High-altitude retinopathy(HAR)is a retinal vascular disorder induced by exposure to high-altitude environments. With the increasing popularity of high-altitude travel, mountaineering, and special occupational activities, worldwide, the incidence of HAR has risen, particularly among individuals with rapid or short-term exposure to elevated altitudes. Most cases of HAR are self-limiting and gradually resolve with descent to lower altitudes. However, severe cases may result in permanent visual function impairment if not recognized and managed promptly. This review systematically summarizes the epidemiology, diagnostic progress, pathogenesis, and prevention and treatment strategies of HAR, with particular emphasis on hypoxia-associated molecular pathways involved in retinal damage, and evaluates current evidence for clinical interventions. Deepened understanding of its pathological mechanisms and clinical management strategies facilitates early identification, targeted intervention, and ocular health protection for populations exposed to high altitudes.

Thymocyte selection-associated high mobility group box (TOX), a member of the high mobility group protein super-family, plays an important role in T cell development, functional maintenance, and exhaustion. It has been recently found that TOX exerts critical immunoregulatory functions during pathogen infections, and TOX expression is strongly associated with the intensity and tolerance of host immune responses. This review systematically summarizes the structural and functional features of TOX and focuses on its expression dynamics, mechanisms of action, and immunomodulatory effects during viral, bacterial, and parasitic infections, which provides a theoretical support to better understanding of the role of TOX in infectious diseases and provides new insights into development of potential immunotherapeutic strategies targeting TOX.

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

Objective To investigate the vasodilatory effect of luteolin on isolated denuded-endothelium rat thoracic aorta(DRTA)vascular rings,and the mechanistic role of the Kv7 ion channel.Methods The tension of DRTA vascular rings was measured using an ex vivo tissue perfusion muscle-tone detection system.DRTA vascular rings were pre-contracted with 60 mmol/L KCl or 0.3 μmol/L U46619,and the effect of luteolin on vascular-ring relaxation was observed at 1,3,10,30,100 and 300 μmol/L.The effects of 4-AP,XE-991,and ML213 on luteolin-induced vasodilation were also observed.The effect of luteolin on KCNQ1-KCNQ5 expression in the thoracic aorta was detected by real-time fluorescence quantitative polymerase chain reaction.Expression levels of Kv7.1 and Kv7.4 proteins in the DRTA were detected by Western blot.Results(1)The luteolin-induced maximum vasodilation rates in DRTA pre-contracted with 60 mmol/L KCl and 0.3 μmol/L U46619 were(97.67±8.51)％and(98.42±9.76)％,respectively.The vasodilation effect was concentration-dependent(P＜0.05).(2)4-AP(3 mmol/L)significantly reduced the vasodilatory effect of luteolin on DRTA vascular rings at 10,30,and 100 μmol/L(P＜0.05),and XE-991(3 μmol/L)significantly reduced the effect of luteolin at 30 and 100 μmol/L(P＜0.05),while ML213(1 μmol/L)significantly enhanced the vasodilatory effect of luteolin at 3,10,and 30 μmol/L(P＜0.05).(3)The relative gene expression levels of each subtype of Kv7 channel in normal DRTA were KCNQ1＞KCNQ5＞KCNQ4＞KCNQ3＞KCNQ2,with KCNQ1 being the most highly expressed.(4)Luteolin significantly enhanced the expression levels of KCNQ1 at 3,10,30,and 100 μmol/L,KCNQ2 at 1,3,10,30,and 100 μmol/L(P＜0.05),KCNQ3 at 3,10,30,and 100 μmol/L,and KCNQ4 at 10,30,and 100 μmol/L(P＜0.05),but did not significantly enhance the expression of KCNQ5 at 1,3,10,30,or 100 μmol/L(P＞0.05).(5)Luteolin significantly increased the expression of Kv7.1 protein in DRTA at 3,10,30,and 100 μmol/L(P＜0.05)and the expression of Kv7.4 at 10,30,and 100 μmol/L(P＜0.05).Conclusions Luteolin-induced dilation of DRTA vascular rings may be related to the enhanced gene expression of KCNQ1-4 and increased expression of Kv7.1 and Kv7.4 channel proteins.

Objective:To evaluate the efficacy and safety of the Chi-BEAM regimen (chidamide combined with carmustine, etoposide, cytarabine, and melphalan) followed by autologous hematopoietic stem cell transplantation (ASCT) in patients with high-risk or relapsed/refractory lymphoma.Methods:This retrospective case series included 78 patients with newly treated high-risk or relapsed/refractory lymphoma who underwent ASCT with the Chi-BEAM conditioning regimen in the Department of Hematology, the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), from June 2021 to May 2024. Descriptive statistics were employed to evaluate clinical characteristics, efficacy, and adverse events. The Kaplan-Meier method was applied to calculate cumulative progression-free survival (PFS) and overall survival (OS) rates.Results:The median age of the 78 evaluable patients was 47 years (range 16-68), with 8 patients (10.3%) aged ≥60 years. At the first post-transplant assessment (3 months), the objective response rate was 94.9% (74/78). The median follow-up was 20.1 months (range 2.9-44.9). The median PFS time was 20.1 months (range 1.6-45.1), with a 2-year cumulative PFS rate of 81.8%. The median OS time was 20.6 months (range 3.1-45.1), with a cumulative 2-year OS rate of 93.2%. The regimen was well-tolerated; mild-to-moderate hypocalcemia within 1 week post-infusion and transient mild erythrocyturia on the infusion day were the primary adverse reactions.Conclusion:The Chi-BEAM regimen combined with ASCT demonstrates both safety and clinical benefit in patients with high-risk or relapsed/refractory lymphoma.

Objective:To evaluate the efficacy and safety of the pegaspargase, etoposide, methotrexate, and dexamethasone (PEMD) regimen in patients with early-stage nonupper respiratory digestive tract or advanced extranodal natural killer/T-cell lymphoma (ENKTL) .Methods:This retrospective analysis included 38 patients with newly diagnosed early-stage non-upper respiratory digestive tract or advanced ENKTL who received PEMD regimen for induction chemotherapy at the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2022. Survival outcomes and prognostic factors were examined by Kaplan-Meier, and the Log-rank test was used to compare survival.Results:The study population had a median age of 48 years (range, 26-72 years) and included 30 males (78.9%) and 8 females (21.1%). 7 patients’ age >60 years (18.4%). The Eastern Cooperative Oncology Group (ECOG) performance score was >1 in 7 patients (18.4%) ; 20 patients (52.6%) had elevated lactate dehydrogenase levels; and 37 patients (97.4%) exhibited extranodal involvement. Using the Ann Arbor staging system, 37 patients (97.4%) were classified as stage Ⅲ-Ⅳ. The median number of treatment cycles was 5 (1-6), and the median follow-up duration was 60 months (24 - 101 months). Interim efficacy assessment revealed an overall response rate of 52.7%. At 2 and 4 years, the progression-free survival (PFS) rates were 34.2% (95% CI 22.0%-53.2%) and 25.5% (95% CI 14.7%-44.4%), respectively, and the overall survival rates were 50.0% (95% CI 36.4%-68.7%) and 45.5% (95% CI 31.4%-65.7%), respectively. The risk factors for worse PFS were ECOG performance score >1 [ HR=3.711 (95% CI 1.494-9.218), P=0.005]; bone marrow infiltration [ HR=2.251 (95% CI 1.026 - 4.938), P=0.043]; and Prognostic Index for Natural Killer/T-Cell Lymphoma score of 3 - 5 [ HR=2.350 (95% CI 1.009 - 5.476), P=0.048]. Multivariate analysis identified ECOG performance score >1 as an independent risk factor for PFS [ HR=7.971 (95% CI 2.222 - 28.591), P=0.001]. The main adverse effect was anemia in 31 patients (81.6%) . Conclusion:The PEMD regimen was safe and effective for patients with newly diagnosed early-stage non-upper respiratory digestive tract or advanced ENKTL.

Objective To investigate the vasodilatory effect of luteolin on isolated denuded-endothelium rat thoracic aorta(DRTA)vascular rings,and the mechanistic role of the Kv7 ion channel.Methods The tension of DRTA vascular rings was measured using an ex vivo tissue perfusion muscle-tone detection system.DRTA vascular rings were pre-contracted with 60 mmol/L KCl or 0.3 μmol/L U46619,and the effect of luteolin on vascular-ring relaxation was observed at 1,3,10,30,100 and 300 μmol/L.The effects of 4-AP,XE-991,and ML213 on luteolin-induced vasodilation were also observed.The effect of luteolin on KCNQ1-KCNQ5 expression in the thoracic aorta was detected by real-time fluorescence quantitative polymerase chain reaction.Expression levels of Kv7.1 and Kv7.4 proteins in the DRTA were detected by Western blot.Results(1)The luteolin-induced maximum vasodilation rates in DRTA pre-contracted with 60 mmol/L KCl and 0.3 μmol/L U46619 were(97.67±8.51)％and(98.42±9.76)％,respectively.The vasodilation effect was concentration-dependent(P＜0.05).(2)4-AP(3 mmol/L)significantly reduced the vasodilatory effect of luteolin on DRTA vascular rings at 10,30,and 100 μmol/L(P＜0.05),and XE-991(3 μmol/L)significantly reduced the effect of luteolin at 30 and 100 μmol/L(P＜0.05),while ML213(1 μmol/L)significantly enhanced the vasodilatory effect of luteolin at 3,10,and 30 μmol/L(P＜0.05).(3)The relative gene expression levels of each subtype of Kv7 channel in normal DRTA were KCNQ1＞KCNQ5＞KCNQ4＞KCNQ3＞KCNQ2,with KCNQ1 being the most highly expressed.(4)Luteolin significantly enhanced the expression levels of KCNQ1 at 3,10,30,and 100 μmol/L,KCNQ2 at 1,3,10,30,and 100 μmol/L(P＜0.05),KCNQ3 at 3,10,30,and 100 μmol/L,and KCNQ4 at 10,30,and 100 μmol/L(P＜0.05),but did not significantly enhance the expression of KCNQ5 at 1,3,10,30,or 100 μmol/L(P＞0.05).(5)Luteolin significantly increased the expression of Kv7.1 protein in DRTA at 3,10,30,and 100 μmol/L(P＜0.05)and the expression of Kv7.4 at 10,30,and 100 μmol/L(P＜0.05).Conclusions Luteolin-induced dilation of DRTA vascular rings may be related to the enhanced gene expression of KCNQ1-4 and increased expression of Kv7.1 and Kv7.4 channel proteins.

Objective:To evaluate the efficacy and safety of the pegaspargase, etoposide, methotrexate, and dexamethasone (PEMD) regimen in patients with early-stage nonupper respiratory digestive tract or advanced extranodal natural killer/T-cell lymphoma (ENKTL) .Methods:This retrospective analysis included 38 patients with newly diagnosed early-stage non-upper respiratory digestive tract or advanced ENKTL who received PEMD regimen for induction chemotherapy at the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2022. Survival outcomes and prognostic factors were examined by Kaplan-Meier, and the Log-rank test was used to compare survival.Results:The study population had a median age of 48 years (range, 26-72 years) and included 30 males (78.9%) and 8 females (21.1%). 7 patients’ age >60 years (18.4%). The Eastern Cooperative Oncology Group (ECOG) performance score was >1 in 7 patients (18.4%) ; 20 patients (52.6%) had elevated lactate dehydrogenase levels; and 37 patients (97.4%) exhibited extranodal involvement. Using the Ann Arbor staging system, 37 patients (97.4%) were classified as stage Ⅲ-Ⅳ. The median number of treatment cycles was 5 (1-6), and the median follow-up duration was 60 months (24 - 101 months). Interim efficacy assessment revealed an overall response rate of 52.7%. At 2 and 4 years, the progression-free survival (PFS) rates were 34.2% (95% CI 22.0%-53.2%) and 25.5% (95% CI 14.7%-44.4%), respectively, and the overall survival rates were 50.0% (95% CI 36.4%-68.7%) and 45.5% (95% CI 31.4%-65.7%), respectively. The risk factors for worse PFS were ECOG performance score >1 [ HR=3.711 (95% CI 1.494-9.218), P=0.005]; bone marrow infiltration [ HR=2.251 (95% CI 1.026 - 4.938), P=0.043]; and Prognostic Index for Natural Killer/T-Cell Lymphoma score of 3 - 5 [ HR=2.350 (95% CI 1.009 - 5.476), P=0.048]. Multivariate analysis identified ECOG performance score >1 as an independent risk factor for PFS [ HR=7.971 (95% CI 2.222 - 28.591), P=0.001]. The main adverse effect was anemia in 31 patients (81.6%) . Conclusion:The PEMD regimen was safe and effective for patients with newly diagnosed early-stage non-upper respiratory digestive tract or advanced ENKTL.

Objective:To evaluate the efficacy and safety of the Chi-BEAM regimen (chidamide combined with carmustine, etoposide, cytarabine, and melphalan) followed by autologous hematopoietic stem cell transplantation (ASCT) in patients with high-risk or relapsed/refractory lymphoma.Methods:This retrospective case series included 78 patients with newly treated high-risk or relapsed/refractory lymphoma who underwent ASCT with the Chi-BEAM conditioning regimen in the Department of Hematology, the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), from June 2021 to May 2024. Descriptive statistics were employed to evaluate clinical characteristics, efficacy, and adverse events. The Kaplan-Meier method was applied to calculate cumulative progression-free survival (PFS) and overall survival (OS) rates.Results:The median age of the 78 evaluable patients was 47 years (range 16-68), with 8 patients (10.3%) aged ≥60 years. At the first post-transplant assessment (3 months), the objective response rate was 94.9% (74/78). The median follow-up was 20.1 months (range 2.9-44.9). The median PFS time was 20.1 months (range 1.6-45.1), with a 2-year cumulative PFS rate of 81.8%. The median OS time was 20.6 months (range 3.1-45.1), with a cumulative 2-year OS rate of 93.2%. The regimen was well-tolerated; mild-to-moderate hypocalcemia within 1 week post-infusion and transient mild erythrocyturia on the infusion day were the primary adverse reactions.Conclusion:The Chi-BEAM regimen combined with ASCT demonstrates both safety and clinical benefit in patients with high-risk or relapsed/refractory lymphoma.

Background::Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons.Methods::We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT.Results::Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9-34.5%) and 43.8% (95% CI, 28.3-59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death.Conclusion::The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons.Trial Registration::ClinicalTrials.gov, NCT02879526.