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To investigate the effect of CT image acquisition parameters on the performance of radiomics in classifying benign and malignant pulmonary nodules (PNs) with respect to nodule size. We retrospectively collected CT images of 696 patients with PNs from March 2015 to March 2018. PNs were grouped by nodule diameter: T1a (diameter ≤ 1.0 cm), T1b (1.0 cm

Background To compare the mechanical characteristics of a percutaneous superior pubic intramedullary screw, percutaneous bridging plate and percutaneous screw-rod system of the anterior ring for the treatment of unilateral vertical pubic fractures to provide a reference for clinical application. Methods A finite element model of pelvic anterior ring injury (unilateral vertical pubic fracture) was produced. The fractures were fixed with a percutaneous superior pubic intramedullary screw, percutaneous bridging plate and percutaneous screw-rod system of the anterior ring and their combinations in 5 types of models. The fracture stabilities under vertical, bilateral and anterior-posterior load were quantified and compared based on the displacement of the hip joints’ midpoint as quantificational index of fracture stability. Results In the condition of bilateral and anterior-posterior load, the vertical, bilateral and anterior-posterior displacements of the hip joints’ midpoint of different models were significantly different respectively. In general, the displacements of the 5 pelvic anterior ring fixations were ranked from maximum to minimum as follows: bridging plate, pelvic anterior screw-rod system, combination of bridging plate and pelvic anterior screw-rod system, superior pubic intramedullary screw and combination of superior pubic intramedullary screw and pelvic anterior screw-rod system. Conclusion For the fixation in unilateral pubic fractures of pelvic ring injury, the percutaneous superior pubic intramedullary screw is optimal, the percutaneous pelvic anterior screw-rod system is the second choice, and percutaneous bridging plate ranks the third. The percutaneous pelvic anterior screw-rod system can significantly increase fixation stability of the percutaneous superior pubic intramedullary screw and the percutaneous bridging plate.

Context The tumor immune microenvironment is associated with clinical outcomes and immunotherapy responsiveness. Objective To investigate the intratumoral immune profile of pituitary adenomas (PAs) and its clinical relevance and to explore a novel immune classification for predicting immunotherapy responsiveness. Design, Patients, and Methods The transcriptomic data from 259 PAs and 20 normal pituitaries were included for analysis. The ImmuCellAI algorithm was used to estimate the abundance of 24 types of tumor-infiltrating immune cells (TIICs) and the expression of immune checkpoint molecules (ICMs). Results The distributions of TIICs differed between PAs and normal pituitaries and varied among PA subtypes. T cells dominated the immune microenvironment across all subtypes of PAs. The tumor size and patient age were correlated with the TIIC abundance, and the ubiquitin-specific protease 8 (USP8) mutation in corticotroph adenomas influenced the intratumoral TIIC distributions. Three immune clusters were identified across PAs based on the TIIC distributions. Each cluster of PAs showed unique features of ICM expression that were correlated with distinct pathways related to tumor development and progression. CTLA4/CD86 expression was upregulated in cluster 1, whereas programmed cell death protein 1/programmed cell death 1 ligand 2 (PD1/PD-L2) expression was upregulated in cluster 2. Clusters 1 and 2 exhibited a “hot” immune microenvironment and were predicted to exhibit higher immunotherapy responsiveness than cluster 3, which exhibited an overall “cold” immune microenvironment. Conclusions We summarized the immune profile of PAs and identified 3 novel immune clusters. These findings establish a foundation for further immune studies on PAs and provide new insights into immunotherapy strategies for PAs.

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 Kashin-Beck disease (KBD) is an endemic osteoarthropathy, and its pathogenesis is still not entirely clear. Pathologically, many KBD changes are similar to those of osteoarthritis (OA). Therefore, this study aimed to identify changes in the levels of potential urinary biomarkers for OA, including C-telopeptide of type II collagen (uCTX-II), type II collagen cleavage neoepitope (uC2C), pyridinoline (uPYD), and uHelix-II, among adults with KBD. Methods Urinary samples of 83 external control (EC) subjects, 91 KBD patients, and 86 internal control (IC) subjects were tested by ELISA after the subjects completed a questionnaire and X-ray examination. Results The medians of the four markers in the KBD group were higher than those in the EC group and those in the IC group. The medians in the grade II KBD group were higher than those in the grade I group but were not statistically significant (P = 0.301, P = 0.408, P = 0.204, and P = 0.898 for uCTX-II, uC2C, uPYD, and uHelix-II, respectively). The area under the curve (AUC) of uCTX-II (0.775) was higher than that of the others (0.672, 0.639, and 0.628 for uC2C, uPYD, and uHelix-II, respectively). Conclusion The levels of uCTX-II, uC2C, uPYD, and uHelix-II were elevated in adults with KBD and showed an increasing trend as the severity of KBD increased. The prediction accuracy of uCTX-II was more useful than that of the others for assisting in the diagnosis of KBD.

Objectives: Our study aimed to investigate the associations of glucose tolerance status with insulin-like growth factor-I (IGF-I) and other clinical laboratory parameters of acromegalic patients before and after the patients underwent transsphenoidal adenomectomy (TSA) by conducting a single-center, retrospective study. Subjects and methods: A total of 218 patients with acromegaly who had undergone TSA as the first treatment were retrospectively analyzed. Serum IGF-I, growth hormone (GH) and glucose levels were measured before and after surgery. Results: The follow-up levels for random GH, GH nadir, and the percentage of the upper limit of normal IGF-I (%ULN IGF-I) were decreased significantly. The percentages of normal (39.0%), early carbohydrate metabolism disorders (33.0%) and diabetes mellitus (28.0%) changed to 70.2%, 16.5% and 13.3%, respectively, after TSA. %ULN IGF-I at baseline was higher in the diabetes mellitus (DM) group than in the normal glucose tolerance group and impaired glucose tolerance (IGT) /impaired fasting glucose (IFG) groups before TSA, and the DM group exhibited a greater reduction in %ULN IGF-I value after surgery. The follow-up %ULN IGF-I value after surgery was significantly lower in the improved group, and Pearson's correlation analysis revealed that the reductions in %ULN IGF-I corresponded with the reductions in glucose level. Conclusion: This study examined the largest reported sample with complete preoperative and follow-up data. The results suggest that the age- and sex-adjusted IGF-I level, which reflects altered glucose metabolism, and the change of it are associated with improved glucose tolerance in acromegalic patients both before and after TSA.

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.

Silent corticotroph adenomas (SCAs) can be redefined according to the 2017 World Health Organization pituitary classification system with the introduction of T‑PIT, a transcription factor. We studied the clinical features of these redefined SCAs.We compared 112 patients with SCAs and 198 patients with silent gonadotroph adenomas (SGAs) who underwent surgery from January 2019 to May 2020.The prevalence of SCAs increased from 21.3 to 30.2% under the new classification rules. T-PIT-positive, adrenocorticotropic hormone-negative SCAs and T-PIT-positive, adrenocorticotropic hormone-positive SCAs exhibited similar clinical features. SCAs exhibited significant female preponderance (90.2% vs. 29.8%, P 0.0001); more frequent invasion (36.6% vs. 7.6%, P 0.0001), especially multiple-site invasion (P 0.0001); and marked cystic changes on imaging compared with SGAs (54.5% vs. 19.2%, P 0.0001). SCAs had a softer tumor consistency (89.2% vs. 61.1%, P 0.0001). Gross total resection was achieved in 66.1% of SCAs and 66.2% of SGAs (P 0.9999). The overall recurrence/progression rates of SCAs and SGAs were 9.8% and 6.6% at 14.1 and 13.5 months of follow-up, respectively (P = 0.3765). The proportion of patients with more than two recurrences requiring multiple surgeries and radiation was similar between SCAs and SGAs (7.1% vs. 3.0%, P = 0.1514). However, multiple recurrences of SCAs affected younger patients than SGAs (39.0 vs. 53.5 years, P = 0.0433).The prevalence of SCAs increased with the introduction of T-PIT. SCAs and SGAs exhibited comparable size and recurrence/progression rates, but SCAs showed increased invasion and more marked cystic change. Aggressive SCAs tended to affect younger patients. Close long-term monitoring for SCA recurrence/progression is required.

Concomitant exotropia have obvious symptoms of eye discomfort in adults, and the presence of ocular surface inflammation in patients may be important mediators between concomitant exotropia and dry eye. Oculus Keratograph eye comprehensive analyzer was performed to detect noninvasive tear break time, noninvasive tear height, and eye red index, while the ocular surface disease index and schirmer I testing were made. The levels of IL-6, IL-10, IL-17A, IL-12P70, INF-γ, and TNF-α were detected in tears in patients with concomitant exotropia and healthy controls matched by age and gender through the Simoa technology. IL-6 was significantly higher in patients with concomitant exotropia ( 4.683 ± 1.329 ) pg/mL than that in normal group ( 1.455 ± 0.391 ) pg/mL, p = 0.0304 . TNF-α was also significantly higher in patients ( 0.2095 ± 0.0703 ) pg/mL than normal group ( 0.0513 ± 0.0149 ) pg/mL, p = 0.0397 . The levels of inflammatory factors in strabismic patients vs. normal controls were as follows: IL-17A (0.1551 pg/mL︰0.0793 pg/mL), IL-10 (0.3358 pg/mL︰0.0513 pg/mL), IL-12p70 (0.0253 pg/mL︰0.0099 pg/mL), and INF-γ (0.0284 pg/mL︰0.009 pg/mL) were detected, and the median of them in concomitant strabismus was 1.96-6.55-fold as much as the control group. High levels of inflammatory cytokines in tears of patients with concomitant exotropia, which may be a potentially factor promoted the occurrence of dry eye in the patients with concomitant exotropia.

BACKGROUND: Our study aimed to determine whether the expression concentration of inflammatory cytokines in ocular surface tears was increased in patients with concomitant strabismus.METHODS: In this study, the concentration of inflammatory cytokines interleukin-6 (IL-6), interleukin-17A (IL-17A), interleukin-10 (IL-10), interleukin-12p70 (IL-12P70), interferon gamma (INF-γ), and tumor necrosis factor- α (TNF-α) were detected in tears in patients with concomitant strabismus and healthy controls matched by age and gender.RESULTS: Our results showed that the concentration of IL-6 and TNF-α were significantly higher in the experimental group compared to the normal group. The concentration of IL-17A, IL-10, IL-12p70, and INF-γ in patients with concomitant strabismus were higher than those in the control group, but not reached the statistically significant.CONCLUSIONS: Our results suggested that most of concomitant strabismus patients have higher concentration of inflammatory cytokines in tears.

Background: The hospital-acquired influenza (HAI) were usually contributed to severe outcomes among the inpatients. Here, we performed a meta-analysis to summarize and quantify the epidemiological and clinical characteristics of HAI. Methods: We performed a literature search thorough PubMed, Web of Science, Cochrane Library, Embase, Scopus and China National Knowledge Infrastructure (CNKI), and Wanfang databases for observational studies. Random/fix-effects models were used to obtain pooled proportion, odds ratio (OR), and weighted mean difference (WMD). Results: A total of 14 studies involving 1483 HAI and 71849 non-hospital-acquired influenza infections (NHAI) cases were included.The proportion of the HAI among the influenza cases was 11.38% (95% confidence interval [CI]: 5.19%–19.55%) and it was increased after 2012 (6.15% vs 12.72%). The HAI cases were significantly older (WMD = 9.51, 95% CI: 0.04–18.98) and the patients with chronic medical diseases were at increased risk of HAI (OR = 1.85, 95% CI: 1.57–2.19). Among them, metabolic disorders (OR = 8.10, 95% CI: 2.46–26.64) ranked the highest danger, followed by malignancy (OR = 3.18, 95% CI: 2.12–4.76), any chronic diseases (OR = 2.81, 95% CI: 1.08–9.31), immunosuppression (OR = 2.13, 95% CI: 1.25–3.64), renal diseases (OR = 1.72, 95% CI:1.40–2.10), heart diseases (OR = 1.52, 95% CI: 1.03–1.44), and diabetes (OR = 1.22, 95% CI: 1.03–1.44). The HAI cases were more likely to experience longer hospital stay (WMD = 10.23, 95% CI: 4.60–15.85) and longer intensive care unit (ICU) stay (WMD = 2.99, 95% CI: 1.50–4.48). In the outcomes within 30 days, those population was still more likely to receive hospitalization (OR = 6.55, 95% CI: 5.19–8.27), death in hospital (OR = 1.99, 95% CI: 1.65–2.40) but less likely to discharged (OR = 0.20, 95% CI: 0.16–0.24). Conclusion: The proportion of the HAI among the influenza cases was relatively high. Reinforcement of the surveillance systems and vaccination of the high-risk patients and their contacts are necessary for the HAI control.

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.

ContextThe accumulation of aberrant lipids and abnormal lipid metabolism in silent corticotroph adenomas (SCAs) could contribute to changes in clinical phenotypes, especially sphenoid sinus invasion.ObjectiveTo systematically investigate lipidomic and transcriptomic alterations associated with invasiveness and their potential molecular mechanisms in SCAs and to provide candidate biomarkers for predicting invasiveness and novel treatment options for invasive SCAs by targeting lipids.MethodsFifty-four SCAs (34 invasive/20 noninvasive) were subjected to lipidomic analysis based on ultraperformance liquid chromatography mass spectrometry, and 42 clinically nonfunctioning pituitary adenomas (23 invasive/19 noninvasive) were subjected to transcriptomic analysis. Differential analysis was performed to determine differential lipids and genes between invasive and noninvasive tumors. A functionally connected network was constructed with the molecular pathways as cores. Multiple machine learning methods were applied to identify the most critical lipids, which were further used to construct a lipidomic signature to predict invasive SCAs by multivariate logistic regression, and its performance was evaluated by receiver operating characteristic analysis.ResultsTwenty-eight differential lipids were identified, and a functionally connected network was constructed with 2 lipids, 17 genes, and 4 molecular pathways. Connectivity Map (CMap) analysis further revealed 32 potential drugs targeting 4 genes and related pathways. The 4 most critical lipids were identified as risk factors contributing to the invasive phenotype. A lipidomic signature was constructed and showed excellent performance in discriminating invasive and noninvasive SCAs.ConclusionsThe lipidomic signature could serve as a promising predictor for the invasive SCA phenotype and provide potential therapeutic targets for SCAs.

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.

BackgroundPrevious studies have shown that patients with long-term diabetes require more opioids after surgery than patients without diabetes. Gestational diabetes mellitus (GDM) normally only lasts for a brief period; nevertheless, its effect on sufentanil consumption after cesarean section is unknown.MethodsThis prospective cohort study included two groups: a GDM group (n = 32) and a matched non-GDM (NGDM) group (n = 32). All patients underwent routine combined spinal-epidural anesthesia for cesarean delivery. Sufentanil consumption through an intravenous patient-controlled analgesia (PCA) pump, the frequency of PCA requests, and visual analog scale (VAS) scores 6 and 24 h after surgery were compared between groups.ResultsSufentanil consumption (μg) 6 h after surgery was higher in the GDM group than in the NGDM group (24.0 ± 6.6 vs 20.1 ± 5.7,P = 0.023). PCA was used more frequently 6 and 24 h after surgery by the GDM group than by the NGDM group (1[0–2] vs 0[0–1],P = 0.001; 6 [1–5] vs 3 [1, 2, 6–8],P = 0.001, respectively). The VAS score during activity 24 h after surgery was higher in the GDM group than in the NGDM group (5 [2, 3] vs 5 [1, 2], respectively,P = 0.03).ConclusionPregnant women with GDM require more opioids during the immediate postoperative period after cesarean section than those without GDM.Clinical trials registrationNo. ChiCTR1800016014, ChenYang, May 6th 2018.

Metformin (MET) is a diabetes drug that activates AMP‐activated protein kinase (AMPK), and is suggested to have anticancer efficacy. Here, we investigated the role of AMPK signalling in prolactinoma (PRLoma), with particular respect to MET and bromocriptine (BC) as a PRLoma treatment. We analysed AMPK phosphorylation, dopamine D2 receptor (D2R), and oestrogen receptor (ER) expression in both BC‐sensitive and ‐resistant PRLoma samples; effects of the AMPK agonist MET (alone or with BC) on in vitro proliferation and apoptosis, xenograft growth and prolactin (PRL) secretion of BC‐sensitive and ‐resistant cells, and ER expression in xenografts. Some BC‐resistant PRLomas showed high D2R expression but extremely low AMPK activation. MET significantly inhibited proliferation of cultured PRLoma cells; MET + BC notably restrained their PRL secretion. MET + BC further decreased tumour growth and serum PRL levels in xenografts than BC treatment alone. ER was down‐regulated after AMPK activation in both cultured cells and xenografts. Together, we propose that the AMPK signalling pathway down‐regulates ERα and ERβ, and suppresses PRLoma growth as well as PRL secretion. Combined MET + BC is a potential treatment for PRLomas.

Background & aims Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. However, the cellular defense mechanisms underlying ALD are not well understood. Recent studies highlighted the involvement of chaperone-mediated autophagy (CMA) in regulating hepatic lipid metabolism. Sorting nexin (SNX)-10 has a regulatory function in endolysosomal trafficking and stabilisation. Here, we investigated the roles of SNX10 in CMA activation and in the pathogenesis of alcohol-induced liver injury and steatosis. Methods Snx10 knockout (Snx10 KO) mice and their wild-type (WT) littermates fed either the Lieber-DeCarli liquid alcohol diet or a control liquid diet, and primary cultured WT and Snx10 KO hepatocytes stimulated with ethanol, were used as in vivo and in vitro ALD models, respectively. Activation of CMA, liver injury parameters, inflammatory cytokines, oxidative stress and lipid metabolism were measured. Results Compared with WT littermates, Snx10 KO mice exhibited a significant amelioration in ethanol-induced liver injury and hepatic steatosis. Both in vivo and in vitro studies showed that SNX10 deficiency upregulated lysosome-associated membrane protein type 2A (LAMP-2A) expression and CMA activation, which could be reversed by SNX10 overexpression in vitro. LAMP-2A interference confirmed that the upregulation of Nrf2 and AMPK signalling pathways induced by SNX10 deficiency relied on CMA activation. Pull-down assays revealed an interaction between SNX10 and cathepsin A (CTSA), a key enzyme involved in LAMP-2A degradation. Deficiency in SNX10 inhibited CTSA maturation and increased the stability of LAMP-2A, resulting in an increase in CMA activity. Conclusions SNX10 controls CMA activity by mediating CTSA maturation, and, thus, has an essential role in alcohol-induced liver injury and steatosis. Our results provide evidence for SNX10 as a potential promising therapeutic target for preventing or ameliorating liver injury in ALD. Lay summary Alcoholic liver disease is a major cause of morbidity and mortality worldwide. Recent studies highlight the involvement of chaperone-mediated autophagy (CMA) in regulating hepatic lipid metabolism. Our study reveals that deficiency of sorting nexin (SNX) 10 increases the stability of LAMP-2A by inhibiting cathepsin A maturation, resulting in the increase of CMA activity and, thus, alleviates alcohol-induced liver injury and steatosis.

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.

Background Transsphenoid surgery (TSS) is a standard treatment modality for Cushing's disease (CD). However, postoperative remission and recurrence rates vary among studies. Here we analyze the diagnosis and outcomes of 341 patients with a preoperative diagnosis of CD undergoing TSS in a single center over a 3-year period. Methods A total of 341 patients were enrolled. Clinical manifestations, imaging results, laboratory workups, and results of inferior petrosal sinus sampling (IPSS) were obtained. Outcomes were obtained with a follow-up length from 12 to 36 months. Results The tumors were mainly of Knosp level 0 (68.57%). The sensitivity of MRI, combined low-dose and high-dose dexamethasone suppression test and IPSS in the diagnosis were 90.83%, 88.53% and 95.57%. The concordance of lateralization by MRI and by IPSS were 78.96% and 61.34% compared with surgery. 2. Outcomes. The overall remission rate was 78.89% (N = 289). Patients undergoing the first TSS (N = 234) had a remission rate of 86.36% for macroadenomas (N = 22) and 83.2% for microadenomas (N = 212). Patients undergoing a second TSS (N = 55) had lower rate of remission of 50.00% for macroadenomas (N = 6) and 61.22% for microadenomas (N = 49). For patients with invasive tumors, the overall remission rate was 26.92% (N = 26), 20.0% for macroadenomas (n = 20) and 50.0% for microadenomas (N = 6). The recurrence rate was 2.42%. Conclusions Pituitary imaging, endocrinological workups and IPSS are sensitive and specific diagnostic modalities for CD, but the lateralization efficacy of MRI and IPSS are unsatisfactory. A higher rate of remission relies on gross resections of tumors.

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.

Objective To assess the efficacy and safety of Reduqing granules in patients with common cold with wind-heat syndrome (CCWHS). Methods A randomized, double-blind, double-dummy, parallel, positive-controlled trial included 72 CCWHS patients was performed. The participants were randomly assigned to two groups, Reduqing (RDQ) group and Lianhuaqingwen (LHQW) group, in a 1:1 ratio. Patients in RDQ group received Reduqing granules and dummy Lianhuaqingwen capsules three times a day and patients in LHQW group received Lianhuaqingwen capsules and dummy Reduqing granules three times daily. The duration of treatment and follow-up were four days. Results There were no statistically significant differences in total markedly effective rate and total effective rate between RDQ group and LHQW group after treatment. Traditional Chinese Medicine (TCM) symptom score was significantly reduced after treatment in RDQ group, as well as in LHQW group. However, the difference of change in TCM symptom score between two groups was not statistically significant ( P > 0.05). There were no significant differences between two groups in the median time to fever relief [RDQ group (4 ± 8) h vs LHQW group (4 ± 5) h] or the median time to fever clearance (RDQ group 47 h vs LHQW 36 h). No serious adverse events were reported during the study. Conclusion Compared with Lianhuaqingwen capsules, Reduqing granules achieved similar therapeutic effect in the treatment of CCWHS and no drug-related adverse events were reported during the study. Therefore, Reduqing granules might be effective and safe in the treatment of CCWHS.

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.

Objective: To investigate the effects of Suo Quan Wan (SQW), a traditional Chinese herbal formula, on the overactive bladder (OAB) of type 2 diabetes mellitus (T2DM) mouse models, particularly on its function of mediating the gene and protein expression levels of myosin Va and SLC17A9. Materials and Methods: After 4 weeks high-fat diet (HFD) feeding, C57BL/6J mice were injected with streptozotocin (100 mg/kg) for four times. After 3 weeks, the diabetic mice were treated with SQW for another 3 weeks. Voided stain on paper assay, fasting blood glucose (FBG) test, and oral glucose tolerance test (OGTT) were conducted. Urodynamic test, tension test [α,β-methylene ATP, electrical-field stimulation (EFS), KCl, and carbachol] and histomorphometry were also performed. Western blot analysis and qPCR assays were used to quantify the expression levels of myosin Va and SLC17A9. Results: The diabetic mice exhibited decreased weight but increased water intake, urine production, FBG, and OGTT. No significant changes were observed after 3 weeks SQW treatment. Urodynamic test indicated that the non-voiding contraction (NVC) frequency, maximum bladder capacity (MBC), residual volume (RV), and bladder compliance (BC) were remarkably increased in the diabetic mice, whereas the voided efficiency (VE) was decreased as a feature of overactivity. Compared with the model mice, SQW treatment significantly improved urodynamic urination with decreased NVC, MBC, RV, and BC, and increased VE. Histomorphometry results showed that the bladder wall of the diabetic mice thickened, and SQW effectively attenuated the pathological alterations. The contract responses of bladder strips to all stimulators were higher in the DSM strips of diabetic mice, whereas SQW treatment markedly decreased the contraction response for all stimuli. Moreover, the protein and gene expression levels of myosin Va and SLC17A9 were up-regulated in the bladders of diabetic mice, but SQW treatment restored such alterations. Conclusion: T2DM mice exhibited the early phase of diabetic bladder dysfunction (DBD) characterized by OAB and bladder dysfunction. SQW can improve the bladder storage and micturition of DBD mice by mediating the protein and gene expression levels of myosin Va and SLC17A9 in the bladder, instead of improving the blood glucose level.

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.

Glioblastoma (GBM) is the most common brain tumor with significant morbidity and mortality. Autophagy plays a vital role in GBM development and progression. We aimed to establish an autophagy-related multigene expression signature for individualized prognosis prediction in patients with GBM. Differentially expressed autophagy-related genes (DE-ATGs) in GBM and normal samples were screened using TCGA. Univariate and multivariate Cox regression analyses were performed on DE-ATGs to identify the optimal prognosis-related genes. Consequently, NRG1 (HR=1.142, P=0.008), ITGA3 (HR=1.149, P=0.043), and MAP1LC3A (HR=1.308, P=0.014) were selected to establish the prognostic risk score model and validated in the CGGA validation cohort. GSEA revealed that these genes were mainly enriched in cancer- and autophagy-related KEGG pathways. Kaplan-Meier survival analysis demonstrated that patients with high risk scores had significantly poorer overall survival (OS, log-rank P= 6.955×10-5). The autophagy signature was identified as an independent prognostic factor. Finally, a prognostic nomogram including the autophagy signature, age, pharmacotherapy, radiotherapy, and IDH mutation status was constructed, and TCGA/CGGA-based calibration plots indicated its excellent predictive performance. The autophagy-related three-gene risk score model could be a prognostic biomarker and suggest therapeutic targets for GBM. The prognostic nomogram could assist individualized survival prediction and improve treatment strategies.

Rationale: Knosp grade 4 adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is a rare cause of Cushing disease. After the 1st surgery, the remission rate among these patients is extremely low. Patient concerns: We presented a case of a 33-year-old female with classical Cushingoid symptoms. Further investigations revealed ATCH-dependent hypercortisolemia, as well as a Knosp grade 4 pituitary macroadenoma. Diagnosis: Cushing disease, caused by a Knosp grade 4 pituitary macroadenoma. Interventions: The patient underwent endoscopic endonasal transsphenoidal surgery with the assistance of intraoperative transsphenoidal Doppler and image-guidance devices. Outcomes: Pathologic examinations confirmed that the lesion was an ACTH-secreting pituitary adenoma. The patient was in biochemical remission after surgery. Her postoperative magnetic resonance imaging showed gross-total tumor resection. There was no evidence of recurrence during the 1-year follow-up. Lessons: With intraoperative Doppler and image-guidance, gross-total resection and biochemical remission can be achieved in Cushing disease when the internal carotid artery is completely encased by the pituitary adenoma.

Coagulative necrotic pituitary apoplexy (CNPA) is a clinical entity with unique intraoperative and histopathological manifestations. We aimed to improve the knowledge of this rare disease through the largest case series published to date. A retrospective review of 21 CNPA patients was performed from among 5095 patients who underwent surgery for pituitary adenomas at a single institution between January 2009 and June 2017. The demographic, clinical, endocrine, neuroimaging, intraoperative, and histopathological findings, management and prognosis were summarized. Headache was the most common symptom that was observed in 21 patients, followed by visual disturbances (17/21, 81.0%), nausea and vomiting (16/21, 76.2%), electrolyte disturbance (13/21, 61.9%), and oculomotor palsies (10/21, 47.6%). Hypopituitarism with at least one anterior pituitary deficiency, especially panhypopituitarism (10/21, 47.6%), was present in 81.0% of patients. Most patients (81.0%) showed typical MRI appearances. All 21 patients underwent transsphenoidal surgery (TSS), and 16 patients had total tumor resection demonstrated by postoperative MRI. Cottage cheese-like necrosis was observed in 16 patients (76.2%) intraoperatively. Histopathology showed large areas of pink, acellular, coagulative necrotic areas in the central zone, and a pseudocapsule in the border zone. After follow-up for 4.3 ± 2.3 years, only 28.6% of patients still suffered from corticotropic deficiency, and 9.5% of patients had gonadotropic deficiency. These patients were administered the appropriate corresponding hormones for life. CNPA can be correctly diagnosed preoperatively by typical clinical and MRI characteristics. Early surgery combined with hyperbaric oxygen therapy early postoperatively usually yields satisfactory endocrine and neuro-ophthalmic outcomes.

Application values of CA125 combined with CA199 and ultrasound combined with computed tomography (CT) in the clinical diagnosis of ovarian cancer were compared. A retrospective analysis was performed on 168 ovarian cancer patients admitted to the Department of Gynecology in Jining No.1 People's Hospital from July 2013 to March 2016. Of the patients 107 with malignant tumors were in the malignant group, and 61 patients with benign tumors were in the benign group. Another 98 healthy controls in the same period were in the normal group. Chemiluminescence was used for the detection of levels of tumor markers CA125 and CA199 in the serum of all patients. CA125 combined with CA199 and color Doppler ultrasound combined with CT scan were used to diagnose and analyze the sensitivity, specificity, accuracy, and positive detection rate of ovarian cancer patients at different stages. The sensitivity, specificity and diagnostic coincidence rate of ultrasound combined with CT in the diagnosis of ovarian cancer were 97.20, 80.32 and 91.07%, respectively, which were significantly higher than the 92.52, 73.77 and 85.71% of serum CA125 combined with CA199. The positive detection rate of ultrasound combined with CT in the early diagnosis of ovarian cancer was 93.55%, higher than 83.87% of CA125 combined with CA199. The sensitivity, specificity, coincidence rate and positive detection rate of ultrasound combined with CT in the diagnosis were higher than those of CA125 combined with CA199. In the actual diagnosis process, these two diagnostic schemes can be selectively and comprehensively applied, so as to make a correct diagnosis, which is of great significance for reducing patient mortality.

To investigate the clinical characteristics of pituitary adenomas in patients under 14 years old. A total of 140 children and adolescents with pituitary adenomas were admitted to Peking Union Medical College Hospital (PUMCH) from December 1987 to December 2014, and their clinical manifestations, hormone secretions, images, pathological types, surgical complications and follow-up characteristics were analyzed. Fifty-eight (41.4%) males and 82 (58.6%) females with a mean age of 12.5 years old (range, 6-14 years old) were included. Regarding tumor type, adrenocorticotropic hormone (ACTH), prolactin (PRL), growth hormone (GH), non-functioning and multiple-secreting adenomas accounted for 35.7%, 25.7%, 12.2%, 25.7%, and 0.7% of the tumors, respectively. Microadenomas, macroadenomas and giant adenomas accounted for 33.6%, 60.0% and 6.4% of the patients, respectively. Approximately 19.3% of the adenomas included in our study were invasive. Trans-sphenoidal approach surgery (TSS) was commonly used and accounted for 97.9% of the cases in our study. Total resection was achieved in 93.6% of the patients, and subtotal resection was performed in the remaining patients. Finally, 113 patients underwent full-term follow-up until 2 years after surgery, and tumors recurred in 32 patients. TSS is the most commonly used surgical procedure in patients younger than 14 years old. No significant differences in surgical outcomes, mortality during the perioperative period or complications were observed between patients younger than 14 years old and similar patients in the general population.

Background Kashin-Beck disease (KBD) is an endemic, chronic, degenerative osteoarthropathy. KBD is usually diagnosed by using X-ray image and clinical symptoms, lacking of serological biomarkers. The serum level of PIICP, PIIANP, and PIIBNP can specifically reflect the damage of the cartilage. So, in this study, the serum levels of PIICP, PIIANP, and PIIBNP were detected in order to determine whether they can be used as potential biomarkers for the diagnosis of KBD. Method Using a status survey, the survey sites were selected in the KBD historical endemic areas and non-endemic areas in Jilin and Heilongjiang provinces. All local residents have undergone clinical examination, X-ray examination of the hands and knees, and questionnaire survey. A total of 554 people were surveyed, and 184 residents who are eligible for inclusion criteria were selected as our subjects. Fifty-six cases were diagnosed as KBD and 63 individuals were included as internal control and 65 subjects were included as external control. And blood samples of surveyed subjects were collected, and the serum was separated to detect the levels of PIICP, PIIANP, and PIIBNP by ELISA. Statistical analysis was performed using the SPSS software. Results There were no statistically significant differences in age and sex among the three groups. The Kruskal-Wallis H test showed that the serum levels of PIICP, PIIANP, and PIIBNP were significantly different among the three groups. Multiple comparisons using Dunnett’s T3 test revealed that serum levels of PIICP, PIIANP, and PIIBNP were significantly lower in KBD patients than in internal and external control. However, there was no significant difference between the internal and external control. Conclusions The results preliminarily indicated that the levels of PIICP, PIIANP, and PIIBNP in serum could reflect the abnormal synthesis of type II collagen in KBD patients and suggested that these indicators might be used as potential biomarkers for the diagnosis of KBD.

When screening for Kashin–Beck disease (KBD) in children, hand X-ray examination is the most important measure. However, there is high rate of misdiagnosis because of confusing X-ray signs. We studied the characteristics of positive and confusing hand X-ray signs. Clinical and radiological examinations were conducted in all 7- to 12-year-olds in selected villages from some KBD and non-KBD areas. We analysed the radiological and epidemiological characteristics of the X-ray signs of KBD and the confusing signs. Images from 3,193 children were valid. No cases of KBD were found. Seventeen children (0.53%) had X-ray signs positive for KBD. The confusing X-ray signs included closure reaction of metaphysis-epiphysis (CRME, 14.28%), thumb variation (0.22%), little finger variation (8.89%), the second metacarpal-phalangeal variation (0.13%) and cystic change (3.85%). The onset of CRME in children occurred earlier in girls (9) than in boys (10). The onset occurred earlier in KBD areas (9) than in non-KBD areas (10). The onset occurred earlier in Han children (9) than in Tibetan children (11). In summary, KBD was effectively controlled in all investigated KBD endemic villages, and the age range should be adjusted to 7- to 11-year-olds in Han children to reduce the misdiagnosis rates in KBD surveillance.

Background To conduct radiologic anatomical study on the relation between S1 sacroiliac screws’ entry points and the route of the pelvic outer superior gluteal artery branches with the aim to provide the anatomical basis and technical reference for the avoidance of damage to the superior gluteal artery during the horizontal sacroiliac screw placement. Methods Superior gluteal artery CTA (CT angiography) vascular imaging of 74 healthy adults (37 women and 37 men) was done with 128-slice spiral CT (computed tomography). The CT attendant-measuring software was used to portray the “safe bony entrance area” (hereinafter referred to as “Safe Area”) of the S1 segment in the standard lateral pelvic view of three-dimensional reconstruction. The anatomical relation between S1 sacroiliac screws’ Safe Area and the pelvic outer superior gluteal artery branches was observed and recorded. The number of cases in which artery branches intersected the Safe Area was counted. The cases in which superior gluteal artery branches disjointed from the Safe Area were identified, and the shortest distance between the Safe Area and the superior gluteal artery branch closest to the Safe Area was measured. Results Three cases out of the 74 sample cases were excluded from this study as they were found to have no bony space for horizontal screw placement in S1 segment. Among the remaining 71 sample cases, there are 32 cases (45.1%) where the deep superior branch of superior gluteal artery passes through the Safe Area of S1 entrance point. There was no distinguishing feature and rule on how the deep superior branches and the Safe Area overlapped. In the 39 cases in which superior gluteal artery branches disjointed from the Safe Area, the deep superior branches of superior gluteal artery were the branches closest to the Safe Area and the part of the branch closest to the Safe Area was located in front of the widest part of the Safe Area. The shortest distance between the deep superior branch and the Safe Area is 0.86 ± 0.84 cm. Conclusion There is a high risk of accidental injury of the deep superior branches of superior gluteal artery in the process of S1 sacroiliac screw placement. Even if the entry points are located in the safe bony entrance area, the absolute secure placement cannot be assured. We suggest that great attention should be paid to make thorough preoperative plans.

Osteoarthritis (OA) is a considerable health problem worldwide, and the prevalence of OA varies in different regions. In this study, the prevalence of OA in Kashin-Beck disease (KBD) and non-KBD endemic areas was examined, respectively. According to monitoring data, 4 types of regions (including none, mild, moderate and high KBD endemic areas) in Heilongjiang and Jilin provinces were selected. All local residents were eligible for inclusion criteria have undergone X-ray images of hands and anteroposterior image of knees. A total of 1673 cases were collected, 1446 cases were analyzed after removing the KBD patients (227). The overall hand OA and knee OA detection rates were 33.3% (481/1446) and 56.6% (818/1446), respectively. After being standardized by age, the detection rate of hand OA in the KBD endemic areas was significantly higher than that in the non-endemic endemic areas. Differently, there was no significant difference in the detection rates of knee OA between the KBD endemic areas and the non-endemic area. The correlation coefficient between the severity of OA and the severity of knee OA was 0.358 and 0.197 in the KBD and non-KBD endemic areas, respectively. Where the KBD historical prevalence level was higher, the severity of the residents' hand OA was more serious. The detection rates of hand OA and knee OA increased with age. The detection rate of knee OA increased with the increase in body mass index. The prevalence of hand OA was closely related to the pathogenic factors of Kashin-Beck disease, and the prevalence of knee OA had no significant correlation with KBD pathogenic factors.

Transsphenoidal surgery is the treatment of choice for most pituitary adenomas (PA), except prolactinomas. Difficulties achieving radical resection with this method are encountered in patients with PAs invading the cavernous sinus (CS), due to the inability of the standard transsphenoidal approach to expose all tumors adequately. This study analyzed methods to resect PAs invading the CS and factors influencing the degree of tumor resection and occurrence of complications. Outcomes were retrospectively analyzed in 52 patients with PA invading the CS who underwent surgery via the extended transsphenoidal approach utilizing multiple techniques, including microscopy, endoscopy, neuronavigation, and intraoperative Doppler ultrasonography. Gross-total resection (GTR) was achieved in 33 patients (63.5 %). GTR rate was significantly higher in patients with Knosp Grade 3 than Knosp Grade 4 (92.3 vs. 53.8 %) and in patients undergoing initial surgery than reoperation (77.1 vs. 35.3 %). One patient (2.9 %) undergoing initial surgery experienced transient cranial nerve palsy, without other postoperative complications. Postoperative complications were significantly higher after reoperation. Firm tumor consistency was significantly more frequent in patients undergoing reoperation than initial surgery (52.9 vs. 8.6 %). Extended transsphenoidal surgery incorporating multiple complementary techniques was highly effective for PAs invading the CS. Postoperative complications rates were relatively low, especially for patients undergoing initial surgery and those with Knosp Grade 3 tumors. Total resection of PAs invading the CS remains challenging, especially in patients undergoing reoperation or having firm tumors.

Objective This study aimed to summarize the diagnosis, therapy, and prognosis of pituitary metastasis. Methods Ten patients from the Department of Neurosurgery of the Peking Union Medical College Hospital from April 1997 to August 2014 were retrospectively analyzed. Results The participants included 7 males (70%) and 3 females (30%), with an average age of 60.4 years. The most common initial clinical feature was visual disability (50%). The postoperative pathology reports indicated 1 case (10%) of metastatic large-cell pulmonary carcinoma, 2 cases (20%) of metastatic small cell pulmonary carcinoma, 2 cases (20%) of clear cell renal carcinoma metastasis, and 5 cases (50%) of metastasis of adenocarcinomas from different areas. All the patients underwent a thorough follow-up, and the average survival was 144 days. Conclusions Pituitary metastasis is a rare disease. Its diagnosis depends on the clinical manifestations and radiologic results. The primary therapeutic method is surgery and subsequent radiotherapy and chemotherapy; however, the prognosis of this disease is poor.

Objective To investigate the clinical characteristics and microsurgical therapy of pituitary adenomas in elderly patients. Method This article describes a retrospective study of 130 pituitary adenomas in elderly patients over 65 years of age who underwent a microsurgical operation using the transsphenoidal approach and were admitted to Peking Union Medical College Hospital (PUMCH) from January 2010 to December 2012. Results A total of 60 (46.2%) males and 70 females (53.8%) were included, and the mean age of the patients was 68.38 years. The main clinical manifestation was visual defects (35.4%), and the levels of growth hormone (GH), insulin-like growth factor-1 (IGF-1), adrenocorticotropic hormone (ACTH), and prolactin (PRL) were increased by 11.5%, 11.5%, 6.2%, and 7.7%, respectively. All patients underwent the transsphenoidal approach. The main comorbidity prior to surgery was hypertension (45.0%), and the average duration of follow-up was 39.6 ± 10.6 months. Tumor recurrence was observed in 19 patients, 17 of which received radiological therapy, and two patients underwent an additional operation at our hospital. The rate of loss to follow-up was 15.9%. Conclusion There was no significant difference in the surgical outcome, mortality in the perioperative period or complications between the elderly patients and the general population. However, the indications for pituitary adenomas in elderly patients still require further age-specific guidelines.

Multidrug resistance (MDR) remains a major clinical obstacle in the treatment of gastric cancer (GC) since it causes tumor recurrence and metastasis. The transcription factor activator protein-2α (AP-2α) has been implicated in drug-resistance in breast cancer; however, its effects on MDR of gastric cancer are far from understood. In this study, we aimed to explore the effects of AP-2α on the MDR in gastric cancer cells selected by vincristine (VCR). Decreased AP-2α levels were markedly detected by RT-PCR and Western blot in gastric cancer cell lines (BGC-823, SGC-7901, AGS, MKN-45) compared with that in the gastric epithelial cell line (GES-1). Furthermore, we found that the expression of AP-2α in SGC7901/VCR or SGC7901/adriamycin (ADR) cells was lower than in SGC7901 cells. Thus, a vector overexpressing AP-2α was constructed and used to perform AP-2α gain-of-function studies in SGC7901/VCR cells. The decreased IC50 values of the anti-cancer drugs in sensitive and resistant cells after transfect with pcDNA3.1/AP-2α were determined in SGC7901/VCR cells by MTT assay. Moreover, flow cytometry analysis indicated that overexpressed AP-2α induced cell cycle arrest in the G0/G1 phase and promoted cell apoptosis of VCR-selected SGC7901/VCR cells. RT-PCR and Western blot demonstrated that overexpressed AP-2α can significantly induce the down-regulation of Notch1, Hes-1, P-gp and MRP1 in SGC7901/VCR cells. Similar effects can be observed when Numb (Notch inhibitor) was introduced. In addition, the intracellular ADR accumulation was markedly detected in AP-2α overexpressed or Numb cells. In conclusion, our results indicate that AP-2α can reverse the MDR of gastric cancer cells, which may be realized by inhibiting the Notch signaling pathway.

Growth hormone (GH)-secreting pituitary adenoma is a chronic disease characterized by excess levels of GH and insulin-like growth factor 1 (IGF-1). Based on our clinical experience and observations, we identified discordant GH and IGF-1 levels after surgery. The risk factors for this phenomenon are unclear, and individualized cure, control criteria, and management after surgery should be considered. Purpose: This study aims to investigate the factors affecting the discordant GH and IGF-1 levels after pituitary surgery in acromegalic patients. Methods: We retrospectively analyzed 146 patients diagnosed with acromegaly caused by GH-secreting pituitary adenoma who had undergone trans-sphenoidal adenectomy (TSA) at Peking Union Medical College Hospital in 2013. Medical histories were obtained for all patients. Hormone levels, biochemical measurements of liver and renal function, and tumor size were recorded before and 3 months after surgery. Results: Among the GH-cured patients who had normal GH levels after TSA, 39.2% (20 of 51) had elevated IGF-1. Acromegalic patients with elevated IGF-1 and normal GH levels after TSA had a significantly higher mean body mass index and percentage of upper limit of normal range IGF-1 than the cured patients (p 25.0 kg/m2 and a percentage of upper limit of normal range IGF-1 higher than 141.5 before TSA might predict the occurrence of hormone-level discordance after surgery. Conclusion: Body mass index and percentage of upper limit of normal range IGF-1 before TSA might constitute prognostic risk factors for discordance in IGF-1 and GH levels in acromegaly. Additional attention should be devoted to potential risk factors for this phenomenon, and methods for modifying the cure and control criteria for acromegaly should be developed.

A total of 184 cases of surgically treated male prolactinoma were analyzed retrospectively to summarize the outcome of this surgical intervention. We analyzed the general characteristics, clinical manifestations, hormone levels, imaging features, preoperative treatments, surgical outcomes, pathology results, and follow-up records for all included patients. The most common clinical manifestations included sexual dysfunction (47.4%), headache (55.9%), and visual disturbance (46.7%). Serum prolactin levels ranged from 150 to 204,952 ng/mL. Tumor size varied from 6 to 70 mm. Pituitary adenomas grew in a parasellar pattern with visual deficits occurring 40.7% of the time. After surgical therapy, 88.6% of patients achieved symptom relief, and 98.4% experienced an immediate postoperative decline in prolactin level. Fifty-seven patients (31.0%) achieved initial remission, and 26 patients (45.6%) experienced recurrence. Hence, our results suggest that in male prolactinoma characterized by a large pituitary diameter and high serum prolactin level, tumor size predicts the degree of gross resection. The prognostic predictors included preoperative tumor growth pattern and Ki-67 index. Citation: Yi-jun S, Mei-ting C, Wei L, Bing X, Yong Y, Ming F, Ren-zhi W. (2016) Surgical treatment for male prolactinoma: a retrospective study of 184 cases

Ethnopharmacological relevance Wang-bi tablet (WB) consists of 17 traditional Chinese medicines and has been used for treating rheumatoid arthritis (RA) in China for many years, however, its pharmacologic mechanism is not clear. Aim of study The aim of this study was to investigate the therapeutic effect of WB on collagen-induced mouse arthritis and explored the underlying mechanism. Materials and methods DBA/1 mice were used to establish a type II collagen-induced arthritis (CIA) model. From the day of arthritis onset, mice were treated daily by gavage with either total glucosides of paeony (TGP, 0.37 g/kg/d) or WB at a lower (1.11 g/kg/d, WBL) or higher dose of (3.33 g/kg/d, WBH) for 8 weeks. The severity of arthritis, levels of cytokines and the activation of signaling pathways were determined. Results Our results revealed that WB treatment effectively alleviated inflammatory symptoms and prevented bone erosions and joint destructions. It obviously decreased the serum concentration of pro-inflammatory cytokines TNF-α, IL-6 and IL-17α, while increased the concentration of anti-inflammatory cytokine IL-10. Interestingly, the proportion of splenic Treg cells were increased significantly. In vitro experiments showed that WB inhibited the differentiation of osteoclasts. Consistently, the mRNA levels of tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CtsK), and the activation of NF-κB and JAK-STAT3 signaling pathways in the paws of CIA mice were inhibited by WB treatment. On the other hand, up-regulation of osteogenic genes Runx2, Osterix mRNA, and activation of Wnt/β-catenin signaling pathway along with a decreased receptor activator of nuclear factor κB ligand (RANKL) expression were found in WB treated mice. Conclusion Our results suggest that the therapeutic effect of Wang-bi tablet could be attributed to its inhibitory activity on NF-κB and STAT3 signaling pathway-mediated osteoclast differentiation, and its enhancement on Wnt/β-catenin signaling pathway-mediated osteoblast functions.

Prolactinoma is one of the most common pituitary tumors, but relatively uncommon in patients under 14 years old. Surgery is the second-line treatment for prolactinoma when patients show resistance or intolerance to medical therapy. There are only a few published series of children who underwent surgery treatment. This study is performed to investigate the clinical manifestation and surgical outcome of pituitary prolactinoma in patients under 14 years old who are resistant or intolerant to medical therapy of dopamine agonist. Thirty-six cases were included in a retrospective review of patients under 14 years old operated for prolactinoma between December 1987 and December 2015. Preoperative radiological and endocrinal evaluation was performed on every patient. All patients received operation with trans-sphenoidal approach. Based on enhanced pituitary magnetic resonance imaging (MRI) taken 2 months after the surgery, total resection was achieved in 16 patients (44.4%) and subtotal resection in 20 (55.6%). Thirty-four cases (94.4%) showed remarkable decrease of prolactin (PRL) level 7 days after surgery, and 16 (44.4%) returned to normal. All patients were followed up for 2 years. Tumor regrowth or recurrence occurred in 5 patients and secondary treatment was applied, including drug treatment in 2 patients, second surgery in 2, and radiotherapy in 1. Trans-sphenoidal pituitary surgery is an effective treatment for prolactinoma in patient under 14 years old. There is no significant difference between the patients under 14 years old and adults for prolactinoma in characteristics and treatment.

Background: Phase II-III trials in patients with untreated and previously treated locally advanced or non-small cell lung cancer (NSCLC) suggested that Endostar was able to enhance the effect of platinum-based chemotherapy (NP regimen) with tolerable adverse effects. Methods Four hundred and eighty six patients were randomized into two arms: study arm A: NP plus Endostar (n = 322; vinorelbine, cisplatin, Endostar), and study arm B: NP plus placebo (n = 164; vinorelbine, cisplatin, 0.9% sodium chloride). Patients were treated every third week for two to six cycles. Results: Overall response rates were 35.4% in arm A and 19.5% in arm B (P = 0.0003). The median time to progression was 6.3 months for arm A and 3.6 months for B, respectively (P 0.05). There were two treatment related deaths in arm A and one in arm B (P > 0.05). The median overall survival was longer in arm A than in arm B (P < 0.0001). Conclusion: Long-term follow-up revealed that the addition of Endostar to an NP regimen can result in a significant clinical and survival benefit in advanced NSCLC patients, compared with NP alone.

Pituitary abscess (PA) is rare and commonly described in case reports or small case series. This study aimed to better determine salient clinical manifestations related to the diagnosis and appropriate treatment of PA using by far the largest case series of this disease. A total of 6361 consecutive patients underwent surgery for pituitary diseases in Peking Union Medical College Hospital between January 1991 and December 2013. Among this cohort, sixty-six patients were diagnosed with PA based on both intraoperative findings and postoperative histopathological evidence. The most common clinical presentation was anterior pituitary hypofunction (81.8 %), followed by common headache (69.7 %), diabetes insipidus (DI; 47.9 %), visual disturbances (45.5 %) and symptoms related to infection (43.9 %). Forty patients (66.7 %) showed typical rim enhancement after gadolinium injection on magnetic resonance imaging (MRI). Most patients (63 of 66, 95.5 %) underwent transsphenoidal surgery (TSS), and the remaining 3 patients (4.5 %) were treated with transcranial surgery (TC). After follow-up for 7.2 ± 4.9 years, PA was diminished in most patients (81.8 %), as demonstrated by post-operative MRI, and eight patients underwent at least one additional operation due to recurrence. For patients with hypopituitarism and DI with rim enhancement on MRI, we should consider the possible diagnosis of PA. Proper use of antibiotics, complete drainage via surgery and hormone replacement for hypopituitarism are the key treatments for PA.