Flap transplantation is a critical surgical strategy for the reconstruction of tissue defects caused by trauma, tumor resection, and congenital malformations, and its survival rate directly determines surgical efficacy and patient prognosis. Following transplantation, flaps inevitably undergo ischemia-reperfusion (I/R) injury, during which oxidative stress, inflammatory responses, and metabolic disturbances are intricately intertwined, ultimately leading to cellular injury and tissue necrosis. Recent studies have demonstrated that multiple forms of programmed cell death—including apoptosis, pyroptosis, ferroptosis, necroptosis, and PANoptosis—play central roles in flap I/R injury. The extensive crosstalk and molecular interactions among these pathways form a highly complex cell death network. Specifically, apoptosis is mediated by the imbalance of Bcl-2 family proteins and the activation of cysteine-dependent aspartate-specific protease (caspase) cascades; pyroptosis is driven by the NLRP3-caspase-1-GSDMD axis, resulting in membrane pore formation and the release of pro-inflammatory cytokines; ferroptosis is characterized by iron-dependent lipid peroxidation and dysfunction of glutathione peroxidase 4 (GPX4); necroptosis is triggered by the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3-MLKL signaling complex, leading to membrane rupture; and PANoptosis represents an integrated form of inflammatory cell death that coordinates multiple death pathways. Importantly, these forms of programmed cell death are not independent but are interconnected through extensive signaling crosstalk. Key regulatory molecules, including caspase-8, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2), collectively modulate the dynamic balance among these pathways. Therefore, the multidimensional interplay and spatiotemporal dynamics of programmed cell death constitute a fundamental pathological basis of flap I/R injury. This review systematically summarizes the latest advances in the mechanisms and interactions of various programmed cell death pathways in flap I/R injury, aiming to elucidate the underlying regulatory network. These insights may provide novel theoretical foundations for optimizing flap protection strategies, improving flap survival, and promoting tissue repair.

Purpose: Due to recent shifts in healthcare reimbursement models, more primary total hip arthroplasties (THAs) are now being performed in the outpatient setting. However, there is a lack of knowledge around the comparative outcomes of revision outpatient THA. Materials and Methods: Adults undergoing revision THA between 2010 and 2020 with 2-year follow-up data were identified on a large insurance claims database. Following stratification by inpatient versus outpatient revision THA, patients from both groups were matched 1:1 by demographics and revision characteristics. Ninety-day postoperative medical and 1- and 2-year postoperative surgical complications after matching were compared. Results: Among 67,570 patients, mean age was 65.3 years, 57.0% were female, and mean Charlson comorbidity index score was 1.72. Subsequent to 1:1 matching, 1,555 inpatient and outpatient revision THA patients were identified. Outpatient THA patients had significantly lower rates of blood transfusions (3.6% vs 5.1%, P=0.049), broken prosthesis (1 year: 0.1% vs.0.6%, P=0.027; 2 years: 0.2% vs. 0.9%, P=0.015), and other postoperative mechanical complications (1 year: 4.9% vs. 7.1%, P=0.010; 2 years: 6.2% vs. 8.4%, P=0.023). Otherwise, the data for outpatient THA patients was not statistically different from inpatient THA patients across all studied complications. Conclusion Outpatient revision THA may be a safe alternative to inpatient revision THA for carefully selected patients. Establishing patient- and case-specific parameters to optimize outcomes, satisfaction, safety, and value is critical.

Purpose: In the existing literature, isolated femoral head and polyethylene liner exchange is commonly performed in revision total hip arthroplasty (THA) for a variety of indications with mixed outcomes. The purpose of this study is to investigate patient outcomes following head-liner exchange and risk factors associated with failure in THA. Materials and Methods: A retrospective chart review from May 2016 to November 2023 was conducted on patients who underwent isolated head-liner exchange at two institutions. Patients had minimum 1-year follow-up periods. For each patient, data such as indication for revision, surgical approach, revision head size, immediate and short-term complications, postoperative disposition, 90-day readmissions, and re-operations were recorded. Results: Out of 175 patients, there were 24 readmissions/emergency department visits within 90 postoperative days (13.7%), 21 subsequent revision surgeries (12.0%), 21 postoperative dislocations (12.0%), and 20 immediate postoperative complications (11.4%). A statistically significant association was demonstrated between indication for revision and postoperative instability (P=0.04). Patients operated upon for instability had higher rates of postoperative instability. Furthermore, patients with reported preoperative dislocation events had higher incidences of postoperative dislocations. Patients discharged to skilled nursing facilities (SNF) were associated with an increased number of hospital readmissions within 90 days of surgery, reoperation, and postoperative dislocation (P<0.05). No statistically significant associations were found between surgical approach and complications. Conclusion This study suggests that, in the context of isolated head-liner exchanges, factors such as preoperative dislocation history, indication for revision, and discharge to SNF are associated with poorer outcomes and complications.

Human NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavoenzyme expressed at high levels in multiple solid tumors, making it an attractive target for anticancer drugs. Bioactivatable drugs targeting NQO1, such as β-lapachone (β-lap), are currently in clinical trials for the treatment of cancer. β-Lap selectively kills NQO1-positive (NQO1⁺) cancer cells by inducing reactive oxygen species (ROS) via catalytic activation of NQO1. In this study, we demonstrated that cryptotanshinone (CTS), a naturally occurring compound, induces NQO1-dependent necrosis without affecting NQO1 activity. CTS selectively kills NQO1⁺ cancer cells by inducing NQO1-dependent necrosis. Interestingly, CTS directly binds to NQO1 but does not activate its catalytic activity. In addition, CTS enables activation of JNK1/2 and PARP, accumulation of iron and Ca²⁺, and depletion of ATP and NAD⁺. Furthermore, CTS selectively suppressed tumor growth in the NQO1⁺ xenograft models, which was reversed by NQO1 inhibitor and NQO1 shRNA. In conclusion, CTS induces NQO1-dependent necrosis via the JNK1/2/iron/PARP/NAD⁺/Ca²⁺ signaling pathway. This study demonstrates the non-enzymatic function of NQO1 in inducing cell death and provides new avenues for the design and development of NQO1-targeted anticancer drugs.

Nuclear receptor corepressor (NCoR1) interacts with various nuclear receptors and regulates the anabolism and catabolism of lipids. An imbalance in lipid/energy homeostasis is also an important factor in obesity and metabolic syndrome development. In this study, we found that the deletion of NCoR1 in intestinal epithelial cells (IECs) mainly activated the nuclear receptor PPARα and attenuated metabolic syndrome by stimulating thermogenesis. The increase in brown adipose tissue thermogenesis was mediated by gut-derived tricarboxylic acid cycle intermediate succinate, whose production was significantly enhanced by PPARα activation in the fed state. Additionally, NCoR1 deletion derepressed intestinal LXR, increased cholesterol excretion, and impaired duodenal lipid absorption by decreasing bile acid hydrophobicity, thereby reversing the possible negative effects of intestinal PPARα activation. Therefore, the simultaneous regulatory effect of intestinal NCoR1 on both lipid intake and energy expenditure strongly suggests that it is a promising target for developing metabolic syndrome treatment.

In order to guide clinical blood transfusion practices for pediatric patients, the National Health Commission has released the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Considering the physiological particularities of the neonatal period, blood transfusion practices for neonates are more complex than those for other children, the guidelines include a separate chapter dedicated to neonatal blood transfusion. This paper interprets the background and evidence for the compilation of the neonatal blood transfusion provisions, hoping to aid in the understanding and implementation of the neonatal blood transfusion section of the guidelines.
Humans ; Infant, Newborn ; Blood Transfusion/standards* ; Practice Guidelines as Topic

Background::Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys. Methods::This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models. Results::A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69] vs. 35.0% [28/80] vs. 51.8% [29/56], P <0.001). In the univariable competing risk analysis, the cumulative regression rate was statistically significantly lower ( P = 0.008), while the cumulative progression rate was higher ( P = 0.017) in ESCdys patients with CDKN2A deletion than in those without CDKN2A deletion. CDKN2A deletion was also an independent predictor of prognosis in ESCdys ( P = 0.004) in the multivariable analysis. Conclusion::The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.

Objective:To investigate the effect of Shenfu injection on serum pepsinogen (PG) Ⅰ, PG Ⅱ and gastrin 17 (G17) in sepsis patients with acute gastrointestinal injury (AGI).Methods:From June 2021 to December 2022, a single-center randomized controlled clinical study was conducted to select patients with sepsis complicated with acute gastrointestinal injury (AGI) admitted to the ICU of the Affiliated Hospital of Xuzhou Medical University. Patients were randomly (random number) divided into Shenfu group and control group. All patients were given routine treatment of sepsis according to the guidelines, including treatment of primary disease, fluid resuscitation and supportive management. The Shenfu group was treated with Shenfu injection at the same time as routine treatment. The gastrointestinal injury indicators (PGⅠ, PGⅡ, G17 and AGI grades) before treatment and on the 3rd and 7th days of treatment, and duration of mechanical ventilation and length of ICU stay of the two groups were recorded and compared.Results:A total of 89 sepsis patients with AGI were enrolled, including 44 patients in the Shenfu group and 45 patients in the control group. Before treatment, there was no statistically significant difference in serum PGⅠ, PGⅡ, and G17 between the two groups of patients (all P>0.05). On the 3rd day of treatment, the serum PGⅠ levels in the Shenfu group were significantly lower than the control group [(156.46±62.90) μg/L vs. (183.03±45.44) μg/L, P<0.05]. There was no statistically significant difference in serum PGⅡ and G17 levels between the two groups (both P>0.05). On the 7th day of treatment, the serum levels of PG I, PG II, and G17 in the Shenfu group were significantly lower than those in the control group [(107.97±23.18) μg/L vs. (154.78±33.11) μg/L, (10.73±5.62) μg/L vs. (13.83±6.30) μg/L, (7.31±3.20) pmol/L vs. (9.29±3.92) pmol/L, all P<0.05]. The AGI grading, duration of mechanical ventilation, and length of ICU stay in Shenfu group were significantly reduced than those in the control group (all P<0.05). Conclusion:Shenfu injection can improve the serum gastric function, lower AGI grading, reduce mechanical ventilation time, and the length of ICU stay in sepsis patients with AGI.

Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells (ECs), to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Lineage-tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, evidence of trans-differentiation of GBM cells into vascular cells was barely detected. Intriguingly, GBM cells could promiscuously express markers for mural cells during gliomagenesis. Furthermore, single-cell RNA sequencing showed that patterns of copy number variations (CNVs) of mural cells and ECs were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Importantly, single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages. Rather than expansion owing to trans-differentiation, vascular cell expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.
Mice ; Animals ; Humans ; Glioblastoma/pathology* ; Endothelial Cells/pathology* ; DNA Copy Number Variations ; Brain/metabolism* ; Brain Neoplasms/pathology*