Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 133
Filter
Add more filters

Country/Region as subject
Publication year range
1.
Cancer Cell Int ; 24(1): 125, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38570787

ABSTRACT

BACKGROUND: Bladder cancer (BCa) stands out as a prevalent and highly lethal malignancy worldwide. Chemoresistance significantly contributes to cancer recurrence and progression. Traditional Tumor Node Metastasis (TNM) stage and molecular subtypes often fail to promptly identify treatment preferences based on sensitivity. METHODS: In this study, we developed a prognostic signature for BCa with uni-Cox + LASSO + multi-Cox survival analysis in multiple independent cohorts. Six machine learning algorithms were adopted to screen out the hub gene, RAC3. IHC staining was used to validate the expression of RAC3 in BCa tumor tissue. RT-qPCR and Western blot were performed to detect and quantify the mRNA and protein levels of RAC3. CCK8, colony formation, wound healing, and flow cytometry analysis of apoptosis were employed to determine cell proliferation, migration, and apoptosis. Molecular docking was used to find small target drugs, PIK-75. 3D cell viability assay was applied to evaluate the ATP viability of bladder cancer organoids before and after PIK-75 treated. RESULTS: The established clinical prognostic model, GIRS, comprises 13 genes associated with gemcitabine resistance and immunology. This model has demonstrated robust predictive capabilities for survival outcomes across various independent public cohorts. Additionally, the GIRS signature shows significant correlations with responses to both immunotherapy and chemotherapy. Leveraging machine learning algorithms, the hub gene, RAC3, was identified, and potential upstream transcription factors were screened through database analysis. IHC results showed that RAC3 was higher expressed in GEM-resistant BCa patients. Employing molecular docking, the small molecule drug PIK-75, as binding to RAC3, was identified. Experiments on cell lines, organoids and animals validated the biological effects of PIK-75 in bladder cancer. CONCLUSIONS: The GIRS signature offers a valuable complement to the conventional anatomic TNM staging system and molecular subtype stratification in bladder cancer. The hub gene, RAC3, plays a crucial role in BCa and is significantly associated with resistance to gemcitabine. The small molecular drug, PIK-75 having the potential as a therapeutic agent in the context of gemcitabine-resistant and immune-related pathways.

2.
Support Care Cancer ; 32(3): 207, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38436749

ABSTRACT

PURPOSE: Children with leukemia may experience a range of chemotherapy-related symptoms. Identifying subgroups and their distinct characteristics of symptoms may improve symptom management. We aimed to identify subgroups and their distinct characteristics of chemotherapy-related symptoms in children with leukemia. METHODS: A cross-sectional survey was conducted among 500 children with leukemia, who completed questionnaires that assessed their demographic and clinical characteristics, as well as the Memorial Symptom Assessment Scale. Latent profile analysis was conducted to identify subgroups of symptoms. Additionally, multiple regression analysis and network analysis were utilized to reveal the characteristics of each subgroup. RESULTS: Four subgroups were identified: "Profile 1: low symptom burden subgroup" (26.2%), "Profile 2: moderate symptom burden subgroup in transitional period" (14.8%), "Profile 3: moderate psychological symptom burden subgroup" (35.6%), and "Profile 4: high symptom burden subgroup" (23.4%). Multiple logistic regression analysis indicated that lower primary caregiver's education level, lower family monthly income, self-paid medical expenses, induction remission period, and consolidation enhancement period were associated with more severe symptoms of subgroups. Network analysis further revealed that nausea was the core symptom in Profiles 1 and 2, while the core symptom in Profile 3 was "I don't look like myself." Additionally, worrying was the core symptom in Profile 4. CONCLUSION: There exists heterogeneity in chemotherapy-related symptoms. Four subgroups and their corresponding characteristics of children with varying symptom severity were identified. Identifying these subgroups will facilitate personalized care, maximize intervention effectiveness, and alleviate symptom burden.


Subject(s)
Leukemia , Child , Humans , Cross-Sectional Studies , Leukemia/drug therapy , Educational Status , Income , Nausea
3.
Support Care Cancer ; 32(5): 314, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38683417

ABSTRACT

PURPOSE: This study aimed to assess the different needs of patients with breast cancer and their families in online health communities at different treatment phases using a Latent Dirichlet Allocation (LDA) model. METHODS: Using Python, breast cancer-related posts were collected from two online health communities: patient-to-patient and patient-to-doctor. After data cleaning, eligible posts were categorized based on the treatment phase. Subsequently, an LDA model identifying the distinct need-related topics for each phase of treatment, including data preprocessing and LDA topic modeling, was established. Additionally, the demographic and interactive features of the posts were manually analyzed. RESULTS: We collected 84,043 posts, of which 9504 posts were included after data cleaning. Early diagnosis and rehabilitation treatment phases had the highest and lowest number of posts, respectively. LDA identified 11 topics: three in the initial diagnosis phase and two in each of the remaining treatment phases. The topics included disease outcomes, diagnosis analysis, treatment information, and emotional support in the initial diagnosis phase; surgical options and outcomes, postoperative care, and treatment planning in the perioperative treatment phase; treatment options and costs, side effects management, and disease prognosis assessment in the non-operative treatment phase; diagnosis and treatment options, disease prognosis, and emotional support in the relapse and metastasis treatment phase; and follow-up and recurrence concerns, physical symptoms, and lifestyle adjustments in the rehabilitation treatment phase. CONCLUSION: The needs of patients with breast cancer and their families differ across various phases of cancer therapy. Therefore, specific information or emotional assistance should be tailored to each phase of treatment based on the unique needs of patients and their families.


Subject(s)
Breast Neoplasms , Data Mining , Humans , Breast Neoplasms/psychology , Breast Neoplasms/therapy , Breast Neoplasms/rehabilitation , Female , Data Mining/methods , Needs Assessment , Internet
4.
Drug Metab Dispos ; 51(5): 591-598, 2023 05.
Article in English | MEDLINE | ID: mdl-36707253

ABSTRACT

The formation and accumulation of payload-containing catabolites (PCCs) from a noncleavable antibody-drug conjugate (ADC) in targeted and normal tissues are directly associated with the therapeutic effect and toxicity of the ADC, respectively. Understanding the PCC formation is important for supporting the payload design and facilitating preclinical evaluation of ADCs. However, detection and identification of PCCs of a noncleavable ADC are challenging due to their low concentrations and unknown structures. The main objective of this study was to develop and apply a generic liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method for profiling PCCs in vitro. Noncleavable ADCs, ado-trastuzumab emtansine (T-DM1) and ADC-1, were incubated in liver lysosomes, liver S9, and/or cancer cells followed by data acquisition using LC-HRMS. Profiling PCCs mainly relied on processing LC-HRMS datasets using untargeted precise and thorough background subtraction (PATBS) processing and targeted product ion filtering (PIF). As a result, 12 PCCs of T-DM1 were detected and structurally characterized in human liver lysosomal incubation, a majority of which consisted of 4-[N-maleimidomethyl]cyclohexane-1-carboxylate (MCC)-DM1 and a few amino acids. Additionally, the incubation of ADC-1 in human, rat, and monkey liver S9 and cancer cells generated one major and three very minor PCCs, verifying the payload design. The results demonstrate that PATBS enabled the comprehensive profiling of PCCs regardless of their molecular weights, charge states, and fragmentations. As a complementary tool, PIF detected specific PCCs with superior sensitivity. The combination of the in vitro metabolism systems and the LC-HRMS method is a useful approach to profiling in vitro PCCs of noncleavable ADCs in support of drug discovery programs. SIGNIFICANCE STATEMENT: Profiling in vitro payload-containing catabolites (PCCs) of a noncleavable antibody-drug conjugate (ADC) is important for optimization of the payload design and preclinical evaluation of ADC. However, currently used analytical approaches often fail to quickly provide reliable PCC profiling results. The work introduces a new liquid chromatography high resolution mass spectrometry method for comprehensive and rapid detection and characterization of PCCs released from a noncleavable ADC in liver lysosomes and S9 incubations.


Subject(s)
Immunoconjugates , Maytansine , Rats , Animals , Humans , Immunoconjugates/chemistry , Ado-Trastuzumab Emtansine , Mass Spectrometry , Liver/metabolism
5.
J Sleep Res ; 32(4): e13828, 2023 08.
Article in English | MEDLINE | ID: mdl-36732290

ABSTRACT

The aim of this study is to explore the association between depression and obstructive sleep apnea, and cardiovascular disease morbidity/all-cause mortality using Sleep Heart Health Study data. This post hoc analysis of a prospective study used patient data from the Sleep Heart Health Study conducted between 1995 and 1998. The association between depression and obstructive sleep apnea, and cardiovascular disease morbidity/all-cause mortality was explored using multivariable Cox proportional hazard models. A total of 4918 participants, 656 (13.3%) with obstructive sleep apnea (obstructive sleep apnea group), 1614 (32.8%) with depression (depression group), 482 (9.8%) with depression and obstructive sleep apnea (depression and obstructive sleep apnea group), and 2166 (44%) with neither obstructive sleep apnea nor depression (health group), were included. The incidence of cardiovascular disease was 24.5%, 31.0%, 31.6% and 41.7% for healthy, depression, obstructive sleep apnea, and depression and obstructive sleep apnea groups, respectively. The risk of cardiovascular disease in depression and obstructive sleep apnea participants was increased compared with that in healthy participants, which was consistent across various definitions of obstructive sleep apnea (hazard ratio [95% confidence interval]: 1.24 [1.06-1.47]; 1.25 [1.05-1.49]; 1.28 [1.06-1.54]; 1.55 [1.22-1.96] for apnea-hypopnea index ≥ 10 per hr, 15 per hr, 20 per hr, 30 per hr, respectively). The risk of all-cause mortality was increased in the depression and obstructive sleep apnea participants (hazard ratio: 1.46; 95% confidence interval: 1.07-1.99) compared with that in healthy participants when the definition of obstructive sleep apnea was apnea-hypopnea index ≥ 30. Participants with depression and obstructive sleep apnea might be at a greater risk of cardiovascular disease, and those with higher apnea-hypopnea index might be at a greater risk of all-cause mortality.


Subject(s)
Cardiovascular Diseases , Sleep Apnea, Obstructive , Humans , Cardiovascular Diseases/complications , Prospective Studies , Depression/complications , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/epidemiology , Incidence
6.
Health Qual Life Outcomes ; 21(1): 91, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37582752

ABSTRACT

BACKGROUND: Fatigue is the most frequent and distressing symptom affecting the physical, cognitive, and affective domains of breast cancer patients. The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) has been widely used in patients with chronic diseases and has shown satisfactory reliability and validity. This study aimed to examine the psychometric properties of the FACIT-F among Chinese patients with breast cancer. METHODS: Using a convenience sampling method, a cross-sectional survey (January 2020 and September 2022) was used with patients recruited from two tertiary hospitals in Shanghai, Mainland China, and a total of 597 patients completed a demographic information questionnaire, the FACIT-F and the Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B). Convergent validity was estimated by calculating the Pearson correlation coefficient of the FACIT-F with the FACT-B. Measurement invariance across age was performed by examining differential item functioning (DIF) across age groups (≤ 60 and > 60 years). The internal consistency and split-half reliability were performed for reliability analysis. Unidimensionality of the scale was evaluated by the principal component analysis by Rasch analysis. Additionally, Rasch analysis was performed for item difficulty levels, and an item-person map was used. RESULTS: No floor/ceiling effects were observed for the FACIT-F. Moderate correlations were found between FACIT-F and FACT-B (r = - 0.342, p < 0.01). Most items showed an absence of DIF regarding age, except for one item. In addition, the FACIT-F showed acceptable internal consistency. Principal component analysis of Rasch residuals showed that the proportion of variance explained by the FACIT-F was 53.3%, and the outfit mean square statistics for the items ranged from 0.68 to 1.90 and the infit MNSQ from 0.63 to 1.73. Additionally, an acceptable response between items and persons was found. CONCLUSIONS: The findings indicate that the Chinese version of the FACIT-F is a valid tool for the measurement of fatigue in breast cancer patients.


Subject(s)
Breast Neoplasms , Humans , Middle Aged , Female , Breast Neoplasms/complications , Psychometrics/methods , Reproducibility of Results , Cross-Sectional Studies , Quality of Life/psychology , China , Chronic Disease , Fatigue/diagnosis , Fatigue/etiology , Fatigue/psychology , Surveys and Questionnaires
7.
BMC Womens Health ; 23(1): 100, 2023 03 10.
Article in English | MEDLINE | ID: mdl-36899332

ABSTRACT

BACKGROUND: Both contextual and cancer-related factors could be identified as causes of the interindividual variability observed for symptoms experienced during breast cancer treatment with chemotherapy. Understanding age differences and the predictors of latent class memberships for symptom heterogeneity could contribute to personalized interventions. This study aimed to identify the role of age differences on cancer-related symptoms in women undergoing chemotherapy for breast cancer in China. METHODS: A cross­sectional survey was conducted among patients with breast cancer in three tertiary hospitals in central China between August 2020 to December 2021. The outcomes of this study included sociodemographic and clinical characteristics, Patient-Reported Outcomes Measurement Information System (PROMIS)-57 and PROMIS-cognitive function short form scores. RESULTS: A total of 761 patients were included, with a mean age of 48.5 (SD = 11.8). Similar scores were observed across age groups for all symptoms except for fatigue and sleep disturbance domains. The most central symptoms varied among each group, and were fatigue, depression, and pain interference for the young-aged, middle-aged, and elderly-aged groups, respectively. In the young-aged group, patients without health insurance (OR = 0.30, P = 0.048) and in the fourth round of chemotherapy or above (OR = 0.33, P = 0.005) were more likely to belong to low symptom classes. In the middle-aged group, patients in menopause (OR = 3.58, P = 0.001) were more likely to belong to high symptom classes. In the elderly-aged group, patients with complications (OR = 7.40, P = 0.003) tended to belong to the high anxiety, depression, and pain interference classes. CONCLUSIONS: Findings from this study indicated that there is age-specific heterogeneity of symptoms present for Chinese women being treated for breast cancer with chemotherapy. Tailored intervention should consider the impact of age to reduce patients' symptom burdens.


Subject(s)
Breast Neoplasms , Middle Aged , Aged , Humans , Female , Breast Neoplasms/psychology , Cross-Sectional Studies , Depression/psychology , Pain/psychology , Fatigue/etiology
8.
Nucleic Acids Res ; 49(22): 12634-12643, 2021 12 16.
Article in English | MEDLINE | ID: mdl-34850916

ABSTRACT

G-quadruplex is an essential element in gene transcription that serves as a promising drug target. Guanine-vacancy-bearing G-quadruplex (GVBQ) is a newly identified G-quadruplex that has distinct structural features from the canonical G-quadruplex. Potential GVBQ-forming motifs are widely distributed in gene promoter regions. However, whether GVBQ can form in genomic DNA and be an effective target for manipulating gene expression is unknown. Using photo-crosslinking, dimethyl sulfate footprinting, exonuclease digestion and in vitro transcription, we demonstrated the formation of a GVBQ in the G-rich nuclease hypersensitivity element within the human PDGFR-ß gene promoter region in both single-stranded and double-stranded DNA. The formation of GVBQ in dsDNA could be induced by negative supercoiling created by downstream transcription. We also found that the PDGFR-ß GVBQ was specifically recognized and stabilized by a new synthetic porphyrin guanine conjugate (mPG). Targeting the PDGFR-ß GVBQ in human cancer cells using the mPG could specifically alter PDGFR-ß gene expression. Our work illustrates that targeting GVBQ with mPG in human cells can regulate the expression level of a specific gene, thus indicating a novel strategy for drug development.


Subject(s)
G-Quadruplexes , Gene Expression Regulation , Promoter Regions, Genetic , Receptor, Platelet-Derived Growth Factor beta/genetics , Base Sequence , DNA/chemistry , DNA, Single-Stranded/chemistry , Humans , Porphyrins/chemistry
9.
Altern Ther Health Med ; 29(2): 168-173, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36455145

ABSTRACT

Context: Anti-mitochondrial antibody M2+ (AMA-M2+) primary bile cholangitis (PBC) is difficult to diagnose, and early diagnosis is the key to ensure effective treatment and the safety of patients. Objective: The study intended to investigate the role of T helper type 17 (Th17) cells and their transcription factors in the early diagnosis of AMA-M2+ PBC to provide an effective guarantee of the ability to predict the prognosis of patients in the future. Design: The research team designed a prospective controlled study. Setting: The study took place at the Affiliated Hospital of Hebei University in Baoding, Hebei, China. Participants: Participants were 30 patients with AMA-M2+ PBC at the hospital between November 2020 and August 2021 and 30 healthy controls who concurrently underwent physical examinations. Outcome Measures: The study measured liver function (LF) and secretion of Th17 and its transcription factors-forkhead box P3 (Foxp3) and RAR-related orphan receptor gamma (RORγt)-and inflammatory factors-interleukin-17 IL-17 and IL-22-in participants' peripheral blood. The study also evaluated Th17 and its transcription factors in AMA-M2+ PBC, determined the expression of phosphorylated proteins using Western blotting, and analyzed the relationship between Th17 and LF. Results: The Th17 in the intervention group's peripheral blood was significantly higher than that of the control group (P < .05), and the sensitivity and specificity of the AMA-M2+ PBC were 63.33% and 96.67%, respectively. The expression of Foxp3 and p-Foxp3 proteins for the intervention was significantly lower (P < .001), while RORγt and P-ROR γ T were significantly higher (P < .001). The levels of interleukin-17 (IL-17) and IL-22 for the intervention group were significantly higher than those for the control group. The Pearson correlation coefficient showed that alanine aminotransferase (ALT), alkaline phosphatase (ALP), and γ-glutamyl transpeptidase (GGT) were positively correlated with Th17 cells, RORγt, IL-17, and IL-22 and negatively correlated with Foxp3. Conclusions: Th17 plays an important role in the early diagnosis of AMA-M2+ PBC, and Th17 and its transcription factors are highly effective for the early diagnosis of AMA-M2+ PBC, which is expected to be a breakthrough in the future diagnosis of the disease.


Subject(s)
Cholangitis , Interleukin-17 , Humans , Nuclear Receptor Subfamily 1, Group F, Member 3 , Prospective Studies , Cholangitis/diagnosis , T-Lymphocytes , Early Diagnosis , Forkhead Transcription Factors
10.
BMC Med Inform Decis Mak ; 23(1): 34, 2023 02 14.
Article in English | MEDLINE | ID: mdl-36788504

ABSTRACT

In recent years, relation extraction on unstructured texts has become an important task in medical research. However, relation extraction requires a large amount of labeled corpus, manually annotating sequences is time consuming and expensive. Therefore, efficient and economical methods for annotating sequences are required to ensure the performance of relational extraction. This paper proposes a method of subsequence and distant supervision based active learning. The method is annotated by selecting information-rich subsequences as a sampling unit instead of the full sentences in traditional active learning. Additionally, the method saves the labeled subsequence texts and their corresponding labels in a dictionary which is continuously updated and maintained, and pre-labels the unlabeled set through text matching based on the idea of distant supervision. Finally, the method combines a Chinese-RoBERTa-CRF model for relation extraction in Chinese medical texts. Experimental results test on the CMeIE dataset achieves the best performance compared to existing methods. And the best F1 value obtained between different sampling strategies is 55.96%.


Subject(s)
Problem-Based Learning , Supervised Machine Learning , Language , China , Reference Books, Medical
11.
Int J Mol Sci ; 24(13)2023 Jun 22.
Article in English | MEDLINE | ID: mdl-37445664

ABSTRACT

Phosphate (Pi) deficiency is one of the most limiting factors for Chinese fir growth and production. Moreover, continuous cultivation of Chinese fir for multiple generations led to the reduction of soil nutrients, which hindered the yield of Chinese fir in southern China. Although NAC (NAM, ATAF, and CUC) transcription factors (TFs) play critical roles in plant development and abiotic stress resistance, it is still unclear how they regulate the response of Chinese fir to phosphate (Pi) starvation. Based on Pi-deficient transcriptome data of Chinses fir root, we identified a NAC transcription factor with increased expression under Pi deficiency, which was obtained by PCR and named ClNAC100. RT-qPCR confirmed that the expression of ClNAC100 in the root of Chinese fir was induced by phosphate deficiency and showed a dynamic change with time. It was positively regulated by ABA and negatively regulated by JA, and ClNAC100 was highly expressed in the roots and leaves of Chinese fir. Transcriptional activation assay confirmed that ClNAC100 was a transcriptional activator. The promoter of ClNAC100 was obtained by genome walking, which was predicted to contain a large number of stress, hormone, and growth-related cis-elements. Tobacco infection was used to verify the activity of the promoter, and the core promoter was located between -1519 bp and -589 bp. We identified 18 proteins bound to the ClNAC100 promoter and 5 ClNAC100 interacting proteins by yeast one-hybrid and yeast two-hybrid, respectively. We speculated that AHL and TIFY family transcription factors, calmodulin, and E3 ubiquitin ligase in these proteins might be important phosphorus-related proteins. These results provide a basis for the further study of the regulatory mechanism and pathways of ClNAC100 under Pi starvation.


Subject(s)
Cunninghamia , Transcription Factors , Transcription Factors/genetics , Transcription Factors/metabolism , Cunninghamia/genetics , Cunninghamia/metabolism , Phosphates/metabolism , Saccharomyces cerevisiae/metabolism , Gene Expression Regulation, Plant
12.
Pak J Med Sci ; 39(5): 1446-1450, 2023.
Article in English | MEDLINE | ID: mdl-37680831

ABSTRACT

Objective: To investigate the clinical effects of HBV infection on patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Methods: This is a prospective study. Thirty patients with RA and 30 patients with SLE admitted to Affiliated Hospital of Hebei University from January 2020 to December 2021 with co-infection of HBV were randomly selected and divided into two groups. Both groups were given anti-HBV treatment. An additional 60 patients with a healthy physical examination during the same period were also selected as a control group. The disease activity, immune function and serum inflammatory factor levels were compared between the RA group and the SLE group before and after treatment. Results: After anti-HBV treatment, DAS scores in the RA group and SLEDAI scores in the SLE group were significantly lower than before treatment(P<0.05). The levels of IgG, IgA, IgM and CD8+ in the RA group and the SLE group after treatment were significantly lower than those before treatment. The levels of CCP, RF, ESR and CRP in the RA group before and after treatment were higher than those in the control group(P<0.05). The levels of ESR and CRP in the SLE group before and after treatment were higher than those in the control group, with statistically significant differences(P<0.05). Conclusion: Patients in the RA and SLE groups after HBV infection have an increased degree of inflammatory response in their organism, an altered normal state of immunoglobulin and T-lymphocyte subsets, and a loss of organism immune function, leading to an increase in disease activity.

13.
BMC Bioinformatics ; 23(1): 70, 2022 Feb 14.
Article in English | MEDLINE | ID: mdl-35164668

ABSTRACT

BACKGROUND: Knowledge of protein motions is significant to understand its functions. While currently available databases for protein motions are mostly focused on overall domain motions, little attention is paid on local residue motions. Albeit with relatively small scale, the local residue motions, especially those residues in binding pockets, may play crucial roles in protein functioning and ligands binding. RESULTS: A comprehensive protein motion database, namely D3PM, was constructed in this study to facilitate the analysis of protein motions. The protein motions in the D3PM range from overall structural changes of macromolecule to local flip motions of binding pocket residues. Currently, the D3PM has collected 7679 proteins with overall motions and 3513 proteins with pocket residue motions. The motion patterns are classified into 4 types of overall structural changes and 5 types of pocket residue motions. Impressively, we found that less than 15% of protein pairs have obvious overall conformational adaptations induced by ligand binding, while more than 50% of protein pairs have significant structural changes in ligand binding sites, indicating that ligand-induced conformational changes are drastic and mainly confined around ligand binding sites. Based on the residue preference in binding pocket, we classified amino acids into "pocketphilic" and "pocketphobic" residues, which should be helpful for pocket prediction and drug design. CONCLUSION: D3PM is a comprehensive database about protein motions ranging from residue to domain, which should be useful for exploring diverse protein motions and for understanding protein function and drug design. The D3PM is available on www.d3pharma.com/D3PM/index.php .


Subject(s)
Proteins , Binding Sites , Databases, Protein , Ligands , Protein Binding , Protein Conformation , Proteins/metabolism
14.
Prostate ; 82(2): 276-285, 2022 02.
Article in English | MEDLINE | ID: mdl-34807458

ABSTRACT

BACKGROUND: Preclinical studies showed that HC-1119, a deuterated version of enzalutamide, could competitively inhibit androgen binding to androgen receptor by blocking the transmission of androgen receptor signaling pathway as enzalutamide, inducing apoptosis of prostate cancer cells and reducing the proliferation of prostate cancer cells. Animal pharmacokinetic studies also show that deuterization of enzalutamide as HC-1119 could retain the basic properties of mother drug, increases the stability of compounds to metabolic enzymes and the drug exposure in vivo, prolong the half-life and reduce the production of metabolites, which may lead to a better efficacy and safety of HC-1119 compared with enzalutamide. METHODS: To evaluate the pharmacokinetics and safety of HC-1119 and the effects of food on pharmacokinetics in healthy adult Chinese men after single-dose administration of HC-1119. A total of 47 Chinese healthy adult male subjects received HC-1119 soft capsule at a single oral dose of 40, 80, or 160 mg followed on fasting or 160 mg after high-fat meal respectively. HC-1119 prototype and its metabolites M1 and M2 in plasma were collected individually in a total 23 time points. Pharmacokinetics were determined by sensitive LC/MS/MS for dose-proportionality study. RESULTS: In subjects taking HC-1119 soft capsules on fasting, Cmax of HC-1119 prototype increased dose-dependently. Either Cmax and AUC0-∞ of M1 or Cmax of M2 showed statistically significant difference. Dose-proportionality evaluation showed linear pharmacokinetic characteristics in Cmax of HC-1119 prototype, Cmax and AUC0-∞ of M2 in dose range of 40-160 mg. Cmax of HC-1119 was significantly different between the two groups as 160 mg HC-1119 on fasting or after a high-fat diet respectively, while the other parameter were not. HC-1119 and its metabolites M1 and M2 showed a linear dynamic trend. CONCLUSIONS: HC-1119 is expected to have lower clinical dose than the similar drug enzalutamide. The absorption of HC-1119 and the main pharmacokinetic parameters of HC-1119 and its metabolites M1 and M2 were not affected by high-fat diet. The clinical application of HC-1119 soft capsule in the later stage can be recommended for both fasting and postprandial. The safety and tolerance were good in this population.


Subject(s)
Benzamides , Cell Proliferation/drug effects , Drug Stability , Food-Drug Interactions , Nitriles , Phenylthiohydantoin , Prostatic Neoplasms , Receptors, Androgen/metabolism , Administration, Oral , Adult , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacokinetics , Benzamides/administration & dosage , Benzamides/adverse effects , Benzamides/pharmacokinetics , Biomarkers, Pharmacological/analysis , Capsules , China , Dose-Response Relationship, Drug , Half-Life , Healthy Volunteers , Humans , Male , Nitriles/administration & dosage , Nitriles/adverse effects , Nitriles/pharmacokinetics , Phenylthiohydantoin/administration & dosage , Phenylthiohydantoin/adverse effects , Phenylthiohydantoin/pharmacokinetics , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Signal Transduction/drug effects
15.
Plant Cell Environ ; 45(8): 2476-2491, 2022 08.
Article in English | MEDLINE | ID: mdl-35689480

ABSTRACT

Inter-tissue communication is instrumental to coordinating the whole-body level behaviour for complex multicellular organisms. However, little is known about the regulation of inter-tissue information exchange. Here we carried out genetic screens for root-to-shoot mobile silencing in Arabidopsis plants with a compromised small RNA-mediated gene silencing movement rate and identified radical-induced cell death 1 (RCD1) as a critical regulator of root-shoot communication. RCD1 belongs to a family of poly (ADP-ribose) polymerase proteins, which are highly conserved across land plants. We found that RCD1 coordinates symplastic and apoplastic movement by modulating the sterol level of lipid rafts. The higher superoxide production in rcd1-knockout plants resulted in lower plasmodesmata (PD) frequency and altered PD structure in the symplasm of the hypocotyl cortex. Furthermore, the mutants showed increased lateral area of tracheary pits, which reduced axial movement. Our study highlights a novel mechanism through which root-to-shoot long-distance signalling can be modulated both symplastically and apoplastically.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Gene Expression Regulation, Plant , Nuclear Proteins/metabolism , Plant Roots/metabolism , Poly(ADP-ribose) Polymerases/genetics , Reactive Oxygen Species/metabolism
16.
Health Qual Life Outcomes ; 20(1): 95, 2022 Jun 15.
Article in English | MEDLINE | ID: mdl-35706033

ABSTRACT

BACKGROUND: The PROMIS-57 is a commonly used self-reported instrument to solve the lack of generalizable and universal measures required to evaluate common symptoms and functions from patients' perspectives. This study aimed to translate the PROMIS-57 into Chinese and psychometrically test the translated instrument on patients with breast cancer. METHODS: Translation, cross­cultural adaptation, and psychometric evaluation of the instrument were performed from June 2020 to June 2021. Eligible patients were recruited and completed the PROMIS-57, Functional Assessment of Cancer Therapy-Breast (FACT-B), and a sociodemographic questionnaire. RESULTS: Data from 602 patients with a mean age of 48.83 years were analyzed. Most domains in the PROMIS-57 showed an absence of floor and ceiling effects. Multi-trait scaling analysis demonstrated acceptable convergent and discriminant validity. The correlations between the PROMIS-57 scores and the selected FACT-B scores supported the criterion validity via the Pearson correlation test. Measurement invariance was supported by the absence of differential item functioning for most items. Cronbach's α of the domains ranged from 0.85-0.95. The unidimensional factor structure of all domains was supported using confirmatory factor analyses. Additionally, most items showed acceptable item information curves and item characteristics curve matrices. CONCLUSION: The Chinese version of the PROMIS-57 was found to be a reliable and valid tool for assessing common symptoms and functions among patients with breast cancer.


Subject(s)
Breast Neoplasms , Quality of Life , Adult , China , Female , Humans , Information Systems , Middle Aged , Patient Reported Outcome Measures , Psychometrics/methods , Reproducibility of Results , Surveys and Questionnaires
17.
Support Care Cancer ; 31(1): 47, 2022 Dec 16.
Article in English | MEDLINE | ID: mdl-36525090

ABSTRACT

PURPOSE: Cancer is a shared stress that can cause psychosocial and emotional burdens for both patients and their partners. This study aimed to identify patterns of dyadic coping (DC) among young and middle-aged women with gynecological cancer and to assess between-group differences. METHODS: Between June 2021 and November 2021, patients with gynecological cancer who received therapy in a tertiary-grade hospital in Shandong, China, completed questionnaires including a demographic questionnaire, the Dyadic Coping Inventory, the PROMIS-Anxiety Short Form, the PROMIS-Depression Short Form, and the revised Conflict Tactics Scale and were classified into subtypes by latent class analysis. RESULTS: The sample consisted of 339 patients. Approximately one-third of the patients, especially cervical cancer patients, were exposed to varying degrees of DC issues. Three patterns were identified: class 1, middle-DC group (33.6%); class 2, low-DC group (32.2%); and class 3, high-DC group (34.2%). Postmenopausal patients were more likely to be included in class 1, while patients with cervical cancer were more likely to be included in class 2 (p < 0.05). Additionally, patients in class 2 were more likely to report insufficient emotional support (p < 0.05). A positive correlation was found for social relationship domains, and a negative correlation was found for anxiety and depression (p < 0.05). CONCLUSION: The findings indicated a high prevalence of DC in young and middle-aged women with gynecological cancer. Overall, participants scored in the low-to-middle range in terms of DC levels, and patients with cervical cancer and those with insufficient emotional support were more likely to report DC issues and require additional attention.


Subject(s)
Social Support , Uterine Cervical Neoplasms , Middle Aged , Humans , Female , Stress, Psychological/epidemiology , Stress, Psychological/etiology , Stress, Psychological/psychology , Latent Class Analysis , Adaptation, Psychological , Depression/epidemiology , Depression/etiology , Depression/psychology
18.
Ann Plast Surg ; 89(1): 59-62, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35502975

ABSTRACT

OBJECTIVE: Tai Chi is an ancient philosophy used to explain the universe. The Tai Chi symbol is represented by Yin/Yang fishes. The authors describe a novel radial forearm flap (RFF) design for the reconstruction of circular defects based on the Tai Chi symbol. METHODS: Eleven consecutive patients with craniofacial skin or mucus defects underwent reconstruction with a Tai Chi RFF. Patient perioperative and follow-up information was collected. RESULTS: The diameter of the Tai Chi RFF was 5 to 6 cm. All flaps healed uneventfully without ischemic problems, and all donor site defects were closed primarily without skin grafts. Remarkably, 2 patients received a tattoo to mark the Tai Chi symbol and greatly appreciate the shape of the flap. CONCLUSIONS: The Tai Chi flap is an economically friendly flap design that can be used to prevent skin grafts while providing psychological comfort to patients.


Subject(s)
Plastic Surgery Procedures , Tai Ji , Forearm/surgery , Humans , Skin Transplantation , Surgical Flaps/surgery
19.
Health Qual Life Outcomes ; 19(1): 149, 2021 May 18.
Article in English | MEDLINE | ID: mdl-34006304

ABSTRACT

BACKGROUND: The diagnosis of breast cancer and the subsequent treatment undermine patients' participation in social activities. This study aimed to carry out a cross-cultural adaption and analysis of the construct validity and reliability of the Chinese version of the PROMIS social function short forms in patients with breast cancer. METHODS: This study utilized a cross-sectional research design, and was registered in the Chinese Clinical Trial Registry (ChiCTR2000035439). After a standardized cross-cultural adaption process, a psychometric evaluation was performed of the Chinese version of the PROMIS social function short forms. Using convenience sampling, eligible patients with breast cancer from tertiary hospitals in China were enrolled from January 2019 to July 2020. Participants completed the sociodemographic information questionnaire, the PROMIS social function short forms, the Functional Assessment of Cancer Therapy-Breast, the PROMIS emotional support short form and the PROMIS anxiety short form. RESULTS: Data were collected from a sample of 633 patients whose mean age was 48.1 years. The measures showed an absence of floor and ceiling effects. Regarding construct validity, the results of confirmatory factor analysis supported the original two-factor structure of the PROMIS social function short forms. In addition, the measures were found to have acceptable known-group validity, measurement invariance, and convergent and discriminate validity. Regarding reliability, the Cronbach's α was high for all items (> 0.70). CONCLUSION: The Chinese version of the PROMIS social function short forms was demonstrated to be a valid and reliable measure for the assessment of social function in Chinese patients with breast cancer. Additional psychometric evaluation is needed to draw firm conclusions.


Subject(s)
Asian People/psychology , Breast Neoplasms/psychology , Psychometrics/standards , Quality of Life/psychology , Social Skills , Surveys and Questionnaires/standards , Adult , Asian People/statistics & numerical data , China , Cross-Sectional Studies , Factor Analysis, Statistical , Female , Humans , Middle Aged , Reproducibility of Results , Surveys and Questionnaires/statistics & numerical data
20.
Support Care Cancer ; 29(11): 6459-6468, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33900457

ABSTRACT

PURPOSE: Conceptualizing cancer as a dyadic stress provides new insight into how stress impacts couples with breast cancer. The present study aimed to identify subgroups with distinct dyadic coping profiles in a sample of Chinese couples with breast cancer and to determine how these subgroups differed in terms of demographic and clinical characteristics in addition to marital adjustment outcomes. METHODS: Using convenience sampling, a cross-sectional survey was conducted. Couples with breast cancer completed the general information questionnaire, the Dyadic Coping Inventory, and the Locke-Wollance Marital Adjustment Test. The modeling was performed using a latent profile analysis to identify the dyadic coping subgroups. Parametric and nonparametric tests were applied to examine between-group differences across the identified classes. RESULTS: The analytical results supported a three-class solution of dyadic coping groups: high (27.4%), medium (32.2%), and low (40.4%). Between-group differences were found in educational background, number of children, postoperative time, and type of surgery. CONCLUSION: Most couples reported low levels of dyadic coping. The couples with an educational level of primary school or below, with one child or who were childless, and who had undergone breast preservation surgery within the past year were more likely to belong to the low dyadic coping group. When supporting couples with breast cancer, it is essential to assess several demographic and clinical risk factors in addition to the marital adjustment level to identify high-risk subgroups that warrant intervention.


Subject(s)
Breast Neoplasms , Adaptation, Psychological , Child , China , Cross-Sectional Studies , Female , Humans , Interpersonal Relations , Spouses
SELECTION OF CITATIONS
SEARCH DETAIL