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.

AIM: To identify the primary active components and underlying mechanisms of Yijing Decoction(YJD)in treating early diabetic retinopathy(DR)based on liquid chromatography-mass spectrometry and network pharmacology.METHODS: Active components of YJD were characterized through LC-MS. Components with optimal ADME(absorption, distribution, metabolism, excretion)properties were selected as key bioactive candidates. Network pharmacology approaches were employed to predict YJD-DR therapeutic targets. Protein-protein interaction(PPI)networks, gene ontology(GO)enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were subsequently conducted to predict core targets and networks. Critical targets and pathways were experimentally validated through Western blot.RESULTS: Ten core therapeutic targets were identified, including TNF, Alb, EGFR, STAT3, PTGS2, ESR1, PPAR, MMP9, TLR4, and MAPK. YJD was related to cancer-related signaling, fluid shear stress and atherosclerosis, and neurodegenerative diseases, encompassing key biological processes such as inflammatory response regulation, programmed cell death activation, and enhanced cell migration. Furthermore, Western blot analysis confirmed that YJD significantly inhibited high glucose-induced phosphorylation of STAT3(P-STAT3/STAT3)and ERK(P-ERK/ERK)in rat retinal microvascular endothelial cells.CONCLUSION: This study revealed YJD's pharmacodynamical basis and its multi-component, multi-target, and multi-paths pharmacology. YJD exerts therapeutic effects on DR by coordinately regulating critical signaling pathways and alleviating intraocular inflammation, thus preserving retinal vascular endothelial cells, maintaining blood-retinal barrier integrity, and facilitating retinal neurovascular repair.

The concept of holism is the core idea of traditional Chinese medicine （TCM）. Various organs and tissues coordinate with each other to maintain the body's life activities， with a close and mutual influence between the spleen， stomach， and the central nervous system （brain）. The gut-brain axis plays an important bridging role between the digestive system and the central nervous system， achieving bidirectional information exchange between the brain and the gastrointestinal tract through complex neuroendocrine and immune mechanisms. The theory of cross-organ interaction involves the mutual influence， coordination， and integration between different organs and systems； multimodality， on the other hand， utilizes multiple sensory modalities， such as vision， hearing， and touch， to convey information. By combining TCM theory with the gut-brain axis theory， a cross-organ multimodal characterization system is established to explore its mechanism and application value in refractory diseases such as functional gastrointestinal disorders， precancerous gastrointestinal diseases， Alzheimer's disease， Parkinson's syndrome， type 2 diabetes， and depression.

Objective:To investigate whether exosomes derived from atorvastatin (ATV)-pretreated human umbilical cord mesenchymal stem cells (ATV-MSC-EXO) alleviate high glucose-induced injury in human retinal vascular endothelial cells (HREC) via the protein kinase B (AKT)/endothelial nitric oxide synthase (eNOS) signaling pathway.Methods:The optimal pretreatment concentration of ATV was determined using the cell counting Kit-8 (CCK-8) assay. Exosomes derived from mesenchymal stem cells (MSC-EXO) and ATV-pretreated MSC (ATV-MSC-EXO) were isolated and extracted, and their morphology and surface markers were characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting (WB). The uptake capacity of exosomes by human retinal vascular endothelial cells (HREC) was evaluated using a fluorescence labeling assay. In vitro cultured HREC were divided into the following groups: normal control group (NC group), high glucose group (HG group), high glucose+MSC-EXO group (MSC-EXO group), high glucose+ATV-MSC-EXO group (ATV-MSC-EXO group), high glucose+ATV-MSC-EXO+AKT inhibitor group (ATV-MSC-EXO-MK-2206-2HCL group), and high glucose+ATV-MSC-EXO+eNOS inhibitor group (ATV-MSC-EXO-L-NAME group). Cell proliferation and apoptosis were detected using CCK-8 and flow cytometry, respectively. The protein expression levels of B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2-associated protein (Bax), and Caspase-3 were measured by WB. In addition, the regulatory effects of ATV-MSC-EXO on the AKT/eNOS signaling pathway and its downstream functional molecules were analyzed by detecting the phosphorylation levels of AKT (P-AKT/AKT) and eNOS (P-eNOS/eNOS) via WB, the mRNA expression levels of AKT and eNOS by quantitative real-time polymerase chain reaction, and the concentrations of nitric oxide (NO) and endothelin-1 (ET-1) using commercial NO and ET-1 assay kits.Results:The optimal pretreatment concentration of ATV was 1 μmol/L. ATV-MSC-EXO exhibited similar morphology and particle size to MSC-EXO and were efficiently taken up by HREC. Under high glucose conditions, ATV-MSC-EXO significantly enhanced the viability of HREC ( F=83.24, P<0.000 1) and inhibited apoptosis ( F=77.39, P<0.000 1). WB analysis further confirmed that ATV-MSC-EXO upregulated the expression of the anti-apoptotic protein Bcl-2 ( F=53.17), while downregulating the pro-apoptotic proteins Bax ( F=36.49) and Caspase-3 ( F=60.75) ( P<0.001). In addition, ATV-MSC-EXO markedly increased the protein levels of P-AKT/AKT ( F=107.60) and P-eNOS/eNOS ( F=38.59), as well as the relative mRNA expression of AKT, eNOS ( F=203.60, 315.00; P<0.000 1). Furthermore, ATV-MSC-EXO promoted NO production ( F=407.40) and suppressed the relative expression of ET-1 ( F=49.76) ( P<0.000 1). Conclusion:ATV-MSC-EXO enhances the viability and inhibits apoptosis of HREC under high glucose conditions by activating the AKT/eNOS signaling pathway.

Objective:To evaluate the efficacy of modified splenic arteriovenous shunt surgery at the distal pancreatic tail in combined pancreas-kidney transplantation.Methods:A retrospective analysis was conducted on 24 recipients who underwent combined pancreas-kidney transplantation with the modified splenic arteriovenous shunt at the pancreatic tail from November 2023 to October 2024 (shunt group) and 231 recipients who received conventional splenic artery and vein ligation since 2016 (ligation group). The incidence of perioperative thrombosis and severe adverse events was compared between the two groups using the chi-square test or Fisher's exact test. Independent sample t-tests were performed to assess postoperative pancreatic and renal function recovery as well as blood perfusion in 15 recipients from the shunt group and 20 from the ligation group who underwent CT perfusion imaging (CTP).Results:The incidence of perioperative splenic arteriovenous thrombosis was lower in the shunt group (0) compared to the ligation group (4.76%, 11/231), though the difference was not statistically significant ( P=0.606). One month postoperatively, the shunt group demonstrated significantly lower serum amylase levels than the ligation group (99.61±19.62 vs. 148.20±70.67 U/L, P=0.018). However, at the time of CTP examination, serum lipase (67.87±32.35 vs. 45.11±17.94 U/L, P=0.014) and creatinine levels (131.79±26.41 vs. 112.1±24.98 μmol/L, P=0.034) were significantly higher in the shunt group. Urea nitrogen levels were also significantly higher in the shunt group both one month postoperatively (11.24±4.64 vs. 8.51±3.01 mmol/L, P=0.043) and at the CTP examination (10.41±1.78 vs. 6.87±1.91 mmol/L, P=0.001). Regarding pancreatic perfusion, blood volume in both the pancreatic head (15.99 ± 3.51 vs. 20.67 ± 5.47 ml/100 g, P = 0.024) and tail (17.19±4.24 vs. 27.40±19.80 ml/100 g, P=0.039) was significantly lower in the shunt group. After one minute of splenic artery perfusion, the shunt group exhibited significantly higher splenic artery blood flow (755.85±101.50 vs. 574.00 ± 142.06 ml·min -1· (100 g) -1, P<0.001) and blood volume (58.90 ±19.93 vs. 23.21±17.02 ml/100 g, P=0.007) compared to the ligation group. These differences persisted after two minutes of perfusion (blood flow: 793.83±68.57 vs. 503.78 ± 130.80 ml·min -1· (100 g) -1, P<0.001; blood volume: 64.22±15.74 vs. 34.32±20.39 ml/100 g, P=0.002). For the transplanted kidney, the shunt group had significantly lower blood flow (113.10±28.55 vs. 232.76±113.37 ml·min -1· (100 g) -1, P<0.001), blood volume (28.95±10.79 vs. 38.36±12.38 ml/100 g, P=0.047), and capillary surface permeability (PS) (26.49±16.57 vs. 43.02±20.37, P = 0.042) in the upper pole. Similar reductions in blood flow, blood volume, and PS were observed in the middle dorsal region ( P=0.018, 0.021, and 0.048, respectively) and lower pole ( P<0.001, P=0.048, and P=0.012, respectively). Conclusion:The modified splenic arteriovenous shunt at the pancreatic tail appears to be a safe and effective approach to reducing the risk of pancreatic graft thrombosis. This technique facilitates effective diversion of pancreatic parenchymal blood flow into the splenic vein, alleviating hyperperfusion of the transplanted pancreas. While renal blood perfusion was reduced postoperatively, it did not adversely affect renal function.

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.

Endometrial cancer is one of the common malignant tumors of the female reproductive system.Its incidence rate in China is second only to cervical cancer,posing a serious threat to women's life and health,and the onset shows a trend of affecting younger individuals.Currently,the primary treatment for endometrial cancer is surgical intervention,and some postoperative patients and those with postoperative recurrence require adjuvant radiotherapy.Pelvic external beam radiotherapy(EBRT)and vaginal brachytherapy(VBT)are two modalities of postoperative radiotherapy.The appropriate postoperative radiotherapy approach should be selected based on individual conditions and guideline recommendations.Most patients can achieve satisfactory treatment outcomes through surgery and postoperative adjuvant radiotherapy.However,the specific indications for postoperative radiotherapy in endometrial cancer patients and the radiotherapy principles for those with postoperative recurrence are relatively complex,and recommendations for radiotherapy modalities in postoperative patients vary slightly across different guidelines.This article reviews the treatment principles for endometrial cancer patients in recent years,as well as the indications for postoperative and post operative recurrent radiotherapy and the radiotherapy techniques,aiming to provide a reference for radiotherapy in the endometrial cancer patients.