Cardiovascular diseases (CVDs) are the leading cause of death worldwide, far exceeding other diseases such as cancer. Myocardial injury is a key link in various CVDs; reducing myocardial injury is an effective means of preventing and treating CVDs. Mitochondrial dysfunction is the pathological basis of various CVDs. Mitophagy, as a process that selectively eliminates damaged or dysfunctional mitochondria, is of enormous significance in maintaining the normal function and structure of mitochondria in cardiomyocytes and alleviating myocardial injury. Therefore, this review systematically analyzes the role of mitophagy in myocardial injury, explores targeted intervention strategies, and hopes to provide a theoretical basis and effective therapeutic targets for clinical practice.

Objective:Sacituzumab govitecan (SG) has emerged as a therapeutic option for various cancers. Increasing reports of SG-associated neutropenia have attracted attention, emphasizing the need to fully characterize this risk. Methods:This study conducted a retrospective pharmacovigilance analysis using the Food and Drug Adverse Event Reporting System (FAERS) database. Cases of neutropenia associated with SG were extracted from the second quarter of 2020 through the second quarter of 2025 for disproportionality analysis. Additionally, a meta-analysis was performed on randomized controlled trials (RCTs) comparing SG (experimental group) with chemotherapy drugs (control group), retrieved from CNKI, Wanfang, VIP, PubMed, the Cochrane Library, EMBASE, and Web of Science. Results:In the FAERS, 500 cases of neutropenia were associated with SG treatment. Among antibody-drug conjugate (ADC) drugs, SG exhibited the strongest positive signal (reported odds ratio (ROR) = 17.91, 95% CI: 16.39-19.56). Subgroup analysis revealed that this signal widely existed in different gender, age, reporting groups and initial indications. Most events occurred within 30 days of initial initiation. Gender (10 days for males vs. 13 days for females, P < 0.05) and initial indications (12 days for breast cancer/lung cancer vs. 8 days for bladder cancer, P < 0.05) were significantly associated with time-to-onset. Five RCTs were included in this meta-analysis. The results showed that for all adverse event (AE) grades, SG is associated with an increased risk of neutropenia (odds ratio (OR) = 2.07, 95% CI: 1.09-3.93, P < 0.05). Subgroup analysis indicated that SG significantly increased the risk of all-grade neutropenia AE in patients with breast cancer (OR = 2.13, 95% CI: 1.68-2.69, P < 0.00001), and a similar trend was observed among bladder cancer patients (P < 0.00001). Although no significant difference emerged in the risk of all-grade AEs for lung cancer patients (P > 0.05), the control group exhibited a tendency toward higher risk, and the SG group demonstrated a significantly lower incidence of grade ≥3 AEs compared to controls (P < 0.05). In addition, the risk of neutropenia did not differ significantly between patients with the UGT1A1*1/*28 and UGT1A1*28/*28 genotypes compared to those with the UGT1A1*1/*1 genotype (P > 0.05). Conclusion:The combined analysis supports an elevated risk of neutropenia associated with SG. This AE exhibits significant cancer species specificity. Early intervention and management of neutropenia are therefore of considerable clinical importance.

[This corrects the article DOI: 10.3389/fcvm.2023.1194771.].

BACKGROUND:Natural killer/T-cell lymphoma (NKTCL) is a highly aggressive malignancy with a dismal prognosis, and gaps remain in understanding the determinants influencing disease outcomes. OBJECTIVE:To characterise the gut microbiota feature and identify potential probiotics that could ameliorate the development of NKTCL. DESIGN:This cross-sectional study employed shotgun metagenomic sequencing to profile the gut microbiota in two Chinese NKTCL cohorts, with validation conducted in an independent Korean cohort. Univariable and multivariable Cox proportional hazards analyses were applied to assess associations between identified marker species and patient outcomes. Tumour-suppressing effects were investigated using comprehensive in vivo and in vitro models. In addition, metabolomics, RNA sequencing, chromatin immunoprecipitation sequencing, Western blot analysis, immunohistochemistry and lentiviral-mediated gene knockdown system were used to elucidate the underlying mechanisms. RESULTS:We first unveiled significant gut microbiota dysbiosis in NKTCL patients, prominently marked by a notable reduction in Faecalibacterium prausnitzii which correlated strongly with shorter survival among patients. Subsequently, we substantiated the antitumour properties of F. prausnitzii in NKTCL mouse models. Furthermore, F. prausnitzii culture supernatant demonstrated significant efficacy in inhibiting NKTCL cell growth. Metabolomics analysis revealed butyrate as a critical metabolite underlying these tumour-suppressing effects, validated in three human NKTCL cell lines and multiple tumour-bearing mouse models. Mechanistically, butyrate suppressed the activation of Janus kinase-signal transducer and activator of transcription pathway through enhancing histone acetylation, promoting the expression of suppressor of cytokine signalling 1. CONCLUSION:These findings uncover a distinctive gut microbiota profile in NKTCL and provide a novel perspective on leveraging the therapeutic potential of F. prausnitzii to ameliorate this malignancy.

From January 2000 to December 2019, the SEER Plus Database collecting human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR; including estrogen receptor [ER] and progesterone receptor [PR]) status for breast cancer (BC) cases. HER2-positive (HER2+) BC is an aggressive type, and HER2-targeted therapies have significantly improved the therapeutic outcome of patients. However, not every HER2+ BC patient achieves optimal benefits from current HER2-targeted therapies. Here, we conducted a detailed analysis to compare the demographic and clinic-pathological characteristics, survival, differential genes and mutations between HR+ and HR– in HER2+ BC patients. In this retrospective cohort study, Joint HR and HER2 status distributions by more than ten specific clinic-pathological characteristics were evaluated by using Pearson’s chi-squared (χ2) test. The transciptome RNA-seqencing (RNA-seq) expression data together with detailed clinic-pathological information of HER2+ BC were from The Cancer Genome Atlas (TCGA) and UCSC Xena. 30,482 (71.02

Background : Pulmonary sclerosing pneumocytoma (PSP) is a rare solitary benign tumor. The unusual multifocal presentation creates a big challenge in diagnosis and management. We report such a case, linking the spectrum morphology of multiple evolving PSP to a novel genetic change for the first time. Case presentation : A 47-year-old asymptomatic, non-smoker female presented with incidental 14 bilateral lung nodules. The initial biopsy strengthened the clinical suspicion of metastatic lung adenocarcinoma. However, no extrapulmonary involvement was detected and the liquid biopsy was also negative. The left upper lobectomy was performed for a definitive diagnosis. This has led to a pathological finding of seven PSP tumors, with the largest 3 cm mass showing characteristic solid, papillary, hemorrhagic and sclerotic patterns, and five smaller nodules showing a spectrum morphology of PSP starting from pneumocytes hyperplasia, evolving to four histological patterns and ended with fibrosis. Somatic Fibroblast Growth Factor Receptor 3 (FGFR3) pE360K mutation is present in the tumors and background lung parenchyma. While additional AKT1 internal tandem duplication (p.R67_L78 dup), which is a known hallmark for PSP, is limited to the largest mass. No other driver gene mutations classic for lung cancer are detected among over 2000 genes examined. Patient is free of recurrence or metastasis during two-year follow up. Conclusion : The diagnosis of PSP could be difficult in small biopsy and frozen. Synchronous presentation of PSP is attributable to the somatic mutation of FGFR3 (pE360K). Secondary AKT abnormality promotes tumor growth but does not change the benign course of PSP in this case. Keywords : FGFR3, multifocal pulmonary sclerosing pneumocytoma, AKT1.

Risk stratification for sudden cardiac death (SCD) mainly relies on severely reduced left ventricular ejection fraction (LVEF), but its poor predictive efficacy fails to meet clinical needs. Myocardial scarring identified using cardiac magnetic resonance (CMR) imaging has emerged as a potent risk indicator for SCD and life-threatening ventricular tachyarrhythmias (LTVTA). This study aimed to develop a risk prediction score for SCD and ventricular tachyarrhythmias in symptomatic heart failure. Consecutive patients with nonischemic heart failure undergoing CMR were monitored from 2018 to 2024. A risk stratification score was developed by integrating CMR parameters with clinical variables. Among the 199 patients, the median LVEF was 32.7%, and the average age was 50.3 ± 15.2 years. During a median observation period of 3 years, 21 (10.5%) patients experienced LTVTA. Among multiple CMR parameters, the presence of late gadolinium enhancement (LGE) was the only independent risk factor for LTVTA. The final risk scoring model comprised the presence of LGE (hazard ratio, 10.68; p = 0.023), assigned a score of 2; syncope (hazard ratio, 4.41; p = 0.003), assigned a score of 1; and nonsustained ventricular tachycardia (hazard ratio, 3.82; p = 0.004), assigned a score of 1. A total score of ≥ 3 was considered high risk. Harrell's C-statistic was 0.814 in the derivation cohort and 0.785 in the external validation cohort. The 3-year cumulative risks for the low- and high-risk groups were 3.6% and 32.8%, respectively. Among CMR parameters, the presence of LGE was identified as the sole independent and strong risk marker of LTVTA. The novel scoring model may assist in the preliminary screening of patients with symptomatic heart failure with a potentially elevated risk.

Purpose:To evaluate the impact of secondary bloodstream infections (BSI) on healthcare quality indicators in patients with cerebral infarction, and to develop a validated predictive model. Methods:This study conducted a retrospective analysis of 7,698 distinct patients with cerebral infarction (2023) from a tertiary hospital in Guangzhou. Patients were categorized into two groups: BSI-negative (n=7,573) and BSI-positive (n=125). Healthcare quality indicators were compared using Mann-Whitney U-test. A predictive model was created using Least Absolute Shrinkage and Selection Operator (LASSO) regression, based on a 7:3 training-validation split. The model's performance was validated through the area under the Receiver Operating Characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). Results:Patients with BSI had significantly prolonged hospital stays (median of 17 days versus 11 days, p<0.001), higher costs (median of 34,859 yuan compared to 16,921 yuan, p<0.001), and increased adverse outcomes (34.4% versus 1.6%, p<0.001). The LASSO analysis identified four predictors: The following variables were found to have a statistically significant relationship to the occurrence of the primary complication: peripherally inserted central venous catheters (PICC) (odds ratio [OR] = 2.791, 95% confidence interval [CI] =1.514-5.148), use of ventilators(VA) (OR = 2.771, 95% CI=1.410-5.443), Indwelling urinary catheters(CAU) (OR = 1.800, 95% CI= 0.990-3.276), and hypoalbuminemia (OR = 3.643, 95% CI=2.195-6.046).The nomogram demonstrated an AUC of 0.789 in the training set and 0.778 in the test set, indicating a satisfactory model fit across data sets. Good model fit based on Hosmer-Lemeshowp-values(Hosmer-LemeshowP=0.338/0.170).DCA indicated a net clinical benefit at risk thresholds of 0-15%. Conclusion:Secondary BSI in patients with cerebral infarction can seriously affect the quality of medical care.The developed nomogram functions as a pragmatic instrument for the preliminary identification of patients at high risk. It facilitates the implementation of targeted interventions, thereby reducing the incidence of BSI and enhancing patient outcomes.

Rocbrutinib, a highly selective, 4th-generation Bruton's tyrosine kinase (BTK) inhibitor, uniquely takes advantages of both covalent irreversible inhibition for wide-type BTK and non-covalent binding for C481-mutant variants. Here, we present the safety and efficacy results from the ongoing phase I trial (LP-168-CN101; NCT04993690) of rocbrutinib in Chinese patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Eligible patients aged 18–80 with a confirmed diagnosis of CLL/SLL were treated with rocbrutinib monotherapy until disease progression or intolerable toxicity. Adverse events (AEs) were graded per CTCAE v5.0, and response was evaluated per 2018 iwCLL criteria. As of April 15, 2025, 41 (untreated (1L), n=12; relapsed/refractory (R/R) BTKi-naïve, n=17; R/R post-BTKi, n=12) CLL/SLL patients were enrolled and treated with rocbrutinib (100 mg ,n=1; 150 mg, n=28; 200 mg, n=10; 300mg, n=2) once daily. The median age was 60 (range, 35-79) years. Of the patients with evaluable samples, 26.9% (7/26) with del(17p), 42.9% (12/28) with TP53 mutation, 63.0% (17/27) with unmutated IGHV and 44.0% (11/25) with complex karyotype. Of the 29 R/R CLL/SLL patients, the median number of prior therapies was 2 (range, 1-5), including prior covalent BTKis (34.5%), BCL2 inhibitors (BCL-2i, 24.1%), and noncovalent BTKis (6.9%). In R/R post-BTKi CLL/SLL patients, most (91.7%) discontinued prior BTKi due to disease progression; 41.6% had prior BCL-2i ; 6/9 (66.7%) carried BTK mutations, including BTKC481S, BTKC481Y/R and BTKL528W. The most common treatment-related AEs (TRAEs, incidence≥20%)(any grade;≥grade 3) included decreased neutrophil count (41.5%; 19.5%), anemia (36.6%; 2.4%), decreased platelet count (29.3%; 2.4%), hyperuricemia (26.8%; 0) and rash (22.0%; 0), most of which were grade 1. No ≥grade 3 atrial fibrillation, hypertension or hemorrhage occurred. Dose interruption due to TRAEs occurred in 8 (19.5%) patients, however, only 1 (2.4%) patient underwent dose reduction. No drug discontinuation or death due to TRAEs has occurred. In 1L patients (n=12), the overall response rate (ORR, partial response with lymphocytosis or better) was 91.7%. The ORR and complete remission (CR)/CR with incomplete marrow recovery (CRi) rates in R/R BTKi-naïve patients (n=17) were 100% and 17.6%, respectively. In R/R post-BTKi patients, rocbrutinib monotherapy achieved 75% ORR including16.7% CR/CRi. In BTKi and BCL-2i double refractory population (n=5), ORR and CR/CRi rates were 80.0% and 40.0%, respectively; 3 patients are still in remission while the other 2 patients both had durable response of more than 17 months. 2 patients with BTKL528W mutation achieved PR and are still on treatment (DOR: 8.1 and 14.0 months). After median follow-up of 7.4 months, all 12 1L patients remained on treatment. In the R/R BTKi naive population (median follow-up 15.8 months), the estimated 12-month PFS rate as 94.1% (95% CI: 65.0-99.1); In the R/R post-BTKi population (median follow-up 15.5 months), the estimated 12-month PFS rate as 83.3% (95% CI: 48.2-95.6). Rocbrutinib has a favorable safety profile and shows durable responses in patients with CLL/SLL, including those with prior BTK inhibitor exposure and/or with covalent and noncovalent BTKi-resistant mutations.

BACKGROUND:Type 2 diabetes mellitus (T2DM) is associated with an increased incidence of atrial fibrillation (AF). However, the exact mechanisms involved have not yet been fully elucidated. Dysregulation of cardiac potassium channels can trigger AF. This study aimed to investigate the mechanisms of abnormal expression of atrial potassium channel proteins Kv1.5, Kv4.2, and Kv4.3 in type 2 diabetic mice. METHODS:The db/db mice and their control littermates were set as the T2DM group and the control (Con) group. Acetylcholine-calcium chloride was injected via the tail veins to induce AF. HL-1 cells were cultured with normal or high-glucose medium and treated with or without Dimethyl Fumarate (DMF) or hemin in vitro. The expression and cellular localization of proteins were evaluated by western blotting and immunofluorescence. RESULTS:The results showed that high glucose impaired the expression of Kv1.5, Kv4.2 and Kv4.3 proteins both in vivo and in vitro, in parallel with a significant down-regulation of polo-like kinase 2 (PLK2), nuclear factor erythroid 2-related factor 2 (Nrf2), p-Nrf2 and heme oxygenase-1 (HO-1) proteins. Moreover, immunofluorescence revealed that both high glucose and PLK2 knockdown could result in reduced Nrf2 and p-Nrf2 expression and subsequent nuclear translocation. While overexpression of PLK2, treatment with DMF, an agonist of Nrf2, or hemin, an inducer of HO-1, could restore the reduction of Kv1.5, Kv4.2 and Kv4.3 proteins caused by high glucose. CONCLUSION:Diabetes reduces the expression of Kv1.5, Kv4.2 and Kv4.3 proteins in atrial cells through inhibition of PLK2/Nrf2/HO-1 pathway, thereby leading to the increased susceptibility to AF in T2DM.

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Circular RNAs (circRNAs) have been identified as important regulators in different developmental processes and disease pathogenesis. The loop structure of circRNAs makes them very stable in different conditions and microenvironments. circRNAs can affect microRNA (miRNA) and RNA binding protein (RBP) activity, encode functional proteins and regulate gene transcription. Recently, two circNFIX variants derived from the same gene, the Nuclear Factor I X (NFIX) gene, were determined as participants in the pathological processes of various diseases such as heart diseases and cancers. Both circNFIX variants are exonic circular RNAs and mainly function by sponging miRNAs. In this review, we summarize the current knowledge on circRNAs, elucidate the origins and properties of two circNFIX variants, explore the roles of two circNFIX variants in different diseases, and present clinical perspectives.

The association of a combination of the TyG index and obesity markers, specifically waist circumference (WC), with cognitive function is unknown. This research investigated the relationship between TyG-WC measurements and cognitive impairment in a low-income population in China; moreover, this study evaluated the role of diabetes mellitus and body mass index (BMI) in modulating this relationship. 1125 eligible individuals aged ≥ 60 years participated in this study. The TyG index and obesity indicators (BMI, WC, and waist-to-height ratio) were calculated for individual participants and categorized into quartiles. Multivariate logistic regression analysis was used to evaluate the correlation between TyG-WC values and cognitive impairment; the possibility of a nonlinear relationship was explored using constrained cubic spline analysis. The participants were divided into different groups according to their diabetes status and BMI category for subgroup analyses. Linear regression was used to investigate the correlation between TyG-WC values and MMSE scores. The prevalence of cognitive impairment in the study participants was 47.3

Purpose: The aim of this study was to investigate the effects and mechanisms of SGLT2 inhibitor empagliflozin on diabetic coronary function. Methods: A rat diabetic model was established by injection of streptozotocin. Rats in the treated group were administered empagliflozin by gavage and rat coronary vascular tensions were measured after eight weeks. Large conductance calcium activated K+ channel currents were recorded using a patch clamp technique, while human coronary artery smooth muscle cells were used to explore the underlying mechanisms. Results: After incubation with empagliflozin (10, 30, 100, 300, 1000 mu mol/L), the Delta relaxation % of rat coronary arteries were 2.459 +/- 1.304, 3.251 +/- 1.119, 6.946 +/- 3.407, 28.36 +/- 11.47, 86.90 +/- 3.868, respectively. Without and with empagliflozin in the bath solution, BK channel opening probabilities at a membrane potential of +60 mV were 0.0458 +/- 0.0517 and 0.3413 +/- 0.2047, respectively (p < 0.05, n = 4 cells). After incubation with iberiotoxin, the Delta tensions of rat coronary arteries in the control (Ctrl), untreated (DM), low empagliflozin (10 mg/kg/d)-treated (DM+L-EMPA) and high empagliflozin (30mg/kg/d)-treated (DM+H-EMPA) group were 103.20 +/- 5.85, 40.37 +/- 22.12, 99.47 +/- 28.51, 78.06 +/- 40.98, respectively (p < 0.01 vs Ctrl, n = 3-7; p < 0.001 vs DM+L-EMPA, n = 5-7). Empagliflozin restored high glucose-induced downregulation of Sirt1, Nrf2, and BK-beta 1, while the effect of empagliflozin disappeared in the presence of EX-527, a Sirt1 selective inhibitor. Conclusion: Empagliflozin has a vasodilation effect on the coronary arteries in a concentration-dependent manner and can activate BK channels via the Sirt1-Nrf2 mechanism.

Background: Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) either fail to respond to initial standard therapy or experience a relapse, resulting in a dismal prognosis. Non-germinal center B-cell-like (GCB) DLBCL has an even worse outcome. The early data of covalent bruton's tyrosine kinase inhibitor (cBTKi) in R/R non-GCB DLBCL showed an overall response rate (ORR）of 20-40%. Rocbrutinib (LP-168) is a highly selective, new-generation BTKi with superb bioavailability and unique dual binding mode: covalent binding, otherwise non-covalent with C481 mutation. Here, we report the safety and efficacy of Rocbrutinib monotherapy in the R/R non-GCB DLBCL from an ongoing phase 1 study (NCT04993690) in B-cell malignancies. Methods: Patients（age>=18 years） with R/R DLBCL after ≥2 prior lines of therapies including ≥1 anti-CD20 antibody-containing regimen were enrolled. Adverse events (AEs) were graded per CTCAE v5.0 and responses of patients with R/R non-GCB DLBCL were assessed according to the Lugano 2014 response criteria. Results: Between 30 July 2021 and 31 May 2024, 33 efficacy evaluable patients with R/R non-GCB DLBCL were enrolled. They received daily treatment of rocbrutinib at 100mg (n=2), 150mg (n=23), 200mg (n=6) and 300mg (n=2) respectively till progressive disease or unacceptable toxicities. The median age was 59 (range, 21-73) years old; 20 (60.6%) were male. One-third of the patients had at least one lesion of >=5cm in diameter. 51.5% had intermediate to high-risk disease per International Prognostic Index (IPI). The median line of prior therapies was 2 (range, 2-5) and most patients (87.9%) were refractory to any prior treatments. The most common treatment emergent adverse events (TEAEs) (occurring in ≥20% patients) were neutrophil count decreased or neutropenia (63.6%), white blood cell count decreased (45.5%), platelet count decreased or thrombocytopenia (45.5%), anemia (30.3%), petechiae (30.3%), lymphocyte count increased (27.3%), lymphocyte count decreased (27.3%), hypertriglyceridemia (24.2%), hyperuricemia (24.2%) and serum creatinine increased (21.2%), most of which were grade 1. 14 (42.4%) patients experienced ≥grade 3 TEAEs . Serious AEs (lung infection, grade 3) occurred in 2 (6.1%) patients. 8 patients (24.2%) had dose interruptions due to AEs, but no AE has led to dose adjustment or drug discontinuation. AE leading to death was reported for one patient (lung infection, not related to rocbrutinib). Of 33 efficacy evaluable patients with median follow-up of 6.7 months (range: 1.8-26.9), 20 (60.6%) achieved response including 11 (33.3%) complete response (CR). For the 10 patients who had received ≥3 lines of therapy previously, the ORR and CR rate was 90% and 50%, respectively. Notably, the response rate of rocbrutinib in patients refractory to last prior therapy (n=28) was 57.1%, with CR rate of 28.6%. As of data cut-off, duration of response (DOR), progression-free survival (PFS), and overall survival (OS) are not mature yet. Conclusion: In conclusion, rocbrutinib has demonstrated a high CR and response rate in heavily pre-treated R/R non-GCB DLBCL with favorable safety profiles. Based on the encouraging data, rocbrutinib has received breakthrough therapy designation for the treatment of patients with non-GCB DLBCL who have received at least 2 lines of prior therapies from China CDE (center of drug evaluation). A Phase 1b study of rocbrtuinib in combination with R-CHOP for untreated non-GCB DLBCL is also ongoing (NCT06251180).

The global incidence and prevalence of arrhythmias are continuously increasing. However, the precise mechanisms of underlying arrhythmogenesis and the optimal measures for effective treatment remain incompletely understood. The inducible form of heme oxygenase, known as heme oxygenase-1 (HO-1), is recognized as a potent antioxidant molecule capable of exerting anti-inflammatory and anti-apoptotic effects. Recent research indicates that HO-1 plays a role in preventing arrhythmias by mitigating cardiac remodeling, including electrical remodeling, ion remodeling, and structural remodeling. This review aimed to consolidate current knowledge regarding the involvement of HO-1 in arrhythmias and elucidate its underlying mechanisms of action.

Currently, glycated hemoglobin A1c (HbA1c) has been widely used to assess the glycemic control of patients with diabetes. However, HbA1c has certain limitations in describing both short-term and long-term glycemic control. To more accurately evaluate the glycemic control of diabetes patients, the continuous glucose monitoring (CGM) technology has emerged. CGM technology can provide robust data on short-term glycemic control and introduce new monitoring parameters such as time in range, time above range, and time below range as indicators of glycemic fluctuation. These indicators are used to describe the changes in glycemic control after interventions in clinical research or treatment modifications in diabetes patient care. Recent studies both domestically and internationally have shown that these indicators are not only associated with microvascular complications of diabetes mellitus but also closely related to cardiovascular disease complications and prognosis. Therefore, this article aims to comprehensively review the association between CGM-based glycemic parameters and cardiovascular disease complications by analyzing a large number of domestic and international literature. The purpose is to provide scientific evidence and guidance for the standardized application of these indicators in clinical practice, in order to better evaluate the glycemic control of diabetes patients and prevent the occurrence of cardiovascular disease complications. This research will contribute to improving the quality of life for diabetes patients and provide important references for clinical decision-making.

Background: High-dose methotrexate (HD-MTX)-based chemotherapy followed by whole-brain radiotherapy is the most commonly used approach for patients with newly diagnosed Primary central nervous system lymphoma (PCNSL). However, HD-MTX is a hospital-based drug requiring adequate fluid management and may not be well tolerated in elderly patients with an increased prevalence of comorbid illness. Fotemustine is a third-generation nitrosourea, which is easily penetrated through the blood-brain barrier (BBB) due to its high fat-soluble and low molecular weight, and is indicated for primary brain tumors and disseminated malignant melanoma. Our Center has innovatively conducted three prospective clinical trials using fotemustine-based regimens for the treatment of newly diagnosed PCNSL patients (Wu J et al, J Neurooncol 2018, Wu J et al, Cancer Biol Med 2021, Zhang X et al, ASH 2022), the results of the above studies suggest that the fotemustine-containing regimen has efficacy in the treatment of newly diagnosed PCNSL and has few toxic side effects. Therefore, this study increased the sample size, extended the follow-up time and set up a control group to analyze the efficacy and safety of fotemustine-containing regimens compared with HD-MTX-containing regimens in the treatment of newly diagnosed PCNSL patients. Methods: From April 2011 to December 2021, 114 patients with newly diagnosed PCNSL who received HD-MTX-containing regimens (HD-MTX plus cytarabine [HD-MA], rituximab, HD-MTX plus temozolomide [R-MT]) or fotemustine-containing regimens (fotemustine, teniposide plus dexamethasone [FTD], fotemustine, temozolomide plus dexamethasone [FVD], rituximab, fotemustine, pemetrexed plus dexamethasone [RFPD]) were retrospectively analyzed in this study. Among them, 27 and 15 patients received the HD-MA and R-MT protocol, respectively; 15, 12, and 45 patients received the FTD, FVD and R-FPD protocol, respectively. Results: Of the 114 patients, the objective response rate (ORR) did not differ significantly between the HD-MTX-containing group and the fotemustine-containing group (67% vs 68%, P=0.879). The median follow-up time for 114 patients was 28.5 months (range 2-122 months). Neither the progression free survival (PFS) (P=0.783) nor the overall survival (OS) (P=0.918) exhibited remarkably difference between HD-MTX-containing group and fotemustine-containing group. Notably, we noted that patients treated with HD-MTX-containing regimens experienced more serious adverse events, including leukopenia, anemia, thrombocytopenia, digestive tract toxicity, and mucosis (all P < 0.05) than those undergoing fotemustine-containing therapeutics. Conclusion: Fotemustine-based chemotherapeutics conferred a safer effect on newly-diagnosed PCNSL patients compared with HD-MTX-containing regimens together with comparable efficiency.