Tag: nevin manimala

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Aug;33(4):966-971. doi: 10.19746/j.cnki.issn.1009-2137.2025.04.006.

ABSTRACT

OBJECTIVE: To analyze clinical characteristics and prognosis of B-cell acute lymphoblastic leukemia (B-ALL) patients with IKZF1 deletion.

METHODS: 72 patients with B-ALL admitted to our hospital from April 2020 to January 2023 were selected, IKZF1 deletion were detected, and clinical characteristics and prognosis were analyzed.

RESULTS: Among the 72 patients, a total of 32 patients (44.4%) were identified with IKZF1 deletions (IKZF1 ⁺ ). There was no statistically significant difference in basic clinical data between patients with normal IKZF1 (IKZF1 ^–) and those with IKZF1 ⁺ (P >0.05). The proportion of patients with IKZF1 ⁺ in Ph⁺ group was significantly higher than that in Ph^– group (P < 0.05). The main types of IKZF1 ⁺ were exon 1-8 deletion (34.4%) and exon 4-7 deletion (31.2%). The median OS and PFS of IKZF1 ^– patients were significantly longer than those of IKZF1 ⁺ patients (OS: 26.0 months vs 16.0 months, χ ²=23.094, P < 0.05; PFS: 26.0 months vs 16.0 months, χ ²=11.150, P < 0.05). Among IKZF1 ⁺ patients, the median OS of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) was significantly longer than that of patients who did not receive allo-HSCT (no reached vs 15.0 months, χ ²=5.685, P < 0.05).

CONCLUSION: IKZF1 deletion is a risk factor affecting the prognosis of B-ALL patients.

PMID:40936117 | DOI:10.19746/j.cnki.issn.1009-2137.2025.04.006

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Aug;33(4):931-938. doi: 10.19746/j.cnki.issn.1009-2137.2025.04.001.

ABSTRACT

OBJECTIVE: To explore the effects of hydroxychloroquine (HCQ) on immune mediators dysregulation in severe infection after chemotherapy in acute myeloid leukemia (AML) and its molecular mechanism.

METHODS: Bone marrow or peripheral blood samples of 36 AML patients with severe infection (AML-SI) and 29 AML patients without infection (AML-NI) after chemotherapy were collected from the First Affiliated Hospital of Gannan Medical University from August 2022 to June 2023. In addition, the peripheral blood of 21 healthy subjects from the same period in our hospital was selected as the control group. The mRNA expressions of CXCL12, CXCR4 and CXCR7 were detected by RT-qPCR technology, and the levels of IL-6, IL-8 and TNF-α were detected by ELISA. Leukemia-derived THP-1 cells were selected and constructed as AML disease model. At the same time, bone marrow mesenchymal stem cells (BM-MSCs) from AML-SI patients were co-cultured with THP-1 cells and divided into Mono group and Co-culture group. THP-1 cells were treated with different concentration gradients of HCQ. The cell proliferation activity was subsequently detected by CCK-8 method and apoptosis was detected by Annexin V/PI double staining flow cytometry. ELISA was used to detect the changes of IL-6, IL-8 and TNF-α levels in the supernatant of the cell co-culture system, RT-qPCR was used to detect the mRNA expression changes of the core members of the CXCL12-CXCR4/7 regulatory axis, and Western blot was used to detect the expressions of apoptosis regulatory molecules and related signaling pathway proteins.

RESULTS: CXCL12, CXCR4, CXCR7, as well as IL-6, IL-8, and TNF-α were all abnormally increased in AML patients, and the increases were more significant in AML-SI patients (P <0.01). Furthermore, there were statistically significant differences between AML-NI patients and AML-SI patients (all P <0.05). HCQ could inhibit the proliferation and induce the apoptosis of THP-1 cells, but the low concentration of HCQ had no significant effect on the killing of THP-1 cells. When THP-1 cells were co-cultured with BM-MSCs of AML patients, the levels of IL-6, IL-8 and TNF-α in the supernatance of Co-culture group were significantly higher than those of Mono group (all P <0.01). After HCQ intervention, the levels of IL-6, IL-8 and TNF-α in cell culture supernatant of Mono group were significantly decreased compared with those before intervention (all P <0.01). Similarly, those of Co-culture group were also significantly decreased (all P <0.001). However, the expression of the core members of the CXCL12-CXCR4/7 regulatory axis was weakly affected by HCQ. HCQ could up-regulate the expression of pro-apoptotic protein Bax, down-regulate the expression of anti-apoptotic protein Bcl-2, as well as simultaneously promote the hydrolytic activation of Caspase-3 when inhibiting the activation level of TLR4/NF-κB pathway, then induce the programmed death of THP-1 cells after intervention.

CONCLUSION: The core members of CXCL12-CXCR4/7 axis and related cytokines may be important mediators of severe infectious immune disorders in AML patients. HCQ can inhibit cytokine levels to reverse immune mediators dysregulation and suppress malignant biological characteristics of leukemia cells. The mechanisms may be related to regulating the expression of Bcl-2 family proteins, hydrolytically activating Caspase-3 and inhibiting the activation of TLR4/NF-κB signaling pathway.

PMID:40936112 | DOI:10.19746/j.cnki.issn.1009-2137.2025.04.001

Orthop Surg. 2025 Sep 11. doi: 10.1111/os.70140. Online ahead of print.

ABSTRACT

OBJECTIVE: This systematic review and network meta-analysis was performed to explore the optimal dose, efficacy, and safety of tranexamic acid (TXA) treatments versus placebo for high tibial osteotomy (HTO) patients.

METHODS: PubMed, Embase, Cochrane Library, Wanfang database, and Chinese National Knowledge Infrastructure (CNKI) databases were searched for the randomized controlled trials (RCTs) meeting prespecified inclusion criteria up to March 2024. Interventions included TXA and placebo treatments. The outcomes included total blood loss, drainage, hemoglobin drop, the occurrence of deep venous thrombosis (DVT) and hematoma. Traditional meta-analysis and network meta-analysis were performed by Stata and R software, respectively.

RESULTS: Traditional meta-analysis revealed that TXA was associated with a decrease in the total blood loss, drainage volume, and hemoglobin drop (p < 0.05). There was no significant difference between TXA and placebo in terms of the occurrence of DVT and hematoma (p > 0.05). Compared with placebo, intravenous (iv) 10 mg/kg, iv 10 mg/kg (3 doses), iv 2 g, iv 2 g (2 doses), iv 2 g + topical (top) 3 g, iv 50 mg/kg, and top 10 mg/kg decreased the total blood loss with statistical significance (p < 0.05). Compared with placebo, iv 10 mg/kg (WMD = -379.91, 95% CI: -378.92, -81.22) decreased the drainage volume with statistical significance. Compared with placebo, iv 10 mg/kg (3 doses), iv 1 g, iv 1 g + top 2 g, iv 2 g + top 1 g, and iv 50 mg/kg decreased the hemoglobin drop with statistical significance. No statistically significant difference was found when the two interventions were compared against each other for the occurrence of DVT and hematoma (p > 0.05). The SUCRA shows that iv 10 mg/kg ranked first for reducing total blood loss (SUCRA, 90.7%) and drainage volume (SUCRA, 94.3%). The SUCRA shows that iv 1 g + top 2 g ranked first (SUCRA, 93.7%) for reducing hemoglobin drop.

CONCLUSION: Administration with TXA was associated with a decrease in blood loss in HTO patients. The optimal dose of TXA for reducing blood loss was iv 10 mg/kg. As for reducing hemoglobin drop, iv 1 g + top 2 g ranked first. Administration of TXA was not associated with an increase in the occurrence of DVT and hematoma. However, most evidence was graded as low/very low confidence due to study limitations, imprecision, and heterogeneity. Therefore, these findings should be interpreted as preliminary signals rather than definitive conclusions. Further high-quality randomized trials are required to validate dose-dependent efficacy and long-term safety outcomes.

PMID:40936101 | DOI:10.1111/os.70140

BMC Glob Public Health. 2025 Sep 12;3(1):76. doi: 10.1186/s44263-025-00189-z.

ABSTRACT

BACKGROUND: Non-pharmaceutical interventions (NPIs) in response to the COVID-19 pandemic necessitated a trade-off between the health impacts of viral spread and the social and economic costs of restrictions. Navigating this trade-off proved consequential, contentious, and challenging for decision-makers.

METHODS: We conduct a cost-effectiveness analysis of NPIs enacted at the state level in the United States (US) in 2020. We combine data on COVID-19 cases, deaths, policies, and the social, economic, and health consequences of infections and interventions within an epidemiological model. We estimate SARS-CoV-2 prevalence, transmission rates, effects of interventions, and costs associated to infections and NPIs in each US state. We use these estimates to quantitatively evaluate the efficacy and gross impacts of the policy schedules implemented during the pandemic. We also derive optimal cost-effective strategies that minimize aggregate costs to society.

RESULTS: We find that NPIs were effective in substantially reducing SARS-CoV-2 transmission, averting 860,000 (95% CI: 560,000-1,190,000) COVID-19 deaths in the US in 2020. Although school closures reduced transmission, their social impact in terms of student learning loss was too costly, depriving the nation of $2 trillion in 2020 US dollars (USD2020), conservatively, in future Gross Domestic Product (GDP). Moreover, this marginal trade-off between school closure and COVID-19 deaths was not inescapable: a combination of other measures would have been enough to maintain similar or lower mortality rates without incurring such profound learning loss. Optimal policies involve consistent implementation of mask mandates, public test availability, contact tracing, social distancing orders, and reactive workplace closures, with no closure of schools. Their use would have reduced the gross impact of the pandemic in the US in 2020 from $4.6 trillion to $1.9 trillion and, with high probability, saved over 100,000 lives.

CONCLUSIONS: US COVID-19 school closure was not cost-effective, but other measures were. While our study focuses on COVID-19 in the US prior to vaccines, our methodological contributions and findings about the cost-effectiveness and optimal structure of NPI policies have implications for the response to future epidemics and in other countries. Our results also highlight the need to address the substantial global learning deficit incurred during the pandemic.

PMID:40936091 | DOI:10.1186/s44263-025-00189-z

BMC Plant Biol. 2025 Sep 12;25(1):1201. doi: 10.1186/s12870-025-07214-1.

ABSTRACT

BACKGROUND: Arbuscular mycorrhizal fungi (AMF) can stimulate root development in plants and enhance their ability to adapt to stress conditions. This study investigated the effects of arbuscular mycorrhizal fungi (AMF) inoculation on the growth, hormone dynamics, and phosphorus (P) metabolism of two wheat cultivars with differing phosphorus utilization efficiencies under both normal and low phosphorus concentration conditions. The research focused on the symbiotic interaction between AMF and these wheat varieties to elucidate their responses to varying phosphorus availability.

RESULT: The experiment showed that phosphorus inefficient wheat SW14 inoculated with AMF for 30 days under low phosphorus stress showed significant enhancement in plant height, biomass, leaf width, stem thickness, root surface area, and vegetative phosphorus content, while total root length and primary root length were reduced, This change in root length was attributed to the fact that the root system undergoes elongation and growth to adapt to the adversity under low phosphorus stress in crops, and inoculation with AMF effectively alleviated the extent of this low phosphorus stress. while IAA, SL, cellulose and lignin hormone levels and APC enzyme activities were significantly elevated, and stem structure was significantly optimized; whereas, the phosphorus-efficient variety, SW2, did not show significant improvement due to its own unique tolerance to low phosphorus stress (Table 2). Transcriptomic profiling identified 2,500 differentially expressed genes (DEGs: 983↑/1,517↓), enriched in ABC transporters (ko02010), Plant hormone signal transduction (ko04075), and MAPK signaling pathway – plant (ko04016), Cutin, suberin and wax biosynthesis(ko00073). WGCNA further resolved that AMF responded to low phosphorus stress by up-regulating the expression of cellulose, lignin, APC synthesis, and IAA/SL-related genes in SW14, with the most relevant phenotypes shown to correlate to primary root length, total root length, root dry weight and stem diameter.

CONCLUSION: AMF inoculation significantly enhanced growth and dry matter accumulation in the low-phosphorus-use-efficiency wheat variety SW14 under phosphorus-deficient stress. This treatment concurrently stimulated IAA, SL, and APC activities, resulting in increased phosphorus uptake/accumulation, notable accumulation of cellulose and lignin, and consequently significantly improved stem strength. Although AMF inoculation improved growth in the high-phosphorus-use-efficiency wheat variety SW2, these enhancements failed to reach statistical significance.

PMID:40936089 | DOI:10.1186/s12870-025-07214-1

Epigenetics Chromatin. 2025 Sep 12;18(1):59. doi: 10.1186/s13072-025-00626-1.

ABSTRACT

DNA-methylation is a key epigenetic mark in chromatin that attenuates chromatin accessibility during transcription, implying a crucial role in gene regulation. Its symmetrical distribution and function is thought to be linked to the periodicity of the DNA helix and the positioning of DNA wrapped around the nucleosome. Epigenomic data suggest that DNA methyltransferases (DNMTs) can methylate DNA when wrapped around a histone octamer. Yet, how this is precisely linked to positioning and periodicity is yet to be elucidated. It has been hypothesized that the observed methylation patterns may be related to the changing accessibility of nucleosome-bound DNA to DNMTs. Here, incorporating NOMe-Seq data, which simultaneously measures nucleosome positioning and DNA methylation at CpG sites across the genome, the interaction of DNMT1 with nucleosomal DNA could be mechanistically modeled and compared to hypothesized dependencies. Furthermore, X-ray structures of DNMT1 were superimposed onto those of nucleosome core complexes at base resolution to determine which histone-bound DNA positions would be sterically accessible or inaccessible to DNMTs. Statistical comparison with experimental NOMe-Seq data revealed that structurally computed DNA accessibility scores can indeed explain DNA methylation patterns in actively transcribed regions with positioned high nucleosome density.

PMID:40936088 | DOI:10.1186/s13072-025-00626-1

BMC Res Notes. 2025 Sep 11;18(1):386. doi: 10.1186/s13104-025-07416-8.

NO ABSTRACT

PMID:40936084 | DOI:10.1186/s13104-025-07416-8

Cardiovasc Diabetol. 2025 Sep 11;24(1):360. doi: 10.1186/s12933-025-02860-z.

ABSTRACT

BACKGROUND: Insulin resistance (IR) has been recognized as a critical factor in the progression of cardiovascular disease (CVD), yet its association with cardiovascular-kidney-metabolic (CKM) syndrome remains incompletely understood. This study aimed to evaluate the impact of IR, as measured by the estimated glucose disposal rate (eGDR), on the risk of future CVD events in individuals with CKM stages 0-3.

METHODS: This study included 325,312 participants from the UK Biobank with CKM stages 0-3. IR was quantified using eGDR, a non-insulin-dependent metric, with lower values indicating greater IR. Participants were stratified into quartiles based on eGDR distribution. The primary outcome was incident CVD, including coronary heart disease, stroke, atrial fibrillation, heart failure, and peripheral artery disease.

RESULTS: In the CKM 0-3 cohort, eGDR demonstrated the highest predictive value for future CVD events among non-insulin-dependent IR metrics. Incorporating eGDR significantly improved the predictive performance of the PREVENT Cardiovascular Disease Risk Equations (AUC: PREVENT Equations + eGDR 0.743 vs. PREVENT Equations 0.719, p < 0.001). Over a median follow-up of 13.57 years, 48,433 incident CVD cases were identified. The adjusted rates of CVD incidence (95% confidence interval [CI]) across eGDR quartiles (Q1-Q4) were 3.84 (3.62-4.07), 3.82 (3.66-3.98), 3.53 (3.41-3.65), and 3.37 (3.25-3.50) per 1000 person-years. RCS analysis revealed a significant nonlinear association between eGDR and CVD incidence (p for overall < 0.001; p for nonlinear = 0.020), with greater risk reduction at higher eGDR levels. A significant trend toward reduced CVD risk was observed across higher eGDR quartiles, with Q3 and Q4 demonstrating statistically significant reductions relative to Q1 (HR 0.920, 95% CI 0.871-0.971; and 0.883, 95% CI 0.827-0.942, respectively; p for trend < 0.001). Kaplan-Meier analysis further confirmed a graded decrease in CVD risk with increasing eGDR levels (log-rank p < 0.001).

CONCLUSION: This study establishes a strong association between IR severity and long-term CVD risk in individuals with CKM syndrome stages 0-3. The eGDR, a reliable surrogate marker of IR, independently predicts future CVD events and provides incremental predictive value beyond the PREVENT equations. These findings underscore the clinical utility of eGDR for risk stratification in CKM populations.

PMID:40936079 | DOI:10.1186/s12933-025-02860-z

Int J Colorectal Dis. 2025 Sep 12;40(1):196. doi: 10.1007/s00384-025-04995-7.

ABSTRACT

PURPOSE: Fistula Laser Closure (FiLaC®) is a sphincter-preserving technique for anal fistulas, but its efficacy and safety remain under discussion. Therefore, we aim to evaluate the efficacy and safety of FiLaC® in the management of patients with cryptoglandular fistulas.

METHODS: A systematic review was performed in MEDLINE, Embase, and Cochrane databases in January 2025, following PRISMA guidelines. We included randomized controlled trials (RCTs) and observational studies assessing FiLaC® for cryptoglandular fistulas, with or without surgical adjunctive measures. The main outcome was the primary healing rate. Secondary outcomes included fistula recurrence, incontinence, reoperation rates, and postoperative complications. Subgroup analyses explored variables related to the primary healing rate. Data are presented as percentages (95% confidence interval). Statistical analyses were performed using R (version 4.4.1 (2024-06-14 (ucrt)).

RESULTS: We included 24 studies with 1,503 patients. The pooled primary healing rate was 57.46% (49.40-65.33). Recurrence occurred in 18.48% of patients (10.14-28.47), while new-onset incontinence was rare (0.57%; 0.00-2.15). The reoperation rate was 36.49% (28.95-44.36), and anal abscesses or infections affected 6.54% (1.93-13.09) of patients. Subgroup analysis showed no statistically significant differences in the primary healing rate based on fistula type, adjunctive measures, or sex. Sensitivity analysis confirmed the robustness of our findings.

CONCLUSIONS: FiLaC® seems to be a safe option with an intermediate healing rate in patients with cryptoglandular fistulas, although it is associated with a considerable recurrence rate. While its sphincter preservation advantage is evident, further RCTs standardizing the technique and adjunctive approaches are needed to optimize outcomes and refine its application in fistula management.

PMID:40936062 | DOI:10.1007/s00384-025-04995-7

Int J Clin Oncol. 2025 Sep 11. doi: 10.1007/s10147-025-02870-7. Online ahead of print.

ABSTRACT

PURPOSE: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, yet comprehensive nationwide epidemiologic data remain limited. This study aimed to provide an updated analysis of UM incidence, survival, and disparities in the United States (US) using near-complete population coverage.

METHODS: We analyzed data from the North American Association of Central Cancer Registries (NAACCR) and US Cancer Statistics (USCS) program between 1995 and 2018, covering 98-100% of the US population. Age-adjusted incidence rates (AAIRs) and relative survival were calculated using SEER*Stat and Joinpoint regression.

RESULTS: A total of 37,917 UM cases were identified, with an overall AAIR of 5.54 per million (95% CI: 5.48-5.59), showing a stable but slightly increasing trend (AAPC = 0.06). Incidence was highest in non-Hispanic whites (6.87 ppm), men (6.25 ppm), and those aged 75-79 years. Geographic variation was notable, with peak incidence in Oregon and Iowa. Most tumors (81.3%) were localized at diagnosis, and 27.4% of patients had another primary malignancy. 5- and 10-year relative survival rates were 83.3% and 73.9%, respectively, with worse outcomes in metastatic disease. A shift toward radiotherapy, especially brachytherapy, was observed, although survival gains remained limited.

CONCLUSIONS: This nationwide study refines US UM incidence estimates and highlights persistent disparities by sex, race, age, and geography. The high prevalence of secondary malignancies underscores the need for genetic counseling and extended surveillance. Despite advances in imaging, local therapies (e.g., brachytherapy, proton therapy), and emerging systemic approaches including immunotherapy, survival improvements in advanced UM remain limited.

PMID:40936061 | DOI:10.1007/s10147-025-02870-7