Objective The aim of this study was to investigate the effect of p38 on stem cell maintenance of pancreatic cancer. Methods Human pancreatic cancer cells PANC-1 were treated with different concentrations of 5-fluorouracil(5-FU)(0.5×IC₅₀, IC₅₀, and 2×IC₅₀) for 24 hours, and VX-702 (p38 phosphorylation inhibitor) was added, and the cells were inoculated in 6-well culture dishes with ultra-low adhesion to observe the changes of sphere tumors. The expression levels of cyclin-dependent kinase 2(CDK2), cyclin B1 and D1, Octamer-binding transcription factor 4(OCT4), SRY-box transcription factor 2(SOX2), Nanog and p38 were measured by Western blot. The mRNA expression levels of p38, OCT4, Nanog and SOX2 were tested by RT-PCR. Cell cycle, apoptosis, and the proportion of CD44⁺CD133⁺PANC-1 cells were evaluated by flow cytometry. Results The results showed that 5-FU inhibited the formation of tumor spheres in PANC-1 cells, increased CD44⁺CD133⁺cell fragments, down-regulated the expression of OCT4, Nanog and SOX2, and inhibited the stemness maintenance of PANC-1 tumor stem cells. Phosphorylation of PANC-1 cells was inhibited by a highly selective p38 MAPK inhibitor, VX-702(p38 mitogen-activated protein kinase inhibitor), which had the same effect as 5-FU treatment. When VX-702 combined with 5-FU was used to treat PANC-1 cells, the therapeutic effect was enhanced. Conclusion p38 inhibitors decreased PANC-1 cell activity and increased cell apoptosis. p38 inhibitors inhibit the stemness maintenance of pancreatic cancer stem cells.
Humans ; Phosphorylation/drug effects* ; Cell Line, Tumor ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors* ; Neoplastic Stem Cells/metabolism* ; Drug Resistance, Neoplasm/drug effects* ; Fluorouracil/pharmacology* ; Pancreatic Neoplasms/pathology* ; Apoptosis/drug effects* ; SOXB1 Transcription Factors/genetics* ; Octamer Transcription Factor-3/genetics*

Spinal cord injury (SCI) is a neurological disorder that occurs after a direct or indirect violent injury to the spinal cord, often resulting in sensory and motor dysfunction below the injury level. Patients with SCI are often paralyzed in bed due to impaired nerve function and there has been no effective treatment for limb paralysis after SCI. As a cutting-edge technology with a multidisciplinary integration of neuroscience, computer science, biological engineering, electronic engineering and psychology, brain-computer interface (BCI) provides a new program for the rehabilitation of SCI patients by changing the traditional brain signal output pathways and realizing the direct connection between the brain and external devices. In order to further understand the application of BCI in SCI rehabilitation, the authors reviewed the classification, basic principles of BCI and the research progress of the application of BCI in SCI rehabilitation, which may provide references for the clinical transformation of BCI.

Objective:To evaluate the efficacy of cyclophosphamide in patients with T-cell large granular lymphocytic leukemia (T-LGLL) and the maintenance of treatment-free remission (TFR) following drug discontinuation.Methods:Clinical data were collected from 37 patients with T-LGLL who received oral cyclophosphamide at the Regenerative Medicine Clinic of the Institute of Hematology and Blood Diseases Hospital between June 2019 and March 2024. Patient clinical characteristics, treatment efficacy, and long-term TFR were analyzed.Results:The median age of the 37 patients was 60 years (range: 37-86), and 22 (59.5%) were male. Anemia was observed in 30 patients (81.1%), and 28 (75.7%) met the diagnostic criteria for secondary pure red cell aplasia. Neutropenia occurred in 15 patients (40.5%), lymphocytosis in 11 (29.7%), and thrombocytopenia in three (8.1%). Sixteen patients (43.2%) had not received prior immunosuppressive therapy (treatment-naive group), while 21 patients (56.8%) were refractory to or had relapsed after immunosuppressive treatment (refractory/relapsed group). All patients met the treatment criteria and received oral cyclophosphamide at doses of 50-100 mg/day. Among the 36 evaluable patients, hematologic remission was achieved in 25 (69.4%), with a median time of 2.0 months (range: 0.7-7.0). There was no statistically significant difference in remission rates between the treatment-naive and refractory/relapsed groups (68.5% vs. 66.7%, P=0.589). Among the 25 patients who achieved hematologic remission, 24 discontinued cyclophosphamide. With a median follow-up of 39.0 months (range: 8.0-56.0), the median TFR duration was not reached. The estimated TFR rates were (90.87± 6.16) % at 12 months and (75.72±11.04) % at 36 months. No significant difference in TFR was observed between the treatment-naive and refractory/relapsed groups ( P=0.451) . Conclusion:Oral cyclophosphamide is effective in the treatment of T-LGLL, and patients may maintain long-term TFR following drug discontinuation.

Objective:To investigate the optical coherence tomography (OCT) imaging features of bullous pemphigoid (BP) and pemphigus.Methods:A total of 23 patients with BP and 18 with pemphigus diagnosed according to clinical manifestations, histopathological and immunological features were collected from Wuhan No.1 Hospital from January to June 2024. OCT imaging was performed in 41 patients to observe the blisters at the lesion sites and their anatomic locations (intraepidermal or subepidermal), intravesicular inflammatory cells and fibrin deposits, dilated vessels in the upper dermis, as well as skin adjacent to the lesions.Results:Among the 23 patients with BP and 18 patients with pemphigus (including 12 with pemphigus vulgaris and 6 with pemphigus foliaceus), there were 20 males and 21 females, and their ages at onset ranged from 20 to 89 years. OCT imaging of blisters in patients with BP showed subepidermal oval to round hyporeflective liquid-filled areas containing highly refractive inflammatory cells and fibrin deposits, with dilated vessels in the upper dermis, while OCT imaging of blisters in patients with pemphigus showed intraepidermal blisters with a few inflammatory cells; the OCT imaging features of both BP and pemphigus were similar to their corresponding histopathological features. The detection rates of intravesicular inflammatory cells and fibrin deposition were significantly higher in the patients with BP (82.61% [19/23], 60.87% [14/23], respectively) than in those with pemphigus (44.44% [8/18], 11.11% [2/18]; χ2 = 6.54, 10.51, P = 0.011, 0.001, respectively). In the OCT images of normal skin adjacent to blisters, subclinical fissures were detected in 17.39% (8/46) of patients with BP and 25.00% (9/36) of patients with pemphigus. Conclusion:OCT imaging could accurately locate the blisters and potential subclinical lesions in normal skin adjacent to blisters in patients with BP and pemphigus, which is helpful for the early auxiliary diagnosis of these two diseases.

Radiation-induced esophageal injury (RIEI) is a frequent complication following radiotherapy for thoracic and head-neck malignancies, which may lead to severe sequelae including esophageal stricture and perforation, adversely affecting patients' quality of life and therapeutic outcomes. With advancements in radiotherapy techniques — particularly the adoption of unconventional fractionation regimens, concurrent chemoradiotherapy, and combined molecular targeted / immunotherapy — the incidence of RIEI has been increasing. In this review, recent advances in understanding the pathogenesis, clinical manifestations, risk factors, and management strategies for RIEI were comprehensively summarized. Current therapeutic approaches have evolved beyond conventional anti-inflammatory and nutritional support to include novel interventions such as targeted therapy, free radical scavengers, and microbiota modulation, etc. Future research should prioritize the development of optimized, individualized prevention and treatment protocols to mitigate RIEI risk and improve patient prognosis.

Objective:To investigate the optical coherence tomography (OCT) imaging features of bullous pemphigoid (BP) and pemphigus.Methods:A total of 23 patients with BP and 18 with pemphigus diagnosed according to clinical manifestations, histopathological and immunological features were collected from Wuhan No.1 Hospital from January to June 2024. OCT imaging was performed in 41 patients to observe the blisters at the lesion sites and their anatomic locations (intraepidermal or subepidermal), intravesicular inflammatory cells and fibrin deposits, dilated vessels in the upper dermis, as well as skin adjacent to the lesions.Results:Among the 23 patients with BP and 18 patients with pemphigus (including 12 with pemphigus vulgaris and 6 with pemphigus foliaceus), there were 20 males and 21 females, and their ages at onset ranged from 20 to 89 years. OCT imaging of blisters in patients with BP showed subepidermal oval to round hyporeflective liquid-filled areas containing highly refractive inflammatory cells and fibrin deposits, with dilated vessels in the upper dermis, while OCT imaging of blisters in patients with pemphigus showed intraepidermal blisters with a few inflammatory cells; the OCT imaging features of both BP and pemphigus were similar to their corresponding histopathological features. The detection rates of intravesicular inflammatory cells and fibrin deposition were significantly higher in the patients with BP (82.61% [19/23], 60.87% [14/23], respectively) than in those with pemphigus (44.44% [8/18], 11.11% [2/18]; χ2 = 6.54, 10.51, P = 0.011, 0.001, respectively). In the OCT images of normal skin adjacent to blisters, subclinical fissures were detected in 17.39% (8/46) of patients with BP and 25.00% (9/36) of patients with pemphigus. Conclusion:OCT imaging could accurately locate the blisters and potential subclinical lesions in normal skin adjacent to blisters in patients with BP and pemphigus, which is helpful for the early auxiliary diagnosis of these two diseases.

Spinal cord injury (SCI) is a neurological disorder that occurs after a direct or indirect violent injury to the spinal cord, often resulting in sensory and motor dysfunction below the injury level. Patients with SCI are often paralyzed in bed due to impaired nerve function and there has been no effective treatment for limb paralysis after SCI. As a cutting-edge technology with a multidisciplinary integration of neuroscience, computer science, biological engineering, electronic engineering and psychology, brain-computer interface (BCI) provides a new program for the rehabilitation of SCI patients by changing the traditional brain signal output pathways and realizing the direct connection between the brain and external devices. In order to further understand the application of BCI in SCI rehabilitation, the authors reviewed the classification, basic principles of BCI and the research progress of the application of BCI in SCI rehabilitation, which may provide references for the clinical transformation of BCI.

Objective:To evaluate the efficacy of cyclophosphamide in patients with T-cell large granular lymphocytic leukemia (T-LGLL) and the maintenance of treatment-free remission (TFR) following drug discontinuation.Methods:Clinical data were collected from 37 patients with T-LGLL who received oral cyclophosphamide at the Regenerative Medicine Clinic of the Institute of Hematology and Blood Diseases Hospital between June 2019 and March 2024. Patient clinical characteristics, treatment efficacy, and long-term TFR were analyzed.Results:The median age of the 37 patients was 60 years (range: 37-86), and 22 (59.5%) were male. Anemia was observed in 30 patients (81.1%), and 28 (75.7%) met the diagnostic criteria for secondary pure red cell aplasia. Neutropenia occurred in 15 patients (40.5%), lymphocytosis in 11 (29.7%), and thrombocytopenia in three (8.1%). Sixteen patients (43.2%) had not received prior immunosuppressive therapy (treatment-naive group), while 21 patients (56.8%) were refractory to or had relapsed after immunosuppressive treatment (refractory/relapsed group). All patients met the treatment criteria and received oral cyclophosphamide at doses of 50-100 mg/day. Among the 36 evaluable patients, hematologic remission was achieved in 25 (69.4%), with a median time of 2.0 months (range: 0.7-7.0). There was no statistically significant difference in remission rates between the treatment-naive and refractory/relapsed groups (68.5% vs. 66.7%, P=0.589). Among the 25 patients who achieved hematologic remission, 24 discontinued cyclophosphamide. With a median follow-up of 39.0 months (range: 8.0-56.0), the median TFR duration was not reached. The estimated TFR rates were (90.87± 6.16) % at 12 months and (75.72±11.04) % at 36 months. No significant difference in TFR was observed between the treatment-naive and refractory/relapsed groups ( P=0.451) . Conclusion:Oral cyclophosphamide is effective in the treatment of T-LGLL, and patients may maintain long-term TFR following drug discontinuation.

Radiation-induced esophageal injury (RIEI) is a frequent complication following radiotherapy for thoracic and head-neck malignancies, which may lead to severe sequelae including esophageal stricture and perforation, adversely affecting patients' quality of life and therapeutic outcomes. With advancements in radiotherapy techniques — particularly the adoption of unconventional fractionation regimens, concurrent chemoradiotherapy, and combined molecular targeted / immunotherapy — the incidence of RIEI has been increasing. In this review, recent advances in understanding the pathogenesis, clinical manifestations, risk factors, and management strategies for RIEI were comprehensively summarized. Current therapeutic approaches have evolved beyond conventional anti-inflammatory and nutritional support to include novel interventions such as targeted therapy, free radical scavengers, and microbiota modulation, etc. Future research should prioritize the development of optimized, individualized prevention and treatment protocols to mitigate RIEI risk and improve patient prognosis.

Objective To explore the effects of fecal microbiota transplantation(FMT)on oxalate metabolism and renal protection in rats fed a high oxalate diet.Methods Twenty-four male SD rats were randomly divided into four groups:SC,SC+FMT,OD+PBS and OD+FMT.The SC group was set as the control group and was fed standard rat chow.The OD+PBS group and OD+FMT group were fed a diet containing 5%oxalate.Starting from day 14,the OD+PBS group,OD+FMT group and SC+FMT group received intragastric administration of PBS solution or filtered faecal microbiota solution from guinea pigs for 7 consecutive days.The 24-hour urine,feces,and venous serum of the rats were collected from the rats of all groups to determine the gut microbiota and biochemical markers.Real-time quantitative PCR and immunohistochemistry were conducted on the rat kidneys to detect the expression of renin,ACE,and OPN.Results The fecal microbiota transplantation altered the gut microbiota of rats.The gut microbiota of the SC+FMT group deviated from that of the SC group and showed increased similarity to that of the guinea pigs.Compared to the OD+PBS group,the OD+FMT group exhibited significant reductions in the urinary oxalate,urinary urea,uric acid,urinary creatinine,serum urea nitrogen/creati-nine,and serum uric acid.Furthermore,after FMT treatment,the OD+FMT group exhibited reduced upregulation of renin mRNA expression and restored downregulation of OPN mRNA expression compared to the OD+PBS group;similar results were obtained from immunohistochemistry.Conclusion Fecal microbiome trans-plantation activated the microbial network in the rat gut,particularly the oxalate-degrading bacteria represented by Muribaculaceae.The kidney injury induced by high oxalate was partially restored by the microbiota network's degradation of oxalate,indicating the protective effect of fecal microbiota transplantation on the rat kidneys.