Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate tumor initiation, progression and metastasis, but their effects in ameloblastoma (AM) have not been reported. In this comprehensive study, we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates. Notably, we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT⁺-AM cells, whereas genetic ablation of PD-L1 exerted opposing inhibitory effects. By performing high-resolution single-cell profiling and thorough immunohistochemical analyses in AM patients, we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors. Our findings revealed that hTERT⁺-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial‒mesenchymal transition. This phenotypic shift is induced by the activation of the PI3K-AKT-mTOR signaling axis; thus, this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence. Importantly, targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patient-derived tumor organoids, highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.
Ameloblastoma/metabolism* ; Humans ; B7-H1 Antigen/metabolism* ; Neoplasm Recurrence, Local/pathology* ; Signal Transduction ; Cell Proliferation ; Up-Regulation ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Telomerase/metabolism* ; Jaw Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Animals ; Cell Line, Tumor ; Female ; Male

Objectives:To analyze the correction of postoperative coronal imbalance in adult degenerative scoliosis patients undergoing spinal fusion surgery,and to explore the impact of leveling of the most tilted vertebra(L4 or L5)in the lumbosacral curve on the correction of coronal imbalance.Methods:A retrospective analysis was conducted on 61 patients(17 male and 44 female;aged 51 to 78 years,mean 63.57±8.41 years;body mass index 15.79-35.55kg/m2,mean 25.83±3.69kg/m2)who underwent degenerative scoliosis correction surgery between January 2019 and March 2023 in Tianjin Union Medical Center.The patients were catego-rized based on the Obeid classification and the length of fusion segments into concave long segment group(17 cases),concave short segment group(15 cases),convex long segment group(15 cases),and convex short seg-ment group(14 cases).Coronal radiographic parameters[Cobb angle,coronal balance distance(CBD),coronal tilt angle]and sagittal radiographic parameters(sagittal vertical axis,thoracic kyphosis,lumbar lordosis,pelvic inci-dence,pelvic tilt,sacral slope)were measured on full spine anteroposterior and lateral X-rays preoperatively and on 3d postoperatively.The postoperative coronal and sagittal imbalance corrections were compared be-tween groups.Pearson correlation analysis was performed to investigate the relationship between the correction ratio of the maximal coronal tilt angle in the lumbosacral curve(L4 or L5)and postoperative CBD.The opera-tive time,blood loss,and visual analogue scale(VAS)pre-and postoperatively were compared between the four groups.Results:The postoperative coronal Cobb angle,CBD,and maximal coronal tilt angle at L4 or L5 of the concave long segment group,convex long segment group,and convex short segment group were statisti-cally different from those before operation(P＜0.05).In the concave short segment group,the postoperative coronal Cobb angle and maximal coronal tilt angle at L4 or L5 were significantly different from those before operation(P＜0.05),while no significant difference was found between pre-and postoperative CBD(P=0.085).Pearson correlation analysis revealed a significant negative correlation(r=-0.570,P＜0.01)between postoperative CBD and coronal tilt correction ratio in the convex group,with the linear regression equation being postoper-ative CBD=32.81-28.38 x coronal tilt correction ratio.When the correction ratio of the maximal coronal tilt angle at L4 or L5 exceeding 45％in convex coronal malalignment patients,it's predicted that the CBD could be corrected to within 20mm.No significant correlation was found between postoperative CBD and the coronal tilt correction ratio in the concave group(r=0.098,P=0.59).Patients in both the convex and concave short segment groups had shorter operative time and less blood loss than long segment groups.Postoperative VAS scores improved significantly in all groups(P＜0.05).Conclusions:In adult degenerative scoliosis patients with convex coronal malalignment,both short and long segment fusions are capable of correcting coronal imbalance.Concave coronal malalignment patients require long segment fusion for the correction of coronal imbalance.To achieve optimal coronal balance in convex coronal malalignment patients,a correction ratio of the maximal coronal tilt angle at L4 or L5 shall exceed 45％.

Bladder cancer is one of the most common malignancy in the urinary system over the world. Urine cytology and cystoscopy are important tools for bladder cancer diagnosis and recurrence monitoring. However, due to the limited sensitivity and invasive procedure, there is an urgent need to develop new non-invasive and highly sensitive liquid biopsy approaches. Urine biopsy is a research focus in the field and has great potential. This review focused on protein-based urine markers (including NMP22, BTA and UroVysion etc.) and DNA or RNA-based urine markers (including cfDNA, AssureMDx and Xpert BC Monitor etc.), which were used for bladder cancer diagnosis and recurrence monitoring, and summarized the sensitivity and specificity of each biomarker as well as their characteristics in the diagnosis and recurrence surveillance of bladder cancer. This study provides theoretical and empirical support for further optimization and application of these biomarkers in clinical practice.

Objective:Through histological analysis, immunofluorescence staining, electrophysiological detection and Sensory and motor function evaluation to investigate the effects of 3D printed hydrogel scaffold combined with bone marrow mesenchymal stem cells (BMSCs) in promoting functional recovery of spinal cord injury.Methods:10% GelMA hydrogel and 10 6 U stem cell suspension were prepared into bioink of appropriate concentration to construct the biomimetic spinal cord scaffold through 3D printing platform. The scaffold was placed in the medium and cultured in an environment of 37 ℃ CO 2 incubator. The microstructure of the scaffolds and the distribution of BMSC in the scaffolds was observed by scanning electron microscope. CAM/PI staining and confocal microscopy were used to observe the survival of stem cells in the scaffolds and determine the biocompatibility of the scaffolds. The scaffolds were implanted into the subcutaneous tissues of the back of rats, and the subcutaneous tissues were determined by HE staining to detect the immunogenicity of the scaffolds. After the rat model of hemicytoma defect was made, stents were transplanted for treatment, and confocal microscopy was used to evaluate the regeneration of neurons and axons in local area of spinal cord injury. At the same time, BBB score was used to evaluate motor function, mechanical pain score was used to evaluate sensory function, and surface electrode detection method was used to evaluate electrophysiological recovery weekly. Results:The long spindle shaped BSMC were uniformly distributed in the scaffold with a loose reticular structure. The scaffolds had good biocompatibility, and the cell survival rate of the prepared scaffolds reached 96% after 24 hours of printing. After 28 days of subcutaneous transplantation, the immune rejection was mild and immunogenicity was low. It was shown that the regenerated spinal cord tissue in the treatment group was significantly increased compared with the control group, which was widely distributed with cells after 28 days by HE staining. It was confirmed that part of the regenerated spinal cord tissue was neurons by immunohistochemical staining.Compared with the injured group, the regeneration of neurons and axons in the treatment group were significantly increased by immunofluorescence staining and confocal microscopy. In the treatment group, the BBB score recovered to 10 points, while the control group only recovered to about 1 point in the first week, which was statistically significant. And it recovered to 17 in the fourth week, while the control group only recovered to about 4 point in the four week, which was statistically significant. The Angle of inclined plate support of the treatment group was restored to 40 degrees, while it was only restored to 22 degrees in the control group. The pain threshold of the treatment group decreased to 18.5 points, which was not statistically different from that of the control group. The latent recovery effect of electrophysiology in the treatment group was the same as that in the sham operation group and better than that in the control group.Conclusion:3D printing hydrogel scaffold with loose network structure is suitable for cell proliferation. It has well biological survival, low cytotoxicity and low immunogenicity, which promoted neurons and axons to recovery and extend so as to effectively promote the recovery of motor function, sensory function and neural signal transmission rate after spinal cord injury.

Objective: To investigate the epidemiological characteristics and its associated risk factors of lower urinary tract symptoms in young Chinese obese males. Methods: A total of 126 young males aged 20-40 years admitted to Beijing Friendship Hospital, Capital Medical University were enrolled into two different groups in this study, including 74 obese patients visited metabolic weight loss clinic were included in the experimental group, and 52 conditionally healthy persons were included in the control group. Blood pressure (systolic blood pressure, diastolic blood pressure), insulin resistance (fasting blood glucose, insulin, C-peptide), blood lipid metabolism (triglycerides, high-density lipoprotein cholesterol), and sex hormones (estrogen) of the two groups of subjects. Hormones, serum testosterone), C-reactive protein (CRP), International prostate symptom score (IPSS) and quality of life score (QOL). were compared between the two groups of subjects. Comparisons of measurement data between groups were statistically analyze by t test, expressed by mean ± standard deviation (Mean±SD); the correlation between body mass index and LUTS was analyzed by Spearman rank correlation, and the risk factors of LUTS and clinical variables were analyzed by univariate logistic regression. The significant variables were analyzed by multivariate logistic regression. Results: There were significant statistical differences between experimental group and control group in terms of systolic blood pressure [(144.30±15.78) mmHg vs (125.9±66.11) mmHg, P<0.001], diastolic blood pressure [(89.46±12.76) mmHg vs (81.35±4.58) mmHg, P=0.001], and fasting blood glucose [(6.73±3.15) mmol/L vs (5.26±1.47) mmol/L, P=0.016], insulin [(26.60±19.09) mg/dL vs (13.43±7.68) mg/dL, P<0.001], C-peptide [(4.20±1.73) ng/mL vs (1.59±0.52) ng/mL, P=0.001], triglycerides [(2.42±1.88) mg/dL vs (1.45±0.79) mg/dL, P=0.007), estrogen [(52.32±21.77) ng/L vs (42.11±12.19) ng/L, P=0.023] and CRP [(6.49±4.96) mg/L vs (1.62±1.53) mg/L, P=0.037], but no statistical difference regarding high-density lipoprotein [(1.10±0.55) mg/dL vs (1.06±0.26) mg/dL, P=0.669] and serum testosterone [(275.00±100.68) ng/dL vs (280.28±85.52) ng/dL, P=0.823]. In addition, the experimental group had higher IPSS[(3.81±1.88) scores vs (0.69±0.30) scores, P<0.001] and QOL scores [(2.76±0.68) scores vs (0.12±0.08) scores, P<0.001] than the control group, and higher risk of LUTS [86.49% vs 42.31%, P<0.001], especially moderate LUTS ( 21.62% vs 0, P=0.011). Spearman rank correlation analysis showed that obesity (body mass index≥30 kg/m²) was significantly associated with moderate LUTS risk (r=0.407, P<0.001); Univariate logistic regression analysis showed that systolic blood pressure, insulin, and C-peptide were important risk factors of moderate LUTS in young obese patients (P=0.009, 0.029, 0.002). Systolic blood pressure and fasting C-peptide were independent risk factors by multivariate logistic regression analysis (P=0.011, 0.003). Conclusions The middle severity of LUTS was prevalent in young obese males, and systolic blood pressure and C-peptide were its significant independent risk factors.

BACKGROUND:Lymph-targeted tracing and therapy based on carbon nanotubes have been one of the hottest researches on targeting tumor diagnosis and treatment. To evaluate the accumulation of carbon nanotubes in axil ary lymph node can provide experimental evidences for developing nano-tracers and drug carriers which are more lymph-specific and more biocompatible. OBJECTIVE:To study the accumulation of the intravenously injected carboxylated single-wal ed carbon nanotubes in axil ary lymph nodes of Sprague-Dawley rats, and to evaluate their effect on blood cel s. METHODS:Sixty-four Sprague-Dawley rats were randomly divided into two groups. Rats in testing group were injected with carboxylated single-wal ed carbon nanotubes suspension (2 mg/kg), while those in control group were injected with 5%glucose solution (1 mL/kg), both through the tail vein, three times per week. Four periods of 7, 60, 90 and 120 days were set (the 120-day period referred to 90 days of administration fol owed by 30 days of drug withdrawal). At the end of each period, eight rats from each group were randomly picked out, to col ect blood samples via the abdominal aorta for blood routine test. Final y the axil ary lymph nodes were observed, and the lymph node samples of rats in the testing group were col ected and analyzed at 120 days by transmission electron microscope. RESULTS AND CONCLUSION:Compared with the control group, black staining of axil ary lymph nodes of rats in testing group was not obvious at the end of the 7-day period. However, with the increase of the dosing periods, the lymph nodes of the rats in the testing group became enlarged, firm and black stained, coupled with a significant rising in the percentage of blood neutrophils. After 30 days of drug withdrawal, the size of the rat axil ary lymph nodes was reduced and black staining partly faded, with the decreasing of blood neutrophil percentage. Under the transmission electron microscope, abundant carboxylated single-wal ed carbon nanotubes were uptaken by lymphocytes to form a large number of phagocytic vacuoles after drug withdrawal for 30 days. It indicates that the short-term tracing of rat axil ary lymph nodes by carboxylated single-wal ed carbon nanotubes injected through the tail vein is relatively weak, while the long-term intravenous injection can cause their accumulation in rat axil ary lymph nodes, coupled with the increase of neutrophils;after drug withdrawal, the carboxylated single-wal ed carbon nanotubes can be slowly cleared by the lymph nodes.

Objective To summarize the clinical experience of combined single-access minimally invasive percutaneous nephrolithotomy (MPCNL) and lithotripsy through flexible ureteroscope in the treatment of staghorn calculi.Methods Fifty-seven cases of renal staghom calculi underwent combined MPCNL and lithotripsy through flexible ureteroscope.The size of calculi was (2.7 cm×3.3 cm-3.8 cm × 5.2 cm),3.7 cm×4.1 cmon average.Results The success rate of stone fragmentation was 80.7% (46/57) after the first stage of operation,duration of which was 128 min on average.The average loss of blood was 80 mL (20 - 150 mL).Eleven patients with residual calculi in the middle and lower calyx were also underwent the second stage of operation after 5 - 7 days.The average operation duration of the second stage was 57 min and the total clearance rate was 93% (53/57).Four cases had a few of residual calculi with size of 0.4 - 0.8 cm and went on with the treatment of extracorporeal shock wave lithotripsy(ESWL).Two cases were stone-free in the follow-up for 3 months.Conclusion MPCNL combined with with lithotripsy through flexible ureteroscope on the treatment of staghom calculi can decrease the therapeutic risk and complication,increase the rate of stone-free and safety.