The association between leptin and diabetes: A meta-analysis.

PURPOSE: The study object was to determine the relationship between leptin and diabetes. METHODS: We searched for the literature on the relationship between leptin and diabetes from PubMed, EMBASE, Cochrane Library, and CNKI databases. We carried out the meta-analysis by calculating the Std. Mean Difference (SMD) and 95% confidence intervals (CIs) to study the relationship between leptin and diabetes. We performed the Chi-square-based Q test and I2 statistics to evaluate the potential heterogeneity, and the sensitivity analysis was performed to evaluate the stability of our results. Moreover, Begg's test was performed to evaluate the publication bias. RESULTS: There are 10 studies in this study for meta-analysis, which include 1879 patients (diabetic (n = 1024); and nondiabetic patients (n = 855)). The results indicated that the levels of serum leptin were significantly increased in patients with diabetes (SMD = 1.78, 95% CI [0.81, 2.76]), especially those with gestational diabetes mellitus compared with controls (SMD = 3.03, 95% CI [1.21, 4.86]). However, the results showed that there was no difference in serum leptin levels between type 2 diabetes and controls (SMD = 0.34, 95% CI [-1.06, 1.74]). CONCLUSIONS: Our analysis indicated that the levels of serum leptin were significantly elevated in patients with diabetes especially those with gestational diabetes mellitus compared with controls.

Camrelizumab and apatinib plus induction chemotherapy and concurrent chemoradiotherapy in stage N3 nasopharyngeal carcinoma: a phase 2 clinical trial.

The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Patients with N3 nasopharyngeal carcinoma have a high risk of distant metastasis, however, if the addition of immunotherapy to standard treatment could improve efficacy is unclear. In this phase II clinical trial (ChiCTR2000032317), 49 patients with stage TanyN3M0 nasopharyngeal carcinoma were enrolled and received the combination of three cycles of induction chemotherapy, camrelizumab and apatinib followed by chemoradiotherapy. Here we report on the primary outcome of distant metastasis-free survival and secondary end points of objective response rate, failure-free survival, locoregional recurrence-free survival, overall survival and toxicity profile. After induction therapy, all patients had objective response, including 13 patients (26.5%) with complete response. After a median follow-up of 28.7 months, the primary endpoint of 1-year distant metastasis-free survival was met for the cohort (1-year DMFS rate: 98%). Grade≥3 toxicity appeared in 32 (65.3%) patients, with the most common being mucositis (14[28.6%]) and nausea/vomiting (9[18.4%]). In this work, camrelizumab and apatinib in combination with induction chemotherapy show promising distant metastasis control with acceptable safety profile in patients with stage TanyN3M0 nasopharyngeal carcinoma.

Primary Surgery Followed by Selective Chemoradiotherapy Versus Preoperative Chemoradiotherapy Followed by Surgery for Locally Advanced Rectal Cancer: A Randomized Clinical Trial.

PURPOSE: The aim of this work was to determine whether locally advanced rectal cancer (LARC) with negative mesorectal fascia (MRF) predicted by magnetic resonance imaging (MRI) can be excluded from preoperative radiation therapy treatment. METHODS AND MATERIALS: This multicenter, open-label, non-inferiority, randomized clinical trial enrolled patients with LARC within 6 to 12 cm from the anal verge and with negative MRI-predicted MRF. Participants were randomized to the intervention group (primary surgery, in which the patients with positive pathologic [CRM] circumferential margins were subjected to chemoradiotherapy [CRT] and those with negative CRM underwent adjuvant chemotherapy according to pathologic staging) or the control group (preoperative CRT, in which all patients underwent subsequent surgery and adjuvant chemotherapy). The primary endpoint was 3-year disease-free survival (DFS). RESULTS: A total of 275 patients were randomly assigned to the intervention (n = 140) and control (n = 135) groups, in which 33.57% and 28.15% patients were at clinical T4 stage and 85.92% and 80.45% patients were at "bad" or "ugly" risk in the intervention and control groups, respectively. There were 2 patients (1.52%) and 1 patient (0.77%) with positive CRM in the intervention and control groups, respectively (P > .05). The non-adherence rates for the intervention and control groups were 3.6% and 23.7%, respectively. After a median follow-up of 34.6 months (IQR, 18.2-45.7), 43 patients had positive events (28 patients and 15 patients in the intervention and control groups, respectively). There were 6 patients (4.4%) with local recurrence in the intervention group and none in the control group, which led to the termination of the trial. The 3-year DFS rate was 81.82% in the intervention group (95% CI, 78.18%-85.46%) and 85.37% in the control group (95% CI, 81.75%-88.99%), with a difference of -3.55% (95% CI, -3.71% to -3.39%; hazard ratio, 1.76; 95% CI, 0.94-3.30). In the per-protocol data set, the difference between 3-year DFS rates was -5.44% (95% CI, -5.63% to -5.25%; hazard ratio, 2.02; 95% CI, 1.01-4.06). CONCLUSIONS: Based on the outcomes of this trial, in patients with LARC and MRI-negative MRF, primary surgery could negatively influence their DFS rates. Therefore, primary surgery was an inferior strategy compared with preoperative CRT followed by surgery and cannot be recommended for patients with LARC.

[Effects of denosumab on bone mineral density around proximal femoral prosthesis after total hip replacement in postmenopausal osteoporotic patients].

OBJECTIVE: To evaluate the effect of denosumab on bone mineral density around proximal femoral prosthesis after total hip arthroplasty(THA) in the postmenopausal osteoporotic patients. METHODS: Fifty-four consecutive patients underwent unilateral primary THA were included in this retrospective study. Twenty-five patients received denosumab for osteoporosis as the treatment group, and the twenty-nine without denosumab were the control group. At 1 week, 3month, 6 months, and 12 months after THA, bone turnover markers and proximal femoral periprosthetic bone mineral density (BMD) were measured. RESULTS: At 3, 6 and 12 months after operation, the level of TRACP-5b in the control group was significantly higher than that in the treatment group (P<0.05);the level of bone-specific alkaline phosphatase (BALP) between two groups showed significant difference in 12 months after operation (control group was higher than treatment group, P<0.05). The BMD of Gruen 1 and Gruen 7 decreased at 3, 6 and 12 months after operation compared with 1 week after operation. Comparing the treatment group and the control group, the differences of the the decrease of BMD in Gruen 1 and Gruen 7 were no significant at 3 months after surgery. In Gruen 1, Gruen 7 at 6 months after operation and Gruen 1, Gruen 7 at 12 months after operation, the decrease of BMD in the control group was significantly higher than that in the treatment group(P<0.05). It is suggested that desudumab could inhibit the loss of BMD after 6 months, and continuously show a protective effect on bone mass at 12 months after operation. CONCLUSION: After THA in postmenopausal patients with osteoporotic femoral neck fracture, Desuzumab can reduce the loss of BMD around the proximal femoral prosthesis and effectively inhibit bone resorption.

Prognostic value of metastatic cervical lymph node stiffness in nasopharyngeal carcinoma: A prospective cohort study.

OBJECTIVES: Extracellular matrix stiffness plays an important role in tumorigenesis. In this study, we assessed the prognostic value of metastatic cervical lymph node (CLN) stiffness measured using ultrasound shear wave elastography (SWE) in patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 325 consecutive patients with NPC and CLN metastases were prospectively enrolled in this study. The association between the CLN stiffness and patient characteristics was also evaluated. Survival analysis was performed for 307 patients with stage M0 disease. Distant metastasis-free survival (DMFS) was the primary endpoint. Log-rank test and multivariate analysis were used to explore the prognostic value of CLN stiffness. RESULTS: Eighteen patients developed distant metastases before treatment (stage M1) and had significantly higher CLN stiffness (Pt-test < 0.001) than the other patients (stage M0). For stage M0 patients, those in the high-stiffness group had lower 3-year DMFS (83.3% vs. 91.7%, P = 0.013) and 3-year progression-free survival (PFS) (78.2% vs. 87.9%, P = 0.015) than those in the low-stiffness group. Multivariate analysis identified CLN stiffness and pretreatment Epstein-Barr virus (EBV) DNA as independent prognostic factors for DMFS and PFS. We further established stiffness-EBV risk stratification based on these two factors. The concordance index, receiver operating characteristic curve, and decision curve analyses showed that our risk stratification outperformed the TNM classification for predicting metastasis. CONCLUSION: The stiffness of metastatic CLN is closely associated with the prognosis of patients with NPC. SWE can be used as a pretreatment examination for CLN-positive patients. A multicenter study is required to verify our results.

TTK is a potential regulator of tumor progression correlated with dedifferentiation and immune cell infiltration in papillary thyroid cancer.

OBJECTIVE: To investigate the role and clinical significance of threonine tyrosine kinase (TTK) in papillary thyroid cancer (PTC). METHODS: TTK expression in PTC and normal groups were compared using TCGA data and in vitro experiments. The prognostic value of TTK and its possible role in PTC dedifferentiation was evaluated. Next, TTK involvement in PTC occurrence and progression was analyzed via in vitro experiments. Subsequently, analyses of enrichment and immune cell infiltration were conducted to reveal the possible mechanism. Finally, we predicted the target miRNAs followed by performing a luciferase reporter experiment. RESULTS: TTK upregulation was observed in PTC, and its elevated level was significantly related to an unfavorable prognosis (P < 0.05). Interestingly, TTK negatively correlated with thyroid differentiation score (TDS), and patients with higher TDS showed longer survival (all P < 0.05). PTC cell growth, migration, and invasion were inhibited upon TTK knockdown. Besides, TTK was involved in metabolic processes and regulated cell adhesion molecules pathway. Its overexpression was positively associated with immune cell infiltrates (P < 0.05). Moreover, miR-582-5p was an upstream target of TTK. CONCLUSION: TTK serves as a potential biomarker for tumorigenesis and prognosis in PTC, especially for those that may differentiate into more aggressive thyroid cancers.

One-Pot Hydrothermal Method Preparation of Cerium-Nitrogen-Codoped Carbon Quantum Dots from Waste Longan Nucleus as a Fluorescent Sensor for Sensing Drug Rifampicin.

Currently, the large-scale application of carbon quantum dots (CQDs) is usually limited by their low quantum yield and detection limit. Herein, the abandoned longan nucleus was used as a carbon source to synthesize cerium-nitrogen-codoped carbon quantum dots (Ce/N-CQDs) with strong luminescence intensity. In this work, the fluorescent properties and fluorescent quantum yield of CQDs may be improved by the single cerium-doped carbon quantum dots (Ce-CQDs) and the single nitrogen-doped carbon quantum dots (N-CQDs). Nevertheless, the Ce/N-CQDs exhibited intense fluorescence with a high quantum yield. Compared with CQDs, the quantum yield of Ce/N-CQDs was significantly increased from 5 to 32% and showed high photostability and good water solubility. The Ce/N-CQDs can be used for the direct detection of rifampicin (RFP) in human serum. The concentration demonstrated a good linear relationship in the range of 1.0 × 10-7-9.0 × 10-6 mol/L, with a detection limit of 9.6 × 10-8 mol/L.

The RNA polymerase II subunit B (RPB2) functions as a growth regulator in human glioblastoma.

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with a poor prognosis. The growth of GBM cells depends on the core transcriptional apparatus, thus rendering RNA polymerase (RNA pol) complex as a candidate therapeutic target. The RNA pol II subunit B (POLR2B) gene encodes the second largest subunit of the RNA pol II (RPB2); however, its genomic status and function in GBM remain unclear. Certain GBM data sets in cBioPortal were used for investigating the genomic status and expression of POLR2B in GBM. The function of RPB2 was analyzed following knockdown of POLR2B expression by shRNA in GBM cells. The cell counting kit-8 assay and PI staining were used for cell proliferation and cell cycle analysis. A xenograft mouse model was established to analyze the function of RPB2 in vivo. RNA sequencing was performed to analyze the RPB2-regulated genes. GO and GSEA analyses were applied to investigate the RPB2-regulated gene function and associated pathways. In the present study, the genomic alteration and overexpression of the POLR2B gene was described in glioblastoma. The data indicated that knockdown of POLR2B expression suppressed tumor cell growth of glioblastoma in vitro and in vivo. The analysis further demonstrated the identification of the RPB2-regulated gene sets and highlighted the DNA damage-inducible transcript 4 gene as the downstream target of the POLR2B gene. The present study provides evidence indicating that RPB2 functions as a growth regulator in glioblastoma and could be used as a potential therapeutic target for the treatment of this disease.

Late-onset mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome with mitochondrial DNA 3243A>G mutation masquerading as autoimmune encephalitis: A case report.

BACKGROUND: Here, we present a unique case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, which initially appeared to be autoimmune encephalitis and was ultimately confirmed as MELAS with the mitochondrial DNA 3243A>G mutation. CASE SUMMARY: A 58-year-old female presented with acute-onset speech impediment and auditory hallucinations, symmetrical bitemporal lobe abnormalities, clinical and laboratory findings, and a lack of relevant prodromal history, which suggested diagnosis of autoimmune encephalitis. Further work-up, in conjunction with the patient's medical history, family history, and lactate peak on brain lesions on magnetic resonance imaging, suggested a mitochondrial disorder. Mitochondrial genome analysis revealed the m.3243A>G variant in the MT-TL1 gene, which led to a diagnosis of MELAS syndrome. CONCLUSION: This case underscores the importance of considering MELAS as a potential cause of autoimmune encephalitis even if patients are over 40 years of age, as the symptoms and signs are atypical for MELAS syndrome.

Du Huo Ji Sheng Tang inhibits Notch1 signaling and subsequent NLRP3 activation to alleviate cartilage degradation in KOA mice.

BACKGROUND: Knee osteoarthritis (KOA) has a complex pathological mechanism and is difficult to cure. The traditional medicine Du Huo Ji Sheng Tang (DHJST) has been used for the treatment of KOA for more than one thousand years, but its mechanism for treating KOA has not been revealed. In our previous study, we confirmed that DHJST inhibited the activation of NLRP3 signaling in rats and humans. In the current study, we aimed to determine how DHJST inhibits NLRP3 to alleviate knee cartilage damage. METHODS: Mice were injected with NLRP3 shRNA or Notch1-overexpressing adenovirus into the tail vein to construct systemic NLRP3 low-expressing or Notch1 high-expressing mice. Mice were injected with papain into the knee joint to replicate the KOA model. DHJST was used to treat KOA model mice with different backgrounds. The thickness of the right paw was measured to evaluate toe swelling. The pathohistological changes and the levels of IL-1ß, MMP2, NLRP3, Notch1, collagen 2, collagen 4, HES1, HEY1, and Caspase3 were detected by HE staining, ELISA, immunohistochemical staining, western blotting, or real-time qPCR. RESULTS: DHJST reduced tissue swelling and serum and knee cartilage IL-1ß levels, inhibited cartilage MMP2 expression, increased collagen 2 and collagen 4 levels, decreased Notch1 and NLRP3 positive expression rates in cartilage, and decreased HES1 and HEY1 mRNA levels in KOA model mice. In addition, NLRP3 interference decreased cartilage MMP2 expression and increased collagen 2 and collagen 4 levels without affecting the expression levels of notch1, HES1 and HEY1 mRNA levels in the synovium of KOA mice. In KOA mice with NLRP interference, DHJST further reduced tissue swelling and knee cartilage damage in mice. Finally, Notch1-overexpressing mice not only showed more severe tissue swelling and knee cartilage degradation but also abolished the therapeutic effect of DHJST on KOA mice. Importantly, the inhibitory effects of DHJST on the mRNA expression of NLRP3, Caspase3 and IL-1ß in the knee joint of KOA mice were completely limited after Notch1 overexpression. CONCLUSION: DHJST significantly reduced inflammation and cartilage degradation in KOA mice by inhibiting Ntoch1 signaling and its subsequent NLRP3 activation in the knee joint.

Visual function and biofeedback training of patients with central vision loss: a review.

Older individuals with macular diseases, such as age-related macular degeneration, experience central vision loss (CVL) due to degeneration of their photoreceptors and retinal cells. Patients with CVL may experience various vision impairments, including of visual acuity, fixation stability, contrast sensitivity, and stereoacuity. After CVL, most patients develop a preferred retinal locus outside the affected macular region, which serves as a new visual reference. In this review, we provide an overview of the visual function and impairment in individuals with CVL. In addition, the important role of biofeedback training on the visual function and activity of individuals with CVL is also reviewed. Accordingly, the location and development of the preferred retinal loci are discussed. Finally, this review discusses how to conduct biofeedback training to treat individuals with CVL.

Self-assembly of cell-embedding reduced graphene oxide/ polypyrrole hydrogel as efficient anode for high-performance microbial fuel cell.

A three-dimensional (3D) macroporous reduced graphene oxide/polypyrrole (rGO/Ppy) hydrogel assembled by bacterial cells was fabricated and applied for microbial fuel cells. By taking the advantage of electroactive cell-induced bioreduction of graphene oxide and in-situ polymerization of Ppy, a facile self-assembly by Shewanella oneidensis MR-1and in-situ polymerization approach for 3D rGO/Ppy hydrogel preparation was developed. This facile one-step self-assembly process enabled the embedding of living electroactive cells inside the hydrogel electrode, which showed an interconnected 3D macroporous structures with high conductivity and biocompatibility. Electrochemical analysis indicated that the self-assembly of cell-embedding rGO/Ppy hydrogel enhanced the electrochemical activity of the bioelectrode and reduced the electron charge transfer resistance between the cells and the electrode. Impressively, extremely high power output of 3366 ± 42 mW m-2 was achieved from the MFC with cell-embedding rGO/Ppy hydrogel rGO/Ppy, which was 8.6 times of that delivered from the MFC with bare electrode. Further analysis indicated that the increased cell loading by the hydrogel and improved electrochemical activity by the rGO/Ppy composite would be the underlying mechanism for this performance improvement. This study provided a facile approach to fabricate the biocompatible and electrochemical active 3D nanocomposites for MFC, which would also be promising for performance optimization of various bioelectrochemical systems.

Soil Microbial Fuel Cell Based Self-Powered Cathodic Biosensor for Sensitive Detection of Heavy Metals.

Soil microbial fuel cells (SMFCs) are an innovative device for soil-powered biosensors. However, the traditional SMFC sensors relied on anodic biosensing which might be unstable for long-term and continuous monitoring of toxic pollutants. Here, a carbon-felt-based cathodic SMFC biosensor was developed and applied for soil-powered long-term sensing of heavy metal ions. The SMFC-based biosensor generated output voltage about 400 mV with the external load of 1000 Ω. Upon the injection of metal ions, the voltage of the SMFC was increased sharply and quickly reached a stable output within 2~5 min. The metal ions of Cd2+, Zn2+, Pb2+, or Hg2+ ranging from 0.5 to 30 mg/L could be quantified by using this SMFC biosensor. As the anode was immersed in the deep soil, this SMFC-based biosensor was able to monitor efficiently for four months under repeated metal ions detection without significant decrease on the output voltage. This finding demonstrated the clear potential of the cathodic SMFC biosensor, which can be further implemented as a low-cost self-powered biosensor.

An automated, fully-integrated nucleic acid analyzer based on microfluidic liquid handling robot technique.

On-site nucleic acid testing (NAT) plays an important role for disease monitoring and pathogen diagnosis. In this work, we developed an automated and fully-integrated nucleic acid analyzer by combining the automated liquid handling robot technique with the microfluidic droplet-based real-time PCR assay technique. The present analyzer could achieve multiple operations including sample introduction, nucleic acid extraction based on magnetic solid-phase extraction, reverse transcription and, sample droplet generation, PCR amplification, real-time and dual fluorescence detection of droplet array. A strategy of constructing an integrated compact and low-cost system was adopted to minimize the analyzer size to 50 × 45 × 45 cm (length × width × height), and reduce the instrument cost to ca. $900 with a single analysis cost less than $5. A simple chip was also designed to pre-load reagents and carry oil-covered PCR reaction droplets. We applied the analyzer to identify eight types of influenza pathogens in human throat swabs, and the results were consistent with the colloidal gold method.

Self-Assembled Microfiber-Like Biohydrogel for Ultrasensitive Whole-Cell Electrochemical Biosensing in Microdroplets.

A novel microfiber-like biohydrogel was fabricated by a facile approach relying on electroactive bacteria-induced graphene oxide reduction and confined self-assembly in a capillary tube. The microfiber-like biohydrogel (d = ∼1 mm) embedded high-density living cells and activated efficient electron exchange between cells and the conductive graphene network. Further, a miniature whole-cell electrochemical biosensing system was developed and applied for fumarate detection under -0.6 V (vs Ag/AgCl) applied potential. Taking advantage of its small size, high local cell density, and excellent electron exchange, this microfiber-like biohydrogel-based sensing system reached a linear calibration curve (R2 = 0.999) ranging from 1 nM to 10 mM. The limit of detection obtained was 0.60 nM, which was over 1300 times lower than a traditional biosensor for fumarate detection in 0.2 µL microdroplets. This work opened a new dimension for miniature whole-cell electrochemical sensing system design, which provided the possibility for bioelectrochemical detection in small volumes or three-dimensional local detection at high spatial resolutions.

The BRD4 Inhibitor dBET57 Exerts Anticancer Effects by Targeting Superenhancer-Related Genes in Neuroblastoma.

Neuroblastoma (NB) is the most common solid tumor of the neural crest cell origin in children and has a poor prognosis in high-risk patients. The oncogene MYCN was found to be amplified at extremely high levels in approximately 20% of neuroblastoma cases. In recent years, research on the targeted hydrolysis of BRD4 to indirectly inhibit the transcription of the MYCN created by proteolysis targeting chimaera (PROTAC) technology has become very popular. dBET57 (S0137, Selleck, TX, USA) is a novel and potent heterobifunctional small molecule degrader based on PROTAC technology. The purpose of this study was to investigate the therapeutic effect of dBET57 in NB and its potential mechanism. In this study, we found that dBET57 can target BRD4 ubiquitination and disrupt the proliferation ability of NB cells. At the same time, dBET57 can also induce apoptosis, cell cycle arrest, and decrease migration. Furthermore, dBET57 also has a strong antiproliferation function in xenograft tumor models in vivo. In terms of mechanism, dBET57 targets the BET protein family and the MYCN protein family by associating with CRBN and destroys the SE landscape of NB cells. Combined with RNA-seq and ChIP-seq public database analysis, we identified the superenhancer-related genes TBX3 and ZMYND8 in NB as potential downstream targets of dBET57 and experimentally verified that they play an important role in the occurrence and development of NB. In conclusion, these results suggest that dBET57 may be an effective new therapeutic drug for the treatment of NB.

A Decade of Scientific and Technological Innovation at Chinese Academy of Medical Sciences & Peking Union Medical College: Retrospect and Prospect.

Focusing on the reform initiatives of Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC) in medical scientific and technological innovation from perspectives of deepening the reform and optimizing the ecosystem of science and technology innovation, this article summarizes the highlights of CAMS & PUMC's efforts in safeguarding people's health and promoting the Healthy China 2030 strategy through scientific and technological innovation in the fields including basic research, disease prevention and treatment, and medical technology in the past ten years. These achievements embody the endeavors and responsibility of CAMS & PUMC in realizing self-reliance and self-improvement of Chinese medical science and technology and highlight its contributions to the development of medical science and technology of China.

Anatomy and clinical application of suprascapular nerve to accessory nerve transfer.

BACKGROUND: Loss of motor function in the trapezius muscle is one complication of radical neck dissection after cutting the accessory nerve (AN) during surgery. Nerve repair is an effective method to restore trapezius muscle function, and includes neurolysis, direct suture, and nerve grafting. The suprascapular nerve (SCN) and AN are next to each other in position. The function of the AN and SCN in shoulder elevation and abduction movement is synergistic. SCN might be considered by surgeons for AN reanimation. AIM: To obtain anatomical and clinical data for partial suprascapular nerve-to-AN transfer. METHODS: Ten sides of cadavers perfused with formalin were obtained from the Department of Human Anatomy, Histology and Embryology, Peking University Health Science Center. The SCN (n = 10) and AN (n = 10) were carefully dissected in the posterior triangle of the neck, and the trapezius muscle was dissected to fully display the accessory nerve. The length of the SCN from the origin of the brachial plexus (a point) to the scapular notch (b point) and the distance of the SCN from the origin point (a point) to the point (c point) where the AN entered the border of the trapezius muscle were measured. The length and branches of the AN in the trapezius muscle were measured. A female patient aged 55 years underwent surgery for partial SCN to AN transfer at Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology. The patient suffered from recurrent upper gingival cancer. Radical neck dissection was performed on the right side, and the right AN was removed at the intersection between the nerve and the posterior border of the SCM muscle. One-third of the diameter of the SCN was cut off, and combined epineurial and perineurial sutures were applied between the distal end of the cut-off fascicles of the SCN and the proximal end of the AN without tension. Both subjective and objective evaluations were performed before, three months after, and nine months after surgery. For the subjective evaluation, the questionnaire included the Neck Dissection Impairment Index (NDII) and the Constant Shoulder Scale. Electromyography was used for the objective examination. Data were analyzed using t tests with SPSS 19.0 software to determine the relationship between the length of the SCN and the linear distance. A P value of < 0.05 was considered as statistically significant. RESULTS: The whole length of the AN in the trapezius muscle was 16.89 cm. The average numbers of branches distributed in the descending, horizontal and ascending portions were 3.8, 2.6 and 2.2, respectively. The diameter of the AN was 1.94 mm at the anterior border of the trapezius. The length of the suprascapular nerve from the origin of the brachial plexus to the scapular notch was longer than the distance of the suprascapular nerve from the origin point to the point where the accessory nerve entered the upper edge of the trapezius muscle. The amplitude of trapezius muscle electromyography indicated that both the horizontal and ascending portions of the trapezius muscle on the right side had better function than the left side nine months after surgery. The results showed that the right-sided supraspinatus and infraspinatus muscles did not lose more function than the left side. CONCLUSION: Based on anatomical data and clinical application, partial suprascapular nerve-to-AN transfer could be achieved and may improve innervation of the affected trapezius muscle after radical neck dissection.

Super-enhancer profiling identifies novel critical and targetable cancer survival gene LYL1 in pediatric acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a myeloid neoplasm makes up 7.6% of hematopoietic malignancies. Super-enhancers (SEs) represent a special group of enhancers, which have been reported in multiple cell types. In this study, we explored super-enhancer profiling through ChIP-Seq analysis of AML samples and AML cell lines, followed by functional analysis. METHODS: ChIP-seq analysis for H3K27ac was performed in 11 AML samples, 7 T-ALL samples, 8 B-ALL samples, and in NB4 cell line. Genes and pathways affected by GNE-987 treatment were identified by gene expression analysis using RNA-seq. One of the genes associated with super-enhancer and affected by GNE-987 treatment was LYL1 basic helix-loop-helix family member (LYL1). shRNA mediated gene interference was used to down-regulate the expression of LYL1 in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells. RESULTS: We identified a total of 200 genes which were commonly associated with super-enhancers in ≧10 AML samples, and were found enriched in regulation of transcription. Using the BRD4 inhibitor GNE-987, we assessed the dependence of AML cells on transcriptional activation for growth and found GNE-987 treatment predominantly inhibits cell growth in AML cells. Moreover, 20 candidate genes were selected by super-enhancer profile and gene expression profile and among which LYL1 was observed to promote cell growth and survival in human AML cells. CONCLUSIONS: In summary, we identified 200 common super-enhancer-associated genes in AML samples, and a series of those genes are cancer genes. We also found GNE-987 treatment downregulates the expression of super-enhancer-associated genes in AML cells, including the expression of LYL1. Further functional analysis indicated that LYL1 is required for AML cell growth and survival. These findings promote understanding of AML pathophysiology and elucidated an important role of LYL1 in AML progression.