Levosimendan Reverses Cardiac Malfunction and Cardiomyocyte Ferroptosis During Heart Failure with Preserved Ejection Fraction via Connexin 43 Signaling Activation.

PURPOSE: In recent decades, the occurrence of heart failure with preserved ejection fraction (HFpEF) has outweighed that of heart failure with reduced ejection fraction by degrees, but few drugs have been demonstrated to improve long-term clinical outcomes in patients with HFpEF. Levosimendan, a calcium-sensitizing cardiotonic agent, improves decompensated heart failure clinically. However, the anti-HFpEF activities of levosimendan and underlying molecular mechanisms are unclear. METHODS: In this study, a double-hit HFpEF C57BL/6N mouse model was established, and levosimendan (3 mg/kg/week) was administered to HFpEF mice aged 13 to 17 weeks. Different biological experimental techniques were used to verify the protective effects of levosimendan against HFpEF. RESULTS: After four weeks of drug treatment, left ventricular diastolic dysfunction, cardiac hypertrophy, pulmonary congestion, and exercise exhaustion were significantly alleviated. Junction proteins in the endothelial barrier and between cardiomyocytes were also improved by levosimendan. Among the gap junction channel proteins, connexin 43, which was especially highly expressed in cardiomyocytes, mediated mitochondrial protection. Furthermore, levosimendan reversed mitochondrial malfunction in HFpEF mice, as evidenced by increased mitofilin and decreased ROS, superoxide anion, NOX4, and cytochrome C levels. Interestingly, after levosimendan administration, myocardial tissue from HFpEF mice showed restricted ferroptosis, indicated by an increased GSH/GSSG ratio; upregulated GPX4, xCT, and FSP-1 expression; and reduced intracellular ferrous ion, MDA, and 4-HNE levels. CONCLUSION: Regular long-term levosimendan administration can benefit cardiac function in a mouse model of HFpEF with metabolic syndromes (namely, obesity and hypertension) by activating connexin 43-mediated mitochondrial protection and sequential ferroptosis inhibition in cardiomyocytes.

Transvaginal natural orifice transluminal endoscopic surgery versus conventional vaginal surgery for sacrospinous ligament fixation of apical compartment prolapse: a retrospective analysis.

BACKGROUND: To objectively assess the safety, feasibility, advantages, and disadvantages of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) versus conventional vaginal (CV) surgery for sacrospinous ligament fixation (SSLF). METHODS: We retrospectively analyzed the data of patients who underwent hysterectomy for SSLF via vNOTES or CV surgery due to apical compartment prolapse between April 2019 and April 2020 at our hospital. The patients were classified into the vNOTES group (n = 31) and CV surgery group (n = 51) based on surgical approach and their general characteristics and perioperative outcomes compared. RESULTS: The two groups had similar general characteristics. The anatomical success and bilateral salpingo-oophorectomy rates were higher in the vNOTES than CV surgery group, while the postoperative stay was shorter in the vNOTES than CV surgery group. All differences were statistically significant. However, there were no statistically significant intergroup differences in operation time, bilateral salpingectomy rate, colporrhaphy rate, postoperative visual analog scale score, estimated blood loss, hemoglobin decrease at 72 h postoperative, maximum body temperature at 72 h postoperative, complication rate, buttock pain, or Pelvic Floor Impact Questionnaire-7 and Pelvic Floor Distress Inventory Questionnaire-20 scores at 1 year postoperative. CONCLUSIONS: VNOTES for SSLF was safe and feasible and resulted in superior objective and subjective outcomes versus CV surgery for SSLF. These findings suggest that vNOTES could be an alternative to CV surgery for SSLF.

Application of anatomy unit resection surgery for lateral basicranial surgical approach in oral squamous carcinoma.

BACKGROUND: The basicranial region lacks definite boundaries and includes various anatomical units. We developed a novel concept of the posterior oral anatomical complex (POAC) to identify these anatomical units in the basicranial region. OSCC with POAC involvement is termed posterior oral squamous cell carcinoma (POSCC) with poor prognosis. The principal aim of this study was to evaluate the effect of anatomy unit resection surgery (AUSR) on patients with POSCC. METHODS: A total of 120 POSCC patients who underwent radical surgical treatment were recruited for this study. These POSCC patients were treated with conventional surgery or AUSR. According to the extent of primary tumor resection in the AUSR group, the lateral basicranial surgical approach can be subdivided into four types: face-lateral approach I, face-lateral approach II, face-median approach or face-median and face-lateral combined approach. Facial nerve function was evaluated according to the House-Brackmann Facial Nerve Grading System. RESULTS: The overall survival rate was 62.5% and 37.5% in the AURS group and conventional group (hazard ratio: 0.59; p < 0.0001), respectively. The disease-free survival rate was 62.5% and 34.3% in the AURS group and conventional group (hazard ratio: 0.43; p = 0.0008), respectively. The local disease control rate in the AURS group (71.4%) was significantly better than that in the conventional group (34.4%) in present study (p < 0.0001). Compared to the conventional group, all the patients undergoing AURS were classified as T4 stage and presented with more lymph node metastasis (71.4%). A total of 20 patients (face-lateral approach I and face-lateral combined approach) were temporarily disconnected from the temporofacial branch of the facial nerve. Fifteen patients exhibited slight paresis, and five patients presented with moderate or severe paresis. The survival rate of zygomatic arch disconnection was 94.6% (54 of 56 patients). CONCLUSION: This lateral basicranial surgical approach based on AUSR improves the survival rate and enhances the local control rate while also preserving a good prognosis without damaging the nerve and zygomatic bone. This surgical approach based on AUSR provides a novel and effective surgical treatment to address POSCC with better prognosis, especially for patients without metastatic lymph nodes.

Hysteropreservation versus hysterectomy in uterine prolapse surgery: a systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: Hysteropreservation and hysterectomy for uterine prolapse have been compared in several randomized controlled trials (RCTs), as the best treatment has not been definitively determined. This study aimed to summarize the available evidence in RCTs of hysteropreservation versus hysterectomy. METHODS: We performed electronic searches in the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure databases for eligible RCTs from inception to June 2020. The relative risks (RRs) and weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were calculated for categorical and continuous variables using random-effects models. RESULTS: Twelve RCTs involving 1177 patients were selected for meta-analysis. There were no significant differences between hysteropreservation and hysterectomy for the incidences of recurrence (RR, 0.55; 95% CI, 0.26-1.19; P = 0.130) and reoperation (RR, 1.15; 95% CI, 0.56-2.37; P = 0.705). Moreover, neither hysteropreservation nor hysterectomy had any significant effect on the risk of constipation (RR, 0.72; 95% CI, 0.15-3.46; P = 0.681), voiding dysfunction (RR, 0.99; 95% CI, 0.54-1.84; P = 0.981), intraoperative bleeding (RR, 0.35; 95% CI, 0.05-2.26; P = 0.271), upper leg dullness (RR, 0.70; 95% CI, 0.15-3.17; P = 0.643), dyspareunia (RR, 1.47; 95% CI, 0.69-3.13; P = 0.317), and wound infection (RR, 1.38; 95% CI, 0.24-7.80; P = 0.714). Furthermore, hysteropreservation was associated with less intraoperative blood loss (WMD, -25.68; 95% CI, -44.39 to -6.96; P = 0.007), shorter duration of surgery (WMD, -11.30; 95% CI, -19.04 to -3.55; P = 0.004), and shorter duration of hospitalization (WMD, -0.63; 95% CI, -1.10 to -0.16; P = 0.009) compared with hysterectomy. CONCLUSION: This study found that both hysteropreservation and hysterectomy have similar effects on recurrence and reoperation rates, while hysteropreservation was superior to hysterectomy in reducing intraoperative blood loss and shortening the duration of surgery and hospitalization.

Transvaginal natural orifice transluminal endoscopic surgery in gynecological procedure: Experience of a Women's and Children's Medical Center from China.

OBJECTIVE: To review of our hospital's experiences in transvaginal natural orifice transluminal endoscopic surgery (vNOTES) and challenges we encountered in performance of the procedure, so as to provide help to medical institutions who are preparing to carry out vNOTES. METHODS: We retrospectively analyzed the data of all patients receiving vNOTES in our hospital from April 2018 to May 2021. Data we collected cover the general characteristics, perioperative outcomes, and complications of the patients. RESULTS: A total of 1147 patients underwent vNOTES in the past 3 years at our hospital. The total numbers of adnexal surgery, myomectomy, hysterectomy, pelvic floor reconstruction surgery, and malignant tumor surgery performed via vNOTES were 902, 98, 82, 51, and 14, respectively. Eighteen patients were converted to transabdominal laparoscopic surgery. A total of 38 patients had complications according to Clavien-Dindo classification, and the total complication rate was 3.31%. Among these cases of complications, 27 were Grade I, 4 were Grade II, and 7 were Grade III. No complications of Grade IV or V were reported. CONCLUSION: The application of vNOTES is safe and feasible for most gynecological surgeries. Moreover, hospitals with traditional laparoscopic equipment are advised to try this technique as there is no need to purchase additional expensive equipment. However, since vNOTES represents a novel approach, the long-term complications and efficacy associated with this technique are pending to be verified through large-scale prospective multicenter randomized controlled studies.

Comparative analysis of vaginal natural orifice transluminal endoscopic surgery versus transumbilical laparoendoscopic single-site surgery in ovarian cystectomy.

AIM: To objectively assess the safety, feasibility, advantages and disadvantages and health economics benefits of vaginal natural orifice transluminal endoscopic surgery (vNOTES) versus transumbilical laparoendoscopic single-site surgery (TU-LESS) in ovarian cystectomy. METHODS: We retrospectively analyzed the data of all patients in our hospital who had undergone vNOTES and TU-LESS ovarian cystectomy due to 'unilateral ovarian cyst' from March 2019 to May 2020. Patients were classified into vNOTES group (86) and TU-LESS group (210) based on surgical paths. The patients' general characteristics and perioperative outcomes were compared. RESULTS: All 296 patients completed surgery with no need to switch to conventional laparoscopy or laparotomy procedures. There were no complications of Grade III, IV, V in Clavien-Dindo classification. There were two patients in the vNOTES group and four patients in the TU-LESS group with complications of Grade I, all of whom were treated with antipyretic drugs for postoperative fever. One patient in the TU-LESS group presented the complication of Grade II and was treated with blood transfusion due to postoperative anemia. The two groups had similar general characteristics. Perioperative outcomes: The visual analogue scale (VAS) scores 24 h postoperation were significantly lower in the vNOTES group than in the TU-LESS group. The cosmetic scores were significantly higher in the vNOTES group than in the TU-LESS group. Postoperative stay and time of flatus after surgery were significantly shorter in the vNOTES group than in the TU-LESS group. There was not significant statistical differences between the two groups in operation time, estimated blood loss, Hb decrease at 48 h postoperation, maximum body temperature in 48 h after surgery and hospital costs. CONCLUSION: It was proved to be safe and feasible in ovarian cystectomy by vNOTES. It worked better than TU-LESS in relieving postoperative pain, shortening postoperative stay and improving cosmetic effects and so on. As an emerging surgical path, large sample multicenter randomized controlled trials are required to further verify its safety and advantages.

Identification and validation of stromal-tumor microenvironment-based subtypes tightly associated with PD-1/PD-L1 immunotherapy and outcomes in patients with gastric cancer.

BACKGROUND: Immunotherapies targeting programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1) have been approved for gastric cancer (GC) patients. However, a large proportion of patients with T-cell-inflamed tumor microenvironment do not respond to the PD-1/PD-L1 blockade. The stromal component of the tumor microenvironment has been associated with immunotherapy. This study aims to explore the clinical significance of the non-immune cells in the tumor microenvironment and their potential as biomarkers for immunotherapy. METHODS: A total of 383 patients with GC from the Cancer Genome Atlas (TCGA) cohort, 300 patients with GC from the GSE62254 cohort in Gene Expression Omnibus (GEO) were included in the study. A stromal score was generated using the ESTIMATE algorithm, and the likelihood of response to PD-1/PD-L1 immunotherapy of GC patients was predicted using the TIDE algorithm. The prognostic value of the stromal score from GC cases was evaluated by the Kaplan-Meier method and Cox regression analysis. Gene set enrichment analysis (GSEA) was also conducted. RESULTS: The stromal score showed significant differences in different molecular subtypes and T stages. Multivariate analyses further confirmed that the stromal score was an independent indicator of overall survival (OS) in the two cohorts. The low stromal score group showed higher tumor mutation burden (TMB) and micro-satellite instability (MSI), and was more sensitive to immune checkpoint inhibitor according to the TIDE algorithm. Activation of the transforming growth factor and epithelial-mesenchymal transition were observed in the high stromal score subtype, which is associated with T-cell suppression, and may be responsible for resistance to PD-1/PD-L1 therapy. BPIFB2 was confirmed as a hub gene relevant to immunotherapy. CONCLUSION: The stromal score was associated with cancer progression and molecular subtypes, and may serve as a novel biomarker for predicting the prognosis and response to immunotherapy in patients with GC.

Retraction Note: Upregulation of the long non-coding RNA AFAP1-AS1 affects the proliferation, invasion and survival of tongue squamous cell carcinoma via the Wnt/ß-catenin signaling pathway.

The authors have retracted this article [1] because there are errors in Figures 4a and 4b.

Upregulation of the long non-coding RNA AFAP1-AS1 affects the proliferation, invasion and survival of tongue squamous cell carcinoma via the Wnt/ß-catenin signaling pathway.

BACKGROUND: Long non-coding RNA (lncRNA) actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) is oriented in an antisense direction to the protein-coding gene AFAP1 in the opposite strand. Previous studies showed that lncRNA AFAP1-AS1 was upregulated and acted as an oncogene in a variety of tumors. However, the expression and biological functions of lncRNA AFAP1-AS1 in tongue squamous cell carcinoma (TSCC) are still unknown. METHODS: The expression level of AFAP1-AS1 was measured in 103 pairs of human TSCC tissues and corresponding adjacent normal tongue mucous tissues. The correlation between AFAP1-AS1 and the clinicopathological features was evaluated using the chi-square test. The effects of AFAP1-AS1 on TSCC cells were determined via a CCK-8 assay, clone formation assay, flow cytometry, wound healing assay and transwell assay. Furthermore, the effect of AFAP1-AS1 knockdown on the activation of the Wnt/ß-catenin signaling pathway was investigated. Finally, CAL-27 cells with AFAP1-AS1 knockdown were subcutaneously injected into nude mice to evaluate the effect of AFAP1-AS1 on tumor growth in vivo. RESULTS: In this study, we found that lncRNA AFAP1-AS1 was increased in TSCC tissues and that patients with high AFAP1-AS1 expression had a shorter overall survival. Short hairpin RNA (shRNA)-mediated AFAP1-AS1 knockdown significantly decreased the proliferation of TSCC cells. Furthermore, AFAP1-AS1 silencing partly inhibited cell migration and invasion. Inhibition of AFAP1-AS1 decreased the activity of the Wnt/ß-catenin pathway and suppressed the expression of EMT-related genes (SLUG, SNAIL1, VIM, CADN, ZEB1, ZEB2, SMAD2 and TWIST1) in TSCC cells. In addition, CAL-27 cells with AFAP1-AS1 knockdown were injected into nude mice to investigate the effect of AFAP1-AS1 on tumorigenesis in vivo. Downregulation of AFAP1-AS1 suppressed tumor growth and inhibited the expression of EMT-related genes (SLUG, SNIAL1, VIM, ZEB1, NANOG, SMAD2, NESTIN and SOX2) in vivo. CONCLUSIONS: Taken together, our findings present a road map for targeting the newly identified lncRNA AFAP1-AS1 to suppress TSCC progression, and these results elucidate a novel potential therapeutic strategy for TSCC.

Papillary Thyroid Carcinoma Incidentally Found in Cervical Lymph Nodes During Neck Dissection for Patients With Tongue Squamous Cell Carcinoma: A 3-Case Report and Literature Review.

The incidence of papillary thyroid carcinoma (PTC) found in the cervical lymph nodes during neck dissection for patients with tongue squamous cell carcinoma (SCC) is infrequent, with the coexistence of PTC and SCC in the same cervical lymph node being the rarest. Some of these patients present with primary lesions in the thyroid gland, whereas others have no obviously malignant thyroid lesion. The reasons behind this clinical phenomenon and the relationship between tongue SCC and PTC found in the cervical lymph nodes are unclear. Moreover, for surgeons, making the choice between thyroid surgery and follow-up is still a clinical dilemma. Of the 956 patients who underwent neck dissection owing to maxillofacial tumors from January 2011 through December 2017 at Second Xiangya Hospital of Central South University, 3 with tongue SCC presented with PTC in the cervical lymph nodes. Neither the preoperative physical examination nor ultrasonography after surgery showed substantial nodules in the thyroid glands of these patients, so none of them underwent thyroid surgery or chemoradiotherapy. At follow-up (1 to 6.5 years), we found no obviously malignant lesions in the patients' thyroid glands or related metastatic disease. Our study suggests that tongue SCC may not affect the occurrence and development of PTC in the cervical lymph nodes. For patients with tongue SCC presenting with PTC in the cervical lymph nodes, it is not necessary to carry out thyroid surgery immediately if ultrasonography shows no substantially malignant lesion in the thyroid gland. Nevertheless, conducting periodic follow-up is very important.

Characteristics and Management of Free Flap Compromise Following Internal Jugular Venous Thrombosis.

PURPOSE: Free flap compromise after internal jugular venous thrombosis (IJVT) occurs fairly infrequently in oral and maxillofacial rehabilitation and reconstruction but could seriously affect the patient's postoperative recovery. The aim of this study was to analyze and discuss the characteristics and management of such flap compromise. PATIENTS AND METHODS: The authors performed a retrospective case series of 13 patients who underwent reconstruction of oral and maxillofacial defects with anterolateral thigh flaps and developed flap compromise from IJVT from July 2014 through December 2016 at the Second Xiangya Hospital of Central South University (Changsha, China). The clinical features of flap compromise are described, and the precautions and improvement measures are reported. RESULTS: All 13 patients were men with an average age of 50.3 years. Flap compromise caused by IJVT occurred on postoperative days 3 to 7, of which 2 flaps were salvaged (15.4%) and 11 flaps failed completely after immediate urgent re-exploration. Four patients presented with orocutaneous fistula after salvage surgery that healed well after a period of wound dressing. CONCLUSIONS: Because of the late occurrence and low salvage rate of flap compromise caused by IJVT, intensive flap monitoring after reconstruction surgery is necessary for patients with free flap transfer.

Reconstruction of Through-and-Through Oromandibular Defects With Combined Fibula Flap and Anterolateral Thigh Flap.

PURPOSE: The reconstruction of massive through-and-through oromandibular defects is still a challenge because no single adequate candidate for a donor site of vascularized bone and a large amount of soft tissue has yet been found. The aim of this study was to evaluate the feasibility and reconstructive efficacy of the combined fibula flap and anterolateral thigh (ALT) flap in tandem for the reconstruction of such defects. PATIENTS AND METHODS: We performed a retrospective case series of patients who had undergone reconstruction of through-and-through oromandibular defects with the combined fibula flap and ALT flap in tandem from January 2012 through December 2014 at the Second Xiangya Hospital. The flap design and the methods for defect reconstruction are described, and the reconstructive efficacy is reported. RESULTS: Of the 14 patients, 13 were men and 1 was a woman, with an average age of 49.36 years. Postoperatively, all flaps survived completely, without vascular compromise or major wound complications. All of the donor sites were closed directly, leaving only linear scars and no thigh or leg motor dysfunction. All patients were followed for approximately 12 to 48 months, and the appearance and oral functions were acceptably recovered in about 90% of the patients. CONCLUSIONS: Because of the convenient flap design, satisfactory functional and esthetic results, and lower complication rates at the donor and recipient sites, the use of a combined fibula flap and ALT flap in tandem is a good choice for the reconstruction of complex through-and-through oromandibular defects.

Up-Regulation of microRNA-183 Promotes Cell Proliferation and Invasion in Glioma By Directly Targeting NEFL.

Glioblastoma multiforme (GBM) is the most common and lethal type of primary malignant brain tumor. In recent years, increasing reports suggest that discovery of microRNAs (miRNAs) might provide a novel therapeutical target for human cancers, including GBM. The expression and roles of microRNA-183 (miR-183) has been explored in several types of human cancers, including in GBM, and plays important roles in tumor initiation and progression. However, its biological functions in GBM remain largely unknown. In this study, we demonstrated that miR-183 was significantly up-regulated in astrocytoma tissues and glioblastoma cell lines. Introduction of miR-183 mimics into U251 cells could promoted, while its antisense oligos inhibited cell proliferation and invasion. Moreover, we identified neurofilament light polypeptide (NEFL) as a novel target gene of miR-183. The expression levels of NEFL are inversely correlated with that of miR-183 in human astrocytoma clinical specimens. In addition, NEFL-siRNA could significantly attenuate the inhibitory effects of knockdown miR-183 on the proliferation and invasion of U251 cells via mTOR signaling pathway. Overall, This study revealed that miR-183 promotes glioma cell proliferation by targeting NEFL, and also demonstrated that miR-183 could be a potential target for GBM treatment.

Longitudinal Contraction Venoplasty in Prevention of Internal Jugular Vein Thrombosis After Free Flap Vascular Anastomosis.

PURPOSE: The vascular anastomosis of free flap with the internal jugular vein stump is susceptible to thrombosis, thus resulting in flap compromise or failure. This study aims to explore the method of longitudinal contraction venoplasty in the prevention of internal jugular vein stump thrombosis after free flap vascular anastomosis and its feasibility. PATIENTS AND METHODS: A retrospective review was performed of 16 patients who underwent internal jugular vein resection because of cancer ablation and longitudinal contraction venoplasty to prevent internal jugular vein stump thrombosis after free flap vascular anastomosis from January 2013 through December 2014 at Second Xiangya Hospital. The methods for longitudinal contraction venoplasty and its efficacy are reported. RESULTS: Venous anastomosis of all flaps was performed with the internal jugular vein stump, and single venous anastomosis was made in all cases. Postoperatively, all flaps survived completely, without vascular compromise. All the patients were followed for approximately 9 to 33 months, and they were satisfied with the esthetic and functional results of the donor and recipient sites after reconstruction. CONCLUSIONS: Longitudinal contraction venoplasty may be an effective new method for prevention of internal jugular vein thrombosis after free flap vascular anastomosis.

Application of Thinned Anterolateral Thigh Flap for the Reconstruction of Head and Neck Defects.

PURPOSE: To evaluate the feasibility and reconstructive efficacy of the thinned anterolateral thigh (ALT) flap for the reconstruction of head and neck defects. PATIENTS AND METHODS: A retrospective review was performed of 43 patients who had undergone reconstruction of head and neck defects with a thinned ALT flap from January 2009 through December 2013 at the Second Xiangya Hospital. The methods for flap thinning and defect reconstruction and reconstructive efficacy are reported. RESULTS: The flaps were 5 cm × 7 cm to 9 cm × 14 cm, and all were harvested from a single cutaneous perforator. Postoperatively, 40 flaps survived completely and 3 flaps experienced partial necrosis. Venous compromise occurred in 2 cases, both of which were salvaged after operative exploration. Of the 43 donor sites, 41 were closed directly and resulted in only linear scars, and 2 were closed using full-thickness skin grafts because the defect was larger. All the patients were followed for approximately 6 to 36 months, and they were satisfied with the esthetic and functional results of the donor and recipient sites after reconstruction. CONCLUSION: With the high success rate of flap transplantation, satisfactory functional and esthetic results, and lower complication rates at the donor and recipient sites, the use of thinned ALT flaps can be a good choice for the reconstruction of head and neck defects in obese patients.

Dustfall Heavy Metal Pollution During Winter in North China.

In order to study heavy metal pollution in dustfall during Winter in North China, forty-four dustfall samples were collected in North China Region from November 2013 to March 2014. Then forty trace elements content were measured for each sample by inductively coupled plasma-mass spectrometry. Finally, the contamination characteristics of the main heavy metals were studied through a multi-method analysis, including variability analysis, Pearson correlation analysis and principal component analysis. Results showed that the relative contents of cadmium (Cd), zinc (Zn), copper (Cu), bismuth (Bi), lead (Pb) exceeded the standards stipulated in Chinese soil elements background values by amazing 4.9 times. In this study, conclusions were drawn that dustfall heavy metal pollution in the region was mainly caused by transport pollution, metallurgy industrial pollution, coal pollution and steel industrial pollution.

[The biological functions and regulations of competing endogenous RNA].

Recent studies demonstrate that RNA species could regulate each other by competing for shared microRNA response elements (MREs). This regulatory model is called competing endogenous RNA (ceRNA). Currently, the identified ceRNAs cover coding and non-coding RNAs. The latter includes pseudogene transcripts, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and so on. In this review, we summarize the biological functions of regulatory networks consisting of various types of ceRNAs and their roles in the pathological and physiological processes. Additionally, several factors that may regulate ceRNAs were discussed.

Application of anteromedial thigh flap for the reconstruction of oral and maxillofacial defects.

PURPOSE: To discuss the vascular anatomy of the anteromedial thigh (AMT) flap and to evaluate the feasibility of the AMT flap for the reconstruction of oral and maxillofacial defects. PATIENTS AND METHODS: A retrospective review was performed of 18 patients who underwent reconstruction of oral and maxillofacial defects with AMT flaps from January 2009 through December 2011 in the Second Xiangya Hospital. Eleven unifoliate AMT flaps were elevated to reconstruct defects of the tongue, soft palate, and floor of the mouth and 7 chimeric anterolateral thigh (ALT) and AMT flaps were harvested to reconstruct through-and-through cheek defects. RESULTS: The flaps were 4 × 6 to 9 × 11 cm(2). All the AMT flaps were nourished by the descending branch (DB) of the lateral circumflex femoral artery. The cutaneous perforators were derived from the rectus femoris branch of the DB in 15 cases and directly from the DB in the other 3 cases. Postoperatively, all flaps survived completely, without major complications. Of the 18 donor sites, 14 were closed directly, leaving only linear scars, and 4 were closed using full-thickness skin grafts owing to larger defects. All patients were followed for approximately 6 to 30 months, and they were satisfied with the esthetic and functional results of the donor and recipient sites after the reconstruction. CONCLUSIONS: Because of easy perforator dissection, the AMT flap can be used as an alternative to the ALT flap or harvested with the ALT flap as chimeric ALT and AMT flaps for the reconstruction of oral and maxillofacial defects.

Development of a Cancer-associated Fibroblast Signature for Evaluating Immunotherapy Response and Prognosis of Hepatocellular Carcinoma.

BACKGROUND: Alcohol abuse, non-alcoholic fatty liver disease (NAFLD), and hepatitis B and C are the main pathogenic factors of hepatocellular carcinoma (HCC). Though the current understanding of risk factors for HCC has been improved, patients with this type of cancer are normally diagnosed at advanced stages, posing significant challenges to effective treatment. METHODS: This study analyzed the HCC datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database (GSE14520 and GSE116174). Stromal and immune cell infiltration in the tumor microenvironment (TME) was quantified by the ESTIMATE algorithm. To identify gene modules associated with cancer-associated fibroblasts (CAFs), weighted gene co-expression network analysis (WGCNA) was performed to develop gene co-expression networks. A CAF prognosis score (CAFPS) model was established based on the prognostic CAF genes screened by univariate and multivariate Cox regression analyses. To determine the role of the genes in the vital module in HCC, we conducted Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Finally, the relationship between CAFPS and drug sensitivity was analyzed using Genomic Data for Cancer Drug Sensitivity (GDSC). RESULTS: In this study, we found significant differences in immune scores, stromal scores, CAFs scores, and CD4/8 T-cell scores between normal samples and samples with different TNM staging. In particular, the proportion of CAFs was higher than all other cells in normal samples. Gene modules related to CAFs were identified by developing a gene co-expression network using WGCNA analysis. The lightyellow and greenyellow modules showed the highest correlation with CAF scores. Univariate COX analysis identified 12 genes related to HCC prognosis from a total of 191 genes in the two modules. The Kaplan-Meier (KM) survival analysis revealed that a high expression of these genes was associated with a lower survival chance. Based on the 12 genes obtained by univariate COX analysis, multivariate COX analysis was performed to construct a risk score model for the characteristics of CAFs (CAFPS). The KM survival curves of patients in the high CAFPS and low CAFPS groups showed that patients in the low CAFPS group had better survival. CONCLUSION: CAFs played a crucial role in the pathogenesis and treatment response of HCC. Targeting the CAFs milieu may provide therapeutic benefits, highlighting the importance of CAFS in developing a personalized treatment for HCC patients. Further studies are required to verify the current findings and explore their implications in clinical settings.

Effect of magnetic resonance imaging in liver metastases.

This letter to the editor is a commentary on a study titled "Liver metastases: The role of magnetic resonance imaging." Exploring a noninvasive imaging evaluation system for the biological behavior of hepatocellular carcinoma (HCC) is the key to achieving precise diagnosis and treatment and improving prognosis. This review summarizes the role of magnetic resonance imaging in the detection and evaluation of liver metastases, describes its main imaging features, and focuses on the added value of the latest imaging tools (such as T1 weighted in phase imaging, T1 weighted out of phase imaging; diffusion-weighted imaging, T2 weighted imaging). In this study, I investigated the necessity and benefits of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid for HCC diagnostic testing and prognostic evaluation.