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1.
iScience ; 27(4): 109553, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38623338

Electrocatalytic generation of H2O2 via the 2-electron pathway of oxygen reduction reaction (2e-ORR) is an attractive technology compared to the anthraquinone process due to convenience and environmental friendliness. However, catalysts with excellent selectivity and high activity for 2e-ORR are necessary for practical applications. Reported here is a catalyst comprising boron-doped porous carbon hollow spheres (B-PCHSs) prepared using the hard template method coupled with borate transesterification. In an alkali electrolyte, the selectivity of B-PCHS for 2e-ORR above 90% in range of 0.4-0.7 VRHE and an onset potential of 0.833 V was obtained. Meanwhile, the generation rate of H2O2 reached 902.48 mmol h-1 gcat-1 at 0.4 VRHE under 59.13 mA cm-2 in batch electrolysis. The excellent catalytic selectivity of B-PCHS for 2e-ORR originates from the boron element, and the catalytic activity of B-PCHS for H2O2 generation is contributed to the morphology of porous hollow spheres, which facilitates mass transfer processes.

2.
Materials (Basel) ; 17(8)2024 Apr 11.
Article En | MEDLINE | ID: mdl-38673105

Electrosynthesis of H2O2 via both pathways of anodic two-electron water oxidation reaction (2e-WOR) and cathodic two-electron oxygen reduction reaction (2e-ORR) in a diaphragm-free bath can not only improve the generation rate and Faraday efficiency (FE), but also simplify the structure of the electrolysis bath and reduce the energy consumption. The factors that may affect the efficiency of H2O2 generation in coupled electrolytic systems have been systematically investigated. A piece of fluorine-doped tin oxide (FTO) electrode was used as the anode, and in this study, its catalytic performance for 2e-WOR in Na2CO3/NaHCO3 and NaOH solutions was compared. Based on kinetic views, the generation rate of H2O2 via 2e-WOR, the self-decomposition, and the oxidative decomposition rate of the generated H2O2 during electrolysis in carbonate electrolytes were investigated. Furthermore, by choosing polyethylene oxide-modified carbon nanotubes (PEO-CNTs) as the catalyst for 2e-ORR and using its loaded electrode as the cathode, the coupled electrolytic systems for H2O2 generation were set up in a diaphragm bath and in a diaphragm-free bath. It was found that the generated H2O2 in the electrolyte diffuses and causes oxidative decomposition on the anode, which is the main influent factor on the accumulated concentration in H2O2 in a diaphragm-free bath.

3.
Res Sq ; 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38645014

We analyzed genomic data derived from the prostate cancer of African and European American men in order to identify differences that may contribute to racial disparity of outcome and that could also define novel therapeutic strategies. In addition to analyzing patient derived next generation sequencing data, we performed FISH based confirmatory studies of Chromodomain helicase DNA-binding protein 1 (CHD1) loss on prostate cancer tissue microarrays. We created CRISPR edited, CHD1 deficient prostate cancer cell lines for genomic, drug sensitivity and functional homologous recombination (HR) activity analysis. We found that subclonal deletion of CHD1 is nearly three times as frequent in prostate tumors of African American men than in men of European ancestry and it associates with rapid disease progression. We further showed that CHD1 deletion is not associated with homologous recombination deficiency associated mutational signatures in prostate cancer. In prostate cancer cell line models CHD1 deletion did not induce HR deficiency as detected by RAD51 foci formation assay or mutational signatures, which was consistent with the moderate increase of olaparib sensitivity. CHD1 deficient prostate cancer cells, however, showed higher sensitivity to talazoparib. CHD1 loss may contribute to worse outcome of prostate cancer in African American men. A deeper understanding of the interaction between CHD1 loss and PARP inhibitor sensitivity will be needed to determine the optimal use of targeted agents such as talazoparib in the context of castration resistant prostate cancer.

4.
Toxicol Sci ; 2024 Apr 11.
Article En | MEDLINE | ID: mdl-38603617

Administration of high dose vitamin K1 (VK1) overcomes coagulopathy and bleeding elicited by acute poisoning with long-acting anti-coagulant rodenticides (LAARs). However, long-term (months) treatment is required due to long LAAR biological half-lives that may lead to poor compliance and recurrent coagulopathy. The half-lives of LAARs are extended by slow metabolism, and similar to warfarin, are thought to undergo enterohepatic recirculation. We now show that treatment with the bile acid sequestrant cholestyramine (CSA) administered concomitantly with VK1 decreases plasma LAAR levels and increases LAAR fecal excretion. Daily CSA treatment for 14 days did not reduce plasma VK1 levels, nor increase prothrombin time. Collectively, these data show that CSA accelerates LAAR clearance from rabbits without adverse effects on VK1 anti-coagulation, and could provide an additional therapeutic option for treatment of LAAR poisoning.

5.
PLoS One ; 19(4): e0297122, 2024.
Article En | MEDLINE | ID: mdl-38662671

Site specific biotinylation of AviTagged recombinant proteins using BirA enzyme is a widely used protein labeling technology. However, due to the incomplete biotinylation reactions and the lack of a purification method specific for the biotinylated proteins, it is challenging to purify the biotinylated sample when mixed with the non-biotinylated byproduct. Here, we have developed a monoclonal antibody that specifically recognizes the non-biotinylated AviTag but not the biotinylated sequence. After a ten-minute incubation with the resin that is conjugated with the antibody, the non-biotinylated AviTagged protein is trapped on the resin while the fully biotinylated material freely passes through. Therefore, our AviTrap (anti-AviTag antibody conjugated resin) provides an efficient solution for enriching biotinylated AviTagged proteins via a simple one-step purification.


Antibodies, Monoclonal , Biotinylation , Antibodies, Monoclonal/chemistry , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism , Humans , Biotin/chemistry , Animals , Carbon-Nitrogen Ligases/chemistry , Carbon-Nitrogen Ligases/metabolism
6.
Materials (Basel) ; 17(7)2024 Apr 04.
Article En | MEDLINE | ID: mdl-38612173

Rechargeable aqueous zinc-ion batteries have attracted a lot of attention owing to their cost effectiveness and plentiful resources, but less research has been conducted on the aspect of high volumetric energy density, which is crucial to the space available for the batteries in practical applications. In this work, highly crystalline V2O5 microspheres were self-assembled from one-dimensional V2O5 nanorod structures by a template-free solvothermal method, which were used as cathode materials for zinc-ion batteries with high performance, enabling fast ion transport, outstanding cycle stability and excellent rate capability, as well as a significant increase in tap density. Specifically, the V2O5 microspheres achieve a reversible specific capacity of 414.7 mAh g-1 at 0.1 A g-1, and show a long-term cycling stability retaining 76.5% after 3000 cycles at 2 A g-1. This work provides an efficient route for the synthesis of three-dimensional materials with stable structures, excellent electrochemical performance and high tap density.

7.
Transl Cancer Res ; 12(10): 2518-2532, 2023 Oct 31.
Article En | MEDLINE | ID: mdl-37969386

Background: Previous studies have verified that NR3C2 inhibits tumor cell proliferation, invasion, and migration. However, there is a lack of independent validation cohorts for verifying the prognostic value of NR3C2 in clear cell renal cell carcinoma (ccRCC), and its underlying antitumor mechanisms remain unclear. Methods: We first obtained dates from the online public databases. Then R language or online public database was used for bioinformatics analyses to evaluate the effect of NR3C2 on the diagnosis, prognosis, and immune microenvironment in ccRCC patients. Finally, the results were verified by our own cohort and immunofluorescence (IF) staining. Results: The present study yielded significant findings regarding the expression of NR3C2 in ccRCC compared to control tissues. Specifically, NR3C2 expression was found to be significantly reduced in ccRCC and was observed to be correlated with tumor stage. Additionally, patients with lower NR3C2 expression exhibited shorter overall survival (OS), disease-specific survival, and progress-free survival. Univariable and multivariate Cox analyses further identified NR3C2 expression as an independent prognostic factor for ccRCC. Receiver operating characteristic (ROC) analysis demonstrated that NR3C2 was a highly accurate marker for distinguishing tumors from normal kidney tissue, with an area under the curve (AUC) of 0.959. Further analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that NR3C2 may play a role in various biological processes and pathways related to tumor immune microenvironment (TIM). The expression of NR3C2 exhibited significant positive correlations with the levels of infiltration of CD4+ and CD8+ T cells, as well as an association with immune checkpoints. Conclusions: Our exploratory study suggested that NR3C2 could serve as a novel biomarker for predicting survival in patients with ccRCC and the molecular mechanisms owe partly to immune cell infiltration.

8.
Sci Rep ; 13(1): 17428, 2023 10 13.
Article En | MEDLINE | ID: mdl-37833334

Early identification of a patient with a high risk of blood transfusion during brain tumor resection surgery is difficult but critical for implementing preoperative blood-saving strategies. This study aims to develop and validate a machine learning prediction tool for intraoperative blood transfusion in brain tumor resection surgery. A total of 541 patients who underwent brain tumor resection surgery in our hospital from January 2019 to December 2021 were retrospectively enrolled in this study. We incorporated demographics, preoperative comorbidities, and laboratory risk factors. Features were selected using the least absolute shrinkage and selection operator (LASSO). Eight machine learning algorithms were benchmarked to identify the best model to predict intraoperative blood transfusion. The prediction tool was established based on the best algorithm and evaluated with discriminative ability. The data were randomly split into training and test groups at a ratio of 7:3. LASSO identified seven preoperative relevant factors in the training group: hemoglobin, diameter, prothrombin time, white blood cell count (WBC), age, physical status of the American Society of Anesthesiologists (ASA) classification, and heart function. Logistic regression, linear discriminant analysis, supporter vector machine, and ranger all performed better in the eight machine learning algorithms with classification errors of 0.185, 0.193, 0.199, and 0.196, respectively. A nomogram was then established, and the model showed a better discrimination ability [0.817, 95% CI (0.739, 0.895)] than hemoglobin [0.663, 95% CI (0.557, 0.770)] alone in the test group (P = 0.000). Hemoglobin, diameter, prothrombin time, WBC, age, ASA status, and heart function are risk factors of intraoperative blood transfusion in brain tumor resection surgery. The prediction tool established using the logistic regression algorithm showed a good discriminative ability than hemoglobin alone for predicting intraoperative blood transfusion in brain tumor resection surgery.


Blood Transfusion , Brain Neoplasms , Humans , Retrospective Studies , Risk Factors , Hemoglobins , Brain Neoplasms/surgery
9.
BMC Geriatr ; 23(1): 606, 2023 09 27.
Article En | MEDLINE | ID: mdl-37759165

BACKGROUND: The quality of life (QoL) of elderly patients with bone trauma is significantly decreased and is affected by many complex factors. This study aims to conduct a half-year follow-up survey to clarify QoL and its influencing factors in elderly patients with bone trauma in order to provide targeted care measures for elderly patients with bone trauma. METHODS: This was a longitudinal observational study. We used the 36-Item Short Form Health Survey (SF-36) to investigate and evaluate the QoL of 100 patients with bone trauma at the time of hospital discharge and 1 month, 3 months, and 6 months after discharge. Our previous study confirmed that the SF-36 had higher reliability and validity for evaluating the QoL of elderly patients with bone trauma. At the same time, we also investigated the age, gender, location of bone trauma, and destination after discharge of those patients. Those factors that might affect the QoL of elderly patients with bone trauma were identified by univariate and multivariate analyses. RESULTS: The total physiological function, role-physical, bodily pain, vitality, social functioning, role-emotional, and mental health scores of elderly patients with bone trauma gradually increased from the time of discharge to 1 month, 3 months, and 6 months after discharge, and there were significant differences (p < 0.001). However, there was no significant difference in the general health score in the different periods (P = 0.095). The total QoL scores also significantly differed (F = 118.61, P < 0.001) at the time of discharge (335.252 ± 127.572) and 1 month (285.149 ± 112.827), 3 months (479.344 ± 153.663), and 6 months after discharge (544.396 ± 166.536). The univariate analysis results showed that the location of bone trauma (P < 0.005) and the destination after discharge (P < 0.001) were the main factors affecting QoL in different periods. The results of the multivariate analysis showed that the location of bone trauma was an important factor affecting QoL (P < 0.005 in different periods). Whether to undergo surgery was a factor affecting the patients' long-term QoL (P < 0.005 at 6 months after discharge). CONCLUSIONS: Although the QoL of elderly patients with bone trauma gradually improves after injury, their recovery time is long, and the influencing factors are complex. Follow-up services should continue for at least six months for these patients, and comprehensive treatment and long-term rehabilitation services should be provided.


Patients , Quality of Life , Aged , Humans , Follow-Up Studies , Reproducibility of Results , Emotions
10.
Nanomaterials (Basel) ; 13(18)2023 Sep 17.
Article En | MEDLINE | ID: mdl-37764604

To improve the water absorbency and water-retention rate of superabsorbent materials, a porous calcium carbonate composite superabsorbent polymer (PCC/PAA) was prepared by copolymerization of acrylic acid and porous calcium carbonate prepared from ground calcium carbonate. The results showed that the binding energies of C-O and C=O in the O 1s profile of PCC/PAA had 0.2 eV and 0.1-0.7 eV redshifts, respectively, and the bonding of -COO- groups on the surface of the porous calcium carbonate led to an increase in the binding energy of O 1s. Furthermore, the porous calcium carbonate chelates with the -COO- group in acrylic acid through the surface Ca2+ site to form multidirectional crosslinking points, which would increase the flexibility of the crosslinking network and promote the formation of pores inside the PCC/PAA to improve the water storage space. The water absorbency of PCC/PAA with 2 wt% porous calcium carbonate in deionized water and 0.9 wt% NaCl water solution increased from 540 g/g and 60 g/g to 935 g/g and 80 g/g, respectively. In addition, since the chemical crosslinker N,N'-methylene bisacrylamide is used in the polymerization process of PCC/PAA, N,N'-methylene bisacrylamide and porous calcium carbonate enhance the stability of the PCC/PAA crosslinking network by double-crosslinking with a polyacrylic acid chain, resulting in the crosslinking network of PCC/PAA not being destroyed after water absorption saturation. Therefore, PCC/PAA with 2 wt% porous calcium carbonate improved the water-retention rate by 244% after 5 h at 60 °C, and the compressive strength was approximately five-times that of the superabsorbent without porous calcium carbonate.

11.
Clin Cancer Res ; 29(17): 3372-3383, 2023 09 01.
Article En | MEDLINE | ID: mdl-37289194

PURPOSE: We explored the clinical and genomic characteristics of hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC) after progression on cyclin-dependent kinase 4 and 6 inhibitors (CDK4 and 6i) ± endocrine therapy (ET) to understand potential resistance mechanisms that may aid in identifying treatment options. EXPERIMENTAL DESIGN: Patients in the United States with HR+, HER2- MBC had tumor biopsies collected from a metastatic site during routine care following progression on a CDK4 and 6i ± ET (CohortPost) or prior to initiating CDK4 and 6i treatment (CohortPre) and analyzed using a targeted mutation panel and RNA-sequencing. Clinical and genomic characteristics were described. RESULTS: The mean age at MBC diagnosis was 59 years in CohortPre (n = 133) and 56 years in CohortPost (n = 223); 14% and 45% of patients had prior chemotherapy/ET, and 35% and 26% had de novo stage IV MBC, respectively. The most common biopsy site was liver (CohortPre, 23%; CohortPost, 56%). CohortPost had significantly higher tumor mutational burden (TMB; median 3.16 vs. 1.67 Mut/Mb, P < 0.0001), ESR1 alteration frequency (mutations: 37% vs. 10%, FDR < 0.0001; fusions: 9% vs. 2%, P = 0.0176), and higher copy-number amplification of genes on chr12q15, including MDM2, FRS2, and YEATS4 versus patients in the CohortPre group. In addition, CDK4 copy-number gain on chr12q13 was significantly higher in CohortPost versus CohortPre (27% vs. 11%, P = 0.0005). CONCLUSIONS: Distinct mechanisms potentially associated with resistance to CDK4 and 6i ± ET, including alterations in ESR1 and amplification of chr12q15 and CDK4 copy-number gain, were identified.


Breast Neoplasms , Humans , Female , Cyclin-Dependent Kinase 4/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Genes, cdc , Genomics
12.
ACS Appl Mater Interfaces ; 15(26): 31533-31542, 2023 Jul 05.
Article En | MEDLINE | ID: mdl-37341628

The electrocatalytic reduction of CO2 to CO with high efficiency is one of the most promising approaches for CO2 conversion due to its considerable economic feasibility and broad application prospects. In this study, three Ag@COF-R (R = -H, -OCH3, -OH) hybrids were facilely fabricated by impregnating silver acetate (AgOAc) into respective covalent organic frameworks (COFs) prepared in advance. They differ significantly in the crystallinity, porosity, distribution, size, and electronic configuration of AgOAc species, which thereby influences both the activity and the selectivity of electrolytic CO2-to-CO transformation. Impressively, Ag@COF-OCH3 provided a high FECO of 93.0% with a high jCO of 213.9 mA cm-2 at -0.87 V (vs reversible hydrogen electrode, RHE) in 1 M KOH using a flow cell. In addition, it exhibited long-term durability at 100 mA cm-2 for 30 h.

13.
Anal Chem ; 95(19): 7503-7511, 2023 05 16.
Article En | MEDLINE | ID: mdl-37130068

Accurate discrimination and classification of unknown species are the basis to predict its characteristics or applications to make correct decisions. However, for biogenic solutions that are ubiquitous in nature and our daily lives, direct determination of their similarities and disparities by their molecular compositions remains a scientific challenge. Here, we explore a standard and visualizable ontology, termed "biogenic solution map", that organizes multifarious classes of biogenic solutions into a map of hierarchical structures. To build the map, a novel 4-dimensional (4D) fingerprinting method based on data-independent acquisition data sets of untargeted metabolomics is developed, enabling accurate characterization of complex biogenic solutions. A generic parameter of metabolic correlation distance, calculated based on averaged similarities between 4D fingerprints of sample groups, is able to define "species", "genus", and "family" of each solution in the map. With the help of the "biogenic solution map", species of unknown biogenic solutions can be explicitly defined. Simultaneously, intrinsic correlations and subtle variations among biogenic solutions in the map are accurately illustrated. Moreover, it is worth mentioning that samples of the same analyte but prepared by alternative protocols may have significantly different metabolic compositions and could be classified into different "genera".


Metabolomics , Metabolomics/methods
14.
BMC Biol ; 21(1): 122, 2023 05 24.
Article En | MEDLINE | ID: mdl-37226197

BACKGROUND: The factors that maintain phenotypic and genetic variation within a population have received long-term attention in evolutionary biology. Here the genetic basis and evolution of the geographically widespread variation in twig trichome color (from red to white) in a shrub Melastoma normale was investigated using Pool-seq and evolutionary analyses. RESULTS: The results show that the twig trichome coloration is under selection in different light environments and that a 6-kb region containing an R2R3 MYB transcription factor gene is the major region of divergence between the extreme red and white morphs. This gene has two highly divergent groups of alleles, one of which likely originated from introgression from another species in this genus and has risen to high frequency (> 0.6) within each of the three populations under investigation. In contrast, polymorphisms in other regions of the genome show no sign of differentiation between the two morphs, suggesting that genomic patterns of diversity have been shaped by homogenizing gene flow. Population genetics analysis reveals signals of balancing selection acting on this gene, and it is suggested that spatially varying selection is the most likely mechanism of balancing selection in this case. CONCLUSIONS: This study demonstrate that polymorphisms on a single transcription factor gene largely confer the twig trichome color variation in M. normale, while also explaining how adaptive divergence can occur and be maintained in the face of gene flow.


Transcription Factors , Trichomes , Transcription Factors/genetics , Trichomes/genetics , Gene Expression Regulation , Alleles , Genomics
15.
ACS Appl Mater Interfaces ; 15(16): 20089-20099, 2023 Apr 26.
Article En | MEDLINE | ID: mdl-37043423

Aqueous zinc-ion batteries are considered as an ideal substitute for lithium-ion batteries due to their abundant resource storage, high safety, and low price. However, zinc anodes exhibit poor reversibility and cyclic stability in most conventional aqueous electrolytes. Herein, an environmentally friendly Zn(CH3SO3)2 electrolyte is proposed to solve the problems of common aqueous electrolytes. The bulky CH3SO3- anions can regulate the solvation structure of Zn2+ by replacing some water molecules in the primary solvation sheath of Zn2+, thus slowing the hydrogen evolution side reactions and formation of zinc dendrite. Additionally, the changing solvation structure weakens the bonding between Zn2+ and the surrounding water molecules, which is conducive to the transport and charge transfer of Zn2+, thus improving the battery capacity. In the Zn(CH3SO3)2 electrolyte, Zn plating/stripping exhibits a high Coulombic efficiency of >98% and long-term cyclic stability over 800 h. The specific capacity of the assembled Zn//V2O5 cell in 3 mol L-1 Zn(CH3SO3)2 reaches 350 mA h g-1 at 0.1 A g-1, much higher than that in the ZnSO4 electrolyte (213 mA h g-1). In conclusion, this work offers insights into the exploration of advanced green electrolyte systems for zinc-ion batteries.

16.
J Colloid Interface Sci ; 638: 629-639, 2023 May 15.
Article En | MEDLINE | ID: mdl-36774876

The zinc-ion battery (ZIB) has been extensively researched as one of the promising electrochemical power sources. However, the problem of Zn-dendrite formation during repeated plating and stripping process seriously hinders the development of ZIBs. Herein, three-dimensional (3D) honeycomb-like porous carbon (HPC) with co-doping of zinc and nitrogen is prepared through confining growth of nanoscale zeolite imidazole framework-8 (ZIF-8) on the well-designed nano-pools walls of HPC followed by pyrolysis at 600 ℃ to obtain the final product ZnN/HPC-600, which exhibits large surface area and abundant zincophilic interfaces, ensuring homogeneous distribution of electronic field and low polarization during cycling process. Importantly, ZnN/HPC-600 facilitates the uniform distribution and migration of Zn2+ in this nano-pools structure, avoiding the growth of dendritic Zn crystal during charging stage. The symmetric and asymmetric cells with Zn/ZnN/HPC-600 anodes are assembled, demonstrating excellent cycling reversibility, good rate performance and long-term stability. Besides, a Zn||MnO2 full cell with Zn/ZnN/HPC-600 anode also exhibits robust cycling stability, fast reaction kinetics and almost 100 % coulombic efficiency. This work offers a novel and efficient carbonaceous nano-pools strategy to realize dendrite-free zinc anode in ZIBs.

17.
Andrology ; 11(6): 1163-1174, 2023 09.
Article En | MEDLINE | ID: mdl-36644916

BACKGROUND: Seminal vesiculitis is a common inflammation in the male genital tract. Etiologically, microbial infection and non-infectious factors can be responsible for seminal vesiculitis. The pathogenic triggers and mechanisms underlying non-infectious seminal vesiculitis remain unclear. OBJECTIVES: To demonstrate that spermatozoa can induce seminal vesiculitis in mice, which could be attributable to spermatozoa-induced innate immune responses in seminal vesicular epithelial cells. MATERIAL AND METHODS: Spermatozoa from epididymis were injected into seminal vesicles at the tail of the gland. Histopathology of seminal vesicles were examined by hematoxylin-eosin staining. Infiltration of leukocytes were identified by immunohistochemistry. Seminal vesicular epithelial cells were isolated from 5-week-old mice and cell types were detected by immunofluoresence. Western blot and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to detect protein and gene expression levels. RESULTS: In vivo, local injection of epididymal spermatozoa into seminal vesicles resulted in seminal vesiculitis characterized by tissue swelling and leukocyte infiltration. In vitro, spermatozoa induced the expression of pro-inflammatory cytokines and chemokines, including TNF-α, IL-6, CXCL10, and MCP1, and the activation of NF-κB in seminal vesicular epithelial cells. DISCUSSION AND CONCLUSION: Spermatozoa may induce seminal vesiculitis through the activation of innate immune responses in seminal vesicular epithelial cells, which provide novel insights into the mechanisms underlying non-infectious seminal vesiculitis.


Genital Diseases, Male , Inflammation , Humans , Male , Mice , Animals , Inflammation/pathology , Genital Diseases, Male/complications , Genitalia, Male/pathology , Seminal Vesicles/metabolism , Seminal Vesicles/pathology , Spermatozoa/pathology
18.
Clin Lymphoma Myeloma Leuk ; 23(1): 57-67, 2023 01.
Article En | MEDLINE | ID: mdl-36335022

PURPOSE: This study describes the treatment patterns and outcomes of patients with CLL/SLL in a de-identified real-world oncology electronic health records database. METHODS: Adult patients with CLL/SLL were eligible if they had received cBTKi therapy, both a cBTKi and a BCL2i, or all 4 drug classes (cBTKi, BCL2i, rituximab, and chemotherapy) at any time during the first 5 lines of therapy. Time-to-event outcomes were evaluated using Kaplan Meier method. No statistical comparisons were conducted; all analyses were descriptive and conducted using SAS Enterprise. RESULTS: A total of 9578 patients were eligible: 52.0% (n = 4983) received at least one cBTKi, 6.1% (n = 581) received both a cBTKi and BCL2i, and 2.3% (n = 218) received all four therapies (cBTKi, BCL2i, rituximab, and chemotherapy). Of those who discontinued these treatments, only 39.5% (n = 1 206/3 577), 59.7% (n = 228/382), and 55.0% (n = 82/149) received subsequent therapy (post-cBTKi, post-cBTKi/post-BCL2i, and post-all 4 therapies, respectively). Median time from treatment discontinuation of these therapies to the discontinuation of subsequent therapy or death was 9.5 months (all patients who discontinued the cBTKi) 5.6 months (those who discontinued both a cBTKi and BCL2i) and 3.9 months (patients who discontinued all four therapies). The median duration of the next treatment among those who received additional therapy was post-cBTKi treatment duration = 4.1 months; post-cBTKi/post-BCL2i treatment duration = 5.5 months; and median duration of the immediate next therapy after discontinuation of all 4 therapies = 5.1 months. CONCLUSIONS: The poor outcomes observed across cohorts in this study demonstrate the need for effective treatments that can improve outcomes in patients with CLL/SLL.


Antineoplastic Agents , Leukemia, Lymphocytic, Chronic, B-Cell , Adult , Humans , Antineoplastic Agents/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Proto-Oncogene Proteins c-bcl-2 , Rituximab/therapeutic use , Treatment Outcome , United States
19.
J Epidemiol ; 2022 Dec 24.
Article En | MEDLINE | ID: mdl-36567130

PurposeTo establish a prospective hospital-based cohort, featured by detailed multidimensional data of trauma patients with active follow-ups, which can be a reliable data source for all studies focusing on the effects or underlying mechanistic pathways of environmental and biological factors on multiple interested trauma-related outcomes, particularly the incidence and trajectory of trauma-related psychopathology, in Chinese population.MethodsThe China Severe Trauma Cohort (CSTC) enrolled all traumatized individuals aged 12 to 80 years admitted to the Trauma Center of West China Hospital between 1st March 2020 and 8th July 2022. The bio-sample and detailed questionnaire data were collected at recruitment, and phone/internet follow-ups were scheduled at 1-, 3-, 6-, 12-months after the baseline. Long-term health outcomes are planned to be obtained from administrative databases through data linkage.ResultsA total of 2,500 trauma patients were enrolled (response rate=87.1%) with an average age of 46.01 years, and most of the participants were males(62.6%). The proportions of participants with blood and fecal sample collected at baseline were 93.8% and 66.3%, respectively. Upon 31st August 2022, the follow-up rate was 90.0%, 77.0%, 76.5%, and 89.0% for 1-, 3-, 6-, and 12-months follow-up, respectively. Fall/wrench (47.6%) and traffic accident (26.2%) were the top causes of current trauma. The most common psychopathology at recruitment was sleep disturbance(39.4%), followed by depression(22.6%), anxiety(18.2%), and acute stress reaction(7.8%), all of which showed recovering trajectories during the follow-up period, particularly the first 3 months after baseline.ConclusionsCSTC provides a platform with multidimensional data to study both short-term and long-term trauma-related health consequences, prompting early identification and intervention for individuals with high risk of health decline after trauma exposures.

20.
Cancers (Basel) ; 14(24)2022 Dec 12.
Article En | MEDLINE | ID: mdl-36551611

TP53 co-mutations have shown association with poor prognosis in various solid tumors. For EGFR-mutated advanced non-small cell lung cancer (aNSCLC), conflicting results exist regarding its impact on survival. Clinical outcomes and genomic data were obtained retrospectively from the real-world (rw) de-identified clinicogenomic database. Patients who initiated therapy for EGFR-mutated aNSCLC between January 2014 and December 2020 were identified. Clinical outcomes were evaluated by TP53-mutational status. In 356 eligible EGFR-mutated aNSCLC patients (median age 68 years), 210 (59.0%) had TP53 co-mutation and 146 (41.0%) had TP53 wild-type tumor. Unadjusted analysis showed significantly shorter survival in patients with TP53 co-mutation versus TP53 wild-type (rw progression-free survival [rwPFS]: HR = 1.4, 95% CI 1.1-1.9, p = 0.0196; overall survival [OS]: HR = 1.6, 95% CI 1.1-2.2, p = 0.0088). Multivariable analysis confirmed independent association between TP53 co-mutation and worse rwPFS (HR = 1.4, 95% CI 1.0-0.9, p = 0.0280) and OS (HR = 1.4, 95% CI 1.0-2.0, p = 0.0345). Directionally consistent findings were observed for response rates, and subgroups by EGFR-activating mutation and first-line (1 L) therapy, with more pronounced negative effect in 1 L EGFR-TKI subgroup. TP53 co-mutations negatively affected survival in patients with EGFR-mutated aNSCLC receiving standard 1 L therapy in real-world practice.

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