Search

This study aimed to develop a mapping function that links the acromegaly quality of life (AcroQoL) questionnaire to EQ-5D-5L to obtain a preference-based utility value to inform economic evaluation. A nationwide cross-sectional questionnaire survey among patients with acromegaly was conducted online in China during 17 December 2019 to 6 January 2020. The study sample was randomly divided into a training set and a validation set. Ordinary least squares (OLS), Tobit, beta-based mixture, and adjusted limited dependent variable mixture models were tested for development of the function in the training set. Total and subscale scores and individual items of AcroQoL were included as predictors in the models along with their squared terms and demographic and clinical characteristics, and selected by backward stepwise selection. The root mean square error, mean absolute error, Akaike’s information criterion, Bayesian information criterion and adjusted R-square were used to assess goodness of fit and predictive ability of the models. There were 424 adult patients with acromegaly eligible for this analysis. Average EQ-5D-5L index score and AcroQoL score for them was 0.82 (SD = 0.15) and 44.3 (SD = 22.9), respectively. A total of 60 candidate models were tested. Considering model simplicity and predictive ability in both training and validation set, the best model was the OLS model using scores of physical dimension and its square term as predictors. A validated mapping function was developed in this study for estimating EQ-5D scores using AcroQoL outcomes. Its external validity can be further tested in other population with Acromegaly.

Pediatric gliomas (PGs) are the most common brain tumors in children and the leading cause of childhood cancer-related death. The understanding of the immune microenvironment is essential for developing effective antitumor immunotherapies. Transcriptomic data from 495 PGs were analyzed in this study, with 384 as a training cohort and 111 as a validation cohort. Macrophages were the most common immune infiltrates in the PG microenvironment, followed by T cells. PGs were classified into 3 immune subtypes (ISs) based on immunological profiling: “immune hot” (IS-I), “immune altered” (IS-II), and “immune cold” (IS-III). IS-I tumors, characterized by substantial immune infiltration and high immune checkpoint molecule (ICM) expression, had a favorable prognosis and were more likely to respond to anti-PD1 and anti-CTLA4 immunotherapies, whereas IS-III tumors, characterized by weak immune infiltration and low ICM expression, had a dismal prognosis and poor immunotherapy responsiveness. IS-II tumors represented a transitional stage. Immune classification was also correlated with somatic mutations, copy number alterations, and molecular pathways related to tumorigenesis, metabolism, and immune responses. Three predictive classifiers using eight representative genes were generated by machine learning methods for immune classification. This study established a reliable immunological profile-based classification system for PGs, providing implications for further immunotherapy strategies., Graphical Abstract, Pediatric gliomas (PGs) are the most common brain tumors in children and the leading cause of childhood cancer-related death. With the use of transcriptomic information, PGs can be classified into 3 immune subtypes: “immune hot” (IS-I), “immune altered” (IS-II), and “immune cold” (IS-III), based on immunological profiling, providing implications for further immunotherapy strategies.

Background Facial abnormality is the most significant feature in acromegaly patients. However, it is unclear whether and how patient facial appearance improves after treatment. This study aimed to identify 3D facial changes in acromegaly patients after surgical treatment. Methods This study included 30 acromegaly patients who underwent resection of a pituitary GH adenoma. The location and extent of facial changes were identified by comparing baseline and 2-year follow-up 3D images of the face. Relationships between facial changes and GH and IGF-1 were evaluated with simple or multivariable linear regression models. Results Significant soft tissue improvements were observed in acromegaly patients with complete remission, especially in the nose and lip region. Significant reductions in nasal width (3.46 mm, P < 0.001), tip protrusion (1.18 mm, P = 0.003), face curve length (3.89 mm, P = 0.004) and vermilion area (1.42 cm3, P = 0.001) were observed at the 2-year follow-up. Further, changes in nasal width were associated with decreases in GH (β = 4.440, P = 0.017), the GH nadir (β = 4.393, P = 0.011) and IGF-1 (β = 5.263, P = 0.002). The associations were maintained after adjusting for confounders. Conclusions Acromegaly patients achieved considerable facial improvements after surgical treatment. The change in nose width was associated with GH and IGF-1 decrease. Better control of patient hormone levels after surgery improves patient facial recovery.

Tumor resection is the first-line therapy for acromegaly patients. In some cases, unsatisfactory intraoperative neuromuscular blockades (NMBs) lead to failed operations. The purpose of this study was to investigate and quantify the NMB status of acromegaly patients and explore the relationship between NMB status and hormone levels and body composition. Twenty patients with untreated acromegaly and seventeen patients with nonfunctioning pituitary adenomas as controls were enrolled in this study. NMB was assessed using the train-of-four (TOF) technique with TOF-Watch® SX. The onset time of NMB, deep neuromuscular blockade duration (DNMBD), and clinical neuromuscular blockade duration (CNMBD) were monitored. We found a significantly longer onset time (110.25 ± 54.90 vs. 75.00 ± 27.56, s, p = 0.017 ), shorter DNMBD (21.99 ± 5.67 vs. 34.96 ± 11.04, min, p < 0.001 ), and shorter CNMBD (33.26 ± 8.09 vs. 46.21 ± 10.89, min, p < 0.001 ) in acromegaly patients compared with the controls. DNMBD and CNMBD decreased in patients with decreasing body fat percentage and increasing growth hormone (GH) level, insulin-like growth factor 1 (IGF-1) level, and GH and IGF-1 burden. The onset time increased with increasing IGF-1 level and GH and IGF-1 burden. Taken together, a unique NMB status was identified in acromegaly patients with the following characteristics: prolonged onset time and shortened DNMBD and CNMBD. Changes in the levels and burdens of GH and IGF-1 and body composition were linearly correlated with intraoperative NMB in acromegaly patients.

Hepatocellular carcinoma (HCC) is the most common type of malignant neoplasm of the liver with high morbidity and mortality. Extensive research into the pathology of HCC has been performed; however, the molecular mechanisms underlying the development of hepatitis B virus-associated HCC have remained elusive. Thus, the present study aimed to identify critical genes and pathways associated with the development and progression of HCC. The expression profiles of the GSE121248 dataset were downloaded from the Gene Expression Omnibus database and the differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analyses were performed by using the Database for Annotation, Visualization and Integrated Discovery. Subsequently, protein-protein interaction (PPI) networks were constructed for detecting hub genes. In the present study, 1,153 DEGs (777 upregulated and 376 downregulated genes) were identified and the PPI network yielded 15 hub genes. GO analysis revealed that the DEGs were primarily enriched in 'protein binding', 'cytoplasm' and 'extracellular exosome'. KEGG analysis indicated that DEGs were accumulated in 'metabolic pathways', 'chemical carcinogenesis' and 'fatty acid degradation'. After constructing the PPI network, cyclin-dependent kinase 1, cyclin B1, cyclin A2, mitotic arrest deficient 2 like 1, cyclin B2, DNA topoisomerase IIα, budding uninhibited by benzimidazoles (BUB)1, TTK protein kinase, non-SMC condensin I complex subunit G, NDC80 kinetochore complex component, aurora kinase A, kinesin family member 11, cell division cycle 20, BUB1B and abnormal spindle microtubule assembly were identified as hub genes based on the high degree of connectivity by using Cytoscape software. In addition, overall survival (OS) and disease-free survival (DFS) analyses were performed using the Gene Expression Profiling Interactive Analysis online database, which revealed that the increased expression of all hub genes were associated with poorer OS and DFS outcomes. Receiver operating characteristic curves were constructed using GraphPad prism 7.0 software. The results confirmed that 15 hub genes were able to distinguish HCC form normal tissues. Furthermore, the expression levels of three key genes were analyzed in tumor and normal samples of the Human Protein Atlas database. The present results may provide further insight into the underlying mechanisms of HCC and potential therapeutic targets for the treatment of this disease.

To elucidate the sleep quality characteristics and factors related to either good or poor sleep quality in acromegaly patients before surgery and to explore sleep quality changes after transsphenoidal surgery and the factors related to these changes.We prospectively enrolled 39 acromegaly patients and 78 patients with nonfunctioning pituitary adenomas. Scales for anxiety, depression, disease stigma and nasal condition were evaluated. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was administered before surgery as well as one month and three months after surgery.A higher percentage of acromegaly patients had poor sleep quality compared to controls (35.9% vs. 5.1%, p 0.001). In addition, acromegaly patients experienced worse subjective sleep quality, extended sleep latency, increased sleep disturbance and decreased daytime functioning. Higher scores for anxiety, disease stigma and sinonasal outcomes were correlated with worse sleep quality in acromegaly patients. At one month after transsphenoidal surgery, we found worse subjective sleep quality, extended sleep latency, shortened sleep duration, impaired sleep efficiency and increased sleep disturbance in acromegaly patients. At three months postoperatively, most impaired PSQI domains in acromegaly patients recovered to preoperative levels. The use of soluble gauze was related to decreased sleep quality at one month after surgery and severe anxiety and depression were related to improved sleep quality at three months after surgery.Sleep quality was reduced in acromegaly patients. Moreover, sleep quality initially worsened after surgery but later recovered. Emotional problems and the use of soluble gauze were related factors.None.

Background Most patients with glioma experience recurrence and have a poor prognosis. Scientometric analysis is effective and widely used to summarize the most influential studies within a certain field. We present the first scientometric analysis of recurrent glioma. Methods We conducted a generalized search for articles on recurrent glioma in the Web of Science database and evaluated the top 100 most cited articles among 4651 articles. Results The number of citations from the top 100 cited articles on recurrent glioma ranged from 149 to 1471; most of these articles were published in oncology-specific journals (66) and were submitted by institutions in the United States (n = 67). The top-cited articles consisted of 98 articles and 2 literature reviews. Articles were classified into 4 major categories based on subject matter: 82 pertained to treatment, 6 pertained to genetic mechanisms, 7 pertained to diagnosis, and 5 pertained to prognosis. Treatment-related articles were subdivided into the following 7 categories: targeted therapy (n = 21), chemotherapy (n = 20), immunotherapy (n = 12), combination therapy (n = 12), radiotherapy (n = 9), surgical resection (n = 6), a new therapy (physiotherapy) (n = 1), and treatment summary (n = 1). Conclusions The results of the analysis indicated that the core problem is the treatment of recurrent glioma. Although the number of citations on targeted therapy and combination therapy has increased in recent years, the proportion of randomized controlled trials, basic medical research, literature reviews, and meta-analyses is relatively low; thus, there is an urgent need to conduct these types of studies on recurrent glioma.

Transcatheter arterial embolization (TAE) plays an important role in clinical liver tumor therapy. However, hypoxia after TAE limit the medium-long term efficacy of TAE. Thus, in our study, we explored the treatment effect and mechanism of combining transcatheter arterial embolization with adopted iodized oil containing Apatinib on suppressing tumor growth and metastasis. We simulated the changing of tumor microenvironment before and after TAE both in vitro and in vivo models. The anti-angiogenic effect of Apatinib was explored by bioassays in human umbilical vein endothelial cells (HUVECs), including cell migration, invasion and apoptosis, tube formation, and wound healing. Further experiments showed that Apatinib inhibited tumor microangiogenesis to achieve the aims of inhibiting tumor growth and recurrence by means of down-regulating the phosphorylation of the RAF-mek-erk, PI3K-akt and P38MAPK pathways. The antitumor growth and anti-angiogenic effect of Apatinib was further validated by the animal experiment. Taken together, we concluded that Apatinib inhibits the angiogenesis and growth of liver cancer by down-regulating the PI3K-akt, RAF-mek-erk and P38MAPK pathways, and has a stronger inhibitory effect in hypoxic environments. Combining TAE with adopted iodized oil containing Apatinib has a stronger inhibitory effect in VX2 liver tumor growth and metastasis, which suggesting such combinations may provide a new target and strategy for interventional therapy of liver cancer.

ObjectiveTo compare the efficacy and safety of transarterial chemoembolization (TACE) combining with sorafenib or apatinib for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT).MethodsFrom June 2015 to March 2020, a total of 89 consecutive advanced HCC patients with PVTT who were treated with sorafenib-TACE (S-TACE) or apatinib-TACE (A-TACE) in our center were enrolled. The overall survival (OS), time to progression (TTP), tumor response, and adverse events in the two groups were compared.ResultsThere were 32 and 41 patients included in the S-TACE group and A-TACE group, respectively. The median follow-up was 10.0 months (range, 3.0–36.0 months) in the whole study. The median OS (11.0 vs. 10.0 months, P = 0.419), median TTP (5.0 vs. 6.0 months, P = 0.073), and tumor response (P = 0.529) between the S-TACE group and the A-TACE group were not significantly different. The adverse events related to sorafenib or apatinib were tolerable.ConclusionS-TACE and A-TACE exhibited comparable prognosis for HCC patients with PVTT, which provide another effective and safe method of A-TACE for these patients except for conventional S-TACE.

Purpose We constructed a self-management program for rectal cancer survivors with colostomies and evaluated the effect of the program on self-efficacy, self-management ability, and incidence of stomal and peristomal complications. Design A prospective, nonrandomized clinical trial. Subjects and setting Participants were recruited from 4 proctology departments in a tertiary hospital in northeast China. Fifty-five were assigned to the intervention group and 56 were assigned to the control group; 26 were lost to follow-up. Therefore, data analysis was based on 43 participants in the intervention group and 42 in the control group. Methods Control group patients received the standard care where guidance and stoma care manuals were given the day before hospital discharge, and regular telephone follow-up twice a month for 3 months. Participants in the experimental group received, in addition to standard care, a self-management program delivered via a multimedia messaging app initiated after discharge available over a 6-week period. Primary outcomes were self-efficacy and self-management ability; we also analyzed the incidence of stomal and peristomal complications as a secondary outcome. Between-groups outcomes were analyzed via a repeated-measures analysis of variance. Results Analysis indicated intervention group participants had higher levels of self-efficacy and self-management of their colostomies than did control group participants. Analysis also revealed intervention group participants had a lower incidence of peristomal complications; no differences in the incidence of stomal complications were found. Conclusions Study findings suggest that use of the multimedia messaging app-based self-management program enhanced self-efficacy and self-management, while reducing the incidence of peristomal complications in rectal cancer survivors with colostomies.

We aimed to investigate the correlations between biochemical and hematological markers and the clinical conditions of brain tumor patients before and after craniotomy. A retrospective study was conducted in 90 brain tumor patients. Age, gender, underlying diseases, tumor size and intraoperative blood loss were recorded. Red blood cell counts and hepatic and renal markers were analyzed preoperatively and postoperatively. Albumin decreased by 5.6 g/L after surgery (p 0.001). Older patients (52 years) and females had lower albumin levels than younger patients and males did. Red blood cell counts and hemoglobin levels decreased significantly on the 1st and increased on the 3rd postoperative day. The blood glucose level increased on the 1st postoperative day and then decreased. Older patients had higher blood glucose levels than younger patients did (p 0.05). The postoperative serum sodium, potassium and calcium levels were within the normal ranges; 37 patients had hypocalcemia (41.1%) and patients with hypokalemia and hyponatremia increased postoperatively. Albumin and hemoglobin levels were linearly correlated (correlation coefficient 0.559, p 0.001). Intraoperative blood loss was correlated with tumor size (p 0.05) but did not affect the decrease in hematological markers. In brain tumor patients, red blood cell counts and hemoglobin and serum albumin levels were significantly decreased after craniotomy; these effects were influenced by gender and age instead of intraoperative blood loss. The postoperative blood glucose level peaked and then decreased; it was affected by age and diabetes mellitus. Electrolytes remained relatively stable. These findings have implications for patient management and postoperative complication prevention.

The purpose of this work was to investigate the plasma pharmacokinetics, intratumoral drug concentration, and tumor necrosis after transarterial chemoembolization (TACE) with doxorubicin-loaded CalliSpheres microspheres (CSMs). Sixty rabbits with liver VX2 tumors were assigned into five groups of 12 rabbits each, which received 4 mg of doxorubicin via intravenous injection (IV group), hepatic arterial infusion (IA group), conventional TACE (cTACE group), CSM-TACE (CSM low-dose group), and 8 mg of doxorubicin via CSM-TACE (CSM high-dose group), respectively. Doxorubicin concentrations in plasma, tumor, and adjacent hepatic parenchyma were measured at various timepoints after treatment, and tumor necrosis percentage and liver enzymes were also assessed. The peak plasma concentration of doxorubicin was significantly lower in the three TACE groups compared to IV and IA group (P

Objective To investigate the validity of discharge ICD-10 codes in detecting the etiology of endogenous Cushing’s syndrome (CS) in hospitalized patients. Methods We evaluated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CS etiology-related ICD-10 codes or code combinations by comparing hospital discharge administrative data (DAD) with established diagnoses from medical records. Results Coding for patients with adrenocortical adenoma (ACA) and those with bilateral macronodular adrenal hyperplasia (BMAH) demonstrated disappointingly low sensitivity at 78.8% (95% CI: 70.1–85.6%) and 83.9% (95% CI: 65.5–93.9%), respectively. BMAH had the lowest PPV of 74.3% (95% CI: 56.4–86.9%). In confirmed ACA patients, the sensitivity for ACA code combinations was higher in patients initially admitted to the Department of Endocrinology before surgery than that in patients directly admitted to the Department of Urology (90.0 vs 73.1%, P = 0.033). The same phenomenon was observed in the PPV for the BMAH code (100.0 vs 60.9%, P = 0.012). Misinterpreted or confusing situations caused by coders (68.1%) and by the omission or denormalized documentation of symptomatic diagnosis by clinicians (26.1%) accounted for the main source of coding errors. Conclusions Hospital DAD is an effective data source for evaluating the etiology of CS but not ACA and BMAH. Improving surgeons’ documentation, especially in the delineation of symptomatic and locative diagnoses in discharge abstracts; department- or disease-specific training for coders and more multidisciplinary collaboration are ways to enhance the applicability of administrative data for CS etiologies.

Objective To investigate the clinical characteristics of delayed remission (DR) of growth hormone (GH)-secreting pituitary adenoma after transsphenoidal adenectomy and inform follow-up treatments. Methods We retrospectively reviewed 87 patients who had undergone transsphenoidal surgery for acromegaly. Demographic, radiological, and endocrinological data were reviewed before, immediately after, 3 months after, and in the long term (2.4 ± 1.1 years) after surgery. The definition of DR was that patients did not achieve GH remission immediately, 3 months, or later after surgery, but did so in the long term without any additional postoperative treatment. Results Fifty-one patients (58.6%) achieved long-term GH remission. There were 24 (27.6%) DR patients immediately postoperatively and 9 (10.3%) DR patients 3 months postoperatively. On average, the 24 DR patients achieved remission at 10.2 (range, 3–32) months. Immediate postoperative random and nadir GH after an oral glucose load were significantly lower in the DR group than in the nonremission group (2.73 ± 3.17 and 2.03 ± 2.59 vs. 8.05 ± 10.35 and 5.55 ± 5.91 μg/L, respectively). Three-month postoperative nadir GH was significantly lower in the DR group than in the nonremission group (1.63 ± 2.82 vs. 3.48 ± 4.25 μg/L, P = 0.007). Immediate postoperative random GH effectively predicted long-term remission (Spearman's ρ = 0.513, area under the curve = 0.905 > 0.90). However, the best predictor of long-term remission was 3-month postoperative nadir GH (Spearman's ρ = 0.728, area under the curve = 0.944 > 0.90), with 76.5% sensitivity and 97.2% specificity. Conclusions For certain groups of patients likely to achieve DR, additional treatments should not be performed early after surgery. Prolonged follow-up and close observation could help determine the therapeutic effect of surgery and guide postoperative treatments.

Hongliang Li,1,* Xiaopeng Guo,1,* Qiutian Li,2,* Pengzhan Ran,1 Xudong Xiang,3 Yuncang Yuan,1 Tianqi Dong,1 Bei Zhu,1 Lei Wang,1 Fangfang Li,1 Chunyan Yang,1 Dengcai Mu,1 Dan Wang,4 Chunjie Xiao,1 Shangyong Zheng1 1School of Medicine, Yunnan University, Kunming, China; 2Department of Oncology, Kunming General Hospital of Chengdu Military Command, Teaching Hospital of Kunming Medical University, Kunming, China; 3Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China; 4Department of Pharmacy, Kunming General Hospital of Chengdu Military Command, Teaching Hospital of Kunming Medical University, Kunming, China *These authors contributed equally to this work Purpose: Emerging evidence suggests that many differentially expressed long non-coding RNAs (lncRNAs) are involved in tumorigenesis. However, the functional roles of these transcripts and the mechanisms responsible for their deregulation in non-small-cell lung cancer (NSCLC) remain elusive. Here, we identified a novel lncRNA (lncRNA 1308), which was significantly upregulated in NSCLC tissues and investigated its biological function and potential molecular mechanism.Methods: Differences in the lncRNA expression profiles between NSCLC and tumor-adjacent normal tissues were assessed by lncRNA expression microarray analysis. The microRNA in vivo precipitation (miRIP) method was used to identify the targeting microRNAs (miRNAs) on lncRNA 1308, and luciferase reporter assays were performed. Loss-of-function studies were used to explore the effect of lncRNA 1308 on lung carcinogenesis in NSCLC cells.Results: The novel lncRNA 1308 was upregulated in NSCLC tissues and cell lines. By using biotin-labeled lncRNA 1308 for miRIP in NSCLC cells and dual-luciferase reporter assays, the results suggested that miRNA-124 was associated with lncRNA 1308. Furthermore, the expression of a disintegrin and a metalloproteinase 15 (ADAM 15) was downregulated in NSCLC cells when silencing of lncRNA 1308, the target of oncogenic miR-124, inhibits NSCLC cell proliferation and invasion. Conversely, the expression of ADAM 15 was significantly increased, when inhibiting the expression of miR-124, and alleviated cell invasion inhibition.Conclusion: The results suggested that lncRNA 1308 may function as a competing endogenous RNA (ceRNA) for miR-124 to regulate cell invasion through the miR-124/ADAM 15 signaling pathway, indicating that lncRNA 1308 plays an important role in the disease progression of NSCLC. Keywords: lung cancer, lncRNA 1308, miR-124, ADAM 15, competing endogenous RNA

Glioblastoma (GBM) is the most malignant and lethal intracranial tumor, with extremely limited treatment options. Immunotherapy has been widely studied in GBM, but none can significantly prolong the overall survival (OS) of patients without selection. Considering that GBM cancer stem cells (CSCs) play a non-negligible role in tumorigenesis and chemoradiotherapy resistance, we proposed a novel stemness-based classification of GBM and screened out certain population more responsive to immunotherapy. The one-class logistic regression algorithm was used to calculate the stemness index (mRNAsi) of 518 GBM patients from The Cancer Genome Atlas (TCGA) database based on transcriptomics of GBM and pluripotent stem cells. Based on their stemness signature, GBM patients were divided into two subtypes via consensus clustering, and patients in Stemness Subtype I presented significantly better OS but poorer progression-free survival than Stemness Subtype II. Genomic variations revealed patients in Stemness Subtype I had higher somatic mutation loads and copy number alteration burdens. Additionally, two stemness subtypes had distinct tumor immune microenvironment patterns. Tumor Immune Dysfunction and Exclusion and subclass mapping analysis further demonstrated patients in Stemness Subtype I were more likely to respond to immunotherapy, especially anti-PD1 treatment. The pRRophetic algorithm also indicated patients in Stemness Subtype I were more resistant to temozolomide therapy. Finally, multiple machine learning algorithms were used to develop a 7-gene Stemness Subtype Predictor, which were further validated in two external independent GBM cohorts. This novel stemness-based classification could provide a promising prognostic predictor for GBM and may guide physicians in selecting potential responders for preferential use of immunotherapy.

PurposeAcromegaly is a rare, intractable endocrine disease. We aimed to describe the patient characteristics, diagnostic delays, treatment patterns, treatment outcomes, comorbidities and treatment costs of acromegaly in China.MethodsThis is a nationwide cross-sectional study. Patients diagnosed with and treated for acromegaly between 1996 and 2019 across China were surveyed via the Chinese Association of Patients with Acromegaly platform.ResultsIn total, 473 patients (58.8% females, mean age at diagnosis: 39.4±9.5 years) were included. The median disease duration was 3 years. The most common symptoms were extremity enlargement (91.8%) and facial changes (90.1%). Overall, 63.0% of patients experienced diagnostic delays within healthcare systems; 63.8% of the delays were ConclusionThis study provides the first comprehensive description of real-world acromegaly data in China, serving as a basis for future population-based studies.

Modern neurosurgery has been developing worldwide for more than a century, whereas in China, as stated in previous literature, only 7 decades have passed since the development of neurosurgery during the early 1950s after World War II and China's War of Liberation. However, as increasing evidence before the wars from medical records, annual hospital reports, and journal archives emerge, the history of neurosurgery in China, especially the initial stage, needs to be reassessed. The establishment of the Peking Union Medical College Hospital (PUMCH) in 1921, funded by the Rockefeller Foundation, marked the start of Western medicine in China. Meanwhile, modern neurosurgery started to take root in the nation. Chinese neurosurgeons at PUMCH, Song-Tao Guan, M.D. and Yi-Cheng Zhao, M.D., both of whom graduated from PUMC and received further training abroad, made great contributions to the initial growth of Chinese neurosurgery. Although neurosurgery experienced slow and even stagnant development in China during the wars that took place from 1941–1949, the prewar period from 1921–1940 witnessed substantial improvement in operative skills, bedside education, resident training, and scientific research in neurosurgery at PUMCH, providing indispensable contributions that have allowed Chinese neurosurgery to flourish during the past 7 decades.

Purpose Cardiac comorbidity is one of the leading causes of death among acromegaly patients. We aimed to investigate the reversibility of acromegalic cardiac involvement after surgical treatment using the gold standard method, cardiovascular magnetic resonance, and to explore the effects of endocrine remission and gender on reversibility. Methods In this single-center, prospective cohort study, fifty untreated acromegaly patients were enrolled. Comprehensive cardiac assessments were performed using a 3.0 T magnetic resonance scanner before and 3 and 12 months after transsphenoidal adenomectomy. Results Preoperatively, left ventricular (LV) enlargement (13.0%), LV systolic dysfunction (6.5%), right ventricular (RV) enlargement (4.3%), RV systolic dysfunction (2.2%) and myocardial fibrosis (12.0%) were identified. On average, the LV and RV ejection fractions of acromegaly patients were higher than the healthy reference values. Male patients had thicker LV myocardia, wider ventricular diameters and more dilated pulmonary artery roots than female patients. After surgery, LV myocardial hypertrophy was reversed, the left atrium was remodeled, and ventricular systolic dysfunction recovered to normal. Cardiac alterations were detected early in the 3rd postoperative month and persisted until the 12th month. The interventricular septum was initially thickened in the 3rd postoperative month and then recovered at the 12th month. Notable postoperative cardiac reversibility was observed in male patients but did not occur in all female patients. Patients achieving endocrine remission with normalized hormone levels had thinner LV myocardia than patients without normalized hormone levels. Conclusion Our findings demonstrated that some of the cardiac involvement in acromegaly patients is reversible after surgical treatment which lowers hormone levels. Endocrine remission and gender significantly impacted postoperative cardiac reversibility.

Context Quality of life (QoL) continues to be impaired in acromegaly after treatment. Objective We conducted the first nationwide survey assessing QoL status among Chinese patients with treated acromegaly and explored correlations with clinical parameters, treatment modalities, and outcomes. Design Cross-sectional study. Setting Survey via Chinese Association of Patients with Acromegaly (CAPA) online platform. Patients Treated patients from CAPA. Main Outcome Measures QoL was assessed using acromegaly QoL questionnaire (AcroQoL), 5-level EuroQoL five-dimensional questionnaire (EQ-5D-5L), and 12-item short-form health survey questionnaire (SF-12). Results Complete, valid questionnaires from 327 patients (mean age: 39.2 years, 61.5% females) at a mean of 10 years after treatment were included. Biochemical control was satisfied in 52.9% of these patients. The controlled patients had significantly better QoL than the uncontrolled patients in all AcroQoL dimensions, most SF-12 dimensions, and pain/discomfort and anxiety/depression dimensions of the EQ-5D-5L. Patients with either controlled or uncontrolled acromegaly had significantly worse QoL than the age- and sex-adjusted population reference in most SF-12 dimensions except for physical functioning. More acromegaly-associated symptoms and comorbidities at follow-up were independent risk factors for decreased QoL across all questionnaires. Medical treatment, especially with somatostatin analogs (SSAs), and radiotherapy were predictors of worse QoL. Female patients had lower scores of physical-related QoL than male patients. Conclusions Our study suggests that biochemical control improved but did not normalize QoL in acromegaly. Numbers of symptoms and comorbidities at follow-up, sex, radiotherapy, and medical treatment with SSAs were factors determining QoL of patients with treated acromegaly.

Objective: Facial changes are common among nearly all acromegalic patients. As they develop slowly, patients often fail to notice such changes before they become obvious. Consequently, diagnosis and treatment are often delayed. So far, convenient and accurate early detection of this disease is still unavailable. This study is designed to combine the use of 3D imaging and machine learning techniques in facial feature analysis and identification of acromegalic patients, in an effort to ascertain how both techniques performed in terms of applicability and value in the early detection of the disease.Methods: One hundred and twenty-four participants including 62 patients with acromegaly and 62 matched controls were enrolled. Using three-dimensional imaging techniques, 58 facial parameters were measured on each face. A two-way analysis of variance (ANOVA) and a post-hoc t-tests were conducted to examine the variations of these parameters with disease status and gender. Using linear discriminant analysis (LDA), we further distinguished patients from controls, characterized what combinations of the parameters could best predict disease state and their relative contributions.Results: Patients are significantly different from normal subjects in many variables, and facial changes of male patients are more significant than female ones. Both male and female patients present following major changes: the increase of facial length and breadth, the widening and elevation of the nose, the thickening of vermilion and the enlargement of the mandible. Facial variables which strongly related to the pathological states can be used to predict the morbid state with high accuracy (prediction accuracies 92.86% in females, p < 0.0001 and 75% in males, p < 0.001). We have further testified that only a few variables play a vital role in disease prediction and the vital combination of variables vary with gender.Conclusions: Three-dimensional imaging enables comprehensive and accurate quantification of facial characteristics, which makes it a promising technique to investigate facial features of acromegalic patients. In combination with machine learning technique, patients can be accurately identified and predicted by their facial variables. This approach might be beneficial for the early detection of acromegalic patients and timely consultation to improve their outcomes.

Purpose: Alternative splicing (AS) was reported to play a vital role in development and progression of glioblastoma (GBM), the most common and fatal brain tumor. Systematic analysis of survival-associated AS event profiles and prognostic prediction model based on multiple AS events in GBM was needed. Methods: Genome-wide AS and RNA sequencing profiles were generated in 152 patients with GBM in the cancer genome atlas (TCGA). Prognosis-associated AS events were screened by integrated Cox regression analysis to construct the prognostic risk score model in the training cohort (n = 101). The AS-based signature and clinicopathologic parameters were applied to construct a prognostic nomogram for 0.5-, 1-, and 3-year OS prediction. Finally, the regulatory networks between prognostic AS events and splicing factors (SFs) were constructed. Results: A total of 1,598 prognosis-related AS events from 1,183 source genes were determined. Eight prognostic risk score model based on integrated AS events and 7 AS types were established, respectively. Concordance index (C-index) and receiver operating characteristic (ROC) curve analysis demonstrated powerful ability in distinguishing patients' outcomes. Only Alternate Donor site (AD) and Exon Skip (ES) signature out of the eight types of AS signature were identified as independent prognostic factors for GBM, which was validated in the internal validation cohort. The nomogram with age, new event, pharmaceutical therapy, radiation therapy, AD signature and ES signature were constructed, with C-index of 0.892 (95% CI, 0.853–0.931; P = 5.13 × 10−15). Calibration plots, ROC, and decision curve analysis suggested excellent predictive performance for the nomogram in both TCGA training cohort and validation cohort. Splicing network indicated distinguished correlations between prognostic AS events and SFs in GBM patients. Conclusions: AS-based prediction model could serve as a promising prognostic predictor and potential therapeutic target for GBM, facilitating better treatment strategies in clinical practice.

BackgroundChest computed tomography (CT) has been widely used to assess pulmonary involvement in COVID-19. We aimed to investigate the correlation between chest CT and clinical features in COVID-19 suspected patients with or without fever.MethodsWe retrospectively enrolled 211 COVID-19 suspected patients who underwent both chest CT and reverse transcription polymerase chain reaction in Wuhan, China. The performance of CT in patients with relevant onset of symptoms, with fever (n = 141) and without fever (n = 70), was assessed respectively.ResultsThe sensitivity of CT for COVID-19 was 97.3%, with area under the curve (AUC) of 0.71 (95% confidence interval [CI], 0.66–0.76). There were 141 suspected patients with fever and 70 without fever. In the fever group, 4 variables were screened to establish the basic model: age, monocyte, red blood cell, and hypertension. The AUC of the basic model was 0.72 (95% CI, 0.63–0.81), while the AUC of the CT-aided model was 0.77 (95% CI, 0.68–0.85), a significant difference (P < .05). In the nonfever group, only dry cough was screened out to establish the basic model. The AUC was 0.76 (95% CI, 0.64–0.88), which was not significantly different than the CT-aided model (P = .08).ConclusionsChest CT has a high sensitivity in patients with COVID-19, and it can improve diagnostic accuracy for COVID-19 suspected patients with fever during the initial screen, whereas its value for nonfever patients remains questionable.

Purpose: To increase knowledge for the early differential diagnosis and accurate therapeutic strategies for pediatric patients with sellar or suprasellar region (SSR) lesions who initially present with central diabetes insipidus (CDI). Methods: This is a retrospective review of 55 pediatric patients (≤14 years old) with identified lesions in the SSR who initially presented with CDI at a large pituitary center between 2012 and 2018. The following data were summarized: demographic, clinical, endocrine, and neuroimaging data, intraoperative findings, histopathological findings, treatments, and prognosis. Results: In our group, the etiologies of the SSR lesions included germ cell tumors (GCTs, 74.5%), Langerhans cell histiocytosis (LCH, 18.2%), and craniopharyngioma (CP, 7.3%). Almost all patients (50/55, 90.9%) showed anterior pituitary dysfunction [multiple axes dysfunction (38), and isolated axis dysfunction (14)], while the GH/IGF-I axis was the most affected. Most GCT patients presented with various clinical manifestations besides CDI and had elevated β-HCG, whereas LCH and CP patients mostly presented few non-specific symptoms besides CDI and most had normal level tumor markers. Sellar MRI demonstrated that posterior pituitary bright spot disappearance occurred in all patients, and pituitary stalk thickening was observed in 96.7% of patients. Treatment varied due to the different etiologies of the SSR lesions. After follow-up for 35.4 ± 20.2 months, the proportions of patients who needed AVP (arginine vasopressin) for GCT, LCH, and CP were 86.5, 100, and 75%, respectively, and the proportions of patients who needed HRT were 89.2, 50, and 75%, respectively. Conclusion: For pediatric SSR lesions that first manifest as CDI, we should comprehensively consider clinical characteristics and imaging features to aid in their early differential diagnosis. Tumor markers and surgical histopathology are also great complements for the differential diagnosis. Additionally, various treatment strategies should be adopted according to different causes to improve the child's prognosis and quality of life.

Cushing's syndrome (CS) provides a unique model for assessing the neurotoxic effect of chronic hypercortisolism on human brains. With the ongoing development of different computer-assisted tools, four research stages emerged, each with its own pearls and pitfalls. This review summarizes current knowledge and describes the dynamic changes of views on the brain changes of CS, especially in the current era of the rapid development of artificial intelligence and big data. The adverse effects of GC on brain are proven to be on structural, functional and cellular levels at the same time.

Purpose. To identify the characteristics of the physical and mental health status of patients with pituitary adenomas, explore the postoperative reversibility of impaired health status, and assess the impact of clinical characteristics, hormone levels, anxiety, depression, and disease stigma on health status. Methods. We prospectively enrolled 147 and 138 patients with nonfunctioning and secretory pituitary adenomas, respectively. Health status was evaluated in 8 domains using the 36-item Short-Form Health Survey before and 3 months after transsphenoidal surgery. The Self-Rating Anxiety Scale, the Self-Rating Depression Scale, and the Stigma Scale for Chronic Illness were used to assess the psychological status. Results. Compared with the healthy population reference values, general physical and mental health, social functioning, and role limitations due to physical and psychological health problems were all found to be significantly impaired in the adenoma patients. Health status was worse in patients with adrenocorticotropic hormone- (ACTH-) secreting and growth hormone- (GH-) secreting adenomas than in patients with nonfunctioning adenomas. Among the patients, 11.6% had anxiety and 30.9% had depression. Higher scores for anxiety, depression, and disease stigma; older age; higher body mass index; and tumor recurrence were independent risk factors for health status impairment in at least one domain. Physical function impairment and role limitations caused by physical health problems became worse after surgery, whereas the mental component of health status remained the same. Conclusion. Health status was impaired in patients with pituitary adenomas, especially secretory adenomas. Physical function and role limitations were worse 3 months after surgery than before surgery. Mental problems, old age, obesity, and tumor recurrence reduced health status.

Introduction: The body of glioma-related literature has grown significantly over the past 25 years. Despite this growth in the amount of published research, gliomas remain one of the most intransigent cancers. The purpose of this study was to analyze the landscape of glioma-related research over the past 25 years using machine learning and text analysis. Methods: In April 2019, we downloaded glioma-related publications indexed in PubMed between 1994 and 2018. We used Python to extract the title, publication date, MeSH terms, and abstract from the metadata of each publication for bibliometric assessment. Latent Dirichlet allocation (LDA) was applied to the abstracts to identify publications' research topics with greater specificity. Results: We identified and analyzed a total of 52,625 publications in our study. We found that research on prognosis and the treatment of glioblastoma increased the most in terms of volume and rate of publications over the past 25 years. However, publications regarding clinical trials accounted for

Transcatheter arterial embolization (TAE) plays an important role in clinical tumor therapy by accomplishing vessel-casting embolization of tumor arteries at all levels and suppressing tumor collateral circulation and vascular re-canalization. In this study, we describe smart blood-vessel-embolic nanogels for improving the anti-tumor efficacy of TAE therapy on hepatocellular carcinoma (HCC). Methods: In this study, an in vitro model composed of two microfluidic chips was used for simulating the tumor capillary network and analyzing artery-embolization properties. Also, blood-vessel-casting embolization of renal arteries was evaluated in normal rabbits. Using a VX2 tumor-bearing rabbit model, the therapeutic efficacy of TAE on HCC was investigated for tumor growth, necrosis, and proliferation. Neovascularization and collateral circulation were evaluated by immunofluorescent detection of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and CD31 following the TAE therapy of VX2 tumor-bearing rabbits. Results: Sufficient embolization of all eight levels of micro-channels was achieved in a tumor-vessel-mimetic model with two microfluidic chips using PIBI-2240, and was further confirmed in renal arteries of normal rabbit. Effective inhibition of tumor collateral circulation and vascular re-canalization was observed in VX2 tumor-bearing rabbits due to the reduced expression levels of HIF-1α, VEGF, and CD31. Conclusions: The exceptional anti-tumor effect of PIBI-2240 observed in this study suggested that it is an excellent blood-vessel-embolic material for tumor TAE therapy.

Background/aims GCNT3 is a member of N-acetylglucosaminyltransferase family involved with mucin biosynthesis. GCNT3 aberrant expression is known to promote the progression of several human cancers. However, its role in tumorigenesis and the progression of non-small cell lung cancer (NSCLC) has not been well-characterized. Our study investigated the functional mechanisms of GCNT3 regulated by microRNAs (miRNAs) in NSCLC. Methods The differential expression of mRNAs in NSCLC tissues and matched adjacent non-cancerous lung tissues from patients in Xuanwei, Yunnan province, China, was screened via mRNA microarray. The expression of GCNT3 and its correlation with NSCLC progression was measured in 92 paired tumor tissues and adjacent normal tissues. The functions of GCNT3 in NSCLC cells and its underlying mechanisms were measured using siRNA and GCNT3-expression vectors. The miRNA immunoprecipitation (miRIP) method was used to identify the miRNAs targeting GCNT3. The protein were measured using western blot assay, and the mRNAs were measured by quantitative real-time PCR (qRT-PCR) assay. Cell proliferation was measured using Cell Counting Kit-8 (CCK-8) and a colony forming assays; cell migration and invasion assays were performed using 24-well Transwell chambers with 8-μm pores filter, and analyses of the cell cycle and apoptosis were performed via flow cytometric analysis. The dual luciferase reporter assay was performed to confirm whether GCNT3 gene was a direct target of miR-302b-3p. Results GCNT3 was found to be highly expressed in both NSCLC tissues and cell lines, and higher expression correlated significantly with advanced tumor-node-metastasis (TNM) stage, positive lymph node metastasis, and poor overall survival. Knockdown of GCNT3 inhibited the proliferation, migration and invasion ability of NSCLC cells, while overexpression facilitated these activities. Further mechanistic experiments using miRIP and dual luciferase reporter assays revealed that GCNT3 was a direct target of miR-302b-3p. Low expression of miR-302b-3p was found in NSCLC cells and negatively correlated with GCNT3 levels, while miR-302b-3p overexpression inhibited the proliferation, migration and invasion of NSCLC cells. Co-transfection with miR-302b-3p and the expression vector of GCNT3 abrogated the effects of mir-302b-3p, confirming that miR-302b-3p inhibited NSCLC progression by targeting GCNT3. Western blotting revealed that E-cadherin, N-cadherin, vimentin, p-Erk and cyclin D1 were downstream molecules of miR-302b-3p/GCNT3 pathway. Conclusion miR-302b-3p/GCNT3 axis regulated cell proliferation, migration, and invasion by activating the Erk signaling pathway and epithelial-mesenchymal transition (EMT), which was identified as a potential therapeutic target for NSCLC.

BACKGROUND AND OBJECTIVES: Cushing’s disease (CD) patients have metabolic abnormalities in the brain caused by excessive exposure to endogenous cortisol. However, the reversibility of brain metabolism of CD patients after treatment remains largely unknown. METHODS: This study recruited 50 CD patients seeking treatment and 34 matched normal controls (NCs). The patients were treated with Transsphenoidal Adenomectomy (TSA) and reexamined 3 months later. Cerebral blood flow (CBF) of the patients were assessed using 3D pseudo-continuous arterial spin labelling (PCASL) imaging before the treatment and at the 3-month follow-up and were compared with CBF measures of the NCs using a whole-brain voxelwise group comparison method. For remitted patients, their CBF measures and hormone level measures, including adrenocorticotropic hormone (ACTH), 24-hour urinary free cortisol (24hUFC) and serum cortisol, were compared before and after the treatment. Finally, a correlation analysis was carried out to explore the relationship between changes of CBF and hormone level measures of the remitted CD patients. RESULTS: After the treatment, 45 patients reached remission. Compared with the NCs, the CD patients before the treatment exhibited significantly reduced CBF in cortical regions, including occipital lobe, parietal lobe, superior/middle/inferior temporal gyrus, superior/middle/inferior frontal gyrus, orbitofrontal cortex, precentral gyrus, middle/posterior cingulate gyrus, and rolandic operculum, as well as significantly increased CBF in subcortical structures, including caudate, pallidum, putamen, limbic lobe, parahippocampal gyrus, hippocampus, thalamus, and amygdala (p

Objective To explore the radiological characteristics of the upper respiratory tract and their correlations with obstructive sleep apnoea/hypopnea syndrome (OSAHS) in patients with acromegaly. Methods Computed tomography (CT) and magnetic resonance imaging (MRI) were performed in untreated patients with acromegaly placed in straight (SHP) and extended head positions (EHP). Overnight polysomnography was performed to evaluate OSAHS, and the apnoea/hypopnea index (AHI) was measured. Results According to the CT findings, a thicker soft palate (1.24 ± 0.22 vs. 1.03 ± 0.22 cm, p = 0.024), larger soft palate cross-sectional area (5.15 ± 1.21 vs. 4.06 ± 1.09 cm2, p = 0.027), and thicker lateral pharyngeal wall (1.01 ± 0.25 vs. 0.79 ± 0.14 cm, p = 0.015) were observed in patients with acromegaly who presented with OSAHS compared with patients without OSAHS. Additionally, the maximal transverse diameter (1.87 ± 0.40 vs. 2.31 ± 0.44 cm, p = 0.015) and cross-sectional area (1.98 ± 0.46 vs. 2.74 ± 1.01 cm2, p = 0.032) of the airway were decreased in the soft palate plane in patients with OSAHS. The AHI was positively correlated with the thickness of the soft palate and lateral pharyngeal wall but negatively correlated with the maximal transverse diameter and cross-sectional area of the airway in the soft palate plane. Conclusions Airway stenosis and pharyngeal tissue hypertrophy are typical characteristics of changes in the structure of the upper respiratory tract in patients with acromegaly who present with OSAHS. AHI is a predictor of the severity of the respiratory tract changes.

To explore coagulation function in patients with brain tumors before and after craniotomy and tumor resection and to analyze its correlation with deep vein thrombosis (DVT).This study enrolled 133 consecutive patients with brain tumors. Coagulation evaluation and limb venous ultrasonography were performed before and after surgery. Clinical characteristics and dynamic changes in coagulation parameters were recorded, and their correlations with DVT were analyzed.The incidence of postoperative DVT in patients with brain tumors was 10.5%. The average age of patients with DVT was older compared with patients without DVT (63.21 ± 11.21 years vs. 50.24 ± 11.95 years, P0.001), and the incidence of hepatitis B (21% vs. 4%, P = 0.035) was higher in patients with DVT compared with patients without DVT. D-dimer and fibrinogen were the most variable parameters during the perioperative period. In patients with DVT, D-dimer levels displayed a "zigzagging-rise" trend and were significantly higher than levels in patients without DVT. Platelet levels displayed a "first-descend-then-rise" trend and were significantly lower in patients with DVT on the second and third postoperative days.In patients with brain tumors, D-dimer and fibrinogen were elevated postoperatively, manifesting as hypercoagulability. Postoperative DVT was correlated with aging and hepatitis B. A "zigzagging-rise" trend of D-dimer and a "sharp-descent" trend of platelets in the early postoperative period might predict DVT in patients with brain tumors.

To investigate the incidence, bacteriologic features, and risk factors of posttranssphenoidal surgery (post-TSS) meningitis and/or bacteremia.This retrospective study included 3242 patients who underwent TSS for pituitary adenoma at the Department of Neurosurgery of Peking Union Medical College Hospital between January 2012 and December 2016. Clinical data for patients with and without post-TSS meningitis and/or bacteremia were compared and analyzed.Meningitis and bacteremia developed after 27 (0.8%) and 26 (0.8%) procedures, respectively, and 6 patients (0.2%) developed both. Gram-positive organisms (coagulase-negative staphylococci, Streptococcus pneumonia, and S viridans) predominated in meningitis, whereas gram-negative organisms (Klebsiella pneumonia, Enterobacter aerogenes, and Escherichia coli) predominated in bacteremia. All identified species were sensitive to amikacin, imipenem, and meropenem. Antibiotic treatment cured 52 patients (7 died). In a multivariate analysis, the risk of meningitis and/or bacteremia was independently associated with diabetes (P0.001; odds ratio [OR], 6.06), previous surgery at the same location (P0.001; OR, 4.23), intraoperative cerebrospinal fluid leakage (P0.001l; OR, 4.63), and an endoscopic approach (P = 0.001; OR, 2.50).Meningitis and/or bacteremia remain critical postoperative complications of TSS for pituitary adenoma. The pathogens with drug sensitivity to antibiotics differed between meningitis and bacteremia. Early blood and cerebrospinal fluid bacterial cultures, drug susceptibility analyses, and appropriate antibiotic treatment can help control the rate of infection.

1) To compare the retinal, choroidal, Haller’s layer, and Sattler’s/choriocapillaris thicknesses of untreated acromegaly patients without chiasm compression or diabetes mellitus and healthy controls. 2) To evaluate the correlations of retinal and choroidal thicknesses with serum growth hormone (GH) and insulin-like growth factor 1 (IGF) burden. This prospective, case-control study included 27 untreated acromegaly patients and 27 sex-matched and age-matched controls. Subfoveal choroidal, Haller’s layer and Sattler’s/choriocapillaris thicknesses were determined by enhanced-depth imaging optical coherence tomography (EDI-OCT). Foveal and macular retinal thicknesses were determined with SD-OCT. GH and IGF-1 burdens were defined as the product of disease duration and treatment-naive serum GH and IGF-1 levels. Compared with healthy controls, patients with acromegaly exhibited significantly increased foveal retinal (p = 0.003), subfoveal choroidal (p

Dysregulated long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play key roles in the development of human cancers. The lncRNA plasmacytoma variant translocation 1 (PVT1) is reported to be an oncogene in a variety of cancers. However, the roles of PVT1-5 and its related miRNAs in lung cancer are poorly understood. In this study, we found that PVT1-5 expression was significantly increased in lung cancer tissues and cell lines. By using biotin-labeled lncRNA-PVT1-5 probe for miRNA in vivo precipitation (miRIP) in lung cancer cells and dual-luciferase reporterassays, we identified that miR-126 was associated with lncRNA-PVT1-5. Furthermore, knockdown of lncRNA-PVT1-5 in cells could down-regulate the expression of SLC7A5, the target of oncogenic miR-126, resulting in the cell proliferation. Conversely, inhibiting the expression of miR-126 markedly increased the expression of SLC7A5 and alleviated cell proliferation inhibition. Thus, our results indicated that lncRNA-PVT1-5 may function as a competing endogenous RNA (ceRNA) for miR-126 to promote cell proliferation by regulating the miR-126/SLC7A5 pathway, suggesting that lncRNA-PVT1-5 plays a crucial role in lung cancer progression and lncRNA-PVT1-5/miR-126/SLC7A5 regulatory network may shed light on tumorigenesis in lung cancer.

TACE (transcatheter arterial chemoembolization) has been recognized as an effective palliative treatment option for patients with HCC, however, the medium-long term efficacy of it remains modest. LY2109761, a TGF-β receptor inhibitor, was confirmed to reduce tumor cell growth, intravasation, and metastatic dissemination of HCC cells through different molecular mechanisms. This study aims to investigate the treatment effect of combining TACE therapy with LY2109761- a TGF-β receptor I kinase inhibitor on suppressing tumor growth and metastasis in a rabbit VX2 tumor model. The molecular mechanisms underlying the biological activities of LY2109761 was also evaluated through an in vitro model. And we found that LY2109761 could inhibit cell proliferation by down-regulating the phosphorylation of Smad-2 as well as improved the therapeutic effect of TACE in a VX2 hepatocellular carcinoma model. And we further found that LY2109761 may play a modulating role in the process of T cell transformation. Hence, based on those obsevations in our research, we concluded that combing LY2109761 with TACE for the treatment of VX2 rabbit liver cancer can help inhibit tumor growth as well as increase the tumor cell necrosis after TACE.

Objective To investigate outcomes and identified risk factors affecting cure and intraoperative cerebrospinal fluid leak after transsphenoidal surgery using a new classification for growth hormone–secreting pituitary adenoma associated with empty sella. Methods In this retrospective cohort study, 51 patients enrolled from January 2010 to June 2016 were categorized into 3 groups using a new classification scheme: grade A, whole tumor occupation area beneath a horizontal line drawn along the lowest level of empty sella; grade B, tumor occupation area that crossed the horizontal line on 1 side; and grade C, tumor occupation area that crossed the horizontal line on 2 sides. Clinical data were collected and analyzed. Results Cure rate for grade A patients (88.24%; 15/17) was significantly higher than cure rate for grade B (55.00%; 11/20) and grade C (50.00%; 7/14) patients. Occurrence of cerebrospinal fluid leaks in grade C patients (35.71%; 5/14) was higher than in grade A patients (5.88%; 1/17). Logistic regression analysis indicated that risk factors affecting cure included large maximum tumor diameter (P = 0.009, odds ratio [OR] = 1.222), high preoperative fasting growth hormone level (P = 0.031, OR = 1.088), and high classification (P = 0.017, OR = 4.485). Risk factor affecting intraoperative cerebrospinal fluid leak was high classification (P = 0.039, OR = 3.580). Conclusions Transsphenoidal surgery is the current optimal treatment strategy. Empty sella increases the difficulty of surgery with a higher incidence of complications. The new classification scheme was better for predicting the surgical outcome for this disease.

Purpose To investigate the characteristics of difficult intubation and identify novel efficient predictors in patients with acromegaly. Methods Patients with either untreated acromegaly or non-functional pituitary adenomas were enrolled. Patients with acromegaly underwent hormone assays, upper airway computed tomography and magnetic resonance imaging examinations and preoperative overnight polysomnography. The modified Mallampati classification, mouth opening, neck circumference, and neck extension were assessed, and the Cormack-Lehane grades and the time of tracheal intubation were recorded. Results Patients with acromegaly had a higher incidence of difficult intubation (62.5%). The time of tracheal intubation was prolonged, the neck circumference was enlarged, and the neck extension was confined. In patients with acromegaly and difficult intubation, the insulin-like growth factor 1 levels and apnea/hypoxia index were significantly higher compared to patients without difficult intubation (1115.40 ± 253.73 vs. 791.67 ± 206.62 ng/ml, P = 0.020; 22.17 ± 23.25 vs. 2.47 ± 2.84, P = 0.026, respectively). The bilateral regression analysis revealed that high levels of insulin-like growth factor 1 were an independent risk factor for developing difficult intubation (p = 0.042, Exp B = 1.006). The modified Mallampati classification was positively correlated with apnea/hypoxia index and could be calculated using the following logarithmic equation: MMC = 0.2982 * ln (AHI) + 2.1836. Conclusions In patients with acromegaly, neck movement is confined, the time of tracheal intubation is prolonged, and the neck circumference is enlarged, and these patients suffer from an increased incidence of difficult intubation (62.5%) during anesthesia induction. The apnea/hypoxia index and insulin-like growth factor 1 levels are both increased in acromegalic patients with difficult intubation, and elevated insulin-like growth factor 1 levels are an independent risk factor of difficult intubation in acromegalic patients.

// Fei Xie 1, * , Xudong Xiang 2, * , Qionglin Huang 1, * , Pengzhan Ran 1 , Yuncang Yuan 1 , Qian Li 1 , Guoxiang Qi 1 , Xiaopeng Guo 1 , Chunjie Xiao 1, ** , Shangyong Zheng 1, ** 1 School of Medicine, Yunnan University, Kunming, Yunnan 650091, P.R. China 2 Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, P.R. China * These authors have contributed equally to this work ** These two authors are co-corresponding authors Correspondence to: Chunjie Xiao, email: chjxiao@ynu.edu.cn Shangyong Zheng, email: shangyong@ynu.edu.cn Keywords: long non-coding RNA, lncRNA-BCAT1, β-catenin, tumor suppressor, colorectal cancer Received: September 23, 2016 Accepted: December 27, 2016 Published: February 17, 2017 ABSTRACT β-catenin plays a major role in tumor development and progression. The present study found that β-catenin was upregulated in 30 samples of colorectal cancer (CRC) tissue as compared to adjacent non-tumor tissues. Analysis of long non-coding RNA (lncRNA) expression profiles using the GSE18560 and GSE44097 datasets, which were generated via the Affymetrix plus 2.0 microarray platform and downloaded from the GEO database, revealed 20 differentially expressed lncRNAs following β-catenin knockdown. We focused on AK091631, a novel lncRNA, which we named lncRNA-β-catenin associated transcript 1 (LncRNA-BCAT1). lncRNA-BCAT1 expression was decreased in CRC tissues, and was negatively associated with β-catenin in both CRC tissues and cell lines. lncRNA-BCAT1 overexpression suppressed CRC cell growth and invasion by downregulating cyclin D1, c-Myc, and MMP-2. These results suggest that lncRNA-BCAT1 overexpression inhibits CRC cell growth and invasion via Wnt/β-catenin pathway blockade, and that lncRNA-BCAT1 is repressed by Wnt/β-catenin signaling. This evidence suggests that lncRNA-BCAT1 is a tumor suppressor and that lncRNA-BCAT1 may be an effective prognostic biomarker in CRC.

Fei Xie,1,* Yuncang Yuan,1,* Luyang Xie,2,* Pengzhan Ran,1 Xudong Xiang,3 Qionglin Huang,1 Guoxiang Qi,1 Xiaopeng Guo,1 Chunjie Xiao,1 Shangyong Zheng1 1School of Medicine, Yunnan University, Kunming, Yunnan, 2Department of Stomatology, Shanghai Tenth People’s Hospital, Shanghai, 3Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China *These authors contributed equally to this work Background: Downregulated expression levels of microRNA-320a (miR-320a) were found in primary breast cancers and colorectal cancer. Previous findings indicated that miRNA-320a may involve in the cancer development. In this study, we explored the roles of miR-320a by targeting c-Myc in the tumor growth of hepatocellular carcinoma (HCC). Methods: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-320a in 50 HCC tissues and four HCC cells. Luciferase reporter assay was conducted to confirm the direct downstream target of miR-320a in HEK-293 cells. The effect of miR-320a on endogenous c-Myc expression was investigated by transfecting miR-320a mimics into HepG2 and QGY-7703 cell lines. The c-Myc and miR-320a expressions were analyzed by immunohistochemistry (IHC) and qRT-PCR in the same HCC tissues. Furthermore, the biological functional correlation of miR-320a with c-Myc was determined by studying the effect of miR-320a mimics or c-Myc small interfering RNA (siRNA) on HCC cell proliferation and invasion. Results: The expression of miR-320a was downregulated in 50 HCC tissues and 4 HCC cells. Luciferase assay revealed that c-Myc is a direct target of miR-320a. IHC and Western blot analysis showed that the c-Myc expression was inhibited by miR-320a in HCC tissues and cell lines. Upregulation of miR-320a suppressed the HCC cell proliferation and invasion capacity induced by inhibiting c-Myc, and the results were consistent with the effects of c-Myc siRNA on tumor suppression. These results revealed that miRNA-320a inhibits tumor proliferation and invasion by targeting c-Myc in HCC cells.Conclusion: Our results showed that miR-320a functions as a tumor suppressor in HCC. By targeting c-Myc directly, miR-320a inhibits the HCC cell growth. Our studies provide evidence of miR-320a as a potentially target for HCC treatment. Keywords: miR-320a, hepatocellular carcinoma, c-Myc, tumor suppressors&nbsp

Purpose: Abnormal glucose metabolism is one of the most frequent acromegaly complications. Improvement of glucose metabolism can be observed only in half of acromegaly patients after surgery. We aimed to investigate the risk factors for determining abnormal glucose metabolism before surgery in patients with acromegaly, and to explore the predictors of improved preoperative glucose intolerance after surgery.Methods: We retrospectively reviewed 64 patients who received transsphenoidal surgery for acromegaly. Growth hormone (GH), insulin-like growth factor-1 (IGF-1) and glucose metabolism were assessed before, immediately after, and 3 months after surgery. Glucose metabolic parameters included glycosylated hemoglobin (HbA1c), plasma glucose (PG), C-peptide (CP), insulin (INS), and the indices of β-cell function, insulin sensitivity, and insulin resistance (IR).Results: Preoperatively, 18 patients (28.1%) had diabetes (DM), 34 (53.1%) had prediabetes (PreDM), and 12 (18.8%) had normal glucose tolerance (NGT). All the indices of pancreatic β-cell function were significantly lower in patients with DM than those with PreDM and NGT (all P < 0.005). IGF-1 was significantly positively correlated with insulin sensitivity and IR (P < 0.05), while GH was not. Postoperatively, glucose tolerance was improved in 71.2% of patients (37/52) with preoperative glucose intolerance. Insulin sensitivity was increased, while β-cell function and IR were decreased in most patients after surgery, regardless of whether their acromegaly achieved remission. A multivariate logistic regression analysis revealed that preoperative fasting C-peptide (FCP, OR = 2.639, P = 0.022), disposition index (DI, OR = 1.397, P = 0.043) and Predictor-2 (OR = 0.578, P = 0.035) were determined to be the predictors for improved glucose tolerance status after surgery. Afterwards, through Receiver operating characteristic (ROC) analyses, FCP >2.445 ng/ml was the best independent predictor, with an 86.6% PPV (positive predictive value) and a 74.5% NPV (negative predictive value).Conclusions: Preoperative high FCP is a promising postsurgical predictor of improved glucose tolerance in patients with acromegaly. Oral glucose tolerance testing (OGTT) and HbA1c should be monitored regularly after surgery, and diabetes management should be adjusted based on the patient's latest glucose tolerance status.

Respiratory disorders are common complications of acromegaly patients. We conducted a large-scale survey in the patients with acromegaly and demonstrated the characteristics of their lung function and blood gas.A prospective cohort study was conducted with 115 patients with active acromegaly and 56 patients with nonfunctioning pituitary adenomas. All patients underwent clinical, biological, radiological, lung functional and blood gas assessments.Acromegaly patients had a higher lung volume than those with nonfunctioning adenomas (forced vital capacity value (FVC) and FVC% predicted: p 0.001). The small airway was less obstructive in acromegaly patients (higher FEV1% predicted, PEF% predicted, MEF75% predicted, MEF50% predicted, MEF25% predicted: p ≤ 0.001 for all analyses, FEV1/FVC: p = 0.151). The average partial pressure of carbon dioxide in acromegaly patients was higher (p 0.001), but there was no significant difference in the average partial pressure of oxygen or oxygen saturation between the two groups (p 0.05). In acromegaly patients, the average age of patients with small airway obstruction was higher than that of patients with normal lung function (p 0.05), but no significant difference in GH or IGF-1 levels between the two groups were found (p 0.05).The acromegaly patients in this cohort had increased lung volume. However, there was no evidence demonstrating hypoxemia in acromegaly patients. The small airway was less obstructive in acromegaly patents. Small airway obstruction was observed in elderly patients with acromegaly.

Fu Xiong,1,2,* Yanyan Cao,1,2,* Xiaopeng Guo,1,2 Hongsen Zhang,1,2 Jihua Wang,1,2 Bin Xiong,1,2 Bin Liang,1,2 Chuansheng Zheng1,2 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, People’s Republic of China; 2Hubei Province Key Laboratory of Molecular Imaging, Wuhan, Hubei 430022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuansheng Zheng Email hqzcsxh@sina.comPurpose: To evaluate the adriamycin (ADM) pervasion distance within tumor stroma after relaxin (RLX) infusion through tumor feeding artery and further investigate the therapeutic effects of RLX infusion combined with transcatheter chemoembolization (TACE) on the rabbit VX2 liver cancer, since the chemotherapy impaired due to limited drug distribution hindered by stiffened tumor stroma.Materials and Methods: In the first part, rabbits received normal saline (NS), RLX or combined with TACE, and the penetration distance of ADM was measured by immunofluorescence and the matrix metalloproteinases (MMPs) were evaluated by gelatin substrate zymography in each group. In the second part, the rabbits received NS, TACE and RLX combined with TACE, respectively. The tumor growth rates, necrosis rates and intrahepatic metastasis were measured, andhematoxylin-eosin (HE), transferase-mediated dUTP-biotin nick end labelling (TUNEL) and Ki67 staining were conducted in each group.Results: In the first part, the expression of MMP-9 was increased in groups treated by RLX compared with NS group, especially three days after RLX infusion (p=0.001). The ADM penetration distance was significantly increased in groups treated by RLX compared with NS group (p< 0.05), and it was farthest three days after RLX infusion. In the second part, compared with the NS and TACE groups, the tumor growth rates, the positive staining rates of Ki67 and the tumor growth rates were significantly decreased in RLX+TACE group (p< 0.05). However, the positive staining rates of TUNEL and the tumor necrosis rates were significantly increased (p< 0.05), andHE staining also revealed higher necrosis rates. The intrahepatic metastasis indicates no difference between the three groups (p=0.273).Conclusion: An increased penetration distance was obtained by RLX infusion through tumor feeding artery, and better therapeutic effects were achieved by RLX combined with TACE.Keywords: relaxin, liver cancer, transcatheter chemoembolization, MMP-9, penetration distance

OBJECTIVECushing’s disease (CD) involves brain impairments caused by excessive cortisol. Whether these impairments are reversible in remitted CD after surgery has long been controversial due to a lack of high-quality longitudinal studies. In this study the authors aimed to assess the reversibility of whole-brain changes in remitted CD after transsphenoidal surgery (TSS), and its correlations with clinical and hormonal parameters, in the largest longitudinal study cohort to date for CD patient brain analysis.METHODSFifty patients with pathologically diagnosed CD and 36 matched healthy controls (HCs) were enrolled in a tertiary comprehensive hospital and national pituitary disease registry center in China. 3-T MRI studies were analyzed using an artificial intelligence–assisted web-based autosegmentation tool to quantify 3D brain volumes. Clinical parameters as well as levels of serum cortisol, adrenocorticotrophic hormone (ACTH), and 24-hour urinary free cortisol were collected for the correlation analysis. All CD patients underwent TSS and 46 patients achieved remission. All clinical, hormonal, and MRI parameters were reevaluated at the 3-month follow-up after surgery.RESULTSWidespread brain volume loss was observed in active CD patients compared with HCs, including total gray matter (p = 0.003, with false discovery rate [FDR] correction) and the frontal, parietal, occipital, and temporal lobes; insula; cingulate lobe; and enlargement of lateral and third ventricles (p < 0.05, corrected with FDR). All affected brain regions improved significantly after TSS (p < 0.05, corrected with FDR). In patients with remitted CD, total gray matter and most brain regions (except the frontal and temporal lobes) showed full recovery of volume, with volumes that did not differ from those of HCs (p > 0.05, corrected with FDR). ACTH and serum cortisol changes were negatively correlated with brain volume changes during recovery (p < 0.05).CONCLUSIONSThis study demonstrates the rapid reversal of total gray matter loss in remitted CD. The combination of full recovery areas and partial recovery areas after TSS is consistent with the incomplete recovery of memory and cognitive function observed in CD patients in clinical practice. Correlation analyses suggest that ACTH and serum cortisol levels are reliable serum biomarkers of brain recovery for clinical use after surgery.

Objective To investigate the clinical characteristics of hypopituitarism and its reversibility after surgery for nonfunctional pituitary adenoma (NFPA); analyze the correlation between tumor size and hypopituitarism incidence; and predict hypopituitarism by tumor volume and maximum diameter. Methods We retrospectively reviewed 164 patients with NFPA who underwent surgical treatment at Peking Union Medical College Hospital from January 2016 to December 2016. Demographic, imaging, and endocrine data were collected during preoperative, postoperative, and long-term follow-up (21.1 ± 3.3 months) periods. Differences in hormone levels were analyzed by paired and independent samples t-tests. The cut-off values of tumor size and volume to predict hypopituitarism were calculated by receiver operating characteristic curves. Results In total, 80.4% (132/164) of patients had anterior pituitary hypofunction and 48.4% patients had hypogonadism; the recovery rate of luteinizing hormone was 80.9%, and follicular-stimulating hormone was 60%. In total, 36.5% of patients had hypothyroidism; the recovery rate of thyroxine was 85%, free thyroxine was 87.8%, and thyroid-stimulating hormone was 100.0%. Finally, 27.4% of patients had insulin-like growth factor 1 (IGF-1)/growth hormone (GH) hypofunction, and the recovery rate of IGF-1 was 77.8%. The preoperative free thyroxine, thyroxine, GH, IGF-1, follicular-stimulating hormone, and luteinizing hormone levels were significantly lower in the giant adenoma group (n = 43) than in the large adenoma group (n = 121). The hypopituitarism predictive cut-off value of tumor volume was 3105.1 mm3 and that of tumor diameter was 23.5 mm. Conclusions NFPA has a significant influence on gonadal hormone, IGF-1/GH, and thyroid hormone. NFPA can cause single- or multiple-hormone reduction in each pituitary target gland. Tumor size is positively correlated with the incidence and degree of hypopituitarism. NFPA-induced hypopituitarism is significantly recovered after surgical treatment.

To explore the clinical characteristics of pituitary adenomas in patients with MEN1 and to summarize treatment strategies for MEN1 in a Chinese population. We retrospectively analyzed 54 MEN1 patients with pituitary adenomas diagnosed at Peking Union Medical College Hospital from March 2003 to January 2017. Clinical data, laboratory testing results, treatments of involved glands and treatment responses were collected and analyzed. The mean age at pituitary adenoma diagnosis was 53.9 ± 17.8. The patients initially consulted the Endocrinology, General Surgery and Neurosurgery departments, in descending frequency. The nonfunctioning adenoma, prolactinoma, GH-secreting adenoma, cosecreting adenoma, and ACTH-secreting adenoma subtypes accounted for 48.1%, 27.8%, 9.3%, 9.3% and 5.6% of the cases, respectively. The remission rate for prolactinomas was 46.2% (6/13) treated with bromocriptine. And the remission rates were 87.5% (7/8) and 100% (3/3) for GH-secreting adenomas and ACTH-secreting adenomas respectively achieved by transsphenoidal surgery. Nineteen (35.2%) patients with asymptomatic nonfunctioning pituitary adenomas showed no progression after a 35-month follow-up with close observation. Regarding treatment priority, patients with thymic carcinoid tumors received first-line surgery, 54% of the patients with enteropancreatic tumors had these tumors treated first, and 26% of all patients had their pituitary adenomas treated first. In acromegalic patients, pituitary lesions tended to be treated first (75%, p = 0.002). PHPT and adrenocortical adenomas can be managed with elective surgery. The treatment of MEN1 requires cooperation between multidisciplinary teams. Individualized treatment according to the severity of glandular involvement is needed. GH-secreting and ACTH-secreting pituitary adenomas require active treatment, while nonfunctioning pituitary adenomas can be observed closely.

Aggressive prolactin pituitary tumors, which exhibit aggressive behaviors and resistance to conventional treatments, are a huge challenge for neurosurgeons. Many studies have investigated the roles of microRNAs (miRNAs) in pituitary tumorigenesis, invasion and metastasis, but few have explored aggressiveness-associated miRNAs in aggressive pituitary tumors. Differentially expressed miRNAs (DEMs) between aggressive and nonaggressive prolactin pituitary tumors were screened using the GSE46294 miRNA expression profile downloaded from the GEO database. The potential target genes of the top three most highly upregulated and downregulated DEMs were predicted by miRTarBase, and potential functional annotation and pathway enrichment analysis were performed using the DAVID database. Protein-protein interaction (PPI) and miRNA-hub gene interaction networks were constructed by Cytoscape software. A total of 43 DEMs were identified, including 19 upregulated and 24 downregulated miRNAs, between aggressive and nonaggressive prolactin pituitary tumors. One hundred and seventy and 680 target genes were predicted for the top three most highly upregulated and downregulated miRNAs, respectively, and these genes were involved in functional enrichment pathways, such as regulation of transcription from RNA polymerase II promoter, DNA-templated transcription, Wnt signaling pathway, protein binding, and transcription factor activity (sequence-specific DNA binding). In the PPI network, the top 10 genes with the highest degree of connectivity of the upregulated and downregulated DEMs were selected as hub genes. By constructing an miRNA-hub gene network, it was found that most hub genes were potentially modulated by hsa-miR-489 and hsa-miR-520b. Targeting hsa-miR-489 and hsa-miR-520b may provide new clues for the diagnosis and treatment of aggressive prolactin pituitary tumors.

Semantic segmentation of colon gland is notoriously challenging due to their complex texture, huge variation, and the scarcity of training data with accurate annotations. It is even hard for experts, let alone computer-aided diagnosis systems. Recently, some deep convolutional neural networks (DCNN) based methods have been introduced to tackle this problem, achieving much impressive performance. However, these methods always tend to miss segmented results for the important regions of colon gland or make a wrong segmenting decision.In this paper, we address the challenging problem by proposed a novel framework through conditional generative adversarial network. First, the generator in the framework is trained to learn a mapping from gland colon image to a confidence map indicating the probabilities of being a pixel of gland object. The discriminator is responsible to penalize the mismatch between colon gland image and the confidence map. This additional adversarial learning facilitates the generator to produce higher quality confidence map. Then we transform the confidence map into a binary image using a fixed threshold to fulfill the segmentation task. We implement extensive experiments on the public benchmark MICCAI gland 2015 dataset to verify the effectiveness of the proposed method. Results demonstrate that our method achieve a better segmentation result in terms of visual perception and two quantitative metrics, compared with other methods.

Introduction Unintentional injuries (UIs) impose a significant burden on low- and middle-income countries (LMICs). However, available UI epidemiological data are limited for LMICs, including China. This article aimed to provide an overview of the UI hospitalization profile, identify risk factors for in-hospital mortality and provide diagnosis-specific survival risk ratios (SRRs) for reference by LMICs using hospital discharge abstract data (DAD) from Beijing, China. Patients and methods A cross-sectional study was conducted for patients sustaining UIs requiring admission. Information was retrieved from 138 hospitals in Beijing to describe the demographics, injury nature, mechanisms, severity and hospital outcomes. Multivariate logistic regression was performed to identify and evaluate risk factors for in-hospital mortality for UIs. Results Falls (57.1%), transport accidents (19.9%) and exposure to inanimate mechanical forces (16.4%) were the leading causes of UI hospitalization. Falls and transport accidents were responsible for 94.2% of the in-hospital deaths caused by UIs. Injury mechanisms differed among sex (χ2 = 5322.1, P Conclusions Hospital DAD are an objective and cost-effective data source that allows for a hospital-based perspective of UI epidemiology. Sex, age, functional status at admission, comorbidities, injury nature, severity and mechanism are significantly associated with the in-hospital mortality of UIs in China. This study generates a reference dataset of diagnosis-specific SRRs from a large trauma population in China, which may be more applicable in injury severity estimation using ICISS in LMICs.

Background Antiepileptic drugs (AEDs) are increasingly used prophylactically during the perioperative period to prevent epilepsy in patients undergoing craniotomy. Evidence concerning the use of AEDs and the incidence, extent and risk factors of hyperammonemia induced by different types of AEDs is lacking. Methods Patients were divided into groups with 3 different AED regimens, levetiracetam, valproate and carbamazepine regimens, and the blood ammonia concentration and liver and coagulation functions were assessed during the perioperative period. Results Sixty-five patients were enrolled consecutively and the postoperative hyperammonemia was found in 46 patients (70.77%), and 45 (97.83%) were asymptomatic. A total of 80.95% of the patients using valproate developed hyperammonemia, and the postoperative blood ammonia concentration continued to rise in 61.90% of these patients. Additionally, valproate had the least impact on liver enzymes. The synthetic function of the liver in patients with higher concentrations of preoperative blood ammonia was more seriously damaged than that in patients with normal postoperative ammonia concentrations. Conclusions Selection of AED for patients undergoing craniotomy should be based on the individual medical situation. Carbamazepine may be a proper choice for the majority of these patients, while valproate is likely to be more appropriate for patients with abnormal liver aminotransferases.