Effects of acute normovolemic hemodilution and allogeneic blood transfusion on postoperative complications of oral and maxillofacial flap reconstruction: a retrospective study.

OBJECTIVE: Patients undergoing oral and maxillofacial flap reconstruction often need blood transfusions due to massive blood loss. With the increasing limitations of allogeneic blood transfusion (ABT), doctors are considering acute normovolemic hemodilution (ANH) because of its advantages. By comparing the differences in the (Δ) blood indices and postoperative complications of patients receiving ABT or ANH during the reconstruction and repair of oral and maxillofacial tumor flaps, this study's purpose was to provide a reference for the clinical application of ANH. METHODS: The clinical data of 276 patients who underwent oral and maxillofacial flap reconstruction from September 25, 2017, to October 11, 2021, in the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, were retrospectively analyzed. According to the intraoperative blood transfusion mode, the patients were divided into two groups: ABT and ANH. The differences in the (Δ) blood indices and the incidence of postoperative complications between the groups were analyzed. RESULTS: Among the 276 patients who had ANH (124/276) and ABT (152/276), there were no differences in (Δ) Hb, (Δ) PT, or (Δ) FIB (P > 0.05), while (Δ) WBC, (Δ) PLT, (Δ) APTT and (Δ) D-dimer were significantly different (P < 0.05). The blood transfusion method was not an independent factor for flap crisis (P > 0.05). The wound infection probability in patients with high post-PTs was 1.953 times greater than that in patients with low post-PTs (OR = 1.953, 95% CI: 1.232 ∼ 3.095, P = 0.004). A normal or overweight BMI was a protective factor for pulmonary infection, and the incidence of pulmonary infection in these patients was only 0.089 times that of patients with a low BMI (OR = 0.089, 95% CI: 0.017 ∼ 0.462). Moreover, a high ASA grade promoted the occurrence of pulmonary infection (OR = 6.373, 95% CI: 1.681 ∼ 24.163). The blood transfusion mode (B = 0.310, ß = 0.360, P < 0.001; ANH: ln hospital stay = 2.20 ± 0.37; ABT: ln hospital stay = 2.54 ± 0.42) improved the length of hospital stay. CONCLUSION: Preoperative and postoperative blood transfusion (Δ) Hb, (Δ) PT, and (Δ) FIB did not differ; (Δ) WBC, (Δ) PLT, (Δ) APTT, and (Δ) D-dimer did differ. There was no difference in the effects of the two blood transfusion methods on flap crisis, incision infection or lung infection after flap reconstruction, but ANH resulted in a 3.65 day shorter average hospital stay than did ABT.

Hyperglycemia Promotes Endothelial Cell Senescence through AQR/PLAU Signaling Axis.

Hyperglycemia is reported to accelerate endothelial cell senescence that contributes to diabetic complications. The underlying mechanism, however, remains elusive. We previously demonstrated AQR as a susceptibility gene for type 2 diabetes mellitus (T2DM) and showed that it was increased in multiple tissues in models with T2DM or metabolic syndrome. This study aimed to investigate the role of AQR in hyperglycemia-induced senescence and its underlying mechanism. Here, we retrieved several datasets of the aging models and found the expression of AQR was increased by high glucose and by aging across species, including C. elegans (whole-body), rat (cardiac tissues), and monkey (blood). we validated the increased AQR expression in senescent human umbilical vein endothelial cells (HUVECs). When overexpressed, AQR promoted the endothelial cell senescence, confirmed by an increased number of cells stained with senescence-associated beta-galactosidase and upregulation of CDKN1A (P21) as well as the prohibited cellular colony formation and G2/M phase arrest. To explore the mechanism by which AQR regulated the cellular senescence, transcriptomic analyses of HUVECs with the overexpression and knockdown of the AQR were performed. We identified 52 co-expressed genes that were enriched, in the terms of plasminogen activation, innate immunity, immunity, and antiviral defense. Among co-expressed genes, PLAU was selected to evaluate its contribution to senescence for its highest strength in the enrichment of the biological process. We demonstrated that the knockdown of PLAU rescued senescence-related phenotypes, endothelial cell activation, and inflammation in models induced by AQR or TNF-α. These findings, for the first time, indicate that AQR/PLAU is a critical signaling axis in the modulation of endothelial cell senescence, revealing a novel link between hyperglycemia and vascular dysfunction. The study may have implications in the prevention of premature vascular aging associated with T2DM.

Progression and postoperative complications of osteoradionecrosis of the jaw: a 20-year retrospective study of 124 non-nasopharyngeal cancer cases and meta-analysis.

BACKGROUND: To assess the contributing risk factors for the progression of, and the postoperative poor prognosis associated with, osteoradionecrosis of jaw (ORNJ) following non-nasopharyngeal cancer treatment in head and neck. METHODS: A retrospective study of 124 non-nasopharyngeal carcinoma patients in head and neck treated at one institution between 2001 and 2020 was conducted. A cumulative meta-analysis was conducted according to PRISMA protocol and the electronic search was performed on the following search engines: PubMed, Embase, and Web of Science. After assessing surgery with jaw lesions as a risk factor for the occurrence of ORNJ, 124 cases were categorized into two groups according to the "BS" classification, after which jaw lesions, chemotherapy, flap reconstruction and onset time of ORNJ were analyzed through the chi-square test and t-test to demonstrate the potential association between them and the progression of ORNJ. Postoperative outcomes of wound healing, occlusal disorders, and nerve injury were statistically analyzed. RESULTS: With the statistically significant results of the meta-analysis (odds ratio = 3.07, 95% CI: 1.84-5.13, p < 0.0001), the chi-square test and t-test were used to validate our hypotheses and identified that surgery with jaw lesions could aggravate the progression and accelerate the appearance of ORNJ. Patients who underwent chemotherapy tended to suffer from severe-to-advanced osteonecrosis but did not shorten the onset time of ORNJ. Flap reconstruction presented obvious advantages in wound healing (p < 0.001) and disordered occlusion (p < 0.005). The mean onset time of ORNJ in non-nasopharyngeal cancer patients (4.5 years) was less than that in patients with nasopharyngeal cancer (NPC) (6.8 years). CONCLUSIONS: Iatrogenic jaw lesions are evaluated as a significant risk factor in the occurrence and progression of ORNJ in non-nasopharyngeal carcinoma patients who tend to have more severe and earlier osteonecrosis after radiotherapy than NPC patients. Flap reconstruction is a better choice for protecting the remaining bone tissue and reducing postoperative complications of ORNJ.

Maximum surgical blood order schedule for flap reconstruction in oral and maxillofacial cancer patients.

BACKGROUND: We established a MSBOS for flap reconstruction in oral and maxillofacial cancer patients. METHOD: We enrolled 2080 cases of oral and maxillofacial flap reconstruction from January 1, 2010 to December 31, 2021. Patient data were collected, including age, sex, BMI, preoperative Hb levels, ASA grade, T stage, flap type, tumor location, and bone flap. Scoring criteria were established based on a multivariate model of independent risk variables and their odds ratios. Two flap-type groups were divided into low-risk, intermediate-risk and high-risk groups by the scoring criteria, and analyzed using univariate and multivariate logistic regression. Perioperative transfusion analysis identified independent risk factors at various Hb levels. The cumulative percentage of patients requiring perioperative blood transfusion for each surgical procedure was calculated to establish the MSBOS. RESULTS: (1) Regression analysis showed that BMI, tumor T staging, ASA grade, preoperative Hb level (male: Hb < 130 g/L, female: Hb < 120 g/L), and bone flap were independent risk factors for perioperative blood transfusion. (2) Regression analysis showed that independent risk factors for perioperative transfusion included the following: BMI, tumor T3-T4 stage, ASA III, IV grade, and free flap/pediculated flap/bone flap in patients with different Hb levels; T3-T4 stage, ASA grade III-IV in mildly anemic patients; and ASA grade III-IV in moderately anemic patients. (3) A MSBOS was established for flap reconstruction in head and neck cancer patients. CONCLUSION: A MSBOS for head and neck cancer procedures was reduced by approximately 30% perioperative blood preparation while ensuring that clinical blood use standards were met. It help optimize blood inventory, and save blood resources.

Genome-Wide Search Links Senescence-Associated Secretory Proteins With Susceptibility for Coronary Artery Disease in Mouse and Human.

Advanced age is an independent risk factor for coronary artery disease (CAD), the leading global cause of mortality. Senescent vascular cells in the atherosclerotic plaques exhibit senescence-associated secretory phenotype (SASP). How SASP contributes to atherosclerosis and CAD, however, remains unclear. Here, we integrated RNA-array datasets of senescent human coronary arterial endothelial cells (HCAECs) and aortic smooth muscle cells (HASMCs) as well as genome-wide association data for CAD. We identified 26 genes from HCAECs and 6 genes from HASMCs related to SASP and CAD in both in-house and published datasets. Of which, Cystatin C (CST3), a CAD susceptibility gene, was found to be expressed in both HCAECs and HASMCs, thus, it was prioritized for further investigation. We demonstrated it was significantly elevated in senescent vascular cells, aged arteries, and early atherosclerosis. In vitro experiments showed that CST3 enhances the monocyte-endothelial cell adhesion. Additionally, ligand-receptor pairing analyses revealed two important pathways, COL4A1-ITGA1 and LPL-LRP1 pathways, linked to the critical processes in the development of atherosclerosis, including cell adhesion, inflammation response, extracellular matrix organization, and lipid metabolism. We further demonstrated a reduced monocyte-endothelial cell adhesion following the knockdown of COL4A1 or ITGA1 and a significantly increased expression of COL4A1, ITGA1, and LPL in arterial intima of aged mice and ApoE-/- mice. Our findings demonstrate that vascular cell-derived SASP proteins increase the CAD susceptibility and identify CST3 functionally contributing to atherosclerosis.

Pan cancer characterization of genes whose expression has been associated with LINE-1 antisense promoter activity.

BACKGROUND: Long interspersed nuclear element-1 (LINE-1 or L1) comprises 17% of the human genome. As the only autonomous and active retrotransposons, L1 may take part in cancer initiation and progression in some ways. The studies of L1 in cancer mainly focus on the impact of L1 insertion into the new genome locus. The L1 5´ untranslated region (UTR) also contains antisense promoter (ASP) activity, generating L1-gene chimeric transcripts to a neighbor exon. Some of these ASP-associated genes have been reported to be overexpressed in cancer and promote cancer cell growth. However, little is known about overall expression patterns and the roles of L1 ASP-associated genes in human cancers. RESULTS: L1 ASP-associated genes were frequently dysregulated in cancer and associated with the cell cycle, the PI3K/AKT pathway, and the GTPase signaling pathway. The expression of L1 ASP-associated genes was correlated with tumor patient prognosis. Hub L1 ASP-associated genes CENPU and MCM2 showed a correlation with immune infiltration, clinical T stage, and cancer stemness in pan-cancer. Knockdown of L1 ASP-associated gene LINC00491 resulted in a significant decrease in tumor growth and migration ability. CONCLUSIONS: The expression of L1 ASP-associated genes is significantly dysregulated at the pan-cancer level, which is closely related to the tumor microenvironment, progression, and patient prognosis. Hub genes CENPU and MCM2 are expected to be new tumor diagnostic markers and therapeutic targets.

Transcriptome Reveals Long Non-coding RNAs and mRNAs Involved in Primary Wool Follicle Induction in Carpet Sheep Fetal Skin.

Murine primary hair follicle induction is driven by the communication between the mesenchyme and epithelium and mostly governed by signaling pathways including wingless-related integration site (WNT), ectodysplasin A receptor (EDAR), bone morphogenetic protein (BMP), and fibroblast growth factor (FGF), as observed in genetically modified mouse models. Sheep skin may serve as a valuable system for hair research owing to the co-existence of sweat glands with wool follicles in trunk skin and asynchronized wool follicle growth pattern similar to that of human head hair follicles. However, the mechanisms underlying wool follicle development remain largely unknown. To understand how long non-coding RNAs (lncRNAs) and mRNAs function in primary wool follicle induction in carpet wool sheep, we conducted high-throughput RNA sequencing and revealed globally altered lncRNAs (36 upregulated and 26 downregulated), mRNAs (228 elevated and 225 decreased), and 80 differentially expressed novel transcripts. Several key signals in WNT (WNT2B and WNT16), BMP (BMP3, BMP4, and BMP7), EDAR (EDAR and EDARADD), and FGF (FGFR2 and FGF20) pathways, and a series of lncRNAs, including XLOC_539599, XLOC_556463, XLOC_015081, XLOC_1285606, XLOC_297809, and XLOC_764219, were shown to be potentially important for primary wool follicle induction. GO and KEGG analyses of differentially expressed mRNAs and potential targets of altered lncRNAs were both significantly enriched in morphogenesis biological processes and transforming growth factor-ß, Hedgehog, and PI3K-Akt signaling, as well as focal adhesion and extracellular matrix-receptor interactions. The prediction of mRNA-mRNA and lncRNA-mRNA interaction networks further revealed transcripts potentially involved in primary wool follicle induction. The expression patterns of mRNAs and lncRNAs of interest were validated by qRT-PCR. The localization of XLOC_297809 and XLOC_764219 both in placodes and dermal condensations was detected by in situ hybridization, indicating important roles of lncRNAs in primary wool follicle induction and skin development. This is the first report elucidating the gene network of lncRNAs and mRNAs associated with primary wool follicle early development in carpet wool sheep and will shed new light on selective wool sheep breeding.