Manganese-derived biomaterials for tumor diagnosis and therapy.

Manganese (Mn) is widely recognized owing to its low cost, non-toxic nature, and versatile oxidation states, leading to the emergence of various Mn-based nanomaterials with applications across diverse fields, particularly in tumor diagnosis and therapy. Systematic reviews specifically addressing the tumor diagnosis and therapy aspects of Mn-derived biomaterials are lacking. This review comprehensively explores the physicochemical characteristics and synthesis methods of Mn-derived biomaterials, emphasizing their role in tumor diagnostics, including magnetic resonance imaging, photoacoustic and photothermal imaging, ultrasound imaging, multimodal imaging, and biodetection. Moreover, the advantages of Mn-based materials in tumor treatment applications are discussed, including drug delivery, tumor microenvironment regulation, synergistic photothermal, photodynamic, and chemodynamic therapies, tumor immunotherapy, and imaging-guided therapy. The review concludes by providing insights into the current landscape and future directions for Mn-driven advancements in the field, serving as a comprehensive resource for researchers and clinicians.

Biomaterial-Based CRISPR/Cas9 Delivery Systems for Tumor Treatment.

CRISPR/Cas9 gene editing technology is characterized by high specificity and efficiency, and has been applied to the treatment of human diseases, especially tumors involving multiple genetic modifications. However, the clinical application of CRISPR/Cas9 still faces some major challenges, the most urgent of which is the development of optimized delivery vectors. Biomaterials are currently the best choice for use in CRISPR/Cas9 delivery vectors owing to their tunability, biocompatibility, and efficiency. As research on biomaterial vectors continues to progress, hope for the application of the CRISPR/Cas9 system for clinical oncology therapy builds. In this review, we first detail the CRISPR/Cas9 system and its potential applications in tumor therapy. Then, we introduce the different delivery forms and compare the physical, viral, and non-viral vectors. In addition, we analyze the characteristics of different types of biomaterial vectors. We further review recent research progress in the use of biomaterials as vectors for CRISPR/Cas9 delivery to treat specific tumors. Finally, we summarize the shortcomings and prospects of biomaterial-based CRISPR/Cas9 delivery systems.

TGFBI: A novel therapeutic target for cancer.

TGFBI, an extracellular matrix protein induced by transforming growth factor ß, has been found to exhibit aberrant expression in various types of cancer. TGFBI plays a crucial role in tumor cell proliferation, angiogenesis, and apoptosis. It also facilitates invasion and metastasis in various types of cancer, including colon, head and neck squamous, renal, and prostate cancers. TGFBI, a prominent p-EMT marker, strongly correlates with lymph node metastasis. TGFBI demonstrates immunosuppressive effects within the tumor immune microenvironment. Targeted therapy directed at TGFBI shows promise as a potential strategy to combat cancer. Hence, a comprehensive review was conducted to examine the impact of TGFBI on various aspects of tumor biology, including cell proliferation, angiogenesis, invasion, metastasis, apoptosis, and the immune microenvironment. This review also delved into the underlying biochemical mechanisms to enhance our understanding of the research advancements related to TGFBI in the context of tumors.

RIRS with FV-UAS vs. MPCNL for 2-3-cm upper urinary tract stones: a prospective study.

To observe the efficacy and safety of retrograde intrarenal surgery (RIRS) combined with flexible vacuum-assisted ureteral access sheath (FV-UAS) and minimally invasive percutaneous nephrolithotomy (MPCNL) in patients with 2-3 cm upper urinary tract stones. A total of 160 patients with 2-3 cm upper urinary tract stones were prospectively randomized into 2 groups-80 in the FV-UAS group and 80 cases as control in the MPCNL group. The stone-free rates (SFRs) at different times (postoperative 1st day and 4th week) were considered as the primary outcome of the study. The secondary end points were operative time, hemoglobin decrease, postoperative hospital stay, and operation-related complications. There was no obvious difference between the two groups in patient's demographics and preoperative clinical characteristics (all P > 0.05). Postoperative data showed that mean decrease in hemoglobin level was less in FV-UAS group than that in MPCNL group (5.3 vs. 10.8 g/L, P < 0.001). Postoperative hospital stay in FV-UAS group was more shorten than that in MPCNL group (2.7 vs. 4.9 days, P < 0.001). There was no statistical significance between the two groups in SFRs during postoperative 1st day and 4th week (both P > 0.05). However, in terms of the rates of bleeding and pain, MPCNL group were both significantly higher than FV-UAS group (6.2 vs. 0.0%, P = 0.023; 16.2 vs. 2.5%, P = 0.003; respectively). Our study showed that RIRS with FV-UAS, a new partnership to treat 2-3 cm upper urinary tract stones, was satisfying as it achieved a high SFR rate and a low rate of complications. This method was safe and reproducible in clinical practice.

The prognosis and treatment of newly diagnosed bone metastasis of head and neck squamous cell cancer: an analysis of racial disparity.

OBJECTIVE: There is a lack of research investigating racial disparity in newly diagnosed head and neck squamous cell carcinoma with isolated bone metastases (HNSCC-BM). This study aims to investigate the clinical characteristics and prognostic factors in HNSCC-BM patients from different racial backgrounds to aid clinical decision making and management. METHODS: We retrieved data from the Surveillance, Epidemiology, and End Results (SEER) database for 345 cases of HNSCC-BM that were diagnosed between 2010 and 2017. Survival was compared using univariate and multivariate Cox proportional hazards models, Kaplan-Meier analysis, and log-rank tests. We also used propensity score matching to adjust for confounders. RESULTS: In white patients, those who were over 40 years of age had a significantly shorter survival (HR, 4.49; 95% CI 1.03-19.56; P < 0.05). Female black patients were found to survive longer compared to male patients (HR, 0.34; 95% CI 0.15-0.76; P < 0.01). Single (never married) Asians had shorter survival than married Asians (HR, 4.68; 95% CI 1.34-16.41; P < 0.05). In all three racial groups, patients who received radiotherapy in addition to chemotherapy did not survive longer than those receiving chemotherapy (P > 0.05). In Asian patients, those who underwent surgery at the primary site combined with chemoradiotherapy had significantly better survival outcomes than those who received chemoradiotherapy (HR: 0.10, 95% CI 0.01-0.88; P = 0.01). CONCLUSION: Prognostic factors differ between HNSCC-BM patients from different racial backgrounds.

Inhibition of autophagy enhances the anticancer effect of Schisandrin B on head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is among the most common malignant tumors worldwide and has a poor prognosis. Autophagy regulation has been proposed as a possible treatment option for HNSCC. Schisandrin B (Sch B) exerts anticancer effects by regulating apoptosis and autophagy, but the anticancer effect of Sch B in HNSCC remains unclear. This study aimed to investigate the effects of Sch B on human Cal27 HNSCC cells and to further reveal its potential regulatory mechanisms. The anticancer effect of Sch B was evaluated in vitro by flow cytometry, clonogenic assays, and Western blot analysis. The regulatory mechanism of Sch B-induced apoptosis and autophagy was further explored by polymerase chain reaction, luciferase assay, and reactive oxygen species (ROS) detection. The results showed that Sch B significantly induced apoptosis and autophagy in Cal27 cells and that inhibition of autophagy enhanced the apoptotic effect of Sch B on Cal27 cells. Additionally, Sch B-activated autophagy in Cal27 cells was dependent on the nuclear factor-kappa B (NF-κB) pathway, and ROS acted as a regulator of the NF-B pathway. N-acetylcysteine, a scavenger of ROS, inhibited Sch B-dependent autophagy via the NF-κB pathway. Based on the results, Sch B is a potential therapeutic agent for HNSCC and activates the NF-κB pathway by increasing ROS production, which subsequently promotes autophagy in HNSCC cells. Therefore, the strategy of enhancing the anticancer effect of Sch B by inhibiting autophagy deserves further attention.

IGF2BP2 acts as a m6A modification regulator in laryngeal squamous cell carcinoma through facilitating CDK6 mRNA stabilization.

Laryngeal squamous cell carcinoma (LSCC) is one of the most commonly seen cancers in the head and neck region with increasing morbidity and mortality globally. N6-methyladenosine (m6A) modification plays a critical role in the carcinogenesis of LSCC. In this study, two datasets from online database were analyzed for differentially expressed genes (DEGs) between LSCC and normal samples. Furthermore, we carried out a series of experiments, including hematoxylin & eosin staining, immunohistochemical (IHC) staining, CCK-8, colony formation, transwell, flow cytometry, xenograft tumor model assays, actinomycin D assay, cycloheximide (CHX) assay, methylated m6A RNA immunoprecipitation (Me-RIP), RNA immunoprecipitation (RIP) assay, to verify the relevant findings in vivo and in vitro. Insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) was identified as an up-regulated m6A regulator in LSCC samples. Lower IGF2BP2 expression was linked to higher survival probability in LSCC and other head and neck squamous cell carcinoma patients. In LSCC cells, IGF2BP2 knockdown attenuated cancer cell aggressiveness, possibly through modulating cell cycle arrest. In the xenograft tumor model derived from IGF2BP2 knocked-down LSCC cells, IGF2BP2 knockdown inhibited tumor growth. IGF2BP2 up-regulated CDK6 expression through facilitating the stability of CDK6 mRNA and protein. CDK6 knockdown caused no changes in IGF2BP2 expression, but partially eliminated the promotive effects of IGF2BP2 overexpression on LSCC cells' aggressiveness. Overexpressed IGF2BP2 in LSCC serves as an oncogenic factor, promoting LSCC cell proliferation and invasion in vitro and tumor growth in a xenograft tumor model in vivo through facilitating CDK6 mRNA stabilization.

Comparative efficacy between retrograde intrarenal surgery with vacuum-assisted ureteral access sheath and minimally invasive percutaneous nephrolithotomy for 1-2†cm infectious upper ureteral stones: a prospective, randomized controlled study.

Objective: To observe the efficacy and safety of retrograde intrarenal surgery combined with vacuum-assisted ureteral access sheath (V-UAS) and minimally invasive percutaneous nephrolithotomy (MPCNL) in patients with 1-2 cm infectious upper ureteral stone. Patients and methods: A total of 173 patients with 1-2 cm infectious upper ureteral stone were prospectively randomized into two groups. Eighty-six in the V-UAS group and 87 cases as control in the MPCNL group. The SFRs at different times (Postoperative 1 day, 2nd week and 4th week) was considered as the primary outcome of the study. The secondary end points were operative time, postoperative hospital stay and operative complications. Results: There was no obvious difference between two groups in patients' demographics and preoperative clinical characteristics (all P > 0.05). Postoperative data showed that the SFR at postoperative 1 day in the V-UAS group was significantly lower than that in the MPCNL group (73.2% vs. 86.2%, P = 0.034). However, there was no statistical significance between two groups in SFRs during postoperative 2 weeks and 4 weeks (All P > 0.05). The levels of WBC, CRP and PCT were all significant lower in the V-UAS group than those in the MPCNL group at the postoperative 24 h and 48 h (all P < 0.05). Postoperative complications included fever (≥38.5°C), bleeding, pain and urosepsis. In terms of the rates of fever, pain and urosepsis, MPCNL group were all significantly higher than those in the V-UAS group (10.3 vs. 2.4%, P = 0.031; 14.9 vs. 2.4%, P = 0.003; 4.6 vs. 0.0%, P = 0.044; respectively). No significant difference was found between two groups in bleeding. Meanwhile, postoperative hospital stay in the V-UAS group was more shorten than that in the MPCNL group (3.7 vs. 5.9 days, P < 0.001). Conclusions: Our study showed that RIRS with V-UAS, a new partnership to treat 1-2 cm infectious upper ureteral stones, was satisfying as it achieved a high SFR rate and a low rate of infectious complications. This method was safe and reproducible in clinical practice.

The Safety and Efficacy of Bipolar Plasma-Kinetic Transurethral Resection of The Prostate in Patients Taking Low-Dose Aspirin.

PURPOSE: To explore the safety and efficacy of bipolar plasma-kinetic transurethral resection of the prostate in patients taking low-dose aspirin. MATERIALS AND METHODS: Benign prostatic hyperplasia (BPH) patients who underwent surgical treatment from November 2018 to May 2020 were retrospectively analyzed, and divided into two groups according to whether taking 100mg aspirin daily aspirin or not. The perioperative indexes, complications and sequelae also were used to evaluate safety. The efficacy was evaluated by the functional outcomes in 3,6,12 months. RESULTS: There were no statistical differences in the baseline characteristics or perioperative indicators and complications and sequelae, except for a longer operative time(90.49 ± 14.34 vs 84.95 ± 15.49; 95%CI: 0.26-10.83; P = .040) and a shorter hospital stay time(HST) (8.52 ± 1.55 vs 9.09 ± 1 .50; 95% CI: 0.21-1.11; P = .042) in the non-aspirin group. During the 12-months follow-up period, the functional outcomes of the two groups were significantly improved except International Index of Erectile Function (IIEF-5). CONCLUSION: Based on our research results, PKRP a safe and effective method for patients with BPH who taking 100mg aspirin daily.

Cell membrane-coated nanomaterials for cancer therapy.

With the development of nanotechnology, nanoparticles have emerged as a delivery carrier for tumor drug therapy, which can improve the therapeutic effect by increasing the stability and solubility and prolonging the half-life of drugs. However, nanoparticles are foreign substances for humans, are easily cleared by the immune system, are less targeted to tumors, and may even be toxic to the body. As a natural biological material, cell membranes have unique biological properties, such as good biocompatibility, strong targeting ability, the ability to evade immune surveillance, and high drug-carrying capacity. In this article, we review cell membrane-coated nanoparticles (CMNPs) and their applications to tumor therapy. First, we briefly describe CMNP characteristics and applications. Second, we present the characteristics and advantages of different cell membranes as well as nanoparticles, provide a brief description of the process of CMNPs, discuss the current status of their application to tumor therapy, summarize their shortcomings for use in cancer therapy, and propose future research directions. This review summarizes the research progress on CMNPs in cancer therapy in recent years and assesses remaining problems, providing scholars with new ideas for future research on CMNPs in tumor therapy.

Emerging biomaterials for tumor immunotherapy.

BACKGROUND: The immune system interacts with cancer cells in various intricate ways that can protect the individual from overproliferation of cancer cells; however, these interactions can also lead to malignancy. There has been a dramatic increase in the application of cancer immunotherapy in the last decade. However, low immunogenicity, poor specificity, weak presentation efficiency, and off-target side effects still limit its widespread application. Fortunately, advanced biomaterials effectively contribute immunotherapy and play an important role in cancer treatment, making it a research hotspot in the biomedical field. MAIN BODY: This review discusses immunotherapies and the development of related biomaterials for application in the field. The review first summarizes the various types of tumor immunotherapy applicable in clinical practice as well as their underlying mechanisms. Further, it focuses on the types of biomaterials applied in immunotherapy and related research on metal nanomaterials, silicon nanoparticles, carbon nanotubes, polymer nanoparticles, and cell membrane nanocarriers. Moreover, we introduce the preparation and processing technologies of these biomaterials (liposomes, microspheres, microneedles, and hydrogels) and summarize their mechanisms when applied to tumor immunotherapy. Finally, we discuss future advancements and shortcomings related to the application of biomaterials in tumor immunotherapy. CONCLUSION: Research on biomaterial-based tumor immunotherapy is booming; however, several challenges remain to be overcome to transition from experimental research to clinical application. Biomaterials have been optimized continuously and nanotechnology has achieved continuous progression, ensuring the development of more efficient biomaterials, thereby providing a platform and opportunity for breakthroughs in tumor immunotherapy.

Preservation of superior laryngeal nerve in transoral surgery: A technology to enhance the recovery of swallowing function after surgery of hypopharyngeal carcinoma.

OBJECTIVES: We intended to preserve the internal branch of superior laryngeal nerve in transoral surgery of hypopharyngeal squamous cell carcinoma and observe swallowing function recovery. METHODS: 26 patients with hypopharyngeal squamous cell carcinoma underwent transoral surgery with the preservation of internal branch of superior laryngeal nerve. Sensation in the pharyngolaryngeal mucosa was tested by flexible laryngoscope and swallow function was evaluated by water swallow test and MD Anderson Dysphagia Inventory questionnaire after surgery. RESULTS: Surgeries were successfully performed in all patients. The internal branch of superior laryngeal nerve were preserved in all patients. Testing of mucosa sensation revealed the presence of the cough reflex in most patients. The water swallow test showed that 12 cases (46.15%) on the 1st day, 23 cases (88.46%) on the 7th day and 25 cases (96.15%) on the 14th day after operation had normal swallowing function. The mean score of MD Anderson Dysphagia Inventory was 98 on the 14th day after operation. All patients achieved an oral soft diet at a median of 3 days (range, 2-6 days), full normal oral diet at a median of 5.5 days (range, 4-10 days) and removal of the nasogastric tube at a median of 6 days (range, 5-11 days). During the two-year follow-up, 3 patients recured, 1 patient died of lung metastasis. CONCLUSIONS: Preserving of the internal branch of superior laryngeal nerve in transoral surgery is feasible, and it can help to achieve a satisfactory recovery of the swallowing function after surgery of hypopharyngeal squamous cell carcinoma.

The application of intraoperative neurophysiological monitoring in selective dorsal neurotomy for primary premature ejaculation: a prospective single-center study.

Selective dorsal neurotomy (SDN) is a surgical treatment for primary premature ejaculation (PE), but there is still no standard surgical procedure for selecting the branches of the dorsal penile nerves to be removed. We performed this study to explore the value of intraoperative neurophysiological monitoring (IONM) of the penile sensory-evoked potential (PSEP) for standard surgical procedures in SDN. One hundred and twenty primary PE patients undergoing SDN were selected as the PE group and 120 non-PE patients were selected as the normal group. The PSEP was monitored and compared between the two groups under both natural and general anesthesia (GA) states. In addition, patients in the PE group were randomly divided into the IONM group and the non-IONM group. During SDN surgery, PSEP parameters of the IONM group were recorded and analyzed. The differences in PE-related outcome measurements between the perioperative period and 3 months' postoperation were compared for the PE patients, and the differences in effectiveness and complications between the IONM group and the non-IONM group were compared. The results showed that the average latency of the PSEP in the PE group was shorter than that in the normal group under both natural and GA states (P < 0.001). Three months after surgery, the significant effective rates in the IONM and non-IONM groups were 63.6% and 34.0%, respectively (P < 0.01), and the difference in complications between the two groups was significant (P < 0.05). IONM might be useful in improving the short-term therapeutic effectiveness and reducing the complications of SDN.

FN1 promotes prognosis and radioresistance in head and neck squamous cell carcinoma: From radioresistant HNSCC cell line to integrated bioinformatics methods.

Background: Radioresistance in head and neck squamous cell carcinoma (HNSCC) patients means response failure to current treatment. In order to screen radioresistant biomarkers and mechanisms associated with HNSCC, differentially expressed genes (DEGs) associated with radioresistance in HNSCC were investigated. Methods: The HNSCC cell line with radioresistance, Hep2-R, was established and detected the radiosensitivity using MTT, colony formation assay and flow cytometry analysis. Clariom™ D chip was applied to compare DEGs between Hep2 and Hep2-R groups and build the differential gene expression profiles associated with radioresistance in HNSCC. Bioinformatic analysis were used to find biological functions and pathways that related to radioresistance in HNSCC, including cell adhesion, cytochrome P450 and drug metabolism. Gene Expression Omnibus (GEO) datasets were selected to verify DEGs between HNSCC radioresistant cells and tissues. The representation of DEGs were validated between HNSCC patients with complete response and post-operative radiation therapy failure. In addition, we evaluated the clinical prognosis of DEGs using The Cancer Genome Atlas (TCGA) database. Results: 2,360 DEGs (|Fold Change|>1.5, p < 0.05) were identified between Hep2 and Hep2-R, including 1,144 upregulated DEGs and 1,216 downregulated DEGs. They were further verified by HNSCC radioresistant cells and tissues in GEO. 13 radioresistant DEGs showed same difference in expression level between cells and tissues. By comparing 13 DEGs with HNSCC patients, upregulations of FN1, SOX4 and ETV5 were found identical with above results. Only FN1 was a prognostic indicator of HNSCC in TCGA. Conclusion: FN1 is the potential novel biomarker for predicting poor prognosis and radioresistance in HNSCC patients. Overexpression of FN1 plays an important role in the tumorigenesis, prognosis and radioresistance of HNSCC.

Malakoplakia of Larynx: A Case Report and Literature Review of Localized Malakoplakia of Larynx.

BACKGROUND: Malakoplakia is a very rare benign granulomatous disease, which can invade multiple organ systems, and is often related to bacterial infection and weak immunity. It is rarely occurred in the larynx, once this happens, the patient would complain of cough, hoarseness, dysphagia, and even dyspnea. METHODS: We reported a case of malakoplakia of larynx. The patient complained of hoarseness and cough. Her lesion was located in the right false vocal cord. six case reports of malacoplakia in larynx were compiled from the literature and integrated with this case report. RESULTS: After excising the tumor, the symptoms of the patient with cough, hoarseness and dysphagia were improved, and there was no recurrence during 1-year follow-up. The postoperative pathological diagnosis is malakoplakia. We found that malacoplakia is more commonly located in the supraglottic region, and we speculate that there may be a relationship between larynx-associated lymphoid tissue (LALT) and laryngeal malakoplakia. The effect of surgical treatment for laryngeal malacoplakia is satisfactory. CONCLUSION: Malakoplakia of the larynx is rare. Bacterial infection, immune deficiency, and the distribution of LALT may be related to the pathogenesis and supraglottic localization of malakoplakia. The symptoms are related to the location and size of the mass and may be serious and fatal. Surgery is an important treatment for preserving laryngeal function and low recurrence rate.

Efficacy of free anterolateral thigh flap and free jejunum in reconstruction for hypopharyngeal and cervical esophagus. / æ¸¸ç¦»è‚¡å‰å¤–ä¾§çš®ç“£å’Œæ¸¸ç¦»ç©ºè‚ é‡å»ºä¸‹å’½é¢ˆæ®µé£Ÿç®¡çš„ç–—æ•ˆ.

OBJECTIVES: Because of its peculiar anatomical location, most patients with hypopharyngeal and cervical esophageal cancer are at advanced stage when they visit the hospital. At present, the treatment for hypopharyngeal and cervical esophageal cancer is primarily surgical resection and radiotherapy. However, due to the wide range of surgical resection, it can often lead to a large range of annular defects. Therefore, the upper digestive tract reconstruction after tumor resection is very important. We use the free anterolateral thigh flap (ALT) and free jejunum (FJ) transfer to reconstruct the hypopharyngeal and cervical esophagus, and to investigate the effect of both reconstruction methods on upper gastrointestinal tract defects. METHODS: A retrospective analysis was conducted to investigate the clinical data of 42 patients with hypopharyngeal and cervical esophageal cancer (Clinical Stage IV) from Jan. 2004 to Jan. 2016 in the Second Xiangya Hospital of Central South University. All patients underwent total laryngopharyngectomy and cervical esophageal resection. The hypopharyngeal circumferential and cervical esophageal defects were reconstructed with free ALT (n=22) or FJ (n=20). Four patients who underwent radiotherapy and chemotherapy before surgery did not receive radiotherapy or chemotherapy after surgery. The remaining 38 patients underwent postoperative radiotherapy and chemotherapy. All patients were followed up by telephone or outpatient review, with a follow-up deadline in Jan. 2021. We compared the differences between the 2 groups in postoperative complications, radiotherapy complications, and survival rate. The differences in individual characteristics between 2 groups were analyzed using Fisher test. The differences in postoperative and radiotherapy complications between two groups were analyzed using χ² test. The 3- and 5-year overall survival rates were calculated using Kaplan-Meier survival curve method. RESULTS: In the ALT group, the postoperative complications mainly included anastomotic fistula, chylous fistula and subcutaneous hematoma of the donor site. The radiotherapy complication was anastomotic stenosis. However, in the FJ group, the postoperative complications mainly included chylous fistula, intestinal obstruction, and intestinal fistula. The radiotherapy complications mainly contained anastomotic fistula and tissue flap necrosis. The cases of postoperative complications in the ALT group and the FJ group were 7 and 5, respectively (P=0.625), and the cases of radiotherapy complications were 3 and 4, respectively (P=0.563). The 3-year overall survival rates in the ALT group and the FJ group were 52.9% and 46.7%, respectively, and the 5-year total survival rates were 35.1% and 31.9%, respectively (P=0.53). The cases of anastomotic stenosis after radiotherapy in the ALT group were more than those in the FJ group (P=0.097). However, the cases of jejunal necrosis and anastomotic fistula after radiotherapy in the FJ group were more than those in the ALT group (P=0.066). CONCLUSIONS: There are no significant differences in postoperative and radiotherapy complications and 3-and 5-year survival rates between the ALT group and the FJ group. The reconstruction with ALT is prone to develop anastomotic stricture. The reconstruction with FJ cannot withstand high-dose radiotherapy. The ALT and FJ are effective methods in the reconstruction of hypopharynx and cervical esophagus. The treatment protocol should be carefully chosen based on its advantages and disadvantages of these 2 methods.

Circ_0000523 regulates miR-1184/COL1A1/PI3K/Akt pathway to promote nasopharyngeal carcinoma progression.

BACKGROUND: The present study is to investigate the biological functions and mechanisms of circular RNA_0000523 (circ_0000523) in nasopharyngeal carcinoma (NPC). METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to examine the expression levels of circ_0000523 and microRNA-1184 (miR-1184) in NPC tissues and cells. Collagen type 1 alpha 1 chain (COL1A1) expression was assessed by qRT-PCR and immunohistochemistry (IHC) assay. Cell proliferation, cell cycle progression, migration and invasion were examined by cell counting kit-8 (CCK-8), 5-bromo-2'-deoxyuridine (BrdU), flow cytometry and Transwell assays. Xenograft nude mouse models were used to investigate the metastatic potential of NPC cells in vivo. The binding relationships between circ_0000523 and miR-1184, and between miR-1184 and COL1A1 were detected by dual-luciferase reporter gene assay. The protein expressions of COL1A1, phosphatidylinositol 3-kinase (p85), phosphorylated (p)-p85, protein kinase B (Akt) and p-Akt were detected through Western blot. The DAVID database was used for the enrichment analysis of the potential targets of miR-1184. RESULTS: Circ_0000523 and COL1A1 mRNA expressions were significantly increased in NPC tissues and cell lines. Circ_0000523 overexpression promoted NPC cell proliferation and accelerated cell cycle progression, whereas miR-1184 overexpression reversed these effects; circ_0000523 knockdown suppressed NPC cell proliferation and induced cell cycle arrest, while miR-1184 inhibition counteracted these effects. MiR-1184 was the downstream target of circ_0000523, and COL1A1 was the target gene of miR-1184 and could be positively modulated by circ_0000523. COL1A1 overexpression increased the expression levels of p-p85 and p-Akt, whereas knocking down COL1A1 repressed their expressions. CONCLUSIONS: Circ_0000523 facilitates NPC progression through regulating the miR-1184/COL1A1 axis.

Changes in laryngopharyngeal reflux after uvulopalatopharyngoplasty for obstructive sleep apnea: An observational study.

PURPOSE: To estimate laryngopharyngeal reflux (LPR) changes after uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea (OSA) using the reflux symptom index (RSI) and reflux finding score (RFS) questionnaires. METHODS: A total of 91 participants were recruited and divided into three groups: control (n = 27), OSA mild to moderate (n = 29), and OSA severe (n = 35) groups according to polysomnography. All participants completed the preoperative RSI, and underwent blinded evaluation on videolaryngoscopy using the RFS questionnaire. Thirty-four OSA patients who underwent UPPP surgery completed postoperative polysomnography and questionnaires again after a 6-month follow-up. RESULTS: The RSI score and RFS were higher in patients with OSA than in those without OSA. Patients with severe OSA also had a higher RSI score and RFS than those with mild to moderate OSA. Apnea and hypopnea index degree and percentage of recording time for <90% oxygen saturation showed positive correlation with LPR symptoms. But the lowest blood oxygen saturation during the recording time was negatively correlated with LPR symptoms. The mean RSI score and RFS before UPPP surgery were 15.88 ± 4.85 and 13.18 ± 4.80, after surgery decreasing to 9.53 ± 4.16 and 8.65 ± 4.87, respectively (P <.05). In 25 patients where surgery was successful, RSI scores, RFSs and individual RSI variables decreased after surgery. CONCLUSIONS: LPR symptoms are common among OSA patients, and the coexistence of OSA and LPR cannot be ignored. Successful UPPP surgery potentially reduces LPR symptoms and improves laryngoscopic signs by alleviating sleep respiratory disorders. Level of Evidence: 3.

MTDH associates with m6A RNA methylation and predicts cancer response for immune checkpoint treatment.

Immune checkpoint blockade (ICB) persistently provides a prognosis improvement but only in a small fraction of patients with cancer due to immunotherapy resistance induced by the consecutive activated oncogenic pathways, including MAPK, Akt, and WNT pathway partially driven by Metadherin (MTDH). However, there is no study to investigate the potential role and mechanisms of MTDH in ICB-treated cancers. Here, we systematically explored the cohorts from The Cancer Genome Atlas (TCGA) and independent cancer cohorts. Elevated MTDH expression was founded to associate with a worse overall survival and poorer immune response in patients with cancer. Dysregulated tumor-infiltrating immune cells and inhibitory immune checkpoint expression were correlated with MTDH expression. Furthermore, the mutual interactions between epithelial-to-mesenchymal-transition, m6A-RNA-methylation, and MTDH may illustrate the potential mechanisms of MTDH resistant to ICB treatment. Although more designed experiments and trials are needed in the future, targeting MTDH may help to overcome immunotherapy resistance in a wide range of cancers.

Metabolic Reprogramming and Immune Evasion in Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant tumor of the nasopharynx mainly characterized by geographic distribution and EBV infection. Metabolic reprogramming, one of the cancer hallmarks, has been frequently reported in NPCs to adapt to internal energy demands and external environmental pressures. Inevitably, the metabolic reprogramming within the tumor cell will lead to a decreased pH value and diverse nutritional supplements in the tumor-infiltrating micro-environment incorporating immune cells, fibroblasts, and endothelial cells. Accumulated evidence indicates that metabolic reprogramming derived from NPC cells may facilitate cancer progression and immunosuppression by cell-cell communications with their surrounding immune cells. This review presents the dysregulated metabolism processes, including glucose, fatty acid, amino acid, nucleotide metabolism, and their mutual interactions in NPC. Moreover, the potential connections between reprogrammed metabolism, tumor immunity, and associated therapy would be discussed in this review. Accordingly, the development of targets on the interactions between metabolic reprogramming and immune cells may provide assistances to overcome the current treatment resistance in NPC patients.