Objective To preliminarily investigate the safety and efficacy of donor pancreas needle biopsy in simultaneous pancreas-kidney transplantation. Methods Clinical data of 7 cases undergoing donor pancreas biopsy were collected retrospectively. All cases underwent donor pancreas biopsy before or during simultaneous pancreas-kidney transplantation. Frozen section or paraffin sectioning techniques were used for tissue preparation, and hematoxylin-eosin and Masson staining were performed to histologically evaluate the donor pancreas. The quality of donor pancreas was comprehensively assessed by combining histological findings with the donor's clinical data. Postoperative follow-up data of 5 simultaneous pancreas-kidney transplant recipients were collected to summarize the safety of donor pancreas biopsy and the prognosis of transplant recipients. Results The 7 pancreas donors were aged 28 to 62 years, with a body mass index ranging from 20.76 to 27.68 kg/m². Liver ultrasound indicated fatty liver in 3 cases, while pancreatic ultrasound did not reveal any significant abnormalities. Among them, biopsy was performed on 2 donors after completion of pancreatic procurement and processing, and the frozen section histology showed moderate acute pancreatitis changes (edema of acinar cells, necrosis and inflammatory cell infiltration). Combined with a serum amylase level elevated more than 3 times the upper limit of normal value, these two donor pancreases were finally discarded. The remaining 5 cases underwent biopsy immediately after pancreatic vascular anastomosis during simultaneous pancreas-kidney transplantation, and histological evaluation was performed on paraffin-embedded sections. No biopsy-related complications (such as bleeding, pancreatic fistula, etc.) occurred after transplantation. One recipient died of severe infection 2 months after transplantation, while the other 4 recipients were followed up for more than 5 years, with well-functioning transplant kidneys and pancreases. Conclusions Donor pancreas biopsy is relatively safe, and the risk of biopsy-related complications after transplantation is controllable. Comprehensive assessment of donor pancreas quality by combining histological evaluation with the donor's clinical indicators is conducive to improving the accuracy of donor pancreas selection and organ utilization.

OBJECTIVE: To discuss the elbow skin fold extension line in Kirschner wire internal fixation of extended supracondylar humeral fractures in children. METHODS: The clinical data of 58 children with extended supracondylar fractures of the humerus who met the selection criteria between August 2021 and July 2024 were retrospectively analyzed. In 28 cases, needle placement of medial epicondyle of humerus was performed with the assistance of the elbow skin fold extension line (study group), and 30 cases were assisted by routine touch of the medial epicondyle of the humerus (control group). There was no significant difference in baseline data such as gender, age, side, cause of injury, Gartland type, Kirschner wire configuration, and time from injury to operation between the two groups ( P>0.05). The closed reduction rate, total operation time, time of medial humeral condyle pin placement, fluoroscopy times during medial pin placement, rate of one-time determination of medial entry point, ulnar nerve injury incidence, and fracture healing time were recorded and compared between the two groups. At the same time, the closed reduction rate of patients with the time from injury to operation ≤24 hours and >24 hours was compared. The elbow function was evaluated by Mayo elbow function score. RESULTS: The closed reduction rate of the study group was significantly higher than that of the control group ( P<0.05). Among all patients, the closed reduction rate of patients with the time from injury to operation ≤24 hours [73.3% (22/30)] was significantly higher than that of patients >24 hours [42.9% (12/28)] ( χ ²=5.545, P=0.019). The total operation time, medial needle placement time, and fluoroscopy times in the study group were significantly less than those in the control group, and the one-time determination rate of medial needle entry point in the study group was significantly higher than that in the control group ( P<0.05). There were 4 cases of ulnar nerve injury in the control group, and no ulnar nerve injury in the study group, but there was no significant difference in the incidence of ulnar nerve injury between the two groups ( P>0.05). All patients were followed up 6-12 months (mean, 8 months). There was no bone nonunion in both groups, and the fracture healing time of the study group was significantly shorter than that of the control group ( P<0.05). Volkmann ischemic contracture, heterotopic ossification, myositis ossificans, and premature epiphyseal closure were not observed after operation. No complications such as loosening or fracture of Kirschner wire occurred. At last follow-up, the Mayo elbow joint function score was used to evaluate function, and there was no significant difference between the two groups ( P>0.05). CONCLUSION In the treatment of extended supracondylar fractures of the humerus in children, the elbow skin fold extension line can help to quickly locate the medial epicondyle of the humerus, quickly insert Kirschner wire, and reduce the operation time and trauma.
Humans ; Humeral Fractures/surgery* ; Bone Wires ; Male ; Female ; Fracture Fixation, Internal/instrumentation* ; Retrospective Studies ; Child ; Elbow Joint/physiopathology* ; Child, Preschool ; Treatment Outcome ; Fracture Healing ; Ulnar Nerve/injuries* ; Adolescent ; Range of Motion, Articular

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective:To explore the efficacy of interventional therapy for transplant renal artery stenosis (TRAS) and the 1-, 2-, and 3-year survival rates of recipients after treatment.Methods:This is a retrospective case series study. Forty TRAS recipients who underwent interventional treatment at Zhengzhou University People's Hospital between April 2016 and April 2021 were included as the study group. The Kaplan-Meier method was used to calculate the survival rates of the transplanted kidneys and recipients, and survival curves were plotted. The improvement in graft function and blood pressure after interventional therapy in the study group was further analyzed.Results:The 1- and 3-year graft survival rates in the study group after interventional therapy were 87.5% and 82.5%, respectively; the 1-, 2-, and 3-year recipient survival rates were all 100%. One month after interventional therapy, the peak systolic velocity (PSV) and resistance index (RI) of the transplanted kidneys were (235.4±135.1) cm/s and 0.60±0.07, respectively, which were significantly different from the pre-treatment values [(482.8±180.6) cm/s and 0.52±0.12, respectively; both P<0.001]. Serum creatinine levels at 1, 2, and 3 years after interventional therapy were (166.6±93.7) μmol/L, (137.4±57.2) μmol/L, and (137.4±57.9) μmol/L, respectively, all significantly lower than the pre-treatment level [(242.9±156.8) μmol/L; P=0.001, P<0.001, and P<0.001, respectively]. Systolic blood pressure at 1, 2, and 3 years after treatment was (138.5±11.1) mmHg (1 mmHg=0.133 kPa), (134.0±12.0) mmHg, and (130.8±10.8) mmHg, respectively, all significantly lower than the pre-treatment value [(153.8±9.8) mmHg; all P<0.001]. Diastolic blood pressure at 1, 2, and 3 years after treatment was (84.4±9.9) mmHg, (83.7±10.1) mmHg, and (81.9±6.9) mmHg, respectively, all significantly lower than the pre-treatment value [(93.5±12.8) mmHg; P=0.002, P=0.001, and P<0.001, respectively]. Conclusions:Interventional therapy can enable the majority of kidney transplant recipients diagnosed with TRAS to avoid the need for further dialysis, and it has positive effects on both transplant renal function and blood pressure control.

Objective:To investigate the efficacy of virtual simulation-guided unilateral locking plate combined with Jail screw technique for double column tibial plateau fractures involving the posterolateral plateau.Methods:A retrospective case series study was conducted to analyze the clinical data of 32 patients with double column tibial plateau fractures involving the posterolateral plateau admitted to Nanjing Drum Tower Hospital Group Suqian Hospital from March 2018 to March 2022, including 20 males and 12 females, aged 37-69 years [(47.5±6.9)years]. According to AO/OTA classification, the fractures were classified as type 41B in 17 patients and type 41C in 15. According to the three-column classification, the fractures were classified as lateral column+posterior column in 17 patients and medial column+posterior column in 15. Virtual simulation technique was used to simulate surgical operation before surgery. After reduction, the patients′ tibial plateau mirror models of the healthy side were used to simulate the implantation of internal fixators on the affected side. The position data of the placed internal fixators were obtained to guide the personalized treatment with unilateral locking plate combined with Jail screw technique. The total number of Jail screws, average number of Jail screws, distribution and accuracy of screw placement, operative duration, intraoperative blood loss, and fracture healing status were recorded. The posterior tibial plateau angle (PTSA), proximal medial tibial angle (MPTA) and Rasmussen anatomical score were compared before operation, at 1, 3, 6, 12 months after operation and at the last follow-up. The Lysholm scores at 6, 12 months after operation and at the last follow-up were used to evaluate the knee function. At the last follow-up, the knee range of motion was measured. Postoperative complications were observed.Results:All the patients were followed up for 28-36 months [(30.7±2.3)months]. The total number of Jail screws inserted was 48, with an average of (1.5±0.5) screws. In the sagittal direction, 1-2 Jail screws were inserted in each patient, with an accuracy rate of 88% (42/48). The operative duration was 78-116 minutes [(98.7±10.5)minutes]. The intraoperative blood loss was 70-120 ml [(96.6±15.6)ml]. All the fractures had healing of stage I, with a healing time of 4-7 months [(5.4±0.9)months]. At 1, 3, 6, 12 months after operation and at last follow-up, the PTSA, MPTA, and Rasmussen anatomical scores were significantly improved when compared with those before operation ( P<0.05), while there was no statistically significant difference between those at various postoperative time points ( P>0.05). The Lysholm knee scores were (83.6±3.9)points, (88.5±3.6)points, and (93.7±2.6)points at 6, 12 months after operation, and at the last follow-up, respectively, which were gradually increased with the passage of the follow-up time ( P<0.05). The range of motion was (121.4±4.6)° in flexion and was 0.0(0.0, 3.0)° in extension at the last follow-up. Two patients had superficial wound infection and 1 had wound dehiscence after operation, which recovered with dressing change or debridement and suturing. No deep infection, vascular injury or nerve damage occurred. Conclusions:The virtual simulation-guided unilateral locking plate combined with Jail screw technique has the advantages of high accuracy of screw placement, shorter operative duration, less intraoperative blood loss, satisfactory fracture reduction, favorable recovery of knee function and range of motion, and fewer postoperative complications in the treatment of double column tibial plateau fractures involving the posterolateral plateau.

Objective:To explore the cut-off value of metastatic lymph node ratio (LNR) for stage N3 gastric cancer and construct a new TNM staging system to predict prognosis.Methods:Clinical data of 4 291 patients from Jan 2004 to Dec 2020 in the SEER database and 567 patients from Jan 2016 to Dec 2020 in the First Affiliated Hospital of Zhengzhou University with stage N3 gastric cancer were collected. A new TNrM staging system and a nomogram model were constructed based on the optimal LNR cut-off value and compared with the 8th TNM staging model in terms of prognostic discrimination, prognostic prediction accuracy, and clinical usefulness.Results:The optimal cut-off value of LNR was 0.5. A TNrM staging system was constructed by combining the Nr stage with the T stage. Univariate and multivariate COX regression analyses showed that the TNrM staging system was a significant prognostic factor (all P<0.05). Based on the 8th TNM and TNrM staging system, two nomograms were constructed in the training set and externally validated in the validation set. Compared with the TNM staging model, the TNrM staging model had a larger C-index and area of time-dependent ROC curve(AUC) (training set: 3-year AUC: 66.5 vs. 74.4, 5-year AUC: 68.9 vs. 75.3; validation set: 3-year AUC: 62.3 vs. 73.1, 5-year AUC: 62.6 vs. 75.8), its overall survival prediction curves were closer to the ideal curve in the calibration curve, and its clinical net benefit was greater in the decision curves. Conclusions:Stage N3 gastric cancer patients with a metastatic lymph node ratio >0.5 have a poor prognosis. The TNrM staging nomogram model constructed based on the lymph node ratio has better prognostic discrimination ability and prediction accuracy and more clinical net benefits compared to the 8th edition of TNM staging nomogram model.

Aim To investigates whether sphingosine-1-phosphate(S1P)regulates the expression of mitochon-drial calcium uniporter(MCU)via the sphingosine-1-phosphate receptor/proline-rich tyrosine kinase 2(S1PR/Pyk2)sig-naling pathway,thereby reducing oxidative stress-induced mitochondrial damage and inhibiting mitochondria-related apopto-sis.Methods Human umbilical vein endothelial cells(HUVEC)were subjected to oxidative damage using hydrogen peroxide(H2O2)as a model.Different concentrations of S1P were applied to the oxidative damaged HUVEC.Addi-tionally,the S1PR1 agonist SEW2871,the S1PR1 inhibitor W146,and the Pyk2 inhibitor PF-562271 were used to explore the specific mechanism of S1P action.Results S1P treatment significantly alleviated oxidative damage in HUVEC and was accompanied by an increase in S1PR1 expression(P<0.05),while S1PR3 expression remained unchanged.Mean-while,the expression levels of Pyk2 and MCU decreased(P<0.05).SEW2871 further reduced mitochondrial damage,whereas W146 exacerbated it(P<0.05).Furthermore,the application of the Pyk2 inhibitor PF-562271 also reduced H2O2-induced mitochondrial damage(P<0.05),further confirming the role of Pyk2 in this process.Conclusion S1P reduces H2O2-induced mitochondrial damage and inhibits mitochondria-related apoptosis in HUVEC by suppressing Pyk2 expression via S1PR1.

BACKGROUND:It has been found that abnormal apoptosis of bone tissue cells induced by abnormal iron metabolism plays an important role in the progression of osteoporosis. OBJECTIVE:To investigate the effect of naringin on iron metabolism and cell apoptosis in bone tissue of rats with osteoporosis. METHODS:Fifty 2-month-old female Sprague-Dawley rats were randomly divided into five groups with 10 rats in each group:sham group,osteoporosis group,naringin low-dose group,naringin high-dose group,and naringin high-dose+DKK-1 group.Except for the sham group,rat models of osteoporosis were established by removing bilateral ovarian tissues in the other groups.At 8 weeks after modeling,rats in the naringin low-and high-dose groups were given 100 and 400 mg/kg/d naringenin by gavage,respectively,and rats in the naringenin high dose+DKK-1 group were given 400 mg/kg/d naringin by gavage and subcutaneous injection of 25 mg/kg/d DKK-1,an inhibitor of the Wnt1 signaling pathway,for 7 consecutive days.Relevant indexes were detected after administration. RESULTS AND CONCLUSION:Compared with the osteoporosis group,naringin could enhance the bone mineral density and serum calcium and superoxide dismutase levels in rats(P<0.05),and reduce the serum levels of osteocalcin,malondialdehyde,and phosphorus(P<0.05),while DKK-1 could partially inhibit the interventional effect of naringin(P<0.05).Results from Micro-CT scanning,hematoxylin-eosin and TUNEL staining showed that compared with the osteoporosis group,naringin significantly improved bone microstructure and reduced the rate of cell apoptosis,while DKK-1 partially inhibited the interventional effect of naringin.Immunofluorescence staining results showed that compared with the osteoporosis group,naringin could reduce the oxygen content,anti-tartaric acid phosphatase expression,and elevate the expression of alkaline phosphatase in active tibia tissues(P<0.05),while DKK-1 could partially inhibit the interventional effect of naringin(P<0.05).Results from Prussian blue staining and immunohistochemical staining showed that compared with the osteoporosis group,naringin reduced iron deposition in bone and liver tissues as well as the expression of transferrin receptor 1(P<0.05),and elevated the protein expression of ferroportin 1(P<0.05)in bone tissue,and DKK-1 partially inhibited the intervention of naringin(P<0.05).PCR and western blot assay of tibia specimens showed that compared with the osteoporosis group,naringin decreased the expression of anti-tartrate acid phosphatase,transferrin receptor 1 and Bax(P<0.05),and elevated the expression of alkaline phosphatase,ferroportin 1,Bcl-2,Wnt1 and β-catenin(P<0.05),while DKK-1 partially inhibited the interfering effect of naringin(P<0.05).To conclude,naringin inhibits the progression of osteoporosis by reducing iron deposition and apoptosis rate in bone tissue,which may be related to the activation of the Wnt1 signaling pathway.

Aim To investigates whether sphingosine-1-phosphate(S1P)regulates the expression of mitochon-drial calcium uniporter(MCU)via the sphingosine-1-phosphate receptor/proline-rich tyrosine kinase 2(S1PR/Pyk2)sig-naling pathway,thereby reducing oxidative stress-induced mitochondrial damage and inhibiting mitochondria-related apopto-sis.Methods Human umbilical vein endothelial cells(HUVEC)were subjected to oxidative damage using hydrogen peroxide(H2O2)as a model.Different concentrations of S1P were applied to the oxidative damaged HUVEC.Addi-tionally,the S1PR1 agonist SEW2871,the S1PR1 inhibitor W146,and the Pyk2 inhibitor PF-562271 were used to explore the specific mechanism of S1P action.Results S1P treatment significantly alleviated oxidative damage in HUVEC and was accompanied by an increase in S1PR1 expression(P<0.05),while S1PR3 expression remained unchanged.Mean-while,the expression levels of Pyk2 and MCU decreased(P<0.05).SEW2871 further reduced mitochondrial damage,whereas W146 exacerbated it(P<0.05).Furthermore,the application of the Pyk2 inhibitor PF-562271 also reduced H2O2-induced mitochondrial damage(P<0.05),further confirming the role of Pyk2 in this process.Conclusion S1P reduces H2O2-induced mitochondrial damage and inhibits mitochondria-related apoptosis in HUVEC by suppressing Pyk2 expression via S1PR1.

Objective To analyze the correlation between ferroptosis and post operative cognitive dysfunction(POCD)in elderly patients with fractures.Methods A total of 120 elderly patients with fracture were divided into the control group and the POCD group according to whether POCD occurred,with 60 cases in each group.Basic data of the two groups were collected.The levels of nerve injury indicators[brain myelin basic protein(MBP),glial fibrillary acidic protein(GFAP)],and fractures markers[glutathione peroxidase 4(GPX4),cyclooxygenase 2(COX2),long-chain acyl-CoA synthase 4(ACSL4)]were detected by enzyme-linked immunosorbent assay at 6 h after surgery.Logistic regression was used to analyze risk factors of POCD in elderly patients with fracture.The correlations between MBP,GFAP and GPX4,COX2 and ACSL4 were analyzed by Pearson correlation analysis.Receiver operating characteristic(ROC)curves were used to analyze predictive values of MBP,GFAP,GPX4,COX2 and ACSL4 levels to POCD.Results The age,proportion of general anesthesia,anesthesia time,intraoperative blood loss and MBP,GFAP,COX2,ACSL4 levels were higher in the POCD group than those in the control group(P＜0.05),while GPX4 was lower than that in the control group(P＜0.05).The levels of MBP and GFAP were negatively correlated with levels of GPX4 in elderly patients with fractures,and positively correlated with levels of COX2 and ACSL4(P＜0.05).Advanced age,general anesthesia,long duration of anesthesia,increased levels of MBP,GFAP,COX2 and ACSL4,and decreased level of GPX4 were independent risk factors for POCD in elderly fracture patients(P＜0.05).The critical values of GPX4,COX2 and ACSL4 for predicting POCD in elderly patients with fractures were GPX4≤23.05 μg/L,COX2≥20.35 μg/L and ACSL4≥237.85 μg/L,and the AUC were 0.869,0.736 and 0.841.The sensitivity was 76.67%,68.33%and 88.33%,and the specificity was 86.67%,78.33%and 75.00%,respectively.The diagnostic efficacy of GFAP,COX2 and ACSL4 was higher than that of MBP and GFAP.Conclusion The incidence of POCD in elderly patients with fracture is associated with ferroptosis,and levels of GPX4,COX2 and ACSL4 have certain predictive value for the incidence of POCD after surgery in elderly patients with fracture.