Effect of postoperative oxygen therapy regimen modification on oxygenation in patients with acute type A aortic dissection.

Objective: In this study, we investigated the effect of various oxygen therapy regimens on oxygenation in patients with acute type A aortic dissection (AAD). Methods: A quasi-randomized controlled trial was conducted, in which patients with AAD hospitalized for surgery from June to September 2021 were assigned to the control group (patients received conventional oxygen therapy after postoperative mechanical ventilation, weaning, and extubation) and those who were admitted from October to December 2021 were assigned to the observation group [patients underwent optimally adjusted therapy based on the treatment of the control group, which mainly included prioritized elevation of positive end-expiratory pressure (PEEP) and restricted use of the fraction of inspired oxygen (FiO2)].The postoperative oxygenation index, blood gas analysis, and duration of mechanical ventilation were compared between the two groups. Results: There were significant differences in oxygenation observed at 2 h postoperatively between the groups. 12, 24, and 72 h postoperatively, the oxygenation index varied significantly between the two groups. There were statistically significant differences in the time effects of the oxygenation index and PaO2 between the two groups, as well as significant differences in the length of stay in the intensive care unit. Conclusion: For the postoperative care of patients with AAD, it is suggested that the minimum FiO2 required for oxygenation of patients be maintained. In addition, it is possible to enhance PEEP as a priority when PaO2 is low.

Technologies of targeting histone deacetylase in drug discovery: Current progress and emerging prospects.

Histone deacetylases (HDACs) catalyze the hydrolysis of acetyl-l-lysine side chains in histones and non-histones, which are key to epigenetic regulation in humans. Targeting HDACs has emerged as a promising strategy for treating various types of cancer, including myeloma and hematologic malignancies. At present, numerous small molecule inhibitors targeting HDACs are actively being investigated in clinical trials. Despite their potential efficacy in cancer treatment, HDAC inhibitors suffer from multi-directional selectivity and preclinical resistance issues. Hence, developing novel inhibitors based on cutting-edge medicinal chemistry techniques is essential to overcome these limitations and improve clinical outcomes. This manuscript presents an extensive overview of the properties and biological functions of HDACs in cancer, provides an overview of the current state of development and limitations of clinical HDAC inhibitors, and analyzes a range of innovative medicinal chemistry techniques that are applied. These techniques include selective inhibitors, dual-target inhibitors, proteolysis targeting chimeras, and protein-protein interaction inhibitors.

KCNE4 expression is correlated with the pathological characteristics of colorectal cancer patients and associated with the radioresistance of cancer cells.

BACKGROUND: Colorectal cancer (CRC) is a common malignancy, and radioresistance limits the effectiveness of radiotherapy for rectal cancer. This study is performed to investigate the role and regulatory mechanism of Potassium Voltage-Gated Channel Subfamily E Regulatory Subunit 4 (KCNE4) in the radioresistance of CRC cells. METHODS: Immunohistochemical staining results of KCNE4 in normal tissues and CRC tissues were obtained from the Human Protein Atlas (HPA) database. The UALCAN database was used for analyzing KCNE4 mRNA expression in normal tissue samples and CRC tissue samples and its relationship with tumor stage. The relationship of KCNE4 expression with prognosis was analyzed utilizing the data of GEPIA database. LinkedOmics database was searched to analyze the co-expressed gene sets of KCNE4 in CRC, and to analyze the signaling pathways related with KCNE4 in CRC. GO and KEGG enrichment analyses were carried out on the co-expressed genes of KCNE4 with DAVID database. Ionizing radiation (IR)-resistant cell lines (HCT116/IR and HT29/IR) were established; cell viability was assessed via cell counting kit-8 (CCK-8) and EdU assays, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was performed for detecting cell apoptosis. Western blotting was carried out to detect the expressions of p-p85 and p-AKT. RESULTS: KCNE4 was highly expressed in CRC tissues and linked to advanced tumor stage, lymph node metastasis and poor prognosis of CRC patients. KCNE4 overexpression promoted HCT116/IR cell proliferation and inhibited the apoptosis, while KCNE4 knockdown suppressed HT29/IR cell proliferation and facilitated the apoptosis. Furthermore, high KCNE4 expression was associated with the activation of the PI3K/AKT signal pathway. CONCLUSION: KCNE4 is associated with the clinicopathological characteristics of CRC patients, and its high expression level contributes to the radioresistance of cancer cells via activating the PI3K/AKT signal pathway.

Estradiol and raloxifene as adjunctive treatment for women with schizophrenia: A meta-analysis of randomized, double-blind, placebo-controlled trials.

OBJECTIVES: We conducted a comprehensive meta-analysis of all available trials to evaluate the efficacy and safety of estrogen and selective estrogen receptor modulators as adjunctive treatment for women with schizophrenia. METHODS: Multiple databases were searched from the inception until March 2022. Only randomized, double-blind, placebo-controlled studies (randomized controlled trials) were included. Mean differences (MDs) and their 95% confidence intervals (CIs) were calculated using random effects models. RESULTS: The meta-analysis included six estradiol versus placebo studies (n = 724) and seven raloxifene versus placebo studies (n = 419), covering a total of 1143 patients. Adjunctive estradiol outperformed the placebo in terms of the Positive and Negative Syndrome Scale (PANSS) total score (MD = -7.29; 95% CI = -10.67 to -3.91; I2  = 59.1%; p < 0.001; k = 9; N = 858), positive symptom score (MD = -1.54; 95% CI = -3.04 to -0.72; I2  = 45.8%; p < 0.001; k = 7; N = 624), negative symptom score (MD = -1.9; 95% CI = -1.77 to -0.34; I2  = 37.6%; p < 0.05; k = 14; N = 1042), and general psychopathology score (MD = -4.27; 95% CI = -7.14 to -1.41; I2  = 76.3%; p < 0.005; k = 7; N = 624). Adjunctive raloxifene outperformed the placebo in terms of the PANSS total score (MD = -6.83; 95% CI = -11.69 to -1.97; I2  = 67.8%; p = 0.006; k = 8; N = 432) and general psychopathology score (MD = -3.82; 95% CI = -6.36 to -1.28; I2  = 65.3%; p < 0.005; k = 8; N = 432). CONCLUSIONS: Our meta-analysis showed that estradiol and raloxifene are effective and safe adjunctive treatments that improve schizophrenia symptoms in women. Moreover, the effects of estradiol and raloxifene differed in terms of timing and dosage. Both are promising adjunctive treatments that merit further study.

Digital navigation and 3D model technology in mandibular reconstruction with fibular free flap: A comparative study.

OBJECTIVE: The low accuracy limits the use of fibular free flap (FFF). We apply digital navigation and 3D printing model technology in mandibular reconstruction to improve FFF's accuracy. METHODS: 34 patients who underwent with FFF to repair mandibular defects were divided into Navigation Group (13 cases, using digital navigation and 3D printing model) and Control Group (21 cases, only 3D printing model). We retrospectively reviewed patients' hospitalization information and evaluated patients by subjective and objective items, such as UW-Qol scale, CT data. RESULTS: The operation time of Navigation Group was higher significantly than Control Group (10.36 ± 1.87vs9.00 ± 1.34 h).There were no significant differences in early postoperative complications. The Qol score of appearance, motion, anxiety were higher significantly in Navigation Group. The CT results showed that mandibular angle deviation and chin deflection of Navigation Group were better significantly than Control Group (1.72 ± 1.29° vs 3.69 ± 1.67°, 2.45 ± 1.39 vs 5.19 ± 2.13 mm). CONCLUSIONS: The digital navigation can improve FFF's accuracy in mandibular reconstruction. It doesn't significantly increase complications. The digital navigation's installation and operation methods should be simplified to shorter operation time and expand its application.

Ran promotes the proliferation and migration ability of head and neck squamous cell carcinoma cells.

HNSCC is an aggressive tumor that often recurrence and metastasis. Although the treatment of HNSCC has improved over the past few decades, it is easy to recurrence even after comprehensive treatment. Ran is a small Ras-related GTPase belonging to the Ras superfamily. Recently, Ran has been proven to be an important oncogene involved in the metastatic progression of many human cancers. But there is seldom research on HNSCC about Ran. This study revealed the relationship between Ran expression and HNSCC characteristics, investigated the expression and role of Ran in HNSCC tissues and cells by means of immunohistochemistry, qRT-PCR, CCK-8, FCM and transwell migration assays. The results indicated that HNSCC tissues had significantly higher Ran expression than adjacent non-tumor tissues. The overall survival rate was significantly lower in patients with Ran-positive tumors than in those with Ran-negative tumors. Moreover, Ran was positively correlated with tumor grade, lymph node metastasis and recurrence. Ran was also high expressed in the HNSCC cell lines (PCI-37B and SCC9) and down regulated of Ran could evidently inhibit their proliferation, migration and down-regulate of Met protein. In conclusion, our findings suggested Ran could promote the proliferation and migration ability of HNSCC cells. Ran may play an important role in the development of HNSCC and may serve as a novel prognostic indicator of HNSCC.

CDHR5 inhibits proliferation of hepatocellular carcinoma and predicts clinical prognosis.

BACKGROUND: As one of the most prevalent malignancies, hepatocellular carcinoma (HCC) ranks the third leading cause of cancer death worldwide. Due to the lack of biomarkers for early diagnosis, the clinical outcome of HCC remains unsatisfied with the current common therapeutic approaches, including surgery and chemotherapies. Thus, sensitive biomarkers and targeted therapies are in great need. AIMS: In this study, we explored and verified whether CDHR5 (cadherin-related family member 5), a cadherin family protein, could serve as the potential biomarkers for HCC in the clinic. METHODS: A retrospective study which contained 154 HCC patients was performed. Chi-square was utilized to analyze the relationship between CDHR5 expression and the clinicopathological features of HCC patients. The Kaplan-Meier method and Cox regression analyses were then used to evaluate the survival of HCC patients. In addition, cell proliferation assay and colony formation assay were performed to examine the effects of CDHR5 on the progression of HepG2 and Huh7 cells. RESULTS: IHC and RT-qPCR revealed that CDHR5 was downregulated in HCC tissues compared with adjacent liver tissues. In addition, CDHR5 expression was significantly correlated with tumor numbers, tumor size, and TNM stage. CDHR5 expression was then shown to be an independent risk factor for survival of HCC patients by survival analysis. In vitro experiments showed that CDHR5 suppressed the proliferation capacity of HCC cells. CONCLUSIONS: Taken together, our study not only identified CDHR5 as a novel prognostic biomarker in HCC but also provided evidence that CDHR5 can inhibit HCC cell proliferation.

Assessment of fibula flap with flexor hallucis longus's effect on head & neck tumor patients' quality of life and function of donor site.

OBJECTIVE: Free fibular flaps (FFFs) have been widely used in mandibular reconstruction. It is still unclear whether retaining flexor hallucis longus (FHL) is needed for flaps. This study introduces a comparison in quality of life and donor-site function between those who have and haven't harvested FHL with FFF. METHODS: Patients with FFFs were single-blind-randomly assigned into the FHL group or nFHL group. Patients were followed up preoperatively and 1, 3 and 6 months postoperatively via subjective evaluations (SF-36/AOFAS) and objective evaluation s(muscle strength and range of motion). Patients' hospitalization and intraoperative information, donor site morbidity were recorded. RESULTS: Each group had 15 patients. The flap harvesting time in FHL group was shorter significantly than nFHL group (125.9 ± 24.8 min vs 146.7 ± 29.9 min, P = 0.048). There were no significant differences in hospitalization information such as operation time, hospitalization days and cost. Donor site morbidities at 1, 3 and 6 months postoperatively showed no significant differences except for the presence of claw toes (nFHL group > FHL group, 40% vs 0, P = 0.017; 53.3% vs 6.7%, P = 0.014; 60.0% vs 13.3%, P = 0.021). There were no significant differences in SF-36 and AOFAS scores. There were no significant differences in muscle strength and range of motion. CONCLUSION: Excision of the FHL lowered the flap harvesting time. It did not increase donor site morbidity. The impacts on patients' quality of life and foot function were the same. The surgeons can use the FHL without considering the influence on patients if not retaining the FHL.

The EZH2- H3K27me3-DNMT1 complex orchestrates epigenetic silencing of the wwc1 gene, a Hippo/YAP pathway upstream effector, in breast cancer epithelial cells.

It is well known that epithelial-mesenchymal transition (EMT) can confer cancer cells with invasive and migratory capabilities associated with distant metastasis. As a key upstream factor in the Hippo pathway, Kibra (wwc1 gene) has been shown to suppress EMT in breast cancer cells, and we have found that its expression is reduced or lost completely in both human breast cancer cell lines and clinical tissue samples, particularly in triple negative breast cancer (TNBC). Unfortunately, the molecular mechanisms underlying this progression-associated event remain to be elucidated. Epigenetic gene silencing is one of the most common causes of suppressed expression of tumor suppressor genes. Furthermore, recent studies have demonstrated that EZH2 can recruit DNA methyltransferases, resulting in DNA methylation and subsequent gene silencing in certain circumstances. Thus, we hypothesized that there may exist a link between EZH2 and DNA methylation in association with wwc1 silencing in breast cancer. To test this hypothesis, we performed bisulfite sequencing, shRNA, co-IP, ChIP, MeDIP and ChIP-qPCR. As expected, RG108 or 5-Aza treatment improved the wwc1 gene transcription and Kibra protein expression. Both bisulfite sequencing and MeDIP demonstrated higher CpG methylation of the wwc1 promoter the TNBC cells (MDA-MB-231) than in luminal breast cancer cells (MCF7). It is noteworthy that ChIP and co-IP assays showed that EZH2, H3K27me3 and DNMT1 are enriched at the wwc1 promoter, and there exist physiologically relevant protein-protein interactions between them. We also found that EZH2 knockdown leads to a partial increase in Kibra expression and a considerable reduction in H3K27 and DNMT1 trimethylation. Moreover, ChIP-qPCR revealed more DNA fragments containing the wwc1 promoter in MDA-MB-231 than in MCF7 cells after immunoprecipitation with EZH2, DNMT1 and H3K27me3 antibodies. Collectively, our results reveal crosstalk between H3K27me3 inhibition catalyzed by EZH2 and CpG island methylation mediated by DNMT1 within the wwc1 promoter, which synergistically silence wwc1 gene expression in TNBC. Based on these results, we conclude that EZH2 shows promise as a potential anti-tumor target.

[Comparison of safe duration of apnea and intubation time in face mask ventilation with air versus 100% oxygen during induction of general anesthesia].

OBJECTIVE: To compare the safe duration of apnea and intubation time between face mask ventilation with air and 100% oxygen during induction of general anesthesia. METHODS: Eighty adult patients with ASA class I or II without predicted difficult airways were scheduled for elective surgery under general anesthesia. The patients were randomized to receive anesthesia induction with preoxygenation [Group 1, n=40, fraction of inspired oxygen (FiO2)=1] or without preoxygenation (Group2, n=40, FiO2=0.21). Two experienced anesthesiologists performed the mask ventilation and tracheal intubation during induction, and the assistants adjusted the oxygen concentration and recorded the pulse oxygen saturation (SpO2) and other variables. The cases where SpO2 decreased to below 90% before accomplishment of intubation were considered unsuccessful, and mask ventilation with 100% oxygen was given. After tracheal intubation, mechanical ventilation was not initiated until the SpO2 decreased to 90%. The number of unsuccessful cases, the safe duration of apnea and intubation time were recorded in the two groups. RESULTS: There was no unsuccessful case in either groups. The safe duration of apnea was 469.5∓143.0 s in Group 1 and 63.6∓20.0 s in Group 2, and the intubation time was 34.4∓12.6 s and 32.8∓9.6 s, respectively. The safe duration of apnea was significantly longer than the intubation time in both groups (P<0.01). The intubation time and the number of cases with SpO2≥90% before completion of tracheal intubation were similar between the two groups. The safe duration of apnea was significantly shorter in Group 2 than in Group 1 (P<0.01) and was correlated with the body mass index of the patients (P<0.05). CONCLUSION: Anesthesia induction without preoxygenation can provide sufficient time for experienced anesthesiologists to complete tracheal intubation.