 cells was enhanced, and the protein expression levels of Bcl-2 and MDM2 were elevated. The protein expression levels of p53, Bax, and caspase-3 were decreased. In addition, plumbagin reversed the effect of overexpression of CKB on the proliferation and apoptosis of Huh-7 cells. In conclusion, plumbagin significantly inhibited the proliferative ability of Huh-7 cells, and the mechanism may be related to the inhibition of CKB expression, activation of the p53 signaling pathway, and regulation of the expression of mitochondrial-associated apoptotic proteins, ultimately inducing cell apoptosis.


Assuntos
Apoptose , Carcinoma Hepatocelular , Proliferação de Células , Neoplasias Hepáticas , Naftoquinonas , Transdução de Sinais , Proteína Supressora de Tumor p53 , Humanos , Naftoquinonas/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo
14.
BMC Geriatr ; 24(1): 401, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711010

RESUMO

BACKGROUND: Preoperative carbohydrate loading in Enhanced Recovery After Surgery is an independent predictor of postoperative outcomes. By reducing the impact of surgical stress response, fasting-induced insulin resistance is modulated. As a clear fluid, consuming carbohydrate drink is safe up to 2 h preoperatively. Widely practiced in abdominal surgeries, its implementation in hip fracture surgeries is yet to be recognized. This study aimed to identify the feasibility of preoperative carbohydrate loading in hip fracture surgery and assess its clinical effects. METHODS: This was a randomized controlled, open labelled trial. Patients ≥ 65 years old without diabetes mellitus, has hip fracture were recruited in a tertiary hospital between November 2020 and May 2021. The intervention was carbohydrate loading versus standard preoperative fasting. RESULTS: Thirty-four ASA I-III patients (carbohydrate loading and control, n = 17 each), mean age 78 years (SEM ± 1.5), mean body mass index 23.7 (SEM ± 0.6 kg/m2) were recruited. Analysis for feasibility of carbohydrate loading (n = 17) demonstrated attrition rate of 29% (n = 5). Otherwise, all recruited patients were compliant (100% compliance) with no adverse events reported. There was no significant difference among groups in the postoperative nausea and vomiting, pain score, fatigue level, muscle strength, postoperative infection and length of hospital stay assessed at 24-48 h postoperatively. CONCLUSION: The implementation of preoperative carbohydrate loading was found to be feasible preoperatively in hip fracture surgeries but requires careful coordination among multidisciplinary teams. An adequately powered randomized controlled study is needed to examine the full benefits of preoperative carbohydrate loading in this group of patients. TRIAL REGISTRATION: This study was registered in ClinicalTrial.gov (ClinicalTrials.gov identifier: NCT04614181, date of registration: 03/11/2020).


Assuntos
Dieta da Carga de Carboidratos , Estudos de Viabilidade , Fraturas do Quadril , Cuidados Pré-Operatórios , Humanos , Idoso , Masculino , Feminino , Fraturas do Quadril/cirurgia , Cuidados Pré-Operatórios/métodos , Dieta da Carga de Carboidratos/métodos , Idoso de 80 Anos ou mais , Jejum/fisiologia , Recuperação Pós-Cirúrgica Melhorada
15.
J Chromatogr A ; 1728: 464987, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-38821034

RESUMO

In this work, we proposed an indirect phase-conversion strategy to construct a new approach for accurately and efficiently determining the permanganate index in water samples via headspace GC measurement. After the reducible substances in water reacted with excess potassium permanganate, the remaining potassium permanganate underwent a reaction with sodium oxalate under acidic conditions. The carbon dioxide generated from the gas-evolving reaction was then analyzed by headspace GC. Our findings showed that this new approach boasts high precision (relative standard deviation ≤ 2.18%) and accuracy for permanganate index analysis, thus validating the effectiveness of this new method in analyzing permanganate index. The introduction of the indirect phase-conversion strategy in this study is expected to set a precedent for further advancements in methodologies designed to indirectly evaluate substances capable of undergoing gas-producing reactions.


Assuntos
Óxidos , Poluentes Químicos da Água , Óxidos/química , Poluentes Químicos da Água/análise , Cromatografia Gasosa/métodos , Permanganato de Potássio/química , Compostos de Manganês/química , Dióxido de Carbono/análise , Dióxido de Carbono/química , Água/química
16.
J Chem Phys ; 160(20)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38804489

RESUMO

The thermophysical properties and elemental abundances of the noble gases in terrestrial materials can provide unique insights into the Earth's evolution and mantle dynamics. Here, we perform extensive ab initio molecular dynamics simulations to determine the melting temperature and sound velocity of neon up to 370 GPa and 7500 K to constrain its physical state and storage capacity, together with to reveal its implications for the deep interior of the Earth. It is found that solid neon can exist stably under the lower mantle and inner core conditions, and the abnormal melting of neon is not observed under the entire temperature (T) and pressure (P) region inside the Earth owing to its peculiar electronic structure, which is substantially distinct from other heavier noble gases. An inspection of the reduction for sound velocity along the Earth's geotherm evidences that neon can be used as a light element to account for the low-velocity anomaly and density deficit in the deep Earth. A comparison of the pair distribution functions and mean square displacements of MgSiO3-Ne and Fe-Ne alloys further reveals that MgSiO3 has a larger neon storage capacity than the liquid iron under the deep Earth condition, indicating that the lower mantle may be a natural deep noble gas storage reservoir. Our results provide valuable information for studying the fundamental behavior and phase transition of neon in a higher T-P regime, and further enhance our understanding for the interior structure and evolution processes inside the Earth.

17.
World J Clin Oncol ; 15(3): 434-446, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38576590

RESUMO

BACKGROUND: The ubiquitin-proteasome pathway (UPP) has been proven to play important roles in cancer. AIM: To investigate the prognostic significance of genes involved in the UPP and develop a predictive model for liver cancer based on the expression of these genes. METHODS: In this study, UPP-related E1, E2, E3, deubiquitylating enzyme, and proteasome gene sets were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, aiming to screen the prognostic genes using univariate and multivariate regression analysis and develop a prognosis predictive model based on the Cancer Genome Atlas liver cancer cases. RESULTS: Five genes (including autophagy related 10, proteasome 20S subunit alpha 8, proteasome 20S subunit beta 2, ubiquitin specific peptidase 17 like family member 2, and ubiquitin specific peptidase 8) were proven significantly correlated with prognosis and used to develop a prognosis predictive model for liver cancer. Among training, validation, and Gene Expression Omnibus sets, the overall survival differed significantly between the high-risk and low-risk groups. The expression of the five genes was significantly associated with immunocyte infiltration, tumor stage, and postoperative recurrence. A total of 111 differentially expressed genes (DEGs) were identified between the high-risk and low-risk groups and they were enriched in 20 and 5 gene ontology and KEGG pathways. Cell division cycle 20, Kelch repeat and BTB domain containing 11, and DDB1 and CUL4 associated factor 4 like 2 were the DEGs in the E3 gene set that correlated with survival. CONCLUSION: We have constructed a prognosis predictive model in patients with liver cancer, which contains five genes that associate with immunocyte infiltration, tumor stage, and postoperative recurrence.

18.
Anal Methods ; 16(16): 2444-2448, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38597248

RESUMO

In this research, for the first time, we introduce a vapor-monitoring headspace strategy to establish a new methodology for determining the water absorbability of cellulose-derived materials. The method involves detecting the water in the gas phase from various cellulose-derived materials after achieving the equilibrium state. By utilizing the headspace technique to monitor the change in water vapor pressure from bound water to free water, a change point indicating the water absorbability can be identified through fitting procedures. The study showed that the newly-established method possesses high precision (relative standard deviation ≤2.92%) and accuracy (relative differences ≤5.74%) for water absorbability analysis. The present method emerges as a facile and reliable tool for measuring water absorbability, and the introduction of the vapor-monitoring headspace strategy is anticipated to inspire the development of a new type of analytical method.

19.
J Hepatocell Carcinoma ; 11: 565-580, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525157

RESUMO

Background/Aims: Plumbagin (PL) has been shown to effe ctively inhibit autophagy, suppressing invasion and migration of hepatocellular carcinoma (HCC) cells. However, the specific mechanism remains unclear. This study aimed to investigate the effect of PL on tumor growth factor (TGF)-ß-induced epithelial-mesenchymal transition (EMT) in HCC. Methods: Huh-7 cells were cultured, and in vivo models of EMT and HCC-associated lung metastasis were developed through tail vein and in situ injections of tumor cells. In vivo imaging and hematoxylin and eosin staining were used to evaluate HCC modeling and lung metastasis. After PL intervention, the expression levels of Snail, vimentin, E-cadherin, and N-cadherin in the liver were evaluated through immunohistochemistry and Western blot. An in vitro TGF-ß-induced cell EMT model was used to detect Snail, vimentin, E-cadherin, and N-cadherin mRNA levels through a polymerase chain reaction. Their protein levels were detected by immunofluorescence staining and Western blot. Results: In vivo experiments demonstrated that PL significantly reduced the expression of Snail, vimentin, and N-cadherin, while increasing the expression of E-cadherin at the protein levels, effectively inhibiting HCC and lung metastasis. In vitro experiments confirmed that PL up-regulated epithelial cell markers, down-regulated mesenchymal cell markers, and inhibited EMT levels in HCC cells. Conclusion: PL inhibits Snail expression, up-regulates E-cadherin expression, and down-regulates N-cadherin and vimentin expression, preventing EMT in HCC cells and reducing lung metastasis.

20.
Am J Case Rep ; 25: e943056, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483097

RESUMO

BACKGROUND Bilious vomiting in a child potentially portends the dire emergency of intestinal malrotation with volvulus, necessitating prompt surgical management, with differentials including small-bowel atresia, duodenal stenosis, annular pancreas, and intussusception. Although the upper-gastrointestinal series (UGI) is the diagnostic investigation of choice, up to 15% of the studies are inconclusive, thereby posing a diagnostic challenge. CASE REPORT We report a case series of 3 children referred for bilious vomiting, whose initial UGI was inconclusive and who were eventually confirmed to have intestinal malrotation at surgery. The first child was a female born at 37 weeks with antenatally diagnosed situs inversus and levocardia, who developed bilious vomiting on day 1 of life. The duodenojejunal flexure (DJ) could not be visualized on the UGI because of faint opacification on first pass of the contrast and subsequent overlap with the proximal jejunal loops. The second child was a male born at 36 weeks, presenting at age 4 months with bilious vomiting of 2 days duration. The third child was a female born at 29 weeks, presenting with bilious aspirates on day 3 of life. UGI for all 3 showed persistent hold-up of contrast at the proximal duodenum with no opacification of the distal duodenum or small bowel.Adjunctive techniques during the UGI and ultrasound examination helped achieve a preoperative diagnosis of malrotation in these children. CONCLUSIONS Application of diagnostic adjuncts to an inconclusive initial UGI may help elucidate a preoperative diagnosis of intestinal malrotation in infantile bilious vomiting.


Assuntos
Atresia Intestinal , Volvo Intestinal , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Duodeno/cirurgia , Atresia Intestinal/complicações , Volvo Intestinal/diagnóstico , Volvo Intestinal/cirurgia , Volvo Intestinal/complicações , Náusea , Vômito/etiologia
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