Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver injury of unknown etiology. The onset of this disease involves the activation and recruitment of diverse immune and non-immune cells, which in turn trigger hepatic damage. Immune checkpoint molecules (ICM) are expressed on the surface of multiple cell types. By regulating cellular functional states, they help limit the intensity and duration of immune responses, thereby preventing excessive inflammation and tissue damage, and maintaining immune homeostasis. In AIH, however, this natural "braking" mechanism is impaired, leading to aberrant activation of both immune and non-immune cells and the breakdown of immune homeostasis. Consequently, ICM are likely to play a critical role in the pathogenesis of AIH. A deeper understanding of the function of ICM in AIH not onlyadvances our insight into the disease mechanism, but also suggests that targeting these molecules may represent a promising therapeutic strategy for the treatment of AIH.

Objective:To investigate the association of monocyte-to-high-density lipoprotein cholesterol ratio (MHR) with the severity of white matter hyperintensities (WMHs) and its spatial distribution.Methods:Patients admitted to the Department of Neurology, Jiangning Hospital Affiliated to Nanjing Medical University due to various chronic diseases or physical examinations between January 2023 and December 2024 were included retrospectively. Past medical history, clinical and imaging data were collected. The Fazekas scale was used to assess the severity of WMHs. According to the scoring results of periventricular WMHs (PVWMHs) and deep WMHs (DWMHs), WMHs were divided into no/mild group (0-1 points) and moderate/severe group (2-3 points). Multivariate logistic regression analysis was used to determine independent correlation factors for the severity of WMHs, PVWMHs, and DWMHs. Results:A total of 357 patients were included, aged 65.42±9.95 years, with 198 males (55.5%). There were 193 patients (54.1%) in the no/mild group and 164 (45.9%) in the moderate/severe group. Univariate analysis showed that the proportion of patients with hypertension, diabetes, history of cerebral infarction and cerebral hemorrhage, carotid plaque, and age, serum creatinine, monocyte count and MHR in the moderate/severe group were significantly higher than those in the no/mild group (all P<0.05). Multivariate logistic regression analysis showed a significant positive correlation between MHR and the severity of WMHs (odds ratio 3.138, 95% confidence interval 1.042-9.451; P=0.042). Further analysis showed a significant positive correlation between MHR and PVWMHs (odds ratio 3.384, 95% confidence interval 1.111-10.305; P=0.032), but no independent correlation with DWMHs. In addition, age and hypertension, diabetes, history of cerebral infarction and cerebral hemorrhage were significantly positively correlated with the severity of WMHs, PVWMHs and DWMHs. Conclusion:MHR is correlated with the severity of WMHs, and higher MHR is significantly associated with PVWMHs, but not with DWMHs.

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

Objective:To explore the surgical strategies and clinical efficacy of open partial nephrectomy in the treatment of renal angiomyolipoma (AML) with inferior vena cava tumor thrombus.Methods:A retrospective analysis was conducted on the clinical data of 5 patients with renal AML and inferior vena cava tumor thrombus who underwent partial nephrectomy at Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from October 2014 to December 2022. There were 2 male and 3 female patients, with a median age of 37 years, ranged from 33 to 45 years. All patients were identified during routine physical examinations. Four patients presented with right-sided lesions, while one had a left-sided lesion. The diameter of the primary tumor within the kidney ranged from 3.0 to 7.0 cm, with a median diameter of 5.5 cm.The length of the tumor thrombus within the inferior vena cava ranged from 1.0 to 6.0 cm, with a median length of 1.5 cm. Among them, 2 patients underwent laparoscopic nephrectomy combined with extracorporeal workbench tumor resection and autologous kidney transplantation (the workbench surgery group), while 3 patients underwent open in-situ partial nephrectomy combined with removal of inferior vena cava tumor thrombus (the in-situ nephron-sparing surgery group). The surgical method of the workbench surgery group: The patients first underwent laparoscopic nephrectomy on the affected side combined with inferior vena cava tumor thrombus removal, then the incision was extended to remove the affected kidney, and table partial nephrectomy was performed. After completely removing the tumor and tumor thrombus within the affected kidney and renal vein, autologous kidney transplantation was performed in the iliac fossa. The surgical method of the in-situ kidney preservation surgery group: The affected kidney, renal artery and vein on the affected side, inferior vena cava, and contralateral renal vein were dissected and exposed. The distal end of the inferior vena cava, the contralateral renal vein, the proximal end of the inferior vena cava, and the renal artery on the affected side were blocked respectively. The venous wall was opened in the middle of the renal vein, and the tumor thrombus was gradually pulled out. According to the pre-marked tumor boundary, the tumor within the kidney was gradually removed by alternate blunt and sharp dissection combined with suction, and the wound surface was sutured layer by layer. The perioperative conditions, complications, and follow-up results of the patients were analyzed.Results:All 5 surgeries were successfully completed, with a median operation time of 100 to 450 minutes and a median operation time of 200 minutes. The intraoperative bleeding volume was 100 to 600 ml, with the median of 150 ml. In the in-situ nephron-sparing surgery group, the renal artery occlusion time was 28 to 41 minutes, and the median occlusion time was 34 minutes. All patients were discharged safely after surgery, and there were no serious perioperative complications. The postoperative pathology of all 5 patients was renal angiomyolipoma, without any epithelioid components. The patients were followed up for 12 to 90 months, with a median follow-up duration of 24 months. None of the 5 patients had tumor recurrence or metastasis, and no patient developed chronic kidney dysfunction during follow-ups.Conclusions:Renal AML with venous tumor thrombus is a challenging clinical problem. In situ open partial nephrectomy or the combined approach through the workbench and autologous kidney transplantation can effectively remove the tumor thrombus and maximize the protection of renal function. For cases of ① multiple or complex renal AML; ② complex vascular system structure within the renal sinus requiring precise anatomy; ③ renal AML with a previous history of hemorrhage, complex adhesions around, and difficult dissociation, table partial nephrectomy combined with inferior vena cava tumor thrombus removal and autologous kidney transplantation can be selected. For cases where the expected surgical operation is simple, in situ open partial nephrectomy can significantly shorten the operation time and reduce surgical trauma.

Objective To explore the sleep quality and mental fatigue level in elderly patients with cerebrovascular small disease(CSVD).Methods A total of 222 patients aged over 65 years old hospitalized due to chronic diseases in Department of Neurology of the Affiliated Jiangning Hospi-tal of Nanjing Medical University from August 2022 to June 2024 were recruited prospectively and continuously.According to the CSVD score,they were divided into a CSVD group(CSVD score≥1,148 cases)and a non-CSVD group(CSVD score=0,74 cases).All the patients were evaluated by sleep quality,fatigue and neuropsychological scale when they were fully cooperated and in good condition.Subsequently,the patients in the CSVD group were further assigned into a good sleep subgroup(117 cases)and a poor sleep subgroup(31 patients).Results The CSVD group had significantly higher total score of Pittsburgh sleep quality index(PSQI),sleep quality score,sleep disturbance score,total score of self-rating fatigue,and mental fatigue score than the non-CSVD group(P＜0.01).The sleep quality score,sleep disturbance score,and mental fatigue score were risk factors for CSVD(P＜0.05).The mental fatigue score was significantly higher in the CSVD patients with poor sleep than those with good sleep(4.13±1.15 vs 2.50±1.92,P＜0.01).Conclusion Elderly CSVD patients were more likely to have decreased sleep quality and mental fatigue,and among them,those with poor sleep quality are prone to having mental fatigue than those with good sleep.

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, which seriously threatens the vision of patients. The pathogenesis of DR Is complex and involves many pathophysiological processes. At present, the treatment methods for DR Mainly include panretinal laser photocoagulation, vitrectomy and vitreous cavity injection, etc. However, each treatment method has certain limitations. In recent years, remarkable progress has been made in the field of drug treatment of DR, especially in anti-vascular endothelial growth factor drugs, anti-inflammatory drugs, anti-oxidative stress damage drugs, neuroprotective agents, gene therapy and stem cell therapy. These drugs not only improve the effectiveness of treatment, but also expand the range of treatment options. In addition, by carrying DR Treatment drugs on carriers such as nanoparticles, hydrogels and photosensitive materials, continuous and efficient release of drugs in the eye is achieved, thereby extending the time interval of administration and reducing the need for frequent treatment of patients. In the future, based on biomarker detection technology, it is expected to promote the development of personalized and precise treatment, which can develop more accurate treatment plans for patients and improve the efficacy.

Objective:To investigate the clinical efficacy and factors influencing treatment of pediatric noninfectious uveitis with Adalimumab (ADA).Methods:A retrospective clinical study. A total of 86 pediatric patients with non-infectious uveitis, diagnosed and treated with ADA at Department of Uveitis Specialist of Xi'an People's Hospital (Xi' an Fourth Hospital) from January 1, 2021 to December 31, 2023, were included in this study. The age of all patients was ≤16 years. Among them, 55 (63.95%, 55/86) patients received ADA combined with one immunosuppressive agent, 28 (32.56%, 28/86) patients received ADA combined with ≥2 immunosuppressive agents, and 3 (3.49%, 3/86) patients received ADA alone without any immunosuppressive agents. All patients underwent best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. The thickness of the retinal nerve fiber layer (RNFL) in the macular region was measured using an OCT device. The cumulative treatment effectiveness rate at 12 months post-treatment was evaluated using the Kaplan-Meier survival analysis. Multivariate analysis was performed using the Cox proportional hazards regression model, and the optimal predictive model was selected based on the Bayesian information criterion. The association between different treatment regimens and various clinical outcomes was assessed.Results:Among the 86 pediatric patients, 42 were male and 44 were female, with a mean age of (10.47±3.23) years. The distribution of uveitis types was as follows: anterior uveitis in 37 cases, intermediate uveitis in 15 cases, posterior uveitis in 10 cases, and panuveitis in 24 cases. Anterior chamber cells (ACC), keratic precipitates, and synechiae were present in 66, 55, and 38 cases, respectively. The cumulative treatment effectiveness at 12 months was 85.1% [95% confidence interval ( CI) 71.9-92.2], with a median time to treatment effectiveness of 3 months. Compared with baseline, after 6 months of treatment, the BCVA, RNFL thickness ( Z=?6.323, ?8.017), and the grading of ACC and vitreous haze ( χ2= ?6.917, ?5.027) showed significant improvement, with statistically significant differences ( P<0.05). Multivariate analysis revealed that ACC (hazard ratio=22.31, 95% CI 2.43-204.68) and anterior uveitis (hazard ratio=3.88, 95% CI 2.03-7.42) were significantly associated with treatment effectiveness ( P<0.05). Patients with ACC had a median time to treatment effectiveness of 2 months, with a 12-month cumulative treatment effectiveness of 95.5% (95% CI 86.3-98.5). Patients with anterior uveitis had a median time to treatment effectiveness of 2 months, with a 12-month cumulative treatment effectiveness of 97.3% (95% CI 81.3-99.6). Patients without anterior uveitis had a median time to treatment effectiveness of 5 months, with a 12-month cumulative treatment effectiveness of 76.7% (95% CI 54.1-88.2). The cumulative recurrence risk at 12 months was 15.6% (95% CI 6.2-24.1). Conclusion:ADA is safe and effective in treating pediatric non-infectious uveitis, and ACC and anterior uveitis are associated with response rate.

Objective To explore the sleep quality and mental fatigue level in elderly patients with cerebrovascular small disease(CSVD).Methods A total of 222 patients aged over 65 years old hospitalized due to chronic diseases in Department of Neurology of the Affiliated Jiangning Hospi-tal of Nanjing Medical University from August 2022 to June 2024 were recruited prospectively and continuously.According to the CSVD score,they were divided into a CSVD group(CSVD score≥1,148 cases)and a non-CSVD group(CSVD score=0,74 cases).All the patients were evaluated by sleep quality,fatigue and neuropsychological scale when they were fully cooperated and in good condition.Subsequently,the patients in the CSVD group were further assigned into a good sleep subgroup(117 cases)and a poor sleep subgroup(31 patients).Results The CSVD group had significantly higher total score of Pittsburgh sleep quality index(PSQI),sleep quality score,sleep disturbance score,total score of self-rating fatigue,and mental fatigue score than the non-CSVD group(P＜0.01).The sleep quality score,sleep disturbance score,and mental fatigue score were risk factors for CSVD(P＜0.05).The mental fatigue score was significantly higher in the CSVD patients with poor sleep than those with good sleep(4.13±1.15 vs 2.50±1.92,P＜0.01).Conclusion Elderly CSVD patients were more likely to have decreased sleep quality and mental fatigue,and among them,those with poor sleep quality are prone to having mental fatigue than those with good sleep.

Objective:To explore the surgical strategies and clinical efficacy of open partial nephrectomy in the treatment of renal angiomyolipoma (AML) with inferior vena cava tumor thrombus.Methods:A retrospective analysis was conducted on the clinical data of 5 patients with renal AML and inferior vena cava tumor thrombus who underwent partial nephrectomy at Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from October 2014 to December 2022. There were 2 male and 3 female patients, with a median age of 37 years, ranged from 33 to 45 years. All patients were identified during routine physical examinations. Four patients presented with right-sided lesions, while one had a left-sided lesion. The diameter of the primary tumor within the kidney ranged from 3.0 to 7.0 cm, with a median diameter of 5.5 cm.The length of the tumor thrombus within the inferior vena cava ranged from 1.0 to 6.0 cm, with a median length of 1.5 cm. Among them, 2 patients underwent laparoscopic nephrectomy combined with extracorporeal workbench tumor resection and autologous kidney transplantation (the workbench surgery group), while 3 patients underwent open in-situ partial nephrectomy combined with removal of inferior vena cava tumor thrombus (the in-situ nephron-sparing surgery group). The surgical method of the workbench surgery group: The patients first underwent laparoscopic nephrectomy on the affected side combined with inferior vena cava tumor thrombus removal, then the incision was extended to remove the affected kidney, and table partial nephrectomy was performed. After completely removing the tumor and tumor thrombus within the affected kidney and renal vein, autologous kidney transplantation was performed in the iliac fossa. The surgical method of the in-situ kidney preservation surgery group: The affected kidney, renal artery and vein on the affected side, inferior vena cava, and contralateral renal vein were dissected and exposed. The distal end of the inferior vena cava, the contralateral renal vein, the proximal end of the inferior vena cava, and the renal artery on the affected side were blocked respectively. The venous wall was opened in the middle of the renal vein, and the tumor thrombus was gradually pulled out. According to the pre-marked tumor boundary, the tumor within the kidney was gradually removed by alternate blunt and sharp dissection combined with suction, and the wound surface was sutured layer by layer. The perioperative conditions, complications, and follow-up results of the patients were analyzed.Results:All 5 surgeries were successfully completed, with a median operation time of 100 to 450 minutes and a median operation time of 200 minutes. The intraoperative bleeding volume was 100 to 600 ml, with the median of 150 ml. In the in-situ nephron-sparing surgery group, the renal artery occlusion time was 28 to 41 minutes, and the median occlusion time was 34 minutes. All patients were discharged safely after surgery, and there were no serious perioperative complications. The postoperative pathology of all 5 patients was renal angiomyolipoma, without any epithelioid components. The patients were followed up for 12 to 90 months, with a median follow-up duration of 24 months. None of the 5 patients had tumor recurrence or metastasis, and no patient developed chronic kidney dysfunction during follow-ups.Conclusions:Renal AML with venous tumor thrombus is a challenging clinical problem. In situ open partial nephrectomy or the combined approach through the workbench and autologous kidney transplantation can effectively remove the tumor thrombus and maximize the protection of renal function. For cases of ① multiple or complex renal AML; ② complex vascular system structure within the renal sinus requiring precise anatomy; ③ renal AML with a previous history of hemorrhage, complex adhesions around, and difficult dissociation, table partial nephrectomy combined with inferior vena cava tumor thrombus removal and autologous kidney transplantation can be selected. For cases where the expected surgical operation is simple, in situ open partial nephrectomy can significantly shorten the operation time and reduce surgical trauma.