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1.
J Gastrointest Oncol ; 15(2): 689-709, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38756630

RESUMEN

Background: While surufatinib, sunitinib, and everolimus have shown efficacy for advanced neuroendocrine neoplasms (NENs) in randomized controlled trials (RCTs), direct comparisons in a real-world setting remain unexplored. This gap highlights the clinical need to understand their comparative effectiveness and safety within the diverse Chinese population. Addressing this, our study provides insights into the real-world performance of these therapies, aiming to inform treatment selection and improve patient outcomes. Methods: A retrospective, observational study was conducted at Fudan University Shanghai Cancer Center, including patients with advanced NENs treated with surufatinib, sunitinib, or everolimus between July 2020 and April 2023. Eligibility criteria focused on histologically confirmed, locally advanced, unresectable, or metastatic NENs, with patients having received at least one month of targeted therapy. We employed inverse probability weighting (IPW) with the propensity score (PS) matching to adjust for the bias of baseline characteristics. The assessment of covariates included age, sex, performance status, primary tumor site, functional status, genetic mutations, tumor differentiation, Ki67 index, tumor grade, metastasis site, and previous therapies. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Results: The study enrolled 123, 56, and 68 locally advanced or metastatic NEN patients treated with surufatinib, sunitinib, and everolimus, respectively. Before adjusting for confounding factors, surufatinib was used less frequently as a first-line treatment compared to sunitinib and everolimus in pancreatic NENs (pNENs) (11.1% vs. 22.1%, P=0.057). Significant differences were noted in prior treatments and tumor characteristics between surufatinib and everolimus groups in extrapancreatic NENs (epNENs) (P<0.05). Post-IPW, these disparities were resolved (P>0.05). Surufatinib demonstrated superior median PFS (mPFS) in both pancreatic [8.30 vs. 6.33 months, hazard ratio (HR) 0.592, P<0.001] and epNENs (8.73 vs. 3.70 months, HR 0.608, P<0.001) compared to everolimus or sunitinib. Notably, male gender (HR 1.75, P=0.001), functional status (HR 2.09, P=0.01), Ki67 index >20% (HR 12.7, P=0.004), previous somatostatin analogue (SSA) treatment (HR 1.73, P=0.001), germline mutation (HR 5.62, P<0.001), poor differentiation (HR 7.45, P<0.001), liver metastasis (HR 1.72, P=0.001) and multiple treatment lines (HR 1.62 for 2nd line, P=0.04; HR 1.88 for ≥3rd line, P=0.01) were identified as negative prognostic factors for PFS. Conversely, dose adjustment (HR 0.63, P=0.009) and treatment with surufatinib (HR 0.58 for pNEN, P<0.001; HR 0.62 for epNEN, P=0.002) were correlated with longer PFS. Conclusions: In a real-world Chinese cohort, surufatinib significantly outperformed sunitinib and everolimus in prolonging PFS among advanced NEN patients, with identifiable clinical features impacting survival, and conclusions regarding superiority should be interpreted with caution due to the retrospective design. Our findings underscore the need for prospective studies to further validate these results and explore additional predictive biomarkers for personalized treatment strategies.

2.
Surg Endosc ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750173

RESUMEN

BACKGROUND: Laparoscopic radical pancreatectomy is safe and beneficial for recectable pancreatic cancer, but the extent of resection for early-stage tumors remains controversial. METHODS: Consecutive patients with left-sided pancreatic cancer who underwent either laparoscopic radical antegrade modular pancreatosplenectomy (LRAMPS, n = 54) or laparoscopic distal pancreatosplecnectomy (LDP, n = 131) between October 2020 and December 2022 were reviewed. The preoperative radiological selection criteria were as follows: (1) tumor diameter ≤ 4 cm; (2) located ≥ 1 cm from the celiac trunk; (3) didn't invade the fascial layer behind the pancreas. RESULTS: After 1:1 propensity score matching (LRAMPS, n = 54; LDP, n = 54), baseline data were well-balanced with no differences. LRAMPS resulted in longer operation time (240.5 vs. 219.0 min, P = 0.020) and higher intraoperative bleeding volume (200 vs. 150 mL, P = 0.001) compared to LDP. Although LRAMPS harvested more lymph nodes (16 vs. 13, P = 0.008), there were no statistically significant differences in lymph node positivity rate (35.2% vs. 33.3%), R0 pancreatic transection margin (94.4% vs. 96.3%), and retroperitoneal margin (83.3% vs. 87.0%) rate. Postoperative complications did not significantly differ between the two groups. However, LRAMPS was associated with increased drainage volume (85.0 vs. 40.0 mL, P = 0.001), longer time to recover semi-liquid diet compared to LDP (5 vs. 4 days, P < 0.001) and increased daily bowel movement frequency. Tumor recurrence pattern and recurrence-free survival were comparable between the two groups, but the adjuvant chemotherapy regimens varied, and the completion rate of the 6-month intravenous chemotherapy was lower in the LRAMPS group compared to the LDP group (51.9% vs. 75.9%, P = 0.016). CONCLUSIONS: LRAMPS did not provide oncological benefits over LDP for left-sided pancreatic cancer within the selection criteria, but it increased operation time, intraoperative bleeding, and postoperative bowel movement frequency. These factors impacted the regimen selection and completion of adjuvant chemotherapy, consequently compromising the potential benefits of LRAMPS in achieving better local control.

3.
Environ Toxicol ; 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38572829

RESUMEN

The number of patients with chronic kidney disease (CKD) is increasing. Oral toxin adsorbents may provide some value. Several uremic toxins, including indoxyl sulfate (IS), p-cresol (PCS), acrolein, per- and poly-fluoroalkyl substances (PFAS), and inflammation markers (interleukin 6 [IL-6] and tumor necrosis factor [TNF]-alpha) have been shown to be related to CKD progression. A total of 81 patients taking oral activated charcoal toxin adsorbents (AC-134), which were embedded in capsules that dissolved in the terminal ileum, three times a day for 1 month, were recruited. The renal function, hemoglobulin (Hb), inflammation markers, three PFAS (PFOA, PFOS, and PFNA), and acrolein were quantified. Compared with the baseline, an improved glomerular filtration rate (GFR) and significantly lower acrolein were noted. Furthermore, the CKD stage 4 and 5 group had significantly higher concentrations of IS, PCS, IL-6, and TNF but lower levels of Hb and PFAS compared with the CKD Stage 3 group at baseline and after the intervention. Hb was increased only in the CKD Stage 3 group after the trial (p = .032). Acrolein did not differ between the different CKD stage groups. Patients with improved GFR (responders) (about 77%) and nonresponders had similar baseline GFR. Responders had higher acrolein and PFOA levels throughout the study and a more significant reduction in acrolein, indicating a better digestion function. Responders had higher acrolein and PFOA levels throughout the study and a more significant reduction in acrolein, while PFOA increased in responders. Both the higher PFOA and lower acrolein may be related to improved eGFR (and possibly to improvements in proteinuria, which we did not measure. Proteinuria is associated with PFAS loss in the urine), AC-134 showed the potential to improve the GFR and decrease acrolein, which might better indicate renal function change. Future studies are needed with longer follow-ups.

4.
J Cancer Res Clin Oncol ; 150(4): 205, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38642154

RESUMEN

PURPOSE: Standard intensive care unit (ICU) admission policies and treatment strategies for patients with cancer are still lacking. To depict the current status of admission, characteristics, and outcomes of patients with cancer in the ICU. METHODS: A multicenter cross-sectional study was performed from May 10, 2021 to July 10, 2021, in the ICU departments of 37 cancer-specialized hospitals in China. Clinical records of all admitted patients aged ≥ 14 years and ICU duration > 24 h with complete data were included. Demographic information, clinical history, severity score at admission, ICU critical condition diagnosis and treatment, ICU and in-hospital outcomes and 90 days survival were also collected. A total of 1455 patients were admitted and stayed for longer than 24 h. The most common primary cancer diagnoses included lung, colorectal, esophageal, and gastric cancer. RESULTS: Patients with lung cancer were admitted more often because of worsening complications that occurred in the clinical ward. However, other cancer patients may be more likely to be admitted to the ICU because of postoperative care. ICU-admitted patients with lung or esophageal cancer tended to have more ICU complications. Patients with lung cancer had a poor overall survival prognosis, whereas patients with colorectal cancer appeared to benefit the most according to 90 days mortality rates. CONCLUSION: Patients with lung cancer require more ICU care due to critical complications and the overall survival prognosis is poor. Colorectal cancer may benefit more from ICU management. This information may be considered in ICU admission and treatment strategies.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Pulmonares , Humanos , Estudios Transversales , Unidades de Cuidados Intensivos , Instituciones Oncológicas , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/terapia , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/terapia , Estudios Retrospectivos , Mortalidad Hospitalaria
5.
Materials (Basel) ; 17(6)2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38541564

RESUMEN

The large-scale ingot of the 7xxx-series aluminum alloys fabricated by direct chill (DC) casting often suffers from foundry defects such as cracks and cold shut due to the formidable challenges in the precise controlling of casting parameters. In this manuscript, by using the integrated computational method combining numerical simulations with machine learning, we systematically estimated the evolution of multi-physical fields and grain structures during the solidification processes. The numerical simulation results quantified the influences of key casting parameters including pouring temperature, casting speed, primary cooling intensity, and secondary cooling water flow rate on the shape of the mushy zone, heat transport, residual stress, and grain structure of DC casting ingots. Then, based on the data of numerical simulations, we established a novel model for the relationship between casting parameters and solidification characteristics through machine learning. By comparing it with experimental measurements, the model showed reasonable accuracy in predicting the sump profile, microstructure evolution, and solidification kinetics under the complicated influences of casting parameters. The integrated computational method and predicting model could be used to efficiently and accurately determine the DC casting parameters to decrease the casting defects.

6.
Biosens Bioelectron ; 255: 116245, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38555770

RESUMEN

Sensitive and accurate analysis of specific subpopulations in circulating extracellular vesicles (EVs) can provide a wealth of information for cancer diagnosis and management. Thus, we propose herein a new electrochemical biosensing method based on a proximity labeling-assisted click conjugation strategy. The method's core design is use of antibody-guided proximity labeling to equip target EVs with a large amount of alkyne groups, so that azide-tagged silver nanoparticles can be accurately loaded onto target EV surfaces, via click conjugation, to generate significant electrochemical responses. Adopting CD44-positive EVs as the model, the electrochemical method was demonstrated by analyzing target EVs across a wide linear range (103-109 particles/mL) with acceptable sensitivity and specificity. Satisfactory utility in clinical blood samples, and versatility with human epidermal growth factor receptor-2-positive EVs as alternative targets, were also shown. This method may thus provide a novel approach to specific subgroup analyses of circulating EVs, and is expected to offer reliable guidance for cancer diagnoses and management strategies.


Asunto(s)
Técnicas Biosensibles , Vesículas Extracelulares , Nanopartículas del Metal , Neoplasias , Humanos , Técnicas Biosensibles/métodos , Plata , Neoplasias/diagnóstico , Neoplasias/metabolismo
7.
Neuroendocrinology ; 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38471465

RESUMEN

Insulinomas are the most frequent functional neuroendocrine tumors of pancreas. In about 10% cases, insulinomas are associated with hereditary syndrome including multiple endocrine neoplasia 1 (MEN1). Herein, we presented a case of 44-year-old female with recurrent hypoglycemia. In December 1998, this patient has undergone resection of two pancreatic lesions due to hypoglycemia and diagnosed as insulinoma. After operation, the symptom of hypoglycemia disappeared. However, from 2021, hypoglycemic symptoms reappeared frequently and even coma. In June 2023, enhanced CT showed multiple pancreatic lesions abundant with blood supply. Fasting serum blood glucose and insulin were 1.73mmol/L and 15.2U/L (2.6-11.8U/L). Germline genes suggested MEN1 pathogenic mutations. 68Ga-DOTANOC PET/CT indicated there were multiple lesions located in the pancreas and duodenum with high expression of somatostatin receptor (SSTR). 68Ga-exendin-4 PET/CT were added to localize the insulinoma. Most lesions with high expression of SSTR in body and tail of pancreas manifested part of them with high uptake of 68Ga-exendin-4, and an additional lesion with high expression of glucagon-like peptide 1 receptor was only detected by 68Ga-exendin-4 PET/CT. It showed highly heterogeneity. From the distal pancreatectomy, a total 5 tumors were found in the body and tail of pancreas, which were diagnosed as neuroendocrine tumors (NETs). After the operation, all the symptoms related to hypoglycemia disappeared. Immunohistochemical results of SSTR2 and insulin were consistent with the imaging finding of dual tracer PET/CT. From this case, combination of 68Ga-DOTANOC and 68Ga-exendin-4 PET/CT was recommended in the patients of MEN1 and insulinoma to estimate the heterogeneity of multiple neuroendocrine tumors that contributing to detect all the NET lesions and locate the tumors with secretion of insulin.

8.
ACS Sens ; 9(2): 759-769, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38306386

RESUMEN

Advanced techniques for both environmental and biological prescription drug monitoring are of ongoing interest. In this work, a fluorescent sensor based on an Eu3+-doped anionic zinc-based metal-organic framework (Eu3+@Zn-MOF) was constructed for rapid visual analysis of the prescription drug molecule demecycline (DEM), achieving both high sensitivity and selectivity. The ligand 2-amino-[1,1'-biphenyl]-4,4'-dicarboxylic acid (bpdc-NH2) not only provides stable cyan fluorescence (467 nm) for the framework through intramolecular charge transfer of bpdc-NH2 infinitesimal disturbanced by Zn2+ but also chelates Eu3+, resulting in red (617 nm) fluorescence. Through the synergy of photoinduced electron transfer and the antenna effect, a bidirectional response to DEM is achieved, enabling concentration quantification. The Eu3+@Zn-MOF platform exhibits a wide linear range (0.25-2.5 µM) to DEM and a detection limit (LOD) of 10.9 nM. Further, we integrated the DEM sensing platform into a paper-based system and utilized a smartphone for the visual detection of DEM in water samples and milk products, demonstrating the potential for large-scale, low-cost utilization of the technology.


Asunto(s)
Medicamentos bajo Prescripción , Zinc , Fluorescencia , Monitoreo Biológico , Prescripciones
9.
Endocrine ; 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38195968

RESUMEN

PURPOSE: To investigate the association between age distribution and synchronous distant metastasis of papillary thyroid carcinoma. METHOD: Patients with PTC who were treated from January 2013 to December 2018 at a single institute in a cancer referral center in China were retrospectively reviewed. A logistic regression model with restricted cubic splines (RCS) was used to examine the association between age at diagnosis and synchronous distant metastasis. RESULTS: A total of 111 patients (0.7%) were diagnosed with distant metastasis. The logistic regression model with RCS revealed a "U-shape" association between age and distant metastasis. The RCS curve suggested a U-shaped pattern. The multivariable regression analysis showed that patients in the age groups ≤21 years (OR 2.33, 95% CI 1.09-4.68, P = 0.022) and >55 years (OR 3.32, 95% CI 1.99-5.46, P < 0.001) had a significantly higher incidence of distant metastasis than patients in the age group of 22 to 55 years. CONCLUSIONS: A U-shaped association was observed between age at diagnosis and synchronous distant metastasis in papillary thyroid carcinoma patients.

11.
World J Surg Oncol ; 22(1): 1, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38169384

RESUMEN

BACKGROUND: There is no evidence supporting the feasibility of laparoscopic pancreaticoduodenectomy (LPD) compared to open pancreatoduodenectomy (OPD) following neoadjuvant chemotherapy (NACT) for pancreatic ductal adenocarcinoma (PDAC). METHODS: The clinical data of consecutive patients with borderline resectable PDAC who received NACT and underwent either LPD or OPD between January 2020 and December 2022 at Fudan University Shanghai Cancer Center was prospectively collected and retrospectively analyzed. RESULTS: The analysis included 57 patients in the OPD group and 20 in the LPD group. Following NACT, the LPD group exhibited a higher median CA19-9 decrease rate compared to the OPD group (85.3% vs. 66.9%, P = 0.042). Furthermore, 3 anatomically borderline PDACs in the LPD group and 5 in the OPD group were downstaged into resectable status (30.0% vs. 12.3%, P = 0.069). According to RECIST criteria, 51 (66.2%) patients in the entire cohort were evaluated as having stable disease. The median operation time for the LPD group was longer than the OPD group (419 vs. 325 min, P < 0.001), while the venous resection rate was 35.0% vs. 43.9%, respectively (P = 0.489). There was no difference in the number of retrieved lymph nodes, with a median number of 18.5 in the LPD group and 22 in the OPD group, and the R1 margin rate (15.0% vs. 12.3%) was also comparable. The incidence of Clavien-Dindo complications (35.0% vs. 66.7%, P = 0.018) was lower in the LPD group compared to the OPD group. Multivariable regression analysis revealed that a tumor diameter > 3 cm before NACT (HR 2.185) and poor tumor differentiation (HR 1.805) were independent risk factors for recurrence-free survival, and a decrease rate of CA19-9 > 70% (OR 0.309) was a protective factor for early tumor recurrence and overall survival. CONCLUSIONS: LPD for PDAC following NACT is feasible and oncologically equivalent to OPD. Effective control of CA19-9 levels is beneficial in reducing early tumor recurrence and improving overall survival.


Asunto(s)
Adenocarcinoma , Carcinoma Ductal Pancreático , Laparoscopía , Neoplasias Pancreáticas , Humanos , Pancreaticoduodenectomía/efectos adversos , Estudios Retrospectivos , Terapia Neoadyuvante/efectos adversos , Recurrencia Local de Neoplasia/etiología , Estudios de Factibilidad , Antígeno CA-19-9 , China , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/cirugía , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Laparoscopía/efectos adversos , Complicaciones Posoperatorias/etiología , Tiempo de Internación
12.
Diabetes ; 73(1): 108-119, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37847928

RESUMEN

Mitochondria, the organelles responsible for generating ATP in eukaryotic cells, have been previously implicated as a contributor to diabetes. However, mitochondrial proteins are encoded by both nuclear DNA (nDNA) and mtDNA. In order to better understand the relative contribution of each of these genomes to diabetes, a chimeric mitochondrial-nuclear exchange (MNX) mouse was created via pronuclear transfer carrying nDNA from a strain susceptible to type 1 diabetes (NOD/ShiLtJ) and mtDNA from nondiabetic C57BL/6J mice. Inheritance of the resulting heteroplasmic mtDNA mixture was then tracked across multiple generations, showing that offspring heteroplasmy generally followed that of the mother, with occasional large shifts consistent with an mtDNA bottleneck in the germ line. In addition, survival and incidence of diabetes in MNX mice were tracked and compared with those in unaltered NOD/ShiLtJ control mice. The results indicated improved survival and a delay in diabetes onset in the MNX mice, demonstrating that mtDNA has a critical influence on disease phenotype. Finally, enzyme activity assays showed that the NOD/ShiLtJ mice had significant hyperactivity of complex I of the electron transport chain relative to MNX mice, suggesting that a particular mtDNA variant (m.9461T>C) may be responsible for disease causation in the original NOD/ShiLtJ strain. ARTICLE HIGHLIGHTS: Mitochondria have been previously implicated in diabetes, but the specific genetic factors remain unclear. To better understand the contributions of mitochondrial genes in nuclear DNA (nDNA) versus mtDNA, we created mitochondrial-nuclear exchange (MNX) mice carrying nDNA from a diabetic strain and mtDNA from nondiabetic mice. Long-term tracking of MNX mice showed occasional large shifts in heteroplasmy consistent with an mtDNA bottleneck in the germ line. In addition, the MNX mice showed improved survival and delayed incidence of diabetes relative to the unaltered diabetic mice, which appeared to be linked to the activity of respiratory complex I.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Genoma Mitocondrial , Animales , Ratones , Diabetes Mellitus Tipo 1/genética , Genoma Mitocondrial/genética , Diabetes Mellitus Experimental/genética , Ratones Endogámicos NOD , Ratones Endogámicos C57BL , ADN Mitocondrial/genética , Modelos Animales de Enfermedad
14.
J Thorac Dis ; 15(11): 6265-6278, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38090319

RESUMEN

Background: N7-methylguanosine (m7G) is an important posttranscriptional modification affecting mRNA and tRNA functions and stability. The genes regulating the m7G process have been previously found involved in the carcinogenesis process. We aimed to analyze the role of m7G-related genes as potential prognostic markers for lung squamous cell carcinoma (LSCC). Methods: Twenty-nine m7G-related genes were selected for the analysis in the LSCC cohort of the Cancer Genome Atlas (TCGA). Univariate, multivariate, and Kaplan-Meier analyses were used to evaluate the predictive value of risk model developed with m7G signature for overall survival (OS).. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of differentially expressed genes (DEGs) were performed for high- and low-risk LSCC groups. Results: We identified 17 differentially expressed m7G methylation-related genes in LSCC versus normal tissues. The expression of five m7G-related genes (EIF3D, LSM1, NCBP2, NUDT10, and NUDT11) was identified as an independent prognostic marker for OS in LSCC patients. A risk model with these five m7G-related genes predicted 2-, and 3-year survival rates of 0.623 and 0.626, respectively. The risk score significantly correlated with OS: LSCC patients with a higher risk score had shorter OS (P<0.01) and it was associated with lower immune response (P<0.01). Conclusions: We developed a novel m7G-related gene signature that can be of great utility to predict the prognosis for patients with LSCC.

15.
Materials (Basel) ; 16(23)2023 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-38068076

RESUMEN

In this study, the effects of the combined addition of CeLa and GdY on the microstructure and mechanical properties of as-cast Al-4Cu-1Mn alloys were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and tensile testing. The results show that the minor addition of CeLa and GdY leads to a refinement of grain size. The addition of CeLa results in the formation of supersaturated vacancies in the Al matrix, whereas the addition of GdY leads to a decrease in the precipitation temperature of the Al2Cu phase. The combined CeLa and GdY additions can significantly increase ultimate tensile strength (UTS) while losing only a small amount of elongation (EL). Compared with the unmodified alloy, the grain size and SDAS of the alloy (0.2 wt.% CeLa + 0.1 wt.% GdY) were diminished by 67.2% and 58.7%, respectively, while maximum hardness and UTS rose by 31.2% and 36.9%, respectively.

16.
Front Pharmacol ; 14: 1283247, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38027003

RESUMEN

Background and objective: Sacituzumab govitecan (SG), the first antibody-drug conjugate targeting human trophoblast cell-surface antigen 2 (Trop-2), has been approved by the Food and Drug Administration (FDA) for the treatment of advanced or metastatic breast cancer and urothelial cancer. However, there is currently a dearth of information regarding the safety profiles of SG in a large sample cohort. The objective of the present study is to investigate SG-related adverse events (AEs) in real-world settings leveraging the FDA Adverse Event Reporting System (FAERS) database to guide the safety management of clinical medication. Methods: The FAERS database was retrospectively queried to extract reports associated with SG from April 2020 to March 2023. To identify and evaluate potential AEs in patients receiving SG, various disproportionality analyses such as reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) were employed. Results: Overall, 2069 reports of SG as the "primary suspect" were identified. Noteworthy, SG was significantly associated with an increased risk of blood lymphatic system disorders (ROR, 7.18; 95% CI, 6.58-7.84) and hepatobiliary disorders (ROR, 2.68; 95% CI, 2.17-3.30) at the System Organ Class (SOC) level. Meanwhile, 61 significant disproportionality preferred terms (PTs) simultaneously complied with all four algorithms were adopted. Therein, anemia, thrombocytopenia, neutropenia, leukopenia, diarrhea, asthenia, alopecia, and electrolyte imbalance were consistent with the common AEs described in the clinical trials and specification of SG. Furthermore, unexpected significant AEs include colitis (ROR, 12.09; 95% CI, 9.1-16.08), heart rate increased (ROR, 5.11; 95% CI, 3.84-6.79), sepsis (ROR, 4.77; 95% CI, 3.59-6.34), cholestasis (ROR, 6.28; 95% CI, 3.48-11.36), blood bilirubin increased (ROR, 4.65; 95% CI, 2.42-8.94) and meningitis (ROR, 7.23; 95% CI, 2.71-19.29) were also be detected. The median time to onset of SG-related AEs was 14 [interquartile range (IQR), 7-52] days, with the majority occurring within the initial month of SG treatment. Conclusion: Our study validates the commonly known AEs and also found some potentially emerging safety issues related to SG in real-world clinical practice, which could provide valuable vigilance evidence for clinicians and pharmacists to manage the safety issues of SG.

17.
Heliyon ; 9(11): e21917, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38027678

RESUMEN

Background: Tumors involving the main pancreatic duct (MPD) used to be a contraindication for enucleation. Methods: Clinical data of consecutive patients with pancreatic tumors who received laparoscopic or robotic enucleation (LEN or REN) between January 2019 and December 2021 at Fudan University Shanghai Cancer Center were analyzed. Results: Ninety-six patients were included in the analysis, with 55 in the LEN group and 41 in the REN group, and no conversion to laparotomy. Most tumors were located in the head of pancreas (71.9 %). The tumor diameter (3.1 vs. 1.9 cm) was larger, and more cystic tumors (92.7 % vs. 56.4 %) and more tumors involving the MPD (34.1 % vs. 3.6 %) were observed in the REN group. MPD support tube insertion was performed in 15 cases, with 11 in the REN group and 4 in the LEN group. The incidence of biochemical and grade B postoperative pancreatic fistula (POPF) was both 46.9 %, and no grade C POPF occurred. Among the 45 patients with grade B POPF, 28 cases (62.2 %) were due to carrying drainage tube >3 weeks without additional treatment, and only 4 cases required invasive treatment. For patients with MPD support tube implantation (n = 15), support tube fall-offs were observed in 12 cases, 2 patients had MPD dilatation, and no MPD stricture, stone formation or pancreatic atrophy was observed during follow-up. Conclusions: The incidence of POPF was high but still controllable without serious complications after minimally invasive enucleation. The MPD is no longer a restricted area, and the robotic system has advantages in handling complex enucleations.

18.
Genes (Basel) ; 14(11)2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-38002975

RESUMEN

In this study, to explore the effect of growth hormone changes on the related genes and regulatory roles of the turtle, PCR amplification, real-time fluorescence quantitative analysis, and enzyme cutting technology were used to clone and sequence the somatostatin (SS) gene, growth hormone receptor (GHR), and insulin-like growth factor-1 (IGF-I) sequence of Chinemys reevesii. The effects of human growth hormone on the mRNA expression of growth-axis-related genes SS, GHR, and IGF-1 in different sexes were observed. The study of the SS gene in turtles using real-time fluorescence quantitative PCR showed that the SS gene was mainly expressed in the nervous system and the digestive system, with the highest expression found in the brain, while the GHR gene and the IGF-I gene were expressed in all tissues of Chinemys reevesii. The SS gene was expressed in the brain, pituitary, liver, stomach, and intestine, with the highest expression in the brain and the lowest expression in the liver. Within 4 weeks of the injection of exogenous growth hormone, the expression level of the SS gene in the brain of both sexes first increased and then decreased, showing a parabolic trend, and the expression level of the experimental group was lower than that of the control group. After the injection of growth hormone (GH), the expression of the GHR gene in the liver of both sexes showed a significant increase in the first week, decreasing to the control group level in the second week, and then gradually increasing. Finally, a significant level of difference in the expression of the GHR gene was reached at 3 and 4 weeks. In terms of the IGF-I gene, the changing trend of the expression level in the liver was the same as that of the GHR gene. After the injection of exogenous growth hormone, although the expression of the SS gene increased the inhibition of the secretion of the GHR gene by the Reeves' turtle, exogenous growth hormone could replace the synthesis of GH and GHR, accelerating the growth of the turtle. The experiments showed that the injection of recombinant human growth hormone affects the expression of SS, GHR, and IGF-1 genes, and promotes the growth of the Reeves' turtle.


Asunto(s)
Hormona de Crecimiento Humana , Tortugas , Masculino , Animales , Femenino , Humanos , Hormona del Crecimiento/genética , Hormona del Crecimiento/metabolismo , Receptores de Somatotropina/genética , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Hormona de Crecimiento Humana/genética , Hormona de Crecimiento Humana/farmacología , Regulación de la Expresión Génica , Somatostatina/genética , Somatostatina/metabolismo
19.
Nano Lett ; 23(23): 10871-10878, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-37955520

RESUMEN

Plasmon-enhanced electrochemistry (PEEC) has been observed to facilitate energy conversion systems by converting light energy to chemical energy. However, comprehensively understanding the PEEC mechanism remains challenging due to the predominant use of ensemble-based methodologies on macroscopic electrodes, which fails to measure electron-transfer kinetics due to constraints from mass transport and the averaging effect. In this study, we have employed nanoparticle impact electrochemistry (NIE), a newly developed electroanalytical technique capable of measuring electrochemical dynamics at a single-nanoparticle level under optimal mass transport conditions, along with microscopic electron-transfer theory for data interpretation. By investigating the plasmon enhanced hydrogen evolution reaction (HER) at individual silver nanoparticles (AgNPs), we have clearly revealed the previously unknown influence of solvent effects within the PEEC mechanism. This finding suggests an additional approach to optimize plasmon-assisted electrocatalysis and electrosynthesis systems.

20.
Medicine (Baltimore) ; 102(46): e36097, 2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-37986320

RESUMEN

Tongue squamous cell carcinoma (TSCC) has a poor prognosis and destructive characteristics. Reliable biomarkers are urgently required to predict disease outcomes and to guide TSCC treatment. This study aimed to develop a multigene signature and prognostic nomogram that can accurately predict the prognosis of patients with TSCC. We screened differentially expressed genes associated with TSCC using The Cancer Genome Atlas dataset. Based on this, we developed a new multi-mRNA gene signature using univariate Cox regression, Least Absolute Shrinkage and Selection Operator regression, and multivariate Cox regression. We used the concordance index to evaluate the accuracy of this new multigene model. Moreover, we performed receiver operating characteristic and Kaplan-Meier survival analyses to assess the predictive ability of the new multigene model. In addition, we created a prognostic nomogram incorporating clinical and pathological characteristics, with the aim of enhancing the adaptability of this model in practical clinical settings. We successfully developed a new prognostic model based on the expression levels of these 3 mRNAs that can be used to predict the prognosis of patients with TSCC. This prediction model includes 3 genes: KRT33B, CDKN2A, and CA9. In the validation set, the concordance index of this model was 0.851, and the area under the curve was 0.778 and 0.821 in the training and validation sets, respectively. Kaplan-Meier survival analysis showed that regardless of whether it was in the training or validation set, the prognosis of high-risk patients was significantly worse than that of low-risk patients (P < .001). Multivariate Cox regression analysis revealed that this model was an independent prognostic factor for patients with TSCC (P < .001). Our study suggests that this 3-gene signature model has a high level of accuracy and predictive ability, is closely related to the overall survival rate of patients with TSCC, and can independently predict the prognosis of TSCC patients with high accuracy and predictive ability.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de la Lengua , Humanos , Neoplasias de la Lengua/genética , Pronóstico , Carcinoma de Células Escamosas/genética , Nomogramas , Genes p16 , ARN Mensajero
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