Association of 8-hydroxy-2'-deoxyguanosine with motoric cognitive risk in elderly Chinese people: RUGAO longevity and aging cross-sectional study.

BACKGROUND: Motor cognitive risk syndrome (MCR) represents a critical pre-dementia and disability state characterized by a combination of objectively measured slow walking speed and subjective memory complaints (SMCs). This study aims to identify risk factors for MCR and investigate the relationship between plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and MCR among Chinese community-dwelling elderly populations. METHODS: A total of 1312 participants were involved in this study based on the data of the Rugao Longevity and Aging Study (RuLAS). The MCR was characterized by SMCs and slow walking speed. The SCCs were defined as a positive answer to the question 'Do you feel you have more problems with memory than most?' in a 15-item Geriatric Depression Scale. Slow walking speed was determined by one standard deviation or more below the mean value of the patient's age and gender group. The plasma of 8-OHdG were measured by a technician in the biochemistry laboratory of the Rugao People's Hospital during the morning of the survey. RESULTS: The prevalence of MCR was found to be 7.9%. After adjusting for covariates, significant associations with MCR were observed in older age (OR 1.057; p = 0.018), history of cerebrovascular disease (OR 2.155; p = 0.010), and elevated 8-OHdG levels (OR 1.007; p = 0.003). CONCLUSIONS: This study indicated the elevated plasma 8-OHdG is significantly associated with increased MCR risk in the elderly, suggesting its potential as a biomarker for early detection and intervention in MCR. This finding underscores the importance of monitoring oxidative DNA damage markers in predicting cognitive and motor function declines, offering new avenues for research and preventive strategies in aging populations.

Ileal collision tumor associated with gastrointestinal bleeding: A case report and review of literature.

BACKGROUND: Collision tumors involving the small intestine, specifically the combination of a hamartomatous tumor and a lipoma, are extremely rare. To our knowledge, no previous case report has described a collision tumor composed of two benign tumors of different origins in the small intestine. CASE SUMMARY: Here, we present the case of an 82-year-old woman who presented with hemorrhagic shock and was found to have a mass measuring approximately 50 mm × 32 mm × 30 mm in the terminal ileum. Based on computed tomography scan findings, the mass was initially suspected to be a lipoma. A subsequent colonoscopy revealed a pedunculated submucosal elevation consisting of two distinct parts with a visible demarcation line. A biopsy of the upper portion suggested a juvenile polyp (JP). Owing to the patient's advanced age, multiple comorbidities, and poor surgical tolerance, a modified endoscopic submucosal dissection was performed. Histopathological examination of the excised mucosal mass revealed a lipoma at the base and a JP at the top, demonstrating evidence of rupture and associated bleeding. The patient's overall health remained satisfactory, with no recurrence of hematochezia during the six-month follow-up period. CONCLUSION: This case report provides new evidence for the understanding of gastrointestinal collision tumors, emphasizing their diverse clinical presentations and histopathological characteristics. It also offers diagnostic and therapeutic insights as well as an approach for managing benign collision tumors.

Concentration-Gradient Structural LiFe0.5Mn0.5PO4/C Prepared via Co-precipitation Reaction for Advanced Lithium-Ion Batteries.

The intrinsically low electronic conductivity and slow ion diffusion kinetics limit further development of olivine LiFexMn1-xPO4 cathode materials. In this paper, with the aim of improving the performance of such materials and alleviating the Jahn-Taller effect of Mn3+ ion, a bimetallic oxalate precursor with gradient distribution of elemental concentration followed with an efficient process is applied to synthesize LiFe0.5Mn0.5PO4 nanocomposite. The results shown that with certain structural modulation of the precursor, the discharge capacity of synthesized LiFe0.5Mn0.5PO4 increased from 149 mAh g-1 to 156 mAh g-1 at 0.1 C, the cycling capacity was also remarkably improved. the Fe0.5Mn0.5C2O4 ⋅ 2H2O-1 precursor with gradient distribution of elemental concentration effectively restricts the reaction between electrode material and electrolyte, thereby alleviates the dissolution of Mn3+ ion, reduces the decay of capacity and improves the stability of the material.

Clinical Insights into Structure, Regulation, and Targeting of ABL Kinases in Human Leukemia.

Chronic myeloid leukemia is a multistep, multi-lineage myeloproliferative disease that originates from a translocation event between chromosome 9 and chromosome 22 within the hematopoietic stem cell compartment. The resultant fusion protein BCR::ABL1 is a constitutively active tyrosine kinase that can phosphorylate multiple downstream signaling molecules to promote cellular survival and inhibit apoptosis. Currently, tyrosine kinase inhibitors (TKIs), which impair ABL1 kinase activity by preventing ATP entry, are widely used as a successful therapeutic in CML treatment. However, disease relapses and the emergence of resistant clones have become a critical issue for CML therapeutics. Two main reasons behind the persisting obstacles to treatment are the acquired mutations in the ABL1 kinase domain and the presence of quiescent CML leukemia stem cells (LSCs) in the bone marrow, both of which can confer resistance to TKI therapy. In this article, we systemically review the structural and molecular properties of the critical domains of BCR::ABL1 and how understanding the essential role of BCR::ABL1 kinase activity has provided a solid foundation for the successful development of molecularly targeted therapy in CML. Comparison of responses and resistance to multiple BCR::ABL1 TKIs in clinical studies and current combination treatment strategies are also extensively discussed in this article.

Association of depressive symptoms with cardiovascular events and plasma BNP: A prospective cohort study of the elderly Chinese population.

OBJECTIVE: To estimate the prevalence of depressive symptoms and to evaluate the associations of mild and significant depressive symptoms with cardiovascular events and plasma BNP levels (which are surrogate endpoints for cardiovascular events) among older adults in a population-based study. METHODS: A population-based prospective study of 1,432 elderly people (aged 70-84 years and without cardiovascular disease) was conducted, and the median duration of follow-up for participants with outcomes was 18 weeks. Depressive symptoms were assessed with the 15-item Geriatric Depression Scale (GDS-15). The hazard ratios (HRs) for the time to events and time to death were calculated using the Cox regression analysis. Multiple linear regression models and Spearman rank correlations were used to examine the association of depressive symptoms with Log BNP values. RESULTS: The prevalence of mild (GDS-15 scores ≥ 6) and significant (GDS-15 scores ≥ 10) depressive symptoms were 7.3% and 2.0% at baseline, respectively. Older adults with significant depressive symptoms exhibited increased risks of time to death (HR: 12.56; 95% CI: 3.58-43.99) and composite cardiovascular endpoints (HR: 3.46; 95% CI: 1.19-3.75). Significant depressive symptoms were associated with Log BNP levels (ß=0.56, P = 0.02). Depressive symptom scores were also associated with Log BNP levels (rs=0.21, P = 0.04) in the older adults with depressive symptoms. CONCLUSIONS: Significant depressive symptoms were associated with a higher risk of cardiovascular events and higher BNP levels in the elderly.

Integration of Single-Cell and Bulk RNA-seq Data to Identify the Cancer-Associated Fibroblast Subtypes and Risk Model in Glioma.

Cancer-associated fibroblasts (CAFs) are an important component of the stroma. Studies showed that CAFs were pivotally in glioma progression which have long been considered a promising therapeutic target. Therefore, the identification of prognostic CAF markers might facilitate the development of novel diagnostic and therapeutic approaches. A total of 1333 glioma samples were obtained from the TCGA and CGGA datasets. The EPIC, MCP-counter, and xCell algorithms were used to evaluate the relative proportion of CAFs in glioma. CAF markers were identified by the single-cell RNA-seq datasets (GSE141383) from the Tumor Immune Single-Cell Hub database. Unsupervised consensus clustering was used to divide the glioma patients into different distinct subgroups. The least absolute shrinkage and selection operator regression model was utilized to establish a CAF-related signature (CRS). Finally, the prognostic CAF markers were further validated in clinical specimens by RT‒qPCR. Combined single-cell RNA-seq analysis and differential expression analysis of samples with high and low proportions of CAFs revealed 23 prognostic CAF markers. By using unsupervised consensus clustering, glioma patients were divided into two distinct subtypes. Subsequently, based on 18 differentially expressed prognostic CAF markers between the two CAF subtypes, we developed and validated a new CRS model (including PCOLCE, TIMP1, and CLIC1). The nomogram and calibration curves indicated that the CRS was an accurate prognostic marker for glioma. In addition, patients in the high-CRS score group had higher immune infiltration and tumor mutation burden levels. Moreover, the CRS score had the potential to predict the response to immune checkpoint blockade (ICB) therapy and chemotherapy. Finally, the expression profiles of three CAF markers were verified by RT‒qPCR. In general, our study classified glioma patients into distinct subgroups based on CAF markers, which will facilitate the development of individualized therapy. We also provided insights into the role of the CRS in predicting the response to ICB and chemotherapy in glioma patients.

Endothelial peroxiredoxin-4 is indispensable for blood-brain barrier integrity and long-term functional recovery after ischemic stroke.

The endothelial lining of cerebral microvessels is damaged relatively early after cerebral ischemia/reperfusion (I/R) injury and mediates blood-brain barrier (BBB) disruption, neurovascular injury, and long-term neurological deficits. I/R induces BBB leakage within 1 h due to subtle structural alterations in endothelial cells (ECs), including reorganization of the actin cytoskeleton and subcellular redistribution of junctional proteins. Herein, we show that the protein peroxiredoxin-4 (Prx4) is an endogenous protectant against endothelial dysfunction and BBB damage in a murine I/R model. We observed a transient upregulation of Prx4 in brain ECs 6 h after I/R in wild-type (WT) mice, whereas tamoxifen-induced, selective knockout of Prx4 from endothelial cells (eKO) mice dramatically raised vulnerability to I/R. Specifically, eKO mice displayed more BBB damage than WT mice within 1 to 24 h after I/R and worse long-term neurological deficits and focal brain atrophy by 35 d. Conversely, endothelium-targeted transgenic (eTG) mice overexpressing Prx4 were resistant to I/R-induced early BBB damage and had better long-term functional outcomes. As demonstrated in cultures of human brain endothelial cells and in animal models of I/R, Prx4 suppresses actin polymerization and stress fiber formation in brain ECs, at least in part by inhibiting phosphorylation/activation of myosin light chain. The latter cascade prevents redistribution of junctional proteins and BBB leakage under conditions of Prx4 repletion. Prx4 also tempers microvascular inflammation and infiltration of destructive neutrophils and proinflammatory macrophages into the brain parenchyma after I/R. Thus, the evidence supports an indispensable role for endothelial Prx4 in safeguarding the BBB and promoting functional recovery after I/R brain injury.

Clinical Efficacy and Long-term Prognosis of High Flux Hemodialysis Combined with Different Frequency Hemodiafiltration in the Treatment of Middle-Aged and Elderly Patients with Uremia.

INTRODUCTION: To analyze the clinical efficacy and long-term prognosis of high flux hemodialysis (HFHD) combined with different frequency hemodiafiltration (HDF) in uremic patients. METHODS: 86 middle-aged and elderly patients with uremia were divided into the HF group (HFHD combined with high-frequency HDF) and the LF group (HFHD combined with low-frequency HDF). The changes between the two groups in various indicators after 12 months of dialysis and the survival rate at 5 years of follow-up were compared. We used SPSS 25.0 software for data analysis. RESULTS: The differences of the levels of serum albumin, hemoglobin and transferrin in HF Group was significantly higher than LF Group before and after treatment (P < .05). The differences of the levels and clearance rate of calcium, phosphorus, parathyroid hormone, ß2-microglobulin and cysteine protease inhibitor C in the patients' blood after dialysis were significantly higher in HF Group than in LF Group (P < .05). The all-cause mortality rate, new cardiovascular event rate, new cerebrovascular event rate, and new infection event rate of HF Group were significantly lower than those of LFHD group, respectively (P < .05). The LF Group had a significantly higher risk of all-cause mortality events, new cardiovascular cerebrovascular and infectious events than the HF Group (P < .05). CONCLUSION: 1 week/time HDF combined with HFHD can more effectively eliminate the vascular related toxins in middle-aged and elderly patients with uremia, improve their nutritional status, treatment effect, and long-term prognosis.  DOI: 10.52547/ijkd.7864.

Lipopolymer mediated siRNA delivery targeting aberrant oncogenes for effective therapy of myeloid leukemia in preclinical animal models.

The clinical development of tyrosine kinase inhibitors (TKI) has led to great strides in improving the survival of chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) patients. But even the new generation TKIs are rendered futile in the face of evolving landscape of acquired mutations leading to drug resistance, necessitating the pursuit of alternative therapeutic approaches. In contrast to exploiting proteins as targets like most conventional drugs and TKIs, RNA Interference (RNAi) exerts its therapeutic action towards disease-driving aberrant genes. To realize the potential of RNAi, the major challenge is to efficiently deliver the therapeutic mediator of RNAi, small interfering RNA (siRNA) molecules. In this study, we explored the feasibility of using aliphatic lipid (linoleic acid and lauric acid)-grafted polymers (lipopolymers) for the delivery of siRNAs against the FLT3 oncogene in AML and BCR-ABL oncogene in CML. The lipopolymer delivered siRNA potently suppressed the proliferation AML and CML cells via silencing of the targeted oncogenes. In both AML and CML subcutaneous xenografts generated in NCG mice, intravenously administered lipopolymer/siRNA complexes displayed significant inhibitory effect on tumor growth. Combining siFLT3 complexes with gilteritinib allowed for reduction of effective drug dosage, longer duration of remission, and enhanced survival after relapse, compared to gilteritinib monotherapy. Anti-leukemic activity of siBCR-ABL complexes was similar in wild-type and TKI-resistant cells, and therapeutic efficacy was confirmed in vivo through prolonged survival of the NCG hosts systemically implanted with TKI-resistant cells. These results demonstrate the preclinical efficacy of lipopolymer facilitated siRNA delivery, providing a novel therapeutic platform for myeloid leukemias.

PARP5A and RNF146 phase separation restrains RIPK1-dependent necroptosis.

Phase separation is a vital mechanism that mediates the formation of biomolecular condensates and their functions. Necroptosis is a lytic form of programmed cell death mediated by RIPK1, RIPK3, and MLKL downstream of TNFR1 and has been implicated in mediating many human diseases. However, whether necroptosis is regulated by phase separation is not yet known. Here, we show that upon the induction of necroptosis and recruitment by the adaptor protein TAX1BP1, PARP5A and its binding partner RNF146 form liquid-like condensates by multivalent interactions to perform poly ADP-ribosylation (PARylation) and PARylation-dependent ubiquitination (PARdU) of activated RIPK1 in mouse embryonic fibroblasts. We show that PARdU predominantly occurs on the K376 residue of mouse RIPK1, which promotes proteasomal degradation of kinase-activated RIPK1 to restrain necroptosis. Our data demonstrate that PARdU on K376 of mouse RIPK1 provides an alternative cell death checkpoint mediated by phase separation-dependent control of necroptosis by PARP5A and RNF146.

Social frailty and the incidence of motoric cognitive risk syndrome in older adults.

INTRODUCTION: Various associations between social factors and motoric cognitive risk syndrome (MCR) have been reported. However, whether social frailty (integrated from multiple social factors) is associated with MCR is still unclear. METHODS: We included 4657 individuals without MCR at Round 1 of the NHATS as the discovery sample, and 3075 newly recruited individuals from Round 5 of the NHATS as the independent validation sample. Social frailty was assessed by five social items. MCR was defined as the presence of both subjective cognitive complaints and slow gait speed in individuals without dementia or mobility disability. RESULTS: Compared with normal individuals, those with social frailty had higher risk of incident MCR (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.34-1.84). Each additional unfavorable social item was associated with an increased risk of MCR (HR: 1.32, 95% CI: 1.22-1.43). DISCUSSION: Social frailty was associated with an increased risk of incident MCR in older adults. HIGHLIGHTS: Various associations between social factors and motoric cognitive risk syndrome (MCR) have been reported. Social frailty that integrated from multiple social factors was associated with an increased risk of incident MCR. Social frailty should be included in the early screening of individuals to identify those at higher risk of MCR.

Diallyl trisulfide and its active metabolite allyl methyl sulfone attenuate cisplatin-induced nephrotoxicity by inhibiting the ROS/MAPK/NF-κB pathway.

Cisplatin, a chemotherapy medication employed in the treatment of various solid tumors, is constrained in its clinical application due to nephrotoxicity. Diallyl trisulfide (DATS), a compound derived from garlic that possessed anticancer and antioxidant properties, can be combined with cisplatin without hindering its antitumor effects. The present investigation examined the defensive properties of DATS and its active metabolites against renal dysfunction caused by cisplatin. We created a mouse model to study renal injury caused by cisplatin and assessed kidney histology, immunochemistry, and serum cytokines. DATS treatment effectively reduced the pathological changes caused by cisplatin by decreasing the levels of renal function markers BUN, CRE, cystatin C, NGAL, inflammatory factors TNF-α, IL-6, and the protein expression of α-SMA, NF-κB, KIM-1. A pharmacokinetic evaluation of DATS found that allyl methyl sulfone (AMSO2) was the most abundant and persistent metabolite of DATS in vivo. Then, we examined the impact of AMSO2 on cell viability, apoptosis, ROS generation, and MAPK/NF-κB pathways in HK-2 cells treated with cisplatin. Cotreatment with AMSO2 effectively hindered the HK-2 cells alterations induced by cisplatin. Furthermore, AMSO2 mitigated oxidative stress through the modulation of MAPK and NF-κB pathways. Our findings indicated that DATS and its active derivative AMSO2 attenuated cisplatin-induced nephrotoxicity. DATS shows potential as a viable treatment for nephrotoxicity caused by cisplatin.

The m6A reader YTHDC2 maintains visual function and retinal photoreceptor survival through modulating translation of PPEF2 and PDE6B.

Inherited retinal dystrophies (IRDs) are major causes of visual impairment and irreversible blindness worldwide, while the precise molecular and genetic mechanisms are still elusive. N6-methyladenosine (m6A) modification is the most prevalent internal modification in eukaryotic mRNA. YTH domain containing 2 (YTHDC2), an m6A reader protein, has recently been identified as a key player in germline development and human cancer. However, its contribution to retinal function remains unknown. Here, we explore the role of YTHDC2 in the visual function of retinal rod photoreceptors by generating rod-specific Ythdc2 knockout mice. Results show that Ythdc2 deficiency in rods causes diminished scotopic ERG responses and progressive retinal degeneration. Multi-omics analysis further identifies Ppef2 and Pde6b as the potential targets of YTHDC2 in the retina. Specifically, via its YTH domain, YTHDC2 recognizes and binds m6A-modified Ppef2 mRNA at the coding sequence and Pde6b mRNA at the 5'-UTR, resulting in enhanced translation efficiency without affecting mRNA levels. Compromised translation efficiency of Ppef2 and Pde6b after YTHDC2 depletion ultimately leads to decreased protein levels in the retina, impaired retinal function, and progressive rod death. Collectively, our finding highlights the importance of YTHDC2 in visual function and photoreceptor survival, which provides an unreported elucidation of IRD pathogenesis via epitranscriptomics.

Effectiveness of inspector mechanism for the emergency infection prevention and control in the SARS-CoV-2 epidemic period: a self-control real-word study.

BACKGROUND: To ensure emergency infection prevention and control (IPC) can be fully supervised and monitored in coronavirus disease (COVID-19) epidemic period, a three-level inspector mechanism called "Internal self-check, Departmental cross-check, and Verification of outstanding key and difficult issues" was established in southwest China. The present study aimed to explore the effectiveness of inspector mechanism for the emergency IPC. METHODS: A self-control real-world study was conducted during COVID-19 epidemic period from 2020 to 2022. An innovative designed mobile phone application was used to realize paperless information transmission and data management. Data were compared between inspection levels using SPSS 19.0 software. RESULTS: A total of 2,800,132 supervision records were collected, including 149,137 comprehensive epidemic IPC projects, 1,410,093 personal protective equipment (PPE) use, 1,223,595 wearing and removing process of PPE and 17,307 ultraviolet light-detectable fluorescent (UV/F) surface marker. During the study period, the inspectors and subjects explored many optimized IPC measures. The compliance rate of check items has exceeded 98%, and internal self-check has a statistically significant higher rate than departmental cross-check (99.95% versus 98.74%, χ2 = 26111.479, P < 0.001). Compare with the failure rate in internal self check, the failure rate of PPE usage and wearing/removing process was statistically higher in departmental cross-check (χ2 = 1957.987, P < 0.001, χ2 = 465.610, P < 0.001, respectively). The overall clearance rate of UV/F surface markers is 87.88%, but there is no statistically significant difference over the three years of the present study (F = 2.902, P = 0.071). CONCLUSIONS: Inspector mechanism for the emergency IPC completed an incredible inspection workload and offered creative assistance to combat the COVID-19 outbreak. These methods and accumulated experiences should be helpful for us to strengthen IPC for future epidemic.

Application of the BOPPPS-CBL model in electrocardiogram teaching for nursing students: a randomized comparison.

BACKGROUND/AIM: Interpreting an electrocardiogram (ECG) is a vital skill for nurses in cardiology. This study aimed to evaluate the efficacy of the bridge-in, objective, preassessment, participatory learning, post-assessment, and summary (BOPPPS) model, when combined with case-based learning (CBL), in enhancing nursing students' ECG interpretation capabilities. MATERIALS & METHODS: Nursing students were randomly divided into two groups: one utilizing the BOPPPS model combined with CBL (BOPPPS-CBL), and the other employing a traditional lecture-based learning (LBL) model. All participants underwent training and completed pre- and post-course quizzes. RESULTS: The BOPPPS-CBL model significantly improved nursing students' abilities in ECG interpretation compared to the traditional LBL model group. The BOPPPS-CBL model proved to be a comprehensive and effective method for enhancing students' attitudes towards teaching and learning. DISCUSSION: Our study demonstrated for the first time that the BOPPPS-CBL model is an innovative and effective method for promoting nurses' accuracy in ECG interpretation. It highlights the potential of this approach as a superior alternative to traditional learning methods.

Association of cardiometabolic multimorbidity with motoric cognitive risk syndrome in older adults.

INTRODUCTION: Motoric cognitive risk syndrome (MCR) is a predementia syndrome that is characterized by cognitive complaints and slow gait. Cardiometabolic multimorbidity (CMM) is associated with an increased risk of dementia. However, the relationship between CMM and MCR is still unclear. METHODS: We included 4744 participants (aged 65+ years) without MCR at baseline from the National Health and Aging Trends Study (NHATS), who were followed-up from 2011 to 2018. CMM was defined as the presence of two or more cardiometabolic diseases (including diabetes mellitus, heart disease, and stroke). RESULTS: CMM was significantly associated with an increased risk of MCR (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.13-1.75) in fully adjusted models. Consistent results were observed from stratified analyses of different subgroups. Increasing numbers of cardiometabolic diseases were dose-dependently associated with increased MCR risk (HR 1.33, 95% CI 1.20-1.48). DISCUSSION: CMM is associated with an increased risk of MCR in older adults. HIGHLIGHTS: Motoric cognitive risk syndrome (MCR) is a predementia syndrome characterized by slow gait speed and cognitive complaints.Cardiometabolic multimorbidity was associated with an increased MCR risk.An increased number of cardiometabolic diseases were dose-dependently associated with increased MCR risk.

Prediction of the mechanism for the combination of diallyl trisulfide and cisplatin against gastric cancer: a network pharmacology study and pharmacological evaluation.

Background: In this research, we aimed to explore the efficacy of diallyl trisulfide (DATS) combined with cisplatin (DDP) for gastric cancer treatment and its underlying mechanism based on network pharmacology. Methods: First, the pharmacological mechanism by which DATS combined with DDP acts against gastric cancer was predicted using network pharmacology. The TTD, GeneCards, and OMIM databases were used to extract drug and disease targets. The David Bioinformatics Resources 6.8 database was used to conduct GO and KEGG analyses. We investigated the efficacy of DATS combined with DDP against gastric cancer in SGC7901 cells and a xenograft model. Furthermore, the specific mechanism of DATS combined with DDP, inferred by network pharmacology, was identified by Western blotting and immunohistochemistry. Results: The combination of DDP and DATS significantly increased cytotoxicity and cell apoptosis compared to the DATS or DDP treatment group in vitro. In addition, continuous intraperitoneal injection of DATS markedly improved the tumor inhibitory effect of DDP in the SGC-7901 tumor-bearing mouse model. Furthermore, network pharmacology and experimental validation studies revealed that the combination of DATS and DDP synergistically enhanced antitumor activity by regulating endoplasmic reticulum stress and inhibiting STAT3/PKC-δ and MAPK signaling pathways. Conclusion: Our study showed that the combination of DATS and DDP could exert outstanding therapeutic effects in gastric cancer. Moreover, network pharmacology coupled with experimental validation revealed the molecular mechanisms of combination therapy for gastric cancer. This study offers a new adjuvant strategy based on DATS and DDP for the treatment of gastric cancer.

Topical Application of Bunazosin Hydrochloride Suppresses Myopia Progression With an Increase in Choroidal Blood Perfusion.

Purpose: The incidence of myopia has rapidly increased in recent decades, making it a growing public health concern worldwide. Interventions to suppress the progression of myopia are needed; one suggested strategy is the prevention of choroidal thinning, which can improve choroidal blood perfusion (ChBP). Bunazosin hydrochloride (BH) is an alpha1-adrenergic blocker and commercialized glaucoma eye drop that increases in blood circulation in the eye. In this study, we evaluated the efficacy of BH in suppressing the progression of myopia in a lens-induced murine model. Methods: Lens-induced myopia was induced in 3-week-old C57BL/6 J mice with -30 diopter (D) lenses for three weeks. Refractive error, axial length, and choroidal thickness were evaluated at three and six weeks of age using an infrared photorefractor and a spectral domain optical coherence tomography (OCT) system. Moreover, ChBP and scleral thickness were evaluated using swept-source OCT and histological analysis. Results: Compared with the controls, the administration of BH eye drops suppressed the myopic shift of refractive error (mean difference ± standard error in the eye with -30 D lens, -13.65 ± 5.69 D vs. 2.55 ± 4.30 D; P < 0.001), axial elongation (0.226 ± 0.013 mm vs. 0.183 ± 0.023 mm; P < 0.05), choroidal thinning (-2.01 ± 1.80 µm vs. 1.88 ± 1.27 µm; P < 0.001), and scleral thinning (11.41 ± 3.91 µm vs. 19.72 ± 4.01 µm; P < 0.01) with myopia progression and increased ChBP (52.0% ± 4.1% vs. 59.5% ± 6.3%; P < 0.05). The suppressive effect of BH eye drops was dose-dependent and higher than that of other glaucoma eye drops and alpha1 blockers. Conclusions: These results demonstrate the potential of BH eye drops in the treatment of myopia and support further investigation of their efficacy in humans. Further studies are needed to determine the mechanism of action and long-term safety of this treatment.

Identification of multivariable microRNA and clinical biomarker panels to predict imatinib response in chronic myeloid leukemia at diagnosis.

Imatinib Mesylate (imatinib) was once hailed as the magic bullet for chronic myeloid leukemia (CML) and remains a front-line therapy for CML to this day alongside other tyrosine kinase inhibitors (TKIs). However, TKI treatments are rarely curative and patients are often required to receive life-long treatment or otherwise risk relapse. Thus, there is a growing interest in identifying biomarkers in patients which can predict TKI response upon diagnosis. In this study, we analyze clinical data and differentially expressed miRNAs in CD34+ CML cells from 80 patients at diagnosis who were later classified as imatinib-responders or imatinib-nonresponders. A Cox Proportional Hazard (CoxPH) analysis identified 16 miRNAs that were associated with imatinib nonresponse and differentially expressed in these patients. We also trained a machine learning model with different combinations of the 16 miRNAs with and without clinical parameters and identified a panel with high predictive performance based on area-under-curve values of receiver-operating-characteristic and precision-recall curves. Interestingly, the multivariable panel consisting of both miRNAs and clinical features performed better than either miRNA or clinical panels alone. Thus, our findings may inform future studies on predictive biomarkers and serve as a tool to develop more optimized treatment plans for CML patients in the clinic.