Mitofusin 2 (MFN2) residing on the outer mitochondrial membrane is a pivotal factor participating in mitochondrial fusion and maintaining mitochondrial morphology. Due to its multifaceted cellular functions, MFN2 is implicated in the pathogenesis of diverse maladies, notably type 2 Charcot-Marie-Tooth disease, which has catalyzed a surge in pharmaceutical endeavors directed towards MFN2. This article reviews the function of MFN2 and its role in a variety of diseases, outlines the current status of drug discovery against MFN2, and summarizes potential drug molecules currently in preclinical research, aiming to provide some reference for the research and development of drugs and therapies targeting MFN2.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective To summarize the clinical effect and adverse reactions of avatrombopag combined with tacrolimus in the treatment of elderly patient with refractory severe aplastic anemia. Methods An elderly patient with refractory severe aplastic anemia was treated with avatrombopag and tacrolimus, and the literature review on the mechanism of action and safety of avatrombopag and tacrolimus was conducted. Results The patient was treated with a combination of cyclosporine, testosterone undecanoate, and itraconazole for 6 months without success, and developed liver and kidney dysfunction. The medication was discontinued, and the patient was treated with a combination of avatrombopag (20 mg, once per day) and tacrolimus (1 mg, twice per day). After 9 months of treatment, the patient's platelet count increased to 54×10⁹/L, the hemoglobin increased to 124 g/L, the white blood cells increased to 8.23×10⁹/L, liver and kidney function also returned to normal level, and no other adverse reactions such as thrombotic events were observed. After treatment, CD4/CD8 decreased, CD8⁺ T cells increased, and the proportion of Treg cells increased as well. Conclusion The combination of avatrombopag and tacrolimus is effective and well tolerated in the treatment of elderly patient with refractory aplastic anemia, but the long-term follow-up observation and continued accumulation of cases are still needed in the future.

Objective The family reconstruction method was used to establish paternity index algorithm for uncle-nephew relationships between two full sibling uncles and one nephew.Methods According to Mendelian genetic law,the family of two known full-sib uncles and one nephew were reconstructed according to the relationship between uncle and nephew,and the test hypothesis was established between two full sibling uncles and one nephew as the uncle-nephew relationship and unrelated individuals,and the paternity index of the uncle-nephew relationship between two full sibling uncles and one nephew was calculated by using Excel.Results Among the 99 genotypic combinations between two full sibling uncles and one nephew,91 of which were consistent with the genetic rules of uncle-nephew relationships,while 8 of which were not.a stepwise mutation model was introduced in the situations that do not conform to the genetic laws of uncle-nephew relationships.The paternity index of uncle-nephew relationship between two full sibling uncles and one nephew can be calculated using Excel.Conclusion The uncle-nephew testing involved by two full sibling uncles makes use of the role of the assistant,and the paternity index of the obtained uncle-nephew relationship is higher than that between two known full-siblings alone and their nephew,which has a good practical value in helping the appraiser to draw a clear appraisal opinion.