ABSTRACT
BACKGROUND: The therapeutic benefit of concurrent chemoradiotherapy (CCRT) in elderly nasopharyngeal carcinoma (NPC) patients remains controversial. This study aimed to investigate the efficacy and toxicity of lobaplatin-based CCRT in elderly patients with NPC. METHODS: We included stage II-IVA NPC patients aged ≥65 years who received lobaplatin concomitant with intensity-modulated radiation therapy (IMRT) between March 2019 and January 2023. Objective response rates and treatment-related toxicity were assessed. Kaplan-Meier's analysis was performed to calculate survival rates. RESULTS: A total of 29 patients were included with a median age of 67 years. There were 19 patients (65.5%) who had comorbidities. All patients had serum EBV-DNA detective before treatment; the median EBV-DNA load was 236 IU/mL. There were 25 (86.2%) patients treated with induction chemotherapy, and the overall response rate was 92.0%. All patients received IMRT and concurrent chemotherapy with lobaplatin. During the CCRT, the most common adverse effect was haematological toxicity. Three patients (10.3%) had grade 3 leucopenia, three patients (10.3%) had grade 3 neutropenia, and eight patients (27.6%) had grade 3-4 thrombocytopenia. The rate of grade 3 mucositis was 34.5%. No patients had liver and kidney dysfunction. The median weight loss was 4 kg during CCRT. After three months of CCRT, the total response rate was 100%. EBV-DNA was not detected in any patients. The median follow-up was 32.1 months. The 3-year locoregional recurrence-free survival, distant metastasis-free survival, progression-free survival and overall survival were 95.8%, 85.7%, 82.5% and 100%, respectively. CONCLUSIONS: Lobaplatin-based CCRT is safe and feasible for elderly NPC patients, with satisfactory short-term survival outcomes and acceptable toxicities. A phase 2 trial is ongoing to investigate the role of lobaplatin-based CCRT on long-term survival and treatment toxicities for this population.
Subject(s)
Chemoradiotherapy , Cyclobutanes , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Organoplatinum Compounds , Radiotherapy, Intensity-Modulated , Humans , Male , Aged , Female , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/mortality , Cyclobutanes/therapeutic use , Cyclobutanes/administration & dosage , Cyclobutanes/adverse effects , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/therapeutic use , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/drug therapy , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Agents/administration & dosage , Retrospective Studies , Survival Rate , Treatment Outcome , Kaplan-Meier EstimateABSTRACT
Background: Persistent human papillomavirus (HPV) infection remains a key risk factor for cervical cancer. HPV-based primary screening is widely recommended in clinical guidelines, and further longitudinal studies are needed to optimize strategies for detecting high-grade cervical lesions compared to cytology. Methods: From November 2015 to December 2023, 31,942 participants were included in the real-world observational study. Among those, 4,219 participants underwent at least two rounds of HPV tests, and 397 completed three rounds of HPV tests. All participants were tested for high-risk types of HPV 16/18/31/33/35/39/45/51/52/56/58/59/66/68 (hrHPV) and low-risk types of HPV6/11 genotyping. Some participants also received cytology or colposcopy with pathology. Results: In the cross-sectional cohort, the prevalence of hrHPV and all HPV subtypes was 6.6% (2,108/31,942) and 6.8% (2,177/31,942), respectively. The three top hrHPV genotypes were HPV52 (1.9%), HPV58 (0.9%), and HPV16 (0.9%). Age distributions showed two peaks at 45-49 and 60-65 years. For the primary screening cohort, the hrHPV prevalence rate increased from 4.8% in 2015-2017 to 7.0% in 2020-2020 and finally reached 7.2% in 2023. For the longitudinal cohort study, the hrHPV prevalence rates in the repeated population (3.9, 5.3, and 6.0%) were lower than the primary hrHPV screening rates (6.6%), which indicated that repeated screening might decrease the prevalence rate. Methodologically, the hrHPV (89.5%) and the screening group of 16 subtypes (92.3%) demonstrated superior sensitivity than the cytology group (54.4%). Moreover, the longitudinal study indicated that the persistent hrHPV subgroup had a significantly higher (p = 0.04) incidence of high-grade squamous intraepithelial lesions and more histology progression events (7/17 vs. 0/5) than the reinfection group. Conclusion: The study indicates a rising high-risk HPV prevalence in Dongguan, with repeated screening reducing this trend. The findings support HPV-based primary screening and might guide HPV vaccination and cervical cancer prevention in South China.
Subject(s)
Human Papillomavirus Viruses , Papillomavirus Infections , Uterine Cervical Neoplasms , Adult , Aged , Female , Humans , Middle Aged , Young Adult , China/epidemiology , Cross-Sectional Studies , Early Detection of Cancer , Genotype , Human Papillomavirus Viruses/genetics , Human Papillomavirus Viruses/isolation & purification , Longitudinal Studies , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , Prevalence , Risk Factors , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/epidemiologyABSTRACT
[This corrects the article DOI: 10.3389/fphar.2020.00695.].
ABSTRACT
Genetic loss-of-function mutations of Nav1.7 channel, abundantly expressed in peripheral nociceptive neurons, cause congenital insensitivity to pain (CIP) in humans, indicating that selective inhibition of the channel may lead to potential therapy of pain disorders. In this study, we investigated a novel compound, 5-chloro-N-(cyclopropylsulfonyl)-2-fluoro-4-(2-(8-(furan-2-ylmethyl)-8-azaspiro [4.5] decan-2-yl) ethoxy) benzamide (QLS-278) that inhibits Nav1.7 channel and exhibits anti-nociceptive activity. Compound QLS-278 exhibits inactivation- and concentration-dependent inhibition of macroscopic currents of Nav1.7 channels stably expressed in HEK293 cells with an IC50 of 1.2 {plus minus} 0.2 µM. QLS-278 causes a hyperpolarization shift of the channel inactivation and delays recovery from inactivation, without an obvious effect on voltage-dependent activation. In mouse DRG neurons, QLS-278 suppresses native TTX-sensitive Nav currents and also reduces neuronal firing. Moreover, QLS-278 dose-dependently relieves neuropathic pain induced by spared nerve injury and inflammatory pain induced by formalin without significant alteration of spontaneous locomotor activity in mice. Altogether, our identification of the novel compound QLS-278 may hold developmental potential for the treatment of chronic pain. Significance Statement QLS-278, a novel voltage-gated sodium Nav1.7 channel blocker, inhibits native TTX-S Na+ current and reduces action potential firings in DRG sensory neurons. QLS-278 also exhibits antinociceptive activity in mouse models of pain, thus demonstrating potential for the development of a treatment for chronic pain.
ABSTRACT
Thyroid cancer incidence increases worldwide annually, primarily due to factors such as ionizing radiation (IR), iodine intake, and genetics. Papillary carcinoma of the thyroid (PTC) accounts for about 80% of thyroid cancer cases. RET/PTC1 (coiled-coil domain containing 6 [CCDC6]-rearranged during transfection) rearrangement is a distinctive feature in over 70% of thyroid cancers who exposed to low doses of IR in Chernobyl and HiroshimaâNagasaki atomic bombings. This study aims to elucidate mechanism between RET/PTC1 rearrangement and IR in PTC. N-thy-ori-3-1 cells were subjected to varying doses of IR (2/1/0.5/0.2/0.1/0.05 Gy) of IR at different days, and result showed low-dose IR-induced RET/PTC1 rearrangement in a dose-dependent manner. RET/PTC1 has been observed to promote PTC both in vivo and in vitro. To delineate the role of different DNA repair pathways, SCR7, RI-1, and Olaparib were employed to inhibit non-homologous end joining (NHEJ), homologous recombination (HR), and microhomology-mediated end joining (MMEJ), respectively. Notably, inhibiting NHEJ enhanced HR repair efficiency and reduced IR-induced RET/PTC1 rearrangement. Conversely, inhibiting HR increased NHEJ repair efficiency and subsequent RET/PTC1 rearrangement. The MMEJ did not show a markable role in this progress. Additionally, inhibiting DNA-dependent protein kinase catalytic subunit (DNA-PKcs) decreased the efficiency of NHEJ and thus reduced IR-induced RET/PTC1 rearrangement. To conclude, the data suggest that NHEJ, rather than HR or MMEJ, is the critical cause of IR-induced RET/PTC1 rearrangement. Targeting DNA-PKcs to inhibit the NHEJ has emerged as a promising therapeutic strategy for addressing IR-induced RET/PTC1 rearrangement in PTC.
ABSTRACT
Evidence regarding the role of dietary patterns in metabolic syndrome (MetS) is limited. The mechanistic links between dietary patterns, insulin resistance, and MetS are not fully understood. This study aimed to evaluate the associations between dietary patterns and the risk of MetS in a Chinese population using a longitudinal design. Data from the China Health and Nutrition Survey, a nationally representative survey, were analyzed. MetS cases were identified based on biomarker data collected in 2009. Factor analysis was employed to identify dietary patterns, while logistic regression models were utilized to examine the association between dietary patterns and MetS. Mediation models were applied to assess multiple mediation effects. Two dietary patterns were revealed by factor analysis. Participants in the higher quartiles of the traditional Chinese dietary pattern had lower odds of MetS than those in the lowest quartile (Q1) (OR = 0.58, 95%CI: 0.48, 0.69 for Q4; OR = 0.75, 95%CI: 0.63, 0.89 for Q3). Conversely, participants in the higher quartiles of the modern Chinese dietary pattern had higher odds of MetS compared to those in the lowest quartile (Q1) (OR = 1.40, 95%CI: 1.17, 1.68 for Q4; OR = 1.27, 95%CI: 1.06, 1.52 for Q3). Significant associations between dietary patterns and MetS were mediated by insulin resistance. Therefore, dietary patterns in Chinese adults are associated with MetS, and these associations appear to be mediated through insulin resistance. These findings underscore the critical role of dietary patterns in the development of MetS and establish a foundation for culturally tailored dietary interventions aimed at reducing rates the prevalence of MetS among Chinese adults.
Subject(s)
Diet , Insulin Resistance , Metabolic Syndrome , Humans , Metabolic Syndrome/epidemiology , Female , Male , Middle Aged , China/epidemiology , Adult , Diet/adverse effects , Risk Factors , Asian People , Aged , Nutrition Surveys , Feeding Behavior , Dietary Patterns , East Asian PeopleABSTRACT
Crack generation and propagation are critical aspects of grinding processes for hard and brittle materials. Despite extensive research, the impact of residual cracks from coarse grinding on the cracks generated during fine grinding remains unexplored. This study aims to bridge this gap by examining the propagation law of existing cracks under indentation using the extended finite element method. The results reveal that prefabricated cracks with depths less than the crack depth produced on an undamaged surface tend to extend further without surpassing the latter. Conversely, deeper prefabricated cracks do not exhibit significant expansion. A novel method combining indentation and prefabricated cracks with fracture strength tests is proposed to determine crack propagation. Silicon wafers with varying damaged surfaces are analyzed, and changes in fracture strength, measured by the ball-on-ring method, are utilized to determine crack propagation. The experimental results confirm the proposed crack evolution law, validated by damage assessments across different grinding processes, which is suitable for crack damage. The findings demonstrate that residual cracks from coarse grinding are negligible in predicting the maximum crack depth during fine grinding. This research provides a crucial foundation for optimizing the wafer thinning process in 3D stacked chip manufacturing, establishing that changes in fracture strength are a reliable indicator of crack propagation feasibility.
ABSTRACT
Mammalian olfactory epithelium has the capacity of self-renewal throughout life. Aging is one of the major causes leading to the olfactory dysfunction. Here, we performed single-cell RNA sequencing (scRNA-seq) analysis on young and aged murine olfactory epithelium (OE) and identified aging-related differentially expressed genes (DEGs) throughout 21 cell types. Aging led to the presence of activated horizontal basal cells (HBCs) in the OE and promoted cellular interaction between HBCs and neutrophils. Aging enhanced the expression of Egr1 and Fos in sustentacular cell differentiation from multipotent progenitors, whereas Bcl11b was downregulated during the sensory neuronal homeostasis in the aged OE. Egr1 and Cebpb were predictive core regulatory factors of the transcriptional network in the OE. Overexpression of Egr1 in aged OE organoids promoted cell proliferation and neuronal differentiation. Moreover, aging altered expression levels and frequencies of olfactory receptors. These findings provide a cellular and molecular framework of OE aging at the single-cell resolution.
ABSTRACT
BACKGROUND: Although recent studies provide mechanistic understanding to the pathogenesis of radiation induced lung injury (RILI), rare therapeutics show definitive promise for treating this disease. Type II alveolar epithelial cells (AECII) injury in various manner results in an inflammation response to initiate RILI. RESULTS: Here, we reported that radiation (IR) up-regulated the TNKS1BP1, causing progressive accumulation of the cellular senescence by up-regulating EEF2 in AECII and lung tissue of RILI mice. Senescent AECII induced Senescence-Associated Secretory Phenotype (SASP), consequently activating fibroblasts and macrophages to promote RILI development. In response to IR, elevated TNKS1BP1 interacted with and decreased CNOT4 to suppress EEF2 degradation. Ectopic expression of EEF2 accelerated AECII senescence. Using a model system of TNKS1BP1 knockout (KO) mice, we demonstrated that TNKS1BP1 KO prevents IR-induced lung tissue senescence and RILI. CONCLUSIONS: Notably, this study suggested that a regulatory mechanism of the TNKS1BP1/CNOT4/EEF2 axis in AECII senescence may be a potential strategy for RILI.
Subject(s)
Alveolar Epithelial Cells , Cellular Senescence , Mice, Inbred C57BL , Mice, Knockout , Animals , Mice , Cellular Senescence/radiation effects , Cellular Senescence/physiology , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/radiation effects , Alveolar Epithelial Cells/pathology , Lung Injury/metabolism , Lung Injury/genetics , Lung Injury/pathology , Elongation Factor 2 Kinase/metabolism , Elongation Factor 2 Kinase/genetics , Humans , Radiation Injuries, Experimental/metabolism , Radiation Injuries, Experimental/pathology , Radiation Injuries, Experimental/genetics , Cells, Cultured , MaleABSTRACT
Histone lysine methyltransferase 2D (KMT2D) is the most frequently mutated epigenetic modifier in head and neck squamous cell carcinoma (HNSCC). However, the role of KMT2D in HNSCC tumorigenesis and whether its mutations confer any therapeutic vulnerabilities remain unknown. Here we show that KMT2D deficiency promotes HNSCC growth through increasing glycolysis. Additionally, KMT2D loss decreases the expression of Fanconi Anemia (FA)/BRCA pathway genes under glycolytic inhibition. Mechanistically, glycolytic inhibition facilitates the occupancy of KMT2D to the promoter/enhancer regions of FA genes. KMT2D loss reprograms the epigenomic landscapes of FA genes by transiting their promoter/enhancer states from active to inactive under glycolytic inhibition. Therefore, combining the glycolysis inhibitor 2-DG with DNA crosslinking agents or poly (ADP-ribose) polymerase (PARP) inhibitors preferentially inhibits tumor growth of KMT2D-deficient mouse HNSCC and patient-derived xenografts (PDXs) harboring KMT2D-inactivating mutations. These findings provide an epigenomic basis for developing targeted therapies for HNSCC patients with KMT2D-inactivating mutations.
Subject(s)
Glycolysis , Squamous Cell Carcinoma of Head and Neck , Animals , Humans , Mice , Glycolysis/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/metabolism , Squamous Cell Carcinoma of Head and Neck/pathology , Cell Line, Tumor , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , BRCA1 Protein/metabolism , BRCA1 Protein/genetics , BRCA1 Protein/deficiency , BRCA2 Protein/genetics , BRCA2 Protein/metabolism , BRCA2 Protein/deficiency , Histone-Lysine N-Methyltransferase/metabolism , Histone-Lysine N-Methyltransferase/genetics , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , Fanconi Anemia/genetics , Fanconi Anemia/metabolism , Gene Expression Regulation, Neoplastic , Xenograft Model Antitumor Assays , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Female , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Signal Transduction , Promoter Regions, Genetic/genetics , Myeloid-Lymphoid Leukemia ProteinABSTRACT
Ovarian cancer (OC) is the deadliest malignancy of the female reproductive system. The standard first-line therapy for OC involves cytoreductive surgical debulking followed by chemotherapy based on platinum and paclitaxel. Despite these treatments, there remains a high rate of tumor recurrence and resistance to platinum. Recent studies have highlighted the potential anti-tumor properties of metformin (met), a traditional diabetes drug. In our study, we investigated the impact of met on the anticancer activities of cisplatin (cDDP) both in vitro and in vivo. Our findings revealed that combining met with cisplatin significantly reduced apoptosis in OC cells, decreased DNA damage, and induced resistance to cDDP. Furthermore, our mechanistic study indicated that the resistance induced by met is primarily driven by the inhibition of the ATM/CHK2 pathway and the upregulation of the Rad51 protein. Using an ATM inhibitor, KU55933, effectively reversed the cisplatin resistance phenotype. In conclusion, our results suggest that met can antagonize the effects of cDDP in specific types of OC cells, leading to a reduction in the chemotherapeutic efficacy of cDDP.
ABSTRACT
Sheep were domesticated in the Fertile Crescent and then spread globally, where they have been encountering various environmental conditions. The Tibetan sheep has adapted to high altitudes on the Qinghai-Tibet Plateau over the past 3000 years. To explore genomic variants associated with high-altitude adaptation in Tibetan sheep, we analyzed Illumina short-reads of 994 whole genomes representing â¼ 60 sheep breeds/populations at varied altitudes, PacBio High fidelity (HiFi) reads of 13 breeds, and 96 transcriptomes from 12 sheep organs. Association testing between the inhabited altitudes and 34,298,967 variants was conducted to investigate the genetic architecture of altitude adaptation. Highly accurate HiFi reads were used to complement the current ovine reference assembly at the most significantly associated ß-globin locus and to validate the presence of two haplotypes A and B among 13 sheep breeds. The haplotype A carried two homologous gene clusters: (1) HBE1, HBE2, HBB-like, and HBBC, and (2) HBE1-like, HBE2-like, HBB-like, and HBB; while the haplotype B lacked the first cluster. The high-altitude sheep showed highly frequent or nearly fixed haplotype A, while the low-altitude sheep dominated by haplotype B. We further demonstrated that sheep with haplotype A had an increased hemoglobin-O2 affinity compared with those carrying haplotype B. Another highly associated genomic region contained the EGLN1 gene which showed varied expression between high-altitude and low-altitude sheep. Our results provide evidence that the rapid adaptive evolution of advantageous alleles play an important role in facilitating the environmental adaptation of Tibetan sheep.
Subject(s)
Altitude , Haplotypes , Animals , Sheep/genetics , Haplotypes/genetics , Adaptation, Physiological/genetics , Transcriptome/genetics , Polymorphism, Single Nucleotide/genetics , Proteomics/methods , beta-Globins/genetics , Acclimatization/genetics , Tibet , MultiomicsABSTRACT
BACKGROUND: Transcolonic endoscopic appendectomy (TEA) is rapidly evolving and has been reported as a minimally invasive alternative to appendectomy. We aimed to characterize the feasibility and safety of a novel unassisted single-channel TEA. METHOD: We retrospectively investigated 23 patients with appendicitis or appendiceal lesions who underwent TEA from February 2016 to December 2022. We collected clinicopathological characteristics, procedurerelated parameters, and followup data and analyzed the impact of previous abdominal surgery and traction technique. RESULTS: The mean age was 56.0 years. Of the 23 patients with appendiceal lesions, fourteen patients underwent TEA and nine underwent traction-assisted TEA (T-TEA). Eight patients (34.8%) had previous abdominal surgery. The En bloc resection rate was 95.7%. The mean procedure duration was 91.1 ± 45.5 min, and the mean wound closure time was 29.4 ± 18.6 min. The wounds after endoscopic appendectomy were closed with clips (21.7%) or a combination of clip closure and endoloop reinforcement (78.3%), and the median number of clips was 7 (range, 3-15). Three patients (13.0%) experienced major adverse events, including two delayed perforations (laparoscopic surgery) and one infection (salvage endoscopic suture). During a median follow-up of 23 months, no residual or recurrent lesions were observed, and no recurrence of abdominal pain occurred. There were no significant differences between TEA and T-TEA groups and between patients with and without abdominal surgery groups in each factor. CONCLUSION: Unassisted single-channel TEA for patients with appendiceal lesions has favorable short- and long-term outcomes. TEA can safely and effectively treat appendiceal disease in appropriately selected cases.
ABSTRACT
This review offered a comprehensive analysis of tendon and ligament injuries, emphasizing the crucial role of tendon-derived stem cells (TDSCs) in tissue engineering as a potential solution for these challenging medical conditions. Tendon and ligament injuries, prevalent among athletes, the elderly, and laborers, often result in long-term disability and reduced quality of life due to the poor intrinsic healing capacity of these avascular structures. The formation of biomechanically inferior scar tissue and a high rate of reinjury underscore the need for innovative approaches to enhance and guide the regenerative process. This review delved into the complexities of tendon and ligament structure and function, types of injuries and their impacts, and the limitations of the natural repair process. It particularly focused on the role of TDSCs within the context of tissue engineering. TDSCs, with their ability to differentiate into tenocytes, are explored in various applications, including biocompatible scaffolds for cell tracking, co-culture systems to optimize tendon-bone healing, and graft healing techniques. The review also addressed the challenges of immunoreactivity post-transplantation, the importance of pre-treating TDSCs, and the potential of hydrogels and decellularized matrices in supporting tendon regeneration. It concluded by highlighting the essential roles of mechanical and molecular stimuli in TDSC differentiation and the current challenges in the field, paving the way for future research directions.
ABSTRACT
BACKGROUND: The rehabilitation of children with disabilities has received considerable attention from the United Nations. However, the state of rehabilitation services for children with disabilities worldwide remains far from optimistic, even in economically affluent middle- and high-income countries. OBJECTIVE: This scoping review aimed to identify the rehabilitation needs of children with disabilities and their barriers to rehabilitation services in middle- and high-income countries. METHODS: A systematic search was conducted using MEDLINE and Web of Science for papers published from January 2013 to December 2023. Studies were included if they were peer-reviewed, full-text articles related to children with disabilities, reporting on their access to rehabilitation services, and conducted in countries classified by the World Bank 2023 as middle- and high-income economies. Exclusion criteria included duplicates, unavailable full texts, and studies without distinct outcomes. A total of 27 studies were selected following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, focusing on children, their families, or service providers. RESULTS: The suitability, availability, and affordability of rehabilitation services were identified as the major needs and barriers for children with disabilities in middle- and high-income countries. This included communication barriers, a need for more personnel and facilities, and the stagnation and inadequacy of economic subsidies. CONCLUSIONS: Middle- and high-income countries have relatively well-established rehabilitation infrastructure and support systems. They are nevertheless insufficient for meeting the needs of children with disabilities. More attention should be paid to these issues to improve the well-being of children with disabilities. The data provided by this review can help raise awareness of rehabilitation needs and barriers at the policy level.
ABSTRACT
This paper reviews the current research progress in the application of Artificial Intelligence (AI) based on ischemic stroke imaging, analyzes the main challenges, and explores future research directions. This study emphasizes the application of AI in areas such as automatic segmentation of infarct areas, detection of large vessel occlusion, prediction of stroke outcomes, assessment of hemorrhagic transformation risk, forecasting of recurrent ischemic stroke risk, and automatic grading of collateral circulation. The research indicates that Machine Learning (ML) and Deep Learning (DL) technologies have tremendous potential for improving diagnostic accuracy, accelerating disease identification, and predicting disease progression and treatment responses. However, the clinical application of these technologies still faces challenges such as limitations in data volume, model interpretability, and the need for real-time monitoring and updating. Additionally, this paper discusses the prospects of applying large language models, such as the transformer architecture, in ischemic stroke imaging analysis, emphasizing the importance of establishing large public databases and the need for future research to focus on the interpretability of algorithms and the comprehensiveness of clinical decision support. Overall, AI has significant application value in the management of ischemic stroke; however, existing technological and practical challenges must be overcome to achieve its widespread application in clinical practice.
ABSTRACT
Thyroid hormone replacement therapy in NPC.
ABSTRACT
Male infertility is a major concern affecting reproductive health. Biallelic deleterious variants of most DNAH gene family members have been linked to male infertility, with intracytoplasmic sperm injection (ICSI) being an efficacious way to achieve offspring. However, the association between DNAH12 and male infertility is still limited. Here, we identified one homozygous variant and two compound heterozygous variants in DNAH12 from three infertile Chinese men. Semen analysis revealed severe asthenozoospermia, abnormal morphology, and structure of sperm flagella. Furthermore, the Dnah12 knock-out mouse revealed severe spermatogenesis failure and validated the same male infertility phenotype. Favorable fertility outcomes were achieved through ICSI in three human individuals and Dnah12 knock-out mice. Collectively, our study indicated that biallelic variants of DNAH12 can induce male infertility in both human beings and mice. Notably, evidence from DNAH12 enhanced that ICSI was an optimal intervention to achieve favorable fertility outcomes for infertile males with DNAH gene family variants.
ABSTRACT
Objective: This study aims to construct a predictive model based on machine learning algorithms to assess the risk of prolonged hospital stays post-surgery for colorectal cancer patients and to analyze preoperative and postoperative factors associated with extended hospitalization. Methods: We prospectively collected clinical data from 83 colorectal cancer patients. The study included 40 variables (comprising 39 predictor variables and 1 target variable). Important variables were identified through variable selection via the Lasso regression algorithm, and predictive models were constructed using ten machine learning models, including Logistic Regression, Decision Tree, Random Forest, Support Vector Machine, Light Gradient Boosting Machine, KNN, and Extreme Gradient Boosting, Categorical Boosting, Artificial Neural Network and Deep Forest. The model performance was evaluated using Bootstrap ROC curves and calibration curves, with the optimal model selected and further interpreted using the SHAP explainability algorithm. Results: Ten significantly correlated important variables were identified through Lasso regression, validated by 1000 Bootstrap resamplings, and represented through Bootstrap ROC curves. The Logistic Regression model achieved the highest AUC (AUC=0.99, 95% CI=0.97-0.99). The explainable machine learning algorithm revealed that the distance walked on the third day post-surgery was the most important variable for the LR model. Conclusion: This study successfully constructed a model predicting postoperative hospital stay duration using patients' clinical data. This model promises to provide healthcare professionals with a more precise prediction tool in clinical practice, offering a basis for personalized nursing interventions, thereby improving patient prognosis and quality of life and enhancing the efficiency of medical resource utilization.
ABSTRACT
We report a case of a 72-year-old female who presented with fever, abdominal pain, and diarrhea accompanied by leukopenia, anemia, and thrombocytopenia. The diagnosis of acute aplastic anemia was confirmed through bone marrow aspiration. Treatment included glucocorticoids, immunoglobulin therapy, and plasma exchange. Subsequently, the patient developed gastrointestinal bleeding and abdominal Computed Tomography (CT) revealed perforation of the transverse colon. Pathological examination of surgically removed diseased tissue confirmed mucor infection. Despite receiving antifungal therapy with amphotericin B, the patient's condition deteriorated due to the sepsis progression. Mucor infection in immunocompromised patients should be vigilant, and early diagnosis may help improve prognosis.