BACKGROUND:U937 cells can be used as a cell model for studying the biological characteristics,signaling pathways,and therapeutic targets of acute myeloid leukemia.Although it has been reported that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia,its biological function in U937 cells remains unclear,and its mechanism of action in the occurrence and development of acute myeloid leukemia needs to be further clarified. OBJECTIVE:To investigate the expression level of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia and its effect on the proliferation and apoptosis of U937 cells. METHODS:RNA-sequencing was used to analyze the bone marrow monocyte samples from acute myeloid leukemia patients,and the differentially expressed gene long non-coding RNA KIAA0125 was screened.The expression of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia was detected by qRT-PCR.The relationship between long non-coding RNA KIAA0125 mRNA expression and prognosis in bone marrow cells of 173 acute myeloid leukemia patients and 70 healthy people was statistically analyzed by GEPIA database.Subsequently,recombinant lentivirus technology and CRISPR/Cas9-SAM technology were used to construct U937 cell lines with knockdown/overexpression of long non-coding RNA KIAA0125.qRT-PCR was used to detect the knockdown/overexpression efficiency of long non-coding RNA KIAA0125.Next,CCK-8 assay,flow cytometry,and western blot assay were used to detect the effects of knockdown/overexpression of long non-coding RNA KIAA0125 on the proliferation and apoptosis of U937 cells.Finally,western blot assay was used to detect the effect of knockdown/overexpressed long non-coding RNA KIAA0125 on Wnt/β-catenin signaling pathway-related proteins. RESULTS AND CONCLUSION:(1)The results of qRT-PCR showed that long non-coding RNA KIAA0125 was highly expressed in peripheral blood of acute myeloid leukemia patients.The results of GEPIA database showed that long non-coding RNA KIAA0125 was highly expressed in bone marrow cells of acute myeloid leukemia patients,and the high expression group had worse overall survival.(2)The knockdown efficiency of long non-coding RNA KIAA0125 in knockdown group was 70%,and the U937 cells that stably down-regulated long non-coding RNA KIAA0125 expression were successfully constructed.The expression of long non-coding RNA KIAA0125 in overexpression group was four times that of vector group,and stable U937 cells were successfully constructed.(3)Knockdown of long non-coding RNA KIAA0125 inhibited the proliferation of U937 cells and promoted their apoptosis.Overexpression of long non-coding RNA KIAA0125 promoted the proliferation of U937 cells but had no significant effect on the apoptosis of U937 cells.(4)Knockdown of long non-coding RNA KIAA0125 inhibited the activity of Wnt/β-catenin signaling pathway,while overexpression of long non-coding RNA KIAA0125 activated Wnt/β-catenin signaling pathway.These results confirm that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia peripheral blood.Long non-coding RNA KIAA0125 may affect the proliferation and apoptosis of U937 cells by regulating the Wnt/β-catenin signaling pathway,and may be a potential prognostic marker for acute myeloid leukemia.

Objective:To systematically analyze the risk factors for knee injury complicated with adolescent tibial tubercle fractures (ATTF).Methods:A retrospective study was conducted to analyze the clinical data of the 90 adolescent patients (the observation group) who had been treated and fully followed up for knee injury complicated with ATTF at Department of Pediatric Orthopedics, The Second General Hospital of Fuzhou from September 2017 to April 2024. There were 86 males and 4 females, with a mean age of 14.0 (13.0, 14.0) years. The injury was on the left side in 51 cases, on the right side in 34 ones, and on the bilateral sides in 5 ones. All their injuries resulted from sports activities. In addition, another contemporary 90 patients with knee injury but no exercise-induced ATTF were enrolled as the control group, including 54 males and 36 females with a mean age of 14.0 (13.0, 14.3) years. Their injury was on the left side in 45 cases, on the right side in 41 ones, and on the bilateral sides in 4 ones. Univariate analysis was conducted to compare gender, age, injury side, height, weight, body mass index, history of Osgood-Schlatter disease (OSD), and injury mechanism between the 2 groups. Variables with P<0.1 were included in a multivariate logistic regression analysis to screen independent risk factors for ATTF. The receiver operating characteristic (ROC) curve was used to evaluate their predictive values. The optimal cutoff value was determined by Youden index. Results:The univariate analysis showed that gender, height, weight, body mass index, and OSD history were significantly correlated with the occurrence of ATTF ( P<0.05). The multivariate logistic regression analysis further confirmed that male ( P=0.017), height ( P=0.021), weight ( P=0.014), body mass index ( P=0.032) and history of OSD ( P=0.003) were independent risk factors for ATTF. The ROC curve analysis showed that weight had the largest area under the curve (AUC) in prediction of the ATTF risk, suggesting that its predictive value was the most significant. Conclusion:Male, height, weight, body mass index, and prior OSD are independent risk factors for ATTF, with the highest predictive value in weight.

Objective:To investigate the dynamic imaging characteristics of hepatocellular carcinoma (HCC) following Yttrium-90 selective internal radiation therapy ( 90Y-SIRT) and to compare these with imaging findings after transarterial chemoembolization (TACE). Methods:This retrospective case-control study included 24 HCC patients who received 90Y-SIRT at Zhongda Hospital, Southeast University, and West China Hospital, Sichuan University, between September 2021 and June 2023, establishing the 90Y-SIRT group. Additionally, 45 HCC patients who underwent their first TACE treatment at Zhongda Hospital, Southeast University during the same period were included as the TACE group. Patients underwent MRI and/or CT follow-ups at 1-3 months (first follow-up) and 3-6 months (second follow-up) after treatment. The analyzed imaging features included tumor characteristics, peritumoral features, and measurements of tumor and liver volumes, with postoperative change rates calculated. Imaging differences between the 90Y-SIRT and TACE groups were statistically compared using the Mann-Whitney U test or χ2 test. Results:At the first follow-up, compared to baseline, a higher proportion of lesions in the 90Y-SIRT group exhibited a reduction in arterial phase enhancement in the viable region (10/13) than in the TACE group (10/29), with a statistically significant difference ( P=0.040). The necrotic region of the tumor on T 1WI showed significantly lower signal intensity in the 90Y-SIRT group than in the TACE group ( Z=2.98, P=0.006). The change in the apparent diffusion coefficient value in the viable region compared to baseline was 157.0×10 -3(-62.0×10 -3, 311.5×10 -3) mm2/s in the 90Y-SIRT group and -56.0×10 -3 (-216.8×10 -3, 110.0×10 -3) mm2/s in the TACE group, with a statistically significant difference ( Z=-2.71, P=0.008). At the first and second follow-up, the contralateral liver lobe volume increased significantly in the 90Y-SIRT group, with a statistically significant difference from the TACE group ( Z=-3.21, -3.78, both P=0.001). Regarding peritumoral imaging characteristics, a statistically significant difference was observed between the two groups in the low signal intensity of the liver lobe or segment where the tumor waslocated during the hepatobiliary phase ( P=0.020, 0.040). Both HCC groups exhibited progressive tumor volume reduction after treatment. In the 90Y-SIRT group, the change rates of lesion volume relative to baseline at the two follow-ups were -23.0% (-45.6%, 7.9%) and -68.7% (-82.7%, -28.5%), respectively. In the TACE group, the values were -29.8% (-53.6%, -2.7%) and -38.0% (-65.3%, -10.7%). The differences between the two groups were not statistically significant ( Z=-0.52, P=0.605; Z=-1.79, P=0.073). Conclusion:There is a statistically significant difference in the tumor imaging features and peritumoral imaging characteristics between 90Y-SIRT and TACE. 90Y-SIRT demonstrates a notable advantage in promoting contralateral liver lobe regeneration while also contributing to tumor size reduction.

Objective:To evaluate the long-term effectiveness of lingual mucosal graft ureteroplasty (LMGU) for managing long-segment (≥5 cm) ureteral strictures in a multi-institutional cohort of patients.Methods:A multi-center retrospective case series study was conducted on clinical data from 42 patients undergoing LMGU for long-segment ureteral strictures (≥5 cm) across five institutions between February 2017 and June 2024. The cohort comprised 31 males and 11 females, with an age of (43.4±12.0) years (range: 15 to 64 years) and a body mass index of (24.6±2.6) kg/m2 (range: 16.0 to 30.0 kg/m2). Strictures involved the left ureter in 24 cases and right ureter in 18 cases, demonstrating a stricture length of (6.4±1.5) cm (range: 5.0 to 11.5 cm). Surgical interventions included either onlay ureteroplasty or augmented anastomotic ureteroplasty, selected according to intraoperative findings. Intraoperative parameters, postoperative complications, and follow-up outcomes were analyzed.Results:Laparoscopic surgery was performed in 22 cases and robot-assisted surgery in 20 cases. Among the 42 patients, 22 underwent onlay ureteroplasty while 20 received augmented anastomotic ureteroplasty. The graft length was (5.9±1.8) cm (range: 3.0 to 12.0 cm), operative time (191.5±55.6) minutes (range: 105.0 to 350.0 minutes), and intraoperative estimated blood loss (86.7±73.6) ml (range: 10.0 to 400.0 ml). All procedures were successfully completed without conversion to open surgery. The postoperative hospital stay was (7.6±2.0) days (range: 4.0 to 15.0 days), with double-J stent removal at 6 to 8 weeks postoperatively. During a follow-up of (49.1±25.0) months (range: 12.0 to 99.0 months), no stricture recurrence was observed in any patient.Conclusion:LMGU is a safe, feasible, and effective long-term technique for managing long-segment (≥5 cm) ureteral strictures.

Objective:To explore the relationship between childhood emotional maltreatment and problematic social media use among college students,and to examine the role of loneliness and physical activity in their relation-ship.Methods:A total of 1 186 college students completed the Childhood Abuse Questionnaire(CTQ-SF)emotion-al maltreatment subscale,Bergen Social Media Addiction Scale(BSMAS),UCLA Loneliness Scale(ULS),and Physical Activity Rating Scale(PARS-3).Results:Childhood emotional maltreatment scores were positively corre-lated with the BSMAS scores(r=0.34,P＜0.01).The loneliness partially mediated the relationship between child-hood emotional maltreatment and problematic social media use,with the mediating effect accounting for 30.75％of the total effect.Physical activity moderated the association between childhood emotional maltreatment and prob-lematic social media use(β=-0.10,P＜0.01).Conclusion:Childhood emotional maltreatment is associated with problematic social media use among college students,mediated by loneliness and moderated by physical activity.

Objective·To evaluate the clearance and pharmacokinetics/pharmacodynamics(PK/PD)of antibiotics from the perspective of protein binding rates in critically ill patients undergoing intermittent hemodialysis(IHD),in order to explore the association between protein binding rate and dialysis clearance of antibiotics,and to provide theoretical basis for developing antibiotic dosing regimens during hemodialysis.Methods·Nineteen patients undergone low-flux hemodialysis and received antibiotic therapy at the Department of Nephrology,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,were enrolled and divided into the meropenem group(n=7),the vancomycin group(n=5)and the ceftriaxone group(n=7)according to the type of antibiotics.A liquid chromatography with tandem mass spectrometry(LC-MS/MS)method was established to detect meropenem,vancomycin,and ceftriaxone in human plasma/serum and dialysate.A two-compartment pharmacokinetic model was established using MATLAB.Instantaneous and total dialysis clearance rates were calculated,and PK/PD parameters were analyzed.Results·No significant differences were found in the clinical characteristics of subjects among the three groups.The dialysis clearance rates were as follows:meropenem group(5.14?5.97 L/h)>vancomycin group(2.87?3.77 L/h)>ceftriaxone group(1.21?1.90 L/h),with statistically significant differences(P<0.001).All three antibiotics showed good fit in the two-compartment pharmacokinetic model with a dialysate chamber(fval%<2),and the calculated PK/PD parameters were consistent with previous literature.For meropenem,the fraction of time that the free drug concentration remained above the minimal inhibitory concentration(%fT>MIC)values were 95.2%,60.8%and 32.4%at minimal inhibitory concentration(MIC)values of 2,8 and 16 μg/mL,respectively.For ceftriaxone(free concentration),the%fT>MIC values were all above 45.0%at MICs of 0.25,4 and 16 μg/mL.For vancomycin,only 14.0%of the trough concentrations reached the target range of 15?20 mg/L.Conclusion·The three antibiotics are well described by the two-compartment model.The plasma protein binding rate has a significant effect on the dialysis clearance of antibiotics in low-flux IHD,with higher protein binding associated with lower clearance.The regimens of meropenem(0.5 g/d)and ceftriaxone(2.0 g/d)are generally effective among patients undergoing low-flux IHD,while the vancomycin regimen with a loading dose of 1.0 g and a maintenance dose of 0.5 g/2 d carries a risk of treatment failure.

BACKGROUND:Relatively or absolutely active bone resorption function of osteoclasts is one of the causative factors of osteoporosis. Therefore,how to inhibit the formation of osteoclasts and reduce the bone resorption activity is a key element in the prevention and treatment of osteoporosis. Liquiritin,which is derived from licorice,plays a role in the clinical treatment of bone diseases,but there are fewer studies addressing the application of liquiritin in osteoporosis and the mechanism is unknown.OBJECTIVE:To confirm,through both in vivo and in vitro experiments,that liquiritin inhibits osteoclast differentiation and alleviates bone loss.METHODS:Cell counting kit-8 was used to detect whether Liquiritin exerts toxic or proliferative effects on mouse bone marrow-derived macrophages,and tartrate-resistant acid phosphatase staining was performed to observe the effect of liquiritin in inhibiting osteoclast differentiation. The affinity of liquiritin binding to proteins related to osteoclast differentiation was verified by network pharmacology. RT-PCR and western blot assays were performed to detect the inhibitory effects of liquiritin on osteoclast-specific protein and gene expression as well as relevant signaling pathways. Finally,the mitigating effect of liquiritin on bone loss was verified in the C57BL/6J mouse osteoporosis model.RESULTS AND CONCLUSION:Liquiritin,at concentrations of 20 μmol/L and below,could inhibit the formation and differentiation of osteoclasts. Concurrently,it exhibited a high affinity with osteoclast-specific proteins such as nuclear factor of activated T-cells 1,Cathepsin K,c-Fos,and matrix metalloproteinase 9,and reduced the relative expression levels of these genes and proteins. Liquiritin could also effectively lower the phosphorylation expression level of JNK in the MAPK signaling pathway at the 15th,30th,45th,and 60th minutes,and it could salvage the degradation of nuclear factor-κB inhibitor α in the nuclear factor-κB signaling pathway at the 60th minute. In vivo experiments demonstrated that liquiritin could mitigate bone loss caused by osteoclasts and improve parameters related to trabecular bone. To conclude,liquiritin possesses the capacity to inhibit osteoclast differentiation and alleviate bone loss,thereby exerting a protective role against osteoporosis.

Objective:To explore the relationship between childhood emotional maltreatment and problematic social media use among college students,and to examine the role of loneliness and physical activity in their relation-ship.Methods:A total of 1 186 college students completed the Childhood Abuse Questionnaire(CTQ-SF)emotion-al maltreatment subscale,Bergen Social Media Addiction Scale(BSMAS),UCLA Loneliness Scale(ULS),and Physical Activity Rating Scale(PARS-3).Results:Childhood emotional maltreatment scores were positively corre-lated with the BSMAS scores(r=0.34,P＜0.01).The loneliness partially mediated the relationship between child-hood emotional maltreatment and problematic social media use,with the mediating effect accounting for 30.75％of the total effect.Physical activity moderated the association between childhood emotional maltreatment and prob-lematic social media use(β=-0.10,P＜0.01).Conclusion:Childhood emotional maltreatment is associated with problematic social media use among college students,mediated by loneliness and moderated by physical activity.

Objective·To evaluate the clearance and pharmacokinetics/pharmacodynamics(PK/PD)of antibiotics from the perspective of protein binding rates in critically ill patients undergoing intermittent hemodialysis(IHD),in order to explore the association between protein binding rate and dialysis clearance of antibiotics,and to provide theoretical basis for developing antibiotic dosing regimens during hemodialysis.Methods·Nineteen patients undergone low-flux hemodialysis and received antibiotic therapy at the Department of Nephrology,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,were enrolled and divided into the meropenem group(n=7),the vancomycin group(n=5)and the ceftriaxone group(n=7)according to the type of antibiotics.A liquid chromatography with tandem mass spectrometry(LC-MS/MS)method was established to detect meropenem,vancomycin,and ceftriaxone in human plasma/serum and dialysate.A two-compartment pharmacokinetic model was established using MATLAB.Instantaneous and total dialysis clearance rates were calculated,and PK/PD parameters were analyzed.Results·No significant differences were found in the clinical characteristics of subjects among the three groups.The dialysis clearance rates were as follows:meropenem group(5.14?5.97 L/h)>vancomycin group(2.87?3.77 L/h)>ceftriaxone group(1.21?1.90 L/h),with statistically significant differences(P<0.001).All three antibiotics showed good fit in the two-compartment pharmacokinetic model with a dialysate chamber(fval%<2),and the calculated PK/PD parameters were consistent with previous literature.For meropenem,the fraction of time that the free drug concentration remained above the minimal inhibitory concentration(%fT>MIC)values were 95.2%,60.8%and 32.4%at minimal inhibitory concentration(MIC)values of 2,8 and 16 μg/mL,respectively.For ceftriaxone(free concentration),the%fT>MIC values were all above 45.0%at MICs of 0.25,4 and 16 μg/mL.For vancomycin,only 14.0%of the trough concentrations reached the target range of 15?20 mg/L.Conclusion·The three antibiotics are well described by the two-compartment model.The plasma protein binding rate has a significant effect on the dialysis clearance of antibiotics in low-flux IHD,with higher protein binding associated with lower clearance.The regimens of meropenem(0.5 g/d)and ceftriaxone(2.0 g/d)are generally effective among patients undergoing low-flux IHD,while the vancomycin regimen with a loading dose of 1.0 g and a maintenance dose of 0.5 g/2 d carries a risk of treatment failure.

Objective:To investigate the dynamic imaging characteristics of hepatocellular carcinoma (HCC) following Yttrium-90 selective internal radiation therapy ( 90Y-SIRT) and to compare these with imaging findings after transarterial chemoembolization (TACE). Methods:This retrospective case-control study included 24 HCC patients who received 90Y-SIRT at Zhongda Hospital, Southeast University, and West China Hospital, Sichuan University, between September 2021 and June 2023, establishing the 90Y-SIRT group. Additionally, 45 HCC patients who underwent their first TACE treatment at Zhongda Hospital, Southeast University during the same period were included as the TACE group. Patients underwent MRI and/or CT follow-ups at 1-3 months (first follow-up) and 3-6 months (second follow-up) after treatment. The analyzed imaging features included tumor characteristics, peritumoral features, and measurements of tumor and liver volumes, with postoperative change rates calculated. Imaging differences between the 90Y-SIRT and TACE groups were statistically compared using the Mann-Whitney U test or χ2 test. Results:At the first follow-up, compared to baseline, a higher proportion of lesions in the 90Y-SIRT group exhibited a reduction in arterial phase enhancement in the viable region (10/13) than in the TACE group (10/29), with a statistically significant difference ( P=0.040). The necrotic region of the tumor on T 1WI showed significantly lower signal intensity in the 90Y-SIRT group than in the TACE group ( Z=2.98, P=0.006). The change in the apparent diffusion coefficient value in the viable region compared to baseline was 157.0×10 -3(-62.0×10 -3, 311.5×10 -3) mm2/s in the 90Y-SIRT group and -56.0×10 -3 (-216.8×10 -3, 110.0×10 -3) mm2/s in the TACE group, with a statistically significant difference ( Z=-2.71, P=0.008). At the first and second follow-up, the contralateral liver lobe volume increased significantly in the 90Y-SIRT group, with a statistically significant difference from the TACE group ( Z=-3.21, -3.78, both P=0.001). Regarding peritumoral imaging characteristics, a statistically significant difference was observed between the two groups in the low signal intensity of the liver lobe or segment where the tumor waslocated during the hepatobiliary phase ( P=0.020, 0.040). Both HCC groups exhibited progressive tumor volume reduction after treatment. In the 90Y-SIRT group, the change rates of lesion volume relative to baseline at the two follow-ups were -23.0% (-45.6%, 7.9%) and -68.7% (-82.7%, -28.5%), respectively. In the TACE group, the values were -29.8% (-53.6%, -2.7%) and -38.0% (-65.3%, -10.7%). The differences between the two groups were not statistically significant ( Z=-0.52, P=0.605; Z=-1.79, P=0.073). Conclusion:There is a statistically significant difference in the tumor imaging features and peritumoral imaging characteristics between 90Y-SIRT and TACE. 90Y-SIRT demonstrates a notable advantage in promoting contralateral liver lobe regeneration while also contributing to tumor size reduction.