α-Ketoglutarate plays an inflammatory inhibitory role by regulating scavenger receptor class a expression through N6-methyladenine methylation during sepsis.

Sepsis arises from an uncontrolled inflammatory response triggered by infection or stress, accompanied by alteration in cellular energy metabolism, and a strong correlation exists between these factors. Alpha-ketoglutarate (α-KG), an intermediate product of the TCA cycle, has the potential to modulate the inflammatory response and is considered a crucial link between energy metabolism and inflammation. The scavenger receptor (SR-A5), a significant pattern recognition receptor, assumes a vital function in anti-inflammatory reactions. In the current investigation, we have successfully illustrated the ability of α-KG to mitigate inflammatory factors in the serum of septic mice and ameliorate tissue damage. Additionally, α-KG has been shown to modulate metabolic reprogramming and macrophage polarization. Moreover, our findings indicate that the regulatory influence of α-KG on sepsis is mediated through SR-A5. We also elucidated the mechanism by which α-KG regulates SR-A5 expression and found that α-KG reduced the N6-methyladenosine level of macrophages by up-regulating the m6A demethylase ALKBH5. α-KG plays a crucial role in inhibiting inflammation by regulating SR-A5 expression through m6A demethylation during sepsis. The outcomes of this research provide valuable insights into the relationship between energy metabolism and inflammation regulation, as well as the underlying molecular regulatory mechanism.

Polyphenols as Potential Antioxidants for the Treatment of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is a common musculoskeletal system disease, which is one of the most important causes of low back pain. Despite the high prevalence of IDD, current treatments are limited to relieving symptoms, and there are no effective therapeutic agents that can block or reverse the progression of IDD. Oxidative stress, the result of an imbalance between the production of reactive oxygen species (ROS) and clearance by the antioxidant defense system, plays an important role in the progression of IDD. Polyphenols are antioxidant compounds that can inhibit ROS production, which can scavenge free radicals, reduce hydrogen peroxide production, and inhibit lipid oxidation in nucleus pulposus (NP) cells and IDD animal models. In this review, we discussed the antioxidant effects of polyphenols and their regulatory role in different molecular pathways associated with the pathogenesis of IDD, as well as the limitations and future prospects of polyphenols as a potential treatment of IDD.

Prehabilitation programs in liver resection: a narrative review.

BACKGROUND AND OBJECTIVE: Liver resection (LR) is a commonly performed surgical procedure for the management of hepatocellular carcinoma and other liver conditions. Despite its benefits in providing patients a potential cure, it is also associated with significant postoperative complications and prolonged recovery periods. In recent years, pre-operative rehabilitation (prehabilitation) has emerged as an up-and-coming strategy to optimize patients' physical, psychological and functional status before LR, leading to improved surgical and patient postoperative outcomes. Hence, our review aims to explore and synthesize the existing literature on prehabilitation in LR to provide an overview of the current evidence to help guide physicians in managing their patients. METHODS: A comprehensive literature search was conducted in multiple electronic databases from inception to July 2023. The search strategy was tailored to capture studies investigating the role of prehabilitation in LR, and the factors that contribute to beneficial outcomes in the postoperative period. KEY CONTENT AND FINDINGS: Prehabilitation programs encompass a multifaceted approach to enhance surgical outcomes and patient well-being. This considers the specific needs of the varying patient populations, such as the elderly, or the cancer ridden. Improving physical fitness, nutritional supplementation and psychological support are the common tenets of prehabilitation. In physical prehabilitation, patients are engaged in intensive physical exercise often by means of a cycle ergometer. Addressing nutritional deficiencies through supplements and dietary interventions is also vital. Psychosocial assessments, advance care planning, music therapy, and progressive relaxation exercises are shown to enhance patient resilience and well-being. In addition, innovative approaches such as optimizing fluid balance, avoiding epidural analgesia, perioperative steroid administration, phosphate correction and branched-chain amino acid supplementation are being explored. CONCLUSIONS: Prehabilitation is important in optimizing patients before LR and is key in improving postoperative outcomes. Several prehabilitation strategies exist, but no formal consensus exists on patient selection and an ideal program.

Icariside â ¡ Attenuates Palmitic Acid-Induced Endothelial Dysfunction Through SRPK1-Akt-eNOS Signaling Pathway.

Background: Endothelial dysfunction is commonly accompanied by a reduced capacity for nitric oxide (NO) production and decreased NO sensitivity, playing a central role in numerous vascular diseases. Saturated free fatty acids are known to reduce NO production and then induce endothelial dysfunction. Alternative splicing participates in the regulation of cellular and tissular homeostasis and is highly regulated by serine-arginine protein kinase (SRPK1). The role of SRPK1 in the biology of endothelial cells remains elusive. Icariside Ⅱ (ICA Ⅱ) has been reported to have protective effects on endothelial function. However, the specific molecular mechanisms are still unknown. The purpose of this study is to explore the role of SRPK1 in the biology of endothelial cells and the underlying mechanism of ICA Ⅱ on palmitic acid (PA) induced endothelial dysfunction. Methods: Endothelial dysfunction was induced using PA in human umbilical vein endothelial cells (HUVECs). The expression and phosphorylation of related proteins in the SRPK1-Akt-eNOS signaling pathway were detected by Western Blot. Cell Counting Kit-8 assay and Ki-67 immunofluorescence were used to estimate cell viability. Endothelial cell function was assessed by detecting NO production using DAF-FM DA. Interaction between ICA Ⅱ and SRPK1 was demonstrated by a biotinylated protein interaction pull-down assay. Results: The expressions of eNOS, Akt, and SRPK1 were down-regulated in the endothelial dysfunction stimulated by PA. SRPK1 inhibitor SPHINX31 restrained endothelial cell viability in a dose-dependent manner. Moreover, inhibition of SRPK1 using SPHINX31 and knockdown of SRPK1 by shRNA also showed a down-regulation of the proteins associated with the SRPK1-Akt-eNOS signaling pathway. Biotinylated protein interaction pull-down assay revealed that ICA Ⅱ could be directly bound with SRPK1. On the other hand, ICA Ⅱ could attenuate the PA-induced endothelial dysfunction and restore cell viability through the SRPK1-Akt-eNOS pathway. Conclusions: ICA Ⅱ, bound with SRPK1, could attenuate the endothelial dysfunction induced by the PA in HUVECs via the SRPK1-Akt-eNOS signaling pathway.

Comparisons and Combined Application of Two-Dimensional and Three-Dimensional Real-time Shear Wave Elastography in Diagnosis of Thyroid Nodules.

Purpose Two-dimensional and three-dimensional real-time shear wave elastography (2D+3D SWE) represents a new technology for the quantification of tissue elasticity. This study investigated whether they could be performed to differentiate between benign and malignant thyroid nodules. Methods Conventional B-mode ultrasound, 2D and 3D SWE were performed in 96 patients with 97 thyroid nodules with pathology results. Results All the elastography values of 2D&3D SWE in malignant thyroid nodules were higher than those in benign nodules. These two elastography methods alone could not improve diagnostic value comparing to B-mode ultrasound significantly. However, B-mode US + 2D SWE (TI-RADS ≥ 4c or S-Emean ≥ 23.75 kPa, suspicious), B-mode US + 3D SWE (TI-RADS ≥ 4c or 3D-T-Emean ≥ 20.75 kPa, suspicious), B-mode US + 2D + 3D SWE (TI-RADS ≥ 4c or S-Emean ≥ 23.75 kPa or 3D-T-Emean ≥ 20.75 kPa, suspicious) had higher sensitivity and accuracy values than those of 3 methods alone but lower specificity values. Among them, B-mode ultrasound + 2D SWE had the highest sensitivity, NPV, accuracy and Youden's index (0.881, 0.788, 0.804 and 0.57). Conclusions 2D SWE or 3D SWE alone could not improve the diagnostic value of differentiating malignant from benign thyroid nodules comparing to conventional B-mode ultrasound. But combination methods could improve the diagnostic value, especially B-mode US + 2D SWE.

TNFSF9 exerts an inhibitory effect on hepatocellular carcinoma.

OBJECTIVE: Tumor necrosis factor superfamily member 9 (TNFSF9), also known as 4-1BBL and CD137L, has been implicated in cancer immunotherapy due to its function as a T-cell co-stimulator. We aimed to investigate the role of TNFSF9 in the cancer pathogenesis in hepatocellular carcinoma (HCC). METHODS: TNFSF9 expression was examined by immunohistochemistry in 106 pairs of HCC and adjacent non-tumorous tissues, and by quantitative polymerase chain reaction and Western blot in HCC cell lines. The impact of TNFSF9 on the proliferation, migration and invasion of HCC cells was determined using the 3-(4,5-diethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) and transwell assays in vitro. We also assessed the influence of TNFSF9 on the growth and metastasis of HCC tumors in an orthotopic mouse model of human HCC. RESULTS: TNFSF9 expression was downregulated in approximately 70% of HCC tissues. A decreased expression of TNFSF9 was also consistently observed in all the four HCC cell lines. Either the overexpression of TNFSF9 or treatment with recombinant TNFSF9 protein could significantly inhibit the proliferation, migration and invasion of Huh7 and SMMC-7721 HCC cells in vitro. The inhibitory effect of TNFSF9 on HCC was further confirmed in vivo. Mice orthotopically transplanted with TNFSF9-overexpressing Huh7 cells developed significantly smaller tumors with less intrahepatic metastasis and distant metastasis compared with the control group. CONCLUSIONS: TNFSF9 may be a tumor suppressor in HCC. Based on its immune stimulatory aspect and the tumor inhibition property, TNFSF9 may be a promising therapeutic target for HCC.

Radioguided parathyroidectomy in patients with secondary hyperparathyroidism due to chronic renal failure.

OBJECTIVE: The aim of the study was to determine the effectiveness of radioguided parathyroidectomy in patients with secondary hyperparathyroidism (sHPT) due to chronic renal failure (CRF). METHODS: Between August 2003 and October 2011, CRF patients undergoing parathyroidectomy for sHPT received conventional parathyroidectomy with preoperative ultrasound localization or radioguided surgery. For radioguided surgery, 370 MBq of (99m)Tc-sestamibi was injected intravenously 1.5-2 h before surgery, and a gamma probe was used intraoperatively to identify the parathyroid glands by radioactivity count. RESULTS: Twenty-five patients underwent conventional parathyroidectomy and 25 underwent radioguided parathyroidectomy. The median patient age was 55 years (range, 37-75 years). In the conventional surgery group, the parathyroid glands were removed in 18 patients, and seven patients experienced recurrence as determined by intact parathyroid hormone (iPTH) levels. One patient in the radioguided surgery group experienced recurrence due to ectopic parathyroid tissue in the mediastinum. The operative time of radioguided surgery was shorter than that of conventional surgery [median (interquartile range), 100.0 (84.0-118.0) vs. 114.0 (103.0-134.0) min, respectively; P=0.015]. On postoperative day 1, iPTH and serum calcium levels were significantly lower in the radioguided surgery group than in the conventional surgery group [median (interquartile range), iPTH: 3 (3-20) vs. 53 (11-230) ng/l; P=0.006, calcium: 1.72 (1.63-1.85) vs. 2.06 (1.92-2.12) mmol/l; P<0.001]. Radioactivity counts of parathyroid glands were significantly higher than in thyroid tissue, lymph nodes, and fat (all, P<0.001). CONCLUSION: Radioguided localization of the parathyroid glands improves the success rate of surgery in patients with CRF undergoing parathyroidectomy for sHPT.

[Detection of lymph node of rabbit thyroid by real-time fluorescence imaging].

OBJECTIVE: To detect the lymph nodes (LN) of rabbit thyroid by fluorescence imaging and to provide experimental evidence for its clinical application. METHODS: Each of 50 lateral thyroid lobes of 25 rabbits was injected with 0.02 ml of indocyanine green (ICG), and 0.02 ml methylene followed. ICG fluorescence was detected using photodynamic eye (PDE). The methylene staining in LN was also observed. The onset time of ICG staining in LN was measured. RESULTS: The detection rate of fluorescence imaging and blue dye imaging were respectively 86.0% (43/50) and 66.0% (33/50), with a significant difference (P = 0.034), and the accuracy were respectively 85.5% (53/62) and 70.7% (41/58). The onset time (x(-) ± s) of ICG staining in LN was (118.3 ± 16.1) s. CONCLUSIONS: Fluorescence imaging showed satisfied detection rate and accuracy. The detection rate of LN by fluorescence imaging was higher than that by blue dye imaging. Fluorescence imaging could be an alternative method for the detection of LN of thyroid in future clinical practice.

[Study of radioactivities in parathyroid and near tissues during radioguided parathyroidectomy].

OBJECTIVE: To determine the radioactivities in parathyroid and near tissues during radioguided parathyroidectomy in patients with hyperparathyroidism and the utility of parathyroidectomy in patients with negative (99m)Tc-sestamibi scans. METHODS: Between August 2010 and August 2011, 21 patients underwent radioguided parathyroidectomy for hyperthyroidism. The levels of parathyroid hormone (PTH) and serum calcium before and after surgery were detected respectively. In vivo and ex vivo radioactivities in parathyroid and near tissues were examined. According to the radioactivity in parathyroid, the patients were divided into two groups, positive group and negative group. All data was descriptively analyzed and underwent a t test and an analysis of variance. RESULTS: In all patients both PTH and calcium levels decreased significantly after parathyroidectomy when compared to those before surgery (t' = 17.71 and t = 10.00, respectively, P < 0.001). In vivo and ex vivo radioactivities in enlarged parathyroid glands were higher than those in thyroid and fat tissue (F = 75.25 and 37.81, respectively, P < 0.001). In vivo and ex vivo radioactivities of the enlarged parathyroid with negative sestamibi scans were significantly greater than background radioactivity. CONCLUSIONS: There are significant differences in (99m)Tc-sestamibi radioactivities among enlarged parathyroid glands, thyroid glands and fat tissues. This radioguided technique is helpful to identify abnormal parathyroid gland in patients with hyperparathyroidism during parathyroidectomy.

[Relationship between cervical micrometastasis and early recurrence and prognosis in laryngeal carcinoma].

OBJECTIVE: To analyse the correlation between the micrometastasis and early recurrence and prognosis in laryngeal cancer. METHODS: Total of 126 patients with laryngeal squamous cell carcinoma were included in the study. The micrometastasis was detected with hematoxylin and eosin staining (HE) and immunohistochemical staining for cytokeratin (CK) of the lymph node specimens after selective neck dissection (II-IV). Chi-square test was used to analyse the relationship between the micrometastasis and early recurrence and prognosis, and Kaplan-Meier method was used for survival analysis. RESULTS: HE staining showed positive micrometastasis in 41 cases and negative micrometastasis in 85 cases in which 33 cases were positive staining for CK. With a following-up of mean 6.3 years, recurrence or metastasis occurred in 15 cases with positive micrometastasis detected by HE staining, 14 cases with CK positive staining and 4 cases with CK negative staining. The correlation between micrometastasis and early recurrence was significant (P < 0.01). The total 5-year survival rate was 79.8%, 10-year survival rate was 60.5%. The 10-year survival rate (52.1%) of the patients with CK positive staining indicating micrometastasis was significantly higher than that of CK negative patients (81.2%, P < 0.01). CONCLUSION: Cervical micrometastasis predicts poor prognosis and early recurrence in patients with laryngeal squamous cell carcinoma.

[Detection of sentinel lymph node of rabbit thyroid by fluorescence imaging].

OBJECTIVE: To detect the sentinel lymph nodes (SLN) of rabbit thyroid by fluorescence imaging and to provide experimental evidence for its clinical application. METHODS: Equal concentration and dose (35 nmol/L, 1 ml) of ICG (indocyanine green) or ICG:CSA (calf serum albumin) complex was injected into rabbit thyroid to measure the their fluorescence amount. Twenty rabbits were randomly divided into ICG group and ICG:CSA group, with 10 rabbits each group, rabbit thyroid was separately injected with 0.02 ml of 100 nmol/L ICG and 0.02 ml of methylene, or 0.02 ml of 35 nmol/L ICG:CSA and 0.02 ml of methylene, and then ICG fluorescence and methylene staining in SLN were detected respectively. RESULTS: Fluorescence amount of ICG:CAS was three times that of ICG with the same concentration and dose. SLNs were showed in all rabbits injected with ICG or ICG:CSA, but found only in 16 of 20 rabbits injected with methylene blue. The accuracy of fluorescence imaging and blue dye imaging were respectively 95.8% and 79.2%. CONCLUSION: Fluorescence imaging, using ICG or ICG:CSA as a tracer, could be an alternative method for the detection of SLN of thyroid in future clinical practice.

[Long-term treatment outcome in patients undergoing cricohyoidoepiglottopexy for glottic carcinoma].

OBJECTIVE: To investigate the long-term results of cricohyoidoepiglottopexy(CHEP) in the treatment of glottic carcinoma. METHODS: A retrospective chart review of 92 consecutive patients who underwent CHEP in the selected institut from January 1990 to December 2008. Of the 92 cases, 41 cases of stage I, 39 cases of stage II, 12 cases of stage III. The time for the decannulation and the removal of the nasal feeding and quality of phonation were used for evaluating postoperative functional rehabilitation. The estimated long-term survival rates were calculated by Kaplan-Meier method. RESULTS: Among 92 patients, 26 cases (27 sides) received neck dissection and lymph nodes were pathologically positive in 3 patients (11.1%). All final surgical margins were negative for tumor invasion. Seven patients had postoperative radiotherapy and one had chemoradiation. Thirteen patients (14.1%) were found local recurrence and nine patients (9.8%) had postoperative metastases. Overall 3-, 5- and 10-year survival rates were 90.0%, 84.5% and 67.0% respectively. Cox multivariate analysis showed that the recurrence had significant influences on the overall survival rate. CONCLUSION: CHEP not only is relatively easy to master, but also effective in the treatment of glottic carcinoma.

[Experimental study of cervical lymph node in thyroid by using radioactive nano tracer].

OBJECTIVE: Using radioactive nano tracer with different sizes (average diameter were 50, 80 and 100 nm) and dosages (0.01 and 0.02 ml) in the thyroids of rabbits, to study the drainage of thyroid to cervical lymph nodes (LNs) in rabbits and to provide experimental evidence for the choice of ideal sizes and dosages of radioactive Nano tracer for the sentinel lymph node biopsy (SLNB) in thyroid cancer patients. METHODS: Thirty adult rabbits were randomly divided into six groups (50 nm - 0.01 ml, 50 nm - 0.02 ml, 80 nm - 0.01 ml, 80 nm - 0.02 ml, 100 nm - 0.01 ml, 100 nm - 0.02 ml of (99m)Tc-Sb(2)S(3)) with five rabbits in each group. A total of 60 sides of thyroids were included. The mean number of LNs with radioactivity, the initial, the strangest and the lasting time of radioactivity in LNs in each group were measured. RESULTS: One to three LNs were identified in one side neck of rabbits, totally 86 LNs. Most of LNs with radioactivity existed in level VI, counting for 75.6% (65/86). (99m)Tc-Sb(2)S(3) with 50 nm particles was significantly better than that with 80 nm or 100 nm particles with regarding the initial and the strangest radioactive time of (99m)Tc-Sb(2)S(3) in LNs (P < 0.05). There were no significant difference in the mean number of LNs with radioactivity, the initial, the strangest and the lasting time of radioactivity between the dosages of 0.01 ml and 0.02 ml of (99m)Tc-Sb(2)S(3) with same size of particles (P > 0.05). CONCLUSION: (99m)Tc-Sb(2)S(3) with 50 nm particles, in the dosage of 0.01 ml or 0.02 ml, could be good choice for SLNB of thyroid cancer.

[Expression of epithelial Na+ channel in human nasal polyp].

OBJECTIVE: To evaluate the expression of epithelial sodium channel in nasal polyps and normal nasal mucosa and to characterize the ENaC-mediated Na(+) absorption and the mechanism of the liquid transport in human upper airway epithelia. METHODS: The tissue from 12 patients with nasal polyps (NP) and the normal ethmoid cornu mucosa (ECM) from 5 patients were obtained through endoscopic surgery. The expression of ENaC was detected by Immunofluorescence and the concentration of ENaC alpha, beta, gamma-mRNA were detected by RT real-time PCR. RESULTS: The ENaC in NP group (35.79 +/- 5.47) was higher than that in ECM group (22.17 +/- 5.43, t = 4.687, P < 0.01). The expression of ENaC-alpha, beta, gamma mRNA in NP group (respectively 2.06 +/- 0.42, 1.97 +/- 0.32, 1.96 +/- 0.54) was higher than that in ECM group (respectively 1.01 +/- 0.10, 0.98 +/- 0.08, 0.97 +/- 0.06; t = 5.482, 6.659, 4.036, all P < 0.01). The mRNA expression of three subunits of ENaC was as follows: alpha > beta > gamma in both groups. The mRNA expression of alpha, beta, gamma subunit of ENaC in NP group was higher than that in ECM group(P < 0.01). The expression of three subunits of ENaC was correlated respectively with that of mRNA in NP group. CONCLUSIONS: The up-regulation of ENaC in human NP was associated with the expression of ENaC mRNA, that made hydrops and might be one of the most important cause of the develop of nasal polyp.