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Objective To discuss the clinical features of preoperative undiagnosed pheochromocytoma in patients with adrenal incidentaloma (AI). Methods The clinical data were retrospectively analyzed of 103 cases of pathologically diagnosed adrenal pheochromocytoma in patients with AI admitted in the General Hospital of Chinese PLA during Mar. 2012 to Dec. 2016. The cases were divided into two groups: patients preoperatively diagnosed as non-function adrenal tumor were assigned as group A (n=16), and preoperatively diagnosed as pheochromocytoma were assigned as group B (n=87). The clinical features, endocrine hormone levels and imaging features of the two groups were analyzed. Results The age when diagnosed as hypertension was higher in group A (55.5±9.1 years) than in group B (43.6±12.3 years, P

Objective To investigate the diagnostic value of different evaluation indexes of captopril challenge test (CCT) on primary aldosteronism. Methods The biochemical parameters were collected of patients with aldosterone producing adenoma (APA, 90 cases), with idiopathic hyperaldosteronism (IHA, 44 cases) and with essential hypertension (EH, 88 cases) who were diagnosed and undergone CCT in the General Hospital of PLA from Jan. 2014 to Mar. 2016. The clinical characteristics were compared, the receiver operating characteristic curve (ROC) was conducted to evaluate the diagnostic value of different evaluation indexes including the absolute value and suppression percentage of aldosterone, the increasing percentage of plasma renin activity (PRA) and the ratio of aldosterone/renin (ARR), and then the optimal diagnostic criteria and its sensitivity and specificity were determined. Results After CCT the suppression percentage of aldosterone in APA, IHA and EH groups were 0.3%, 0.7% and 4.0%, respectively. The increasing percentage of renin in APA, IHA and EH groups was 0(0, 1), 0.25(0, 1) and 0.97(0.23, 2.27), respectively. The increasing percentage of renin in primary aldosterone group was significantly lower than that in EH group (P

High-resolution capillary zone electrophoresis - mass spectrometry (CZE-MS) has been of increasing interest for the analysis of biopharmaceuticals. In this work, a combination of middle-down and intact CZE-MS analyses has been implemented for the characterization of a biotherapeutic monoclonal antibody (mAb) with a variety of post-translational modifications (PTMs) and glycosylation structures. Middle-down and intact CZE separations were performed in an acidified methanol-water background electrolyte on a capillary with a positively charged coating (M7C4I) coupled to an Orbitrap mass spectrometer using a commercial sheathless interface (CESI). Middle-down analysis of the IdeS-digested mAb provided characterization of PTMs of digestion fragments. High resolution CZE enabled separation of charge variants corresponding to 2X-deamidated, 1X-deamidated, and non-deamidated forms at baseline resolution. In the course of the middle-down CZE-MS analysis, separation of glycoforms of the FC /2 fragment was accomplished due to hydrodynamic volume differences. Several identified PTMs were confirmed by CZE-MS2 . Incorporation of TCEP-HCl reducing agent in the sample solvent resulted in successful analysis of reduced forms without the need for alkylation. CZE-MS studies on the intact mAb under denaturing conditions enabled baseline separation of the 2X-glycosylated, 1X-glycosylated, and aglycosylated populations as a result of hydrodynamic volume differences. The presence of a trace quantity of dissociated light chain was also detected in the intact protein analysis. Characterization of the mAb under native conditions verified identifications achieved via intact analysis and allowed for quantitative confirmation of proteoforms. Analysis of mAbs using CZE-MS represents a complementary approach to the more conventional liquid-chromatography - mass spectrometry-based approaches.

Real-time release testing (RTRT) is defined as "the ability to evaluate and ensure the quality of in-process and/or final drug product based on process data, which typically includes a valid combination of measured material attributes and process controls" (ICH Q8[R2]). This article discusses sensors (process analytical technology, PAT) and control strategies that enable RTRT for the spectrum of critical quality attributes (CQAs) in biopharmaceutical manufacturing. Case studies from the small-molecule and biologic pharmaceutical industry are described to demonstrate how RTRT can be facilitated by integrated manufacturing and multivariable control strategies to ensure the quality of products. RTRT can enable increased assurance of product safety, efficacy, and quality-with improved productivity including faster release and potentially decreased costs-all of which improve the value to patients. To implement a complete RTRT solution, biologic drug manufacturers need to consider the special attributes of their industry, particularly sterility and the measurement of viral and microbial contamination. Continued advances in on-line and in-line sensor technologies are key for the biopharmaceutical manufacturing industry to achieve the potential of RTRT. Related article: http://onlinelibrary.wiley.com/doi/10.1002/bit.26378/full.

Objective To analyze the relationship between the brain functional alterations of patients with Cushing's disease (CD) and patients' mental symptom by applying the Evaluating Emotional Scales and task functional magnetic resonance imaging (Task fMRI). Methods Task fMRI was performed on 8 patients with diagnosed CD admitted in the Department of Endocrinology of Chinese PLA General Hospital from Nov. 2015 to Nov. 2016 and 21 healthy people with matched age, gender and education level as control. Meanwhile, Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Positive and Negative Affective Scale (PANAS) and Cushing Quality of Life Scale (Cushing QOL) were obtained to assess the brain functions. Results Significant depression and anxiety were observed in patients with CD, and their positive affective score was substantially lower while the negative affective score was relatively higher compared with that in the controls. Task fMRI revealed that, when watching the positive pictures, the activation degree of left cerebellum and right postcentral gyrus weakened in CD patients than in the controls, and the positive correlations existed between the activation degree of left cerebellum and the 16 o'clock adrenocorticotrophic hormone (ACTH) level, and between the activation degree of right postcentral gyrus and the urinary free cortisol (UFC) level in CD patients. In contrast, when watching the negative pictures, the activation degree of left cerebellum, bilateral parahippocampal gyrus and left inferior frontal gyrus was weakened in CD patients than in the controls, and the activation degree of left cerebellum was negatively correlated to the 0 o'clock cortisol level and SAS score, but is positively correlated to the UFC level. When watching the neutral pictures, the activation degree of left cerebellum and left parahippocampal gyrus was weakened in CD patients than in the controls. Conclusions CD patients may have impaired brain function with depression and anxiety mental symptoms. By Task fMRI, it can be found that the weakened activation degree of left inferior frontal gyrus, right postcentral gyrus, bilateral parahippocampal gyrus and left cerebellum may be related to CD patients' mental symptoms. DOI: 10.11855/j.issn.0577-7402.2017.07.02

Objective To evaluate the clinical characteristics of patients with growth-hormone adenoma (GHA) and summarize the diagnosis and treatment experience. Methods The clinical data of 338 GHA cases at the General Hospital of PLA from Jan. 1990 to Dec. 2016 were collected, of which 252 cases with more complete clinical data were retrospectively analyzed including their general situation, medical history, laboratory tests and auxiliary examinations, and treatment modalities and outcomes. Parts of the patients were followed up. Results The cases of hospitalized GHA patients have increased year by year since 1990, and the number of patients admitted in the last 3 years accounted for 56.2% of the total number of cases. The sex ratio for GHA patients was nearly 1:1. Age of visiting followed Gaussian distribution while the 41-50 age group occupied the largest part. The most typical sign is hand and foot enlargement (60.7%), followed by the hypertrophy of nasal ala. The most common symptoms are headache (42.5%), hypopsia, visual field defect and diplopia. More than half of GHA patients were complicated with prediabetes and diabetes (72.6%), sleep apnea (69.5%), goiter or thyroid nodularity (56.4%), cardiac insufficiency (57.0%) and colon polyp (54.1%); while the percentages of cases undergone the relevant examination in the total number of cases were as follows: 75g OGTT test (42.1%), polysomnography (23.4%), thyroid ultrasound (37.3%), echocardiogram (47.6%) and colonoscopy (14.7%); GHA was 23.37±1.42μg/L and IGF-1 was 804.28±273.93ng/ml on average; 85.0% of somatotroph tumors are macroadenoma. Surgery remains the mainstay of therapy to GHA, while medical therapy was selected by less patients. During the follow-up, only 38.0% of GHA patients can be contacted, among them the remission rate decreased to 40.5%. The positive rate of long-term remission evaluated by early postoperative GHA level was consistent with that confirmed by the long-term follow-up (χ2=3.368, P>0.05). Conclusions The number of hospitalized GHA patients have increased recent years. The common clinical signs and symptoms are somatic enlargement and nonspecific headache. Due to uncompleted screening, GHA associated complications are always misdiagnosed; It is essential to establish a sound model of follow-up to improve patients' quality of life. The early postoperative GHA levels may predict the prognosis of surgery. DOI: 10.11855/j.issn.0577-7402.2017.07.04

Objective To comparatively analyze the clinical characteristics of thyrotropin-secreting pituitary adenomas (TSH-omas). Methods The clinical features, laboratory variables, imaging and pathological results were retrospectively compared and analyzed of 26 cases with TSH-omas admitted in Chinese PLA General Hospital from Feb. 2006 to Oct. 2016 and 20 cases with TSH-omas admitted in Shanghai Huashan Hospital from Apr. 2006 to Apr. 2013. Results The female ratio was slightly higher in patients of Chinese PLA General Hospital than in Huashan Hospital [(57.7%(15/26) vs. 45.0%(9/20)], while the mean age was similar [39.5±14.1(18-67 years) vs. 40.0±14.5(17-74 years)]. The most common chief complaint was thyrotoxicosis [73.1%(19/26) vs. 55.0%(11/20)], and mild-to-moderate goiter was the most common symptom. The mean serum TSH levels in Chinese PLA General Hospital and in Huashan Hospital were 5.06(2.97-6.27)mU/L and 6.16(3.76-10.91)mU/L respectively, and patients with normal serum TSH levels were more common in Chinese PLA General Hospital than in Huashan Hospital [57.7%(15/26) vs. 40.0%(8/20)]. Microadenoma was more common in Chinese PLA General Hospital than in Huashan Hospital [34.62%(9/26) vs. 20.0%(4/20)], while macroadenoma was more common in Huashan Hospital than in Chinese PLA General Hospital [20.0%(4/20) vs. 7.7%(2/26)]. Microadenoma was more common in female patients of the both groups [66.7%(6/9) vs. 75.0%(3/4)], while macroadenoma was all found in male patients. Tumor invasion of surrounding tissue and structure was often found in macroadenoma. In terms of octreotide inhibition test, the range of 24h TSH inhibition rate was roughly the same in the two groups (37.4%-91.8% and 46.5%-94.1%, respectively). Mixed adenoma was rare among all the pathologically confirmed cases. In Chinese PLA General Hospitals, TSH immunoreactive negative neoplastic cells were found in 3 of 8 cases, and octreotide scanning showed negative in 2 of 12 cases. Conclusions Patients with TSH-omas in the two hospitals show similarities but also some significant differences in the clinical features. Overall, the domestic patients with TSH-omas are diagnosed without gender difference according to the reports in China. The mean age at diagnosis is significantly younger than that in foreign data. Microadenoma is more common in females, while macroadenoma is more common in males. Serum TSH levels can be normal in patients with TSH-omas. Immunostaining and/or octreotide scanning for TSH can be negative. DOI: 10.11855/j.issn.0577-7402.2017.07.03

Smart city has been greatly promoted by the adoption of information and communication technology. At the same time, data integrity becomes an urgent necessity in cloud storage scenario. When smart city meets cloud, if the data are damaged or corrupted, it will be a serious security loophole of smart city. Recently, numerous remote data auditing (RDA) protocols have been presented, among which Sookhak et al. put forward a dynamic remote data auditing protocol to deal with this major concern. In this paper, we found that this protocol has inherent security flaws, thus fails to achieve its original goal. Specifically, this protocol is vulnerable to two types of attacks, namely replace attack and replay attack. We show the details that how a malicious server can deceive data owners to believe that the data are maintained well by launching such attacks. Then, we describe an improved RDA protocol with provable security by utilizing algebraic signature to fix those security flaws. We employ the rank-based Merkle Hash Tree to achieve verifiable dynamic data operations for our RDA protocol. We also provide detailed security proof of the proposed RDA protocol.

OBJECTIVE To explore the correlation between effect of PIO (pioglitazone, PIO) on learning as well as memory and ERK1/2 (extracellular signal regulated kinase 1/2, ERK1/2) pathway in T2DM (type 2 diabetes mellitus, T2DM) rats, further to elucidate the potential mechanism of PIO in improvement of learning and memory. METHODS 12-week-old male SD rats (number of 10 per group) were randomly divided into control group (CON), T2DM group (DM) and T2DM +PIO group (DM + PG). Rats in DM and DM + PG groups were given high fat diet for 20 weeks, then treated with Streptozotocin (27 mg/kg) by intraperitoneal injection at 21week. After 72 h, the FBG (fasting blood glucose, FBG) was greater than 7.0 mmol/L can considered T2DM rats. DM + PG group was treated with PIO (10 mg·kg −1 ·d −1 ) by gavage daily. After Hyperinsulinemic-Euglycemic Clamp Study and Morris water maze test at 30-week, all of animals were sacrificed. The expressions of RKIP (Raf-1 kinase inhibitor protein, RKIP) and ERK1/2 in hippocampus were detected using Western Blot and real-time PCR. RESULTS The FBG level: DM group (7.68 ± 0.54 mmol/L) was higher than CON group (5.35 ± 0.63 mmol/L) and DM + PG group (6.07 ± 0.84 mmol/L), the differences were considered statistically significant (P −1 ·d −1 ) was less than CON group (27.64 ± 3.87 mg·kg −1 ·d −1 ) and DM + PG group (26.04 ±5.41 mg·kg −1 ·d −1 ), the differences were considered statistically significant (P 0.05); The relative content of p-ERK1/2 protein in CON group and DM + PG group rats dorsal were higher than those in group DM, the difference was considered statistically significant (P 0.05). CONCLUSION Activation of ERK1/2 signal transduction pathway via reducing RKIP in the hippocampus may be one of the mechanisms of PIO to improve the learning and memory of the T2DM rats.

Type 2 diabetes mellitus (T2DM), which is characterized by the combination of relative insulin deficiency and insulin resistance, cannot be reversed with existing therapeutic strategies. Transplantation of insulin-producing cells (IPCs) was once thought to be the most promising strategy for treating diabetes, but the pace from the laboratory to clinical application has been obstructed due to its drawbacks. Mesenchymal stem cells (MSCs) harbor differentiation potential, immunosuppressive properties, and anti-inflammatory effects, and they are considered an ideal candidate cell type for treatment of DM. MSC-related research has demonstrated exciting therapeutic effects in glycemic control both in vivo and in vitro, and these results now have been translated into clinical practice. However, some critical potential problems have emerged from current clinical trials. Multi-center, large-scale, double-blind, and placebo-controlled studies with strict supervision are required before MSC transplantation can become a routine therapeutic approach for T2DM. We briefly review the molecular mechanism of MSC treatment for T2DM as well as the merits and drawbacks identified in current clinical trials.

Objective The role of M2 macrophages infusion in dealing with obesity is still little known. In this study, the therapeutic effects of M2 macrophages infusion were investigated. Methods High fat diet (HFD) was used to induce obesity in C57BL/6N mice. 5 × 10 5 M2 macrophages, derived from the bone marrow, were injected into obese mice through the tail vein twice with an interval of one week. Results One week after the second injection, weight of inguinal adipose pad was significantly decreased. Accordingly, the adipocyte size of epididymal and inguinal adipose tissue (EAT and INAT) shrank. To our interest, we found that the infused M2 macrophages were homed to EAT, reversing the disturbed homeostasis of high M1 to low M2 in obese mice. Meanwhile, EAT with remodeled macrophages' homeostasis expressed less MCP-1, accompanying with decreased recruitment of inflammatory CCR2 + CX3CR1 low Ly6C + monocytes from the blood in M2 infusion group. Further, increased M2 in EAT contribute to enhanced expression of UCP1 expression in EAT, which helped to ameliorate insulin resistance and, subsequently, improve the serum level of triglycerides (TG) and low density lipoprotein cholesterol (LDL-c). Conclusions These findings highlighted that M2 macrophages infusion could ameliorate obesity as well as obesity-related insulin resistance, suggesting an effective and healthy weight loss strategy.

Objective To explore the potential influence of gender on screening value of aldosterone-renin ratio (ARR) for primary aldosteronism (PA). Methods The biochemical parameters were collected of 451 PA patients and 300 essential hypertension (EH) patients who were diagnosed in the General Hospital of PLA from 1992 to 2014. Each group was then divided into two groups by gender. The clinical characteristics were compared and then the receiver operating characteristic curve (ROC) was conducted to evaluate the best cut-off value. Results The plasma aldosterone concentration (PAC), serum sodium and ARR were much higher, but the plasma rennin activity (PRA), serum potassium and BMI were much lower in PA patients than in EH patients (P0.05). The best cut-off value of ARR in male PA patients was 19.11, the relevant area under the curve (AUC) was 0.968, the sensitivity and specificity was 92.44% and 93.08%, and the Youden index (YI) was 0.86. The best cut-off value of ARR in female PA patients was 27.26, with AUC 0.956, sensitivity 92.07%, specificity 90.00% and YI 0.82, respectively. If the cut-off value was set at 27.26 in males, the specificity would rise a little, but the sensitivity and YI would sharply decrease. Similarly, the sensitivity would increase a little but the specificity and YI would fall substantially if the cut-off value in females was set at 19.11. The best cut-off value of ARR in men was smaller than the official value recommended by guidelines. Conclusion Gender is an important factor should be considered while ARR is used in PA screening, and the cut-off value of ARR in screening female PA patients should be setting higher. DOI: 10.11855/j.issn.0577-7402.2017.01.10

Objective To analyze the pathology of the patients with nonfunctional adrenal tumor (NFA), and explore the optimal diameter cut-off value. Methods The clinical data of 243 patients with NFA, evaluated in the Department of Endocrinology and operated in the Department of Urology of General Hospital of Chinese PLA from Feb. 1996 to Jan. 2016, were collected. The patients were divided into two groups according to pathology: those in real demand of surgery were classified to the surgery-need group (n=57), while the others were categorized as the surgery-unwanted group (n=186). The general situation, pathological type and tumor diameter of the two groups and the factors affecting the surgery were analyzed, and the ROC curve was used to explore the optimal surgery cut-off value, which represents the maximum value of the sum of sensitivity and specificity. Results Of the 57 patients in surgery-need group (27 males and 30 females), the lesions were on the right in 31 cases, on the left in 25 cases, and on bilateral sides in 1 case; the median of lesion diameter was 4.5cm, and the average age was 41.5±12.1 years old. Of the 186 patients in surgery-unwanted group (87 males and 99 females), the lesions were on the right in 99 cases, on the left in 86 cases, and on bilateral sides in 1 case; the median of lesion diameter was 3.0cm, and the average age was 50.6±10.9 years old. Logistic regression revealed that lesion diameter might be a risk factor (OR=1.340, 95%CI 1.266-1.418, P=0.000) and age be a protective factor (OR=0.942, 95%CI 0.929-0.955, P=0.000) for real demand of surgery. The area under the ROC curve (AUC) of lesion diameter was 0.757(95%CI 0.681-0.833). The optimal cut-off value was 4.1cm (sensitivity 60.7% and specificity 83.0%). Conclusions Younger patients with bigger lesion diameter may have greater possibility for surgery. The optimal surgery cut-off value of the lesion diameter is 4.1cm. DOI: 10.11855/j.issn.0577-7402.2016.11.11

Purpose This study evaluated shear wave elastography (SWE) and SWE combined with the Ki-67 index as novel predictive modalities for the pathological response of invasive breast cancer to neoadjuvant chemotherapy (NAC). Methods The prospective study recruited 66 eligible patients from July 2014 to November 2015. Tumour stiffness, which corresponds with tumour progression and invasiveness, was assessed by quantitative SWE 1 d before biopsy (time point t0, elasticity E0), 1 d before next NAC cycle (t1−t5, E1−E5), and 1 d before surgery (t6, E6). The relative changes in SWE parameters after the first and second NAC cycles were considered as the variables [ΔE (t1), ΔE (t2)]. The pathological response was classified according to the residual cancer burden (RCB) protocol. Correlations between RCB scores and variables were evaluated. The predictive diagnostic performances of SWE parameters, Ki-67 index, and the predictive RCB (predRCB) score determined by a linear regression model were compared. Results Some immunohistochemical and molecular factors and SWE parameters were significantly different among the three RCB groups. The ΔE mean (t2) and Ki-67 had significantly better diagnostic performance than other parameters regarding predicting the pathological response (the RCB-I response and RCB-III resistance). However, the correlation between ΔE mean (t2) and Ki-67 index was significantly weaker as a diagnostic predictor ( r = 0.29). We generated a new predictive modality, predRCB, which is a multivariable linear regression model that combines ΔE mean (t2) and the Ki-67 index. The predRCB modality showed better diagnostic performance than SWE parameters and Ki-67 index alone. Conclusion Our findings highlight the potential utility for adding the Ki-67 index to the SWE results, which may improve the predictive power of SWE and facilitate personalising the treatment regimens of patients with breast cancer. These results should be validated in the future by performing a multicentre prospective study with a larger cohort.

Sensor Pattern Noise (SPN) has proven to be an effective fingerprint for source camera identification, while its estimation accuracy heavily relies on denoising algorithm. In this paper, an effective source camera identification scheme based on Multi-Scale Expected Patch Log Likelihood (MSEPLL) denoising algorithm is proposed, firstly. With enhanced prior modeling across multiple scales, MSEPLL can accurately restore the original image. As a consequence, estimated SPN is less influenced by image content. Secondly, the source camera identification problem is formulated by hypothesis testing, where normalized correlation coefficient is adopted for SPN detection. Finally, the effectiveness of the proposed method is verified by abundant experiments in terms of identification accuracy as well as receiver operating characteristic. Performance improvement is more prominent for small image patches, which is more conducive to real forensics applications.

Nonalcoholic fatty liver disease (NAFLD) is increasingly common among patients with type 2 diabetes mellitus (T2DM). The two conditions can act synergistically to produce adverse outcomes. However, the therapeutic options for patients with NAFLD and T2DM are currently limited. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) have shown therapeutic potential for diabetes and hepatic disorders such as liver cirrhosis and fulminant hepatic failure. The present study is aimed at investigating the effect of human UC-MSCs on a mouse model of NAFLD and T2DM, characterized by obesity-induced hyperglycaemia, dyslipidaemia, hepatic steatosis, and liver dysfunction. Thirty-week-old male C57BL/6 db/db mice were infused with human UC-MSCs or phosphate-buffered saline (PBS) via the tail vein once a week for six weeks. Age-matched male C57BL/6 wild-type db/+ mice were used as controls. Body weight and random blood glucose were measured every week. One week after the sixth infusion, intraperitoneal glucose tolerance tests and insulin tolerance tests were performed and the blood and liver were harvested for biochemical and histopathological examinations. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR), immunofluorescence staining, and western blot were performed to monitor the expression of the lipid metabolism- and regulatory pathway-related genes. UC-MSC infusions significantly ameliorated hyperglycaemia, attenuated the elevation of hepatic transaminases, and decreased lipid contents, including triglyceride, total cholesterol, and low-density lipoprotein cholesterol. Moreover, histological lesions in the liver diminished markedly, as evidenced by reduced lipid accumulation and attenuated hepatic steatosis. Mechanistically, UC-MSCs were found to regulate lipid metabolism by increasing the expression of fatty acid oxidation-related genes and inhibiting the expression of lipogenesis-related genes, which were associated with the upregulation of the HNF4α-CES2 pathway. Our results demonstrate that human UC-MSCs can ameliorate NAFLD and reverse metabolic syndrome in db/db mice. Thus, UC-MSCs may serve as a novel therapeutic agent for T2DM patients with NAFLD.

Based on convolutional neural network (CNN), the problem of robust patch level camera model identification is studied in this paper. Firstly, an effective feature representation is proposed by concatenating a multiscale residual prediction module as well as the original RGB images. Motivated by exploration of multi-scale characteristic, the multiscale residual prediction module automatically learn the residual images to avoid the subsequent CNN being affected by the scene content. Color channel information is integrated for enhanced diversity of CNN inputs. Secondly, a modified richer convolutional feature network is presented for robust camera model identification by fully exploiting the learnt features. Finally, the effectiveness of the proposed method is verified by abundant experimental results at the patch level, which is more difficult than image level experiments.

Selection of high-producing lead and backup cell lines with high-fidelity primary structure is a major goal of cell line development of protein therapeutics. Conventional techniques for sequence variant analysis, such as mass spectrometry (MS) and next-generation sequencing (NGS) have limitations on the sample number and turnaround time, thus often are only applied at the final stages of development, where an undesired lead or backup clone could cause a significant delay in project timeline. Here we presented a high-throughput (HT) peptide mapping workflow which can be applied at early stages of cell line selection for testing of a batch of 30-40 clones within 2-week turnaround while reporting valuable information on sequence variants and posttranslational modifications (PTMs). The successful application of this workflow was demonstrated for two mAb programs. Multiple clones were removed from a total of 33 mAb-1 clones using various criteria: nine clones contained at least one1% upregulated unknown peptide ions, 11 clones contained at least eight0.1% upregulated unknowns, and six clones contained upregulated critical PTMs. For mAb-2, light chain (LC) sequence extension of approximately 30 amino acids were detected in 6 out of 36 clones at levels up to 11%. Besides, a Q to H mutation at ~30% was detected in the heavy chain (HC) of a single clone. Q to H mutation has mass change of 9.00 Da and failed to be detected by intact mass analysis. Rapid PTM quantitation also facilitated the selection of clones with desirable quality attributes, such as N-glycan profile. Hence, we demonstrated a risk-reducing strategy where abnormal clones could be detected at earlier stages of cell line selection, which should result in reduced and more predictable timeline of cell line development.

Dialogue summarization extracts useful information from a dialogue. It helps people quickly capture the highlights of a dialogue without going through long and sometimes twisted utterances. For customer service, it saves human resources currently required to write dialogue summaries. A main challenge of dialogue summarization is to design a mechanism to ensure the logic, integrity, and correctness of the summaries. In this paper, we introduce auxiliary key point sequences to solve this problem. A key point sequence describes the logic of the summary. In our training procedure, a key point sequence acts as an auxiliary label. It helps the model learn the logic of the summary. In the prediction procedure, our model predicts the key point sequence first and then uses it to guide the prediction of the summary. Along with the auxiliary key point sequence, we propose a novel Leader-Writer network. The Leader net predicts the key point sequence, and the Writer net predicts the summary based on the decoded key point sequence. The Leader net ensures the summary is logical and integral. The Writer net focuses on generating fluent sentences. We test our model on customer service scenarios. The results show that our model outperforms other models not only on BLEU and ROUGE-L score but also on logic and integrity.

The lined seahorse Hippocampus erectus is an economically important aquaculture species; however, the low survival rate of juvenile seahorses severely restricts their large-scale cultivation. According to previous research, dead juvenile seahorses (4-6 cm) showed symptoms of suspected enteritis, including abdominal depression, raised cloaca, partial hepatic congestion, and yellow sticky liquid filling the intestine. Here, we isolated a Gram-negative bacterium from diseased juvenile seahorses and tentatively named the strain HEL-5. Healthy juvenile seahorses were then challenged with the strain through intraperitoneal injection, with results confirming that HEL-5 was pathogenic for seahorses at a median lethal dose of 5.81 × 105 CFU g-1 fish weight. Based on morphological observations, biochemical characteristics, and sequence analysis of 16S rRNA and housekeeping genes (gyrB, ftsZ, and gapA), we identified HEL-5 as Vibrio tubiashii. Histopathological observations revealed that V. tubiashii was capable of causing lytic necrosis of hepatocytes and forming obvious necrotic foci, and renal pathology was characterized by tubular collapse and tubular epithelial-cell shedding into the lumen accompanied by a large number of inflammatory cells infiltrating the tissues of the intestines and kidneys. Antimicrobial-susceptibility testing showed that the strain was highly sensitive to macrolides, chloramphenicol, sulfonamides, aminoglycosides, and cephalosporins. These findings represent the first report of isolation of V. tubiashii from diseased juvenile seahorses and provide a foundation for the prevention and treatment of vibrio disease in seahorse aquaculture.

To ivestigate the effect of daily walking number on clinical, inflammatory and nutritional indexes for patients with chronic kidney disease.90 non-dialysis patients with chronic kidney disease were selected and randomly divided equally into three groups, for groups A, B and C. 30 patients for group A were asked for the number of daily walk should less than 5 000 steps, while group B patients were asked for 5 000-9 999 steps of walk and group C for more than 10 000 steps. Basic treatments were given for each group of patients and basic information, clinical, inflammatory and nutritional datas of patients were collected.87 patients with chronic kidney disease completed the study, with baseline data between group A, B, C (Walking does not increase the burden of the kidney, but can improve the nutrition and clinical indicators of patients, reduce inflammation.

Introduction The efficacy and safety of vildagliptin alone or with metformin is well established by randomized trials, but it is unknown whether it can be extrapolated to the real-world setting in Chinese patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the effectiveness and safety of vildagliptin add-on to metformin versus dual oral antidiabetes drug (OAD), non-vildagliptin combination therapies in real-world Chinese patients with T2DM. Methods The China Prospective Diabetes Study was a post-marketing, prospective, multicenter, observational, real-world study conducted in 52 centers. Patients inadequately controlled with OAD monotherapy and who initiated vildagliptin add-on to metformin (VM cohort) or two OADs other than vildagliptin (comparator cohort) were included for the present analysis. The composite primary endpoint was glycated hemoglobin (HbA1c)

Objective: To investigate the role of PSMA in the differential diagnosis of adrenocortical carcinoma samples (ACCs) and adrenocortical adenoma samples (ACAs), to validate the prognostic role of PSMA in patients with ACCs, and to explore the possibility that this marker can differentiate localized ACCs from adrenal metastases from other sites.Methods: PSMA protein expression in tissue samples from 50 ACCs, 90 ACAs (including 20 from patients who presented with Cushing's syndrome, 20 aldosterone-producing adenomas and 50 non-functional tumors) and 10 tissues that were metastases from other primary sites was assessed by immunohistochemistry. The clinical and pathological characteristics were compared, the intensity and density were analyzed, and the prognostic role was evaluated.Results: The analysis of clinical and pathological features revealed that the size of ACCs was greater than that of benign tissues and the ACC patients were older than the ACA patients (p < 0.01). The percentage of PSMA-positive vessels, the mean intensity and the degree of staining density were found to be significantly lower in ACAs than in ACCs (p < 0.01). In these 140 samples, 60% of the ACCs were grouped in the positive category. The samples were negative for metastases that were from other primary sites. The ENSAT stage and Ki-67 were correlated with PSMA expression. The survival distribution revealed that high PSMA expression did not show any prognostic relevance in the current ACCs series. Those samples with a score of > 3.5 were 75 times more likely to be malignant (OR = 75). We established a cut-off score of 3.5 (p < 0.05), which had 46% sensitivity and 99% specificity. Paralleling PSMA and Ki-67 maximized the area under the curve, with 72% sensitivity and 100% specificity.Conclusions: Our results strongly confirm that PSMA is helpful for distinguishing benign from malignant tumors and that its high expression levels correlate with a high ENSAT stage and high proliferation. The combination of PSMA and Ki-67 can be particularly useful. Furthermore, PSMA might be a useful tool for the identification of localized adrenal carcinoma and metastatic carcinoma.

ObjectivesThis study aims to summarise the features and trends of thyroid carcinoma in the past two decades in China.Design, setting and participantsClinical data obtained from 10 798 patients treated by thyroidectomy from 1994 to 2015 at the Department of General Surgery of the People’s Liberation Army General Hospital, Beijing, China were retrospectively analysed.Outcome measuresIncidence and histopathological features of thyroid cancer were compared and the risk factors for local lymph node metastasis analysed.ResultsOur data indicated a significant increase in the detection of thyroid cancer (from 16.8% to 69.8%, p<0.01). Among the 5235 thyroid cancer cases, papillary thyroid carcinoma (PTC) was the most common histotype, accounting for 95.1% of all malignancies over the 22-year period. Among the 4979 PTCs, micro-PTCs (mPTC) with the largest diameter ≤10 mm has gradually become the dominant form, and its percentage in PTCs has increased from 13.3% in the biennial period of 1994–1995 to 51.2% in 2010–2011. Furthermore, the size of the tumour has decreased significantly from 2.3±1.1 cm in 1994 to 1.2±0.9 cm in the largest diameter (p1 cm and male gender were the main risk factors for local lymph node metastasis (LNM), whereas patients over 45 years had lower risk.ConclusionsDuring the 22-year period, an increased detection of thyroid cancer, particularly mPTC, was found while the occurrence of LNM decreased. Our results suggest that the current preoperative diagnosis and risk stratification are adequate, supporting the published guidelines for the diagnosis of thyroid cancer.

Selection of high-producing lead and backup cell lines with high-fidelity primary structure is a major goal of cell line development of protein therapeutics. Conventional techniques for sequence variant analysis, such as mass spectrometry (MS) and next-generation sequencing (NGS) have limitations on the sample number and turnaround time, thus often are only applied at the final stages of development, where an undesired lead or backup clone could cause a significant delay in project timeline. Here we presented a high-throughput (HT) peptide mapping workflow which can be applied at early stages of cell line selection for testing of a batch of 30–40 clones within 2-week turnaround while reporting valuable information on sequence variants and posttranslational modifications (PTMs). The successful application of this workflow was demonstrated for two mAb programs. Multiple clones were removed from a total of 33 mAb-1 clones using various criteria: nine clones contained at least one >1% upregulated unknown peptide ions, 11 clones contained at least eight >0.1% upregulated unknowns, and six clones contained upregulated critical PTMs. For mAb-2, light chain (LC) sequence extension of approximately 30 amino acids were detected in 6 out of 36 clones at levels up to 11%. Besides, a Q to H mutation at ~30% was detected in the heavy chain (HC) of a single clone. Q to H mutation has mass change of 9.00 Da and failed to be detected by intact mass analysis. Rapid PTM quantitation also facilitated the selection of clones with desirable quality attributes, such as N-glycan profile. Hence, we demonstrated a risk-reducing strategy where abnormal clones could be detected at earlier stages of cell line selection, which should result in reduced and more predictable timeline of cell line development.

In this paper, we focus on graph representation learning of heterogeneous information network (HIN), in which various types of vertices are connected by various types of relations. Most of the existing methods conducted on HIN revise homogeneous graph embedding models via meta-paths to learn low-dimensional vector space of HIN. In this paper, we propose a novel Heterogeneous Graph Structural Attention Neural Network (HetSANN) to directly encode structural information of HIN without meta-path and achieve more informative representations. With this method, domain experts will not be needed to design meta-path schemes and the heterogeneous information can be processed automatically by our proposed model. Specifically, we implicitly represent heterogeneous information using the following two methods: 1) we model the transformation between heterogeneous vertices through a projection in low-dimensional entity spaces; 2) afterwards, we apply the graph neural network to aggregate multi-relational information of projected neighborhood by means of attention mechanism. We also present three extensions of HetSANN, i.e., voices-sharing product attention for the pairwise relationships in HIN, cycle-consistency loss to retain the transformation between heterogeneous entity spaces, and multi-task learning with full use of information. The experiments conducted on three public datasets demonstrate that our proposed models achieve significant and consistent improvements compared to state-of-the-art solutions.

N-glyco-occupancy and afucoslyation level are two important quality attributes associated with N-glycosylation of therapeutic monoclonal antibodies (mAbs). We report here a fast mass spectrometry-based workflow for quantification of N-glycan site-occupancy and afucoslyation level of mAbs with improved throughput, precision, sensitivity and robustness. This method uses the deglycosylation after the first GlcNAc and inter-chain reduction of the mAbs, followed by liquid chromatography/mass spectrometry (LC-MS) analysis. The entire process can be completed within one hour, which provides a rapid quantitation of N-glyco-occupancy and afucosylation to support high-throughput cell line selection and process development for mAb biopharmaceuticals.

Objective To investigate the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on macrophage polarization under hypoxia. Methods hUC-MSCs were obtained by explants adherent culture and cultured under normoxia (21% O2) and hypoxia (5% O2). The multi-directional differentiation of hUC-MSCs was observed by osteogenic and adipogenic differentiation induction. Live/death staining was performed to detect the cell viability, and ELISA was executed to detect the protein content in supernatant of hUC-MSCs. Transwell chamber was employed to co-culture the hUC-MSCs cultured under normoxia and hypoxia and macrophage (THP-1) stimulated by lipopolysaccharide (IPS), then the polarization of THP-1 was detected by immunofluorescence, and the secretions of inflammatory factor and anti-inflammatory factor of THP-1 were detected by ELISA. Results hUC-MSCs cultured under hypoxia showed the ability of osteogenic and adipogenic multi-directional differentiation. Live/death staining showed the high cell viability of hUC-MSCs cultured under normoxia and hypoxia. The expression levels of prostaglandin E2 (PGE2) and indoleamine 2,3-dioxygenase (IDO) were significantly higher in the hUC-MSCs cultured under hypoxia than in those cultured under normoxia. hUCMSCs cultured under hypoxia promoted the polarization of THP-1 to M2, obviously reduced the expression of TNF-α and IL-1β, and increased the expression of IL-10 significantly. Conclusion hUC-MSCs cultured under hypoxia may promote the polarization of THP-1 to M2 and improve the viability of anti-inflammatory. DOI: 10.11855/j.issn.0577-7402.2016.07.01

Objective To study the therapeutic effect of exosome derived from lipopolysaccharides (LPS) priming mesenchymal stem cells (MSCs) for diabetic wound healing. Methods Human umbilical cord MSCs were treated with LPS (100ng/ml) for 2 days, the supernatant were then collected, and exosomes were harvested by density gradient centrifugation and identified. Diabetic cutaneous wounds were prepared and the animals were divided into the following three groups: control group, untreated MSCs derived exosome (un-exosome) treatment group and LPS primed MSCs derived exosome (LPS-exosome) treatment group. Exosomes (60μg) were injected dispersively into the wound edge daily for 10 days. After treatment, the therapeutic results were evaluated by gross observation of the wounds, the expression levels of inflammation related factors and macrophage subtype markers in the injured sites were detected by qRT-PCR at day 3, 7 and 14 after treatment. Results Compared with control group, the diabetic wound healing was obviously improved in LPS-exosome treatment group after treatment for 7 and 14 days, with faster wound close, depressed expression of pro-inflammatory factors IL -1, IL -12 and M1 macrophage surface marker iNOS, and up-regulation of anti-inflammatory factors IL-10, TGF-βand M2 macrophage surface marker CD163, the differences were significant (P

Objective To compare the effects on type 2 diabetes of mesenchymal stem cells (MSCs) derived from bone marrow and adipose tissue. Methods Thirty type 2 diabetic rat models were established by an eight weeks high-fat diet (HFD) with a low dose streptozotocin (STZ, 25mg/kg), and randomly assigned into three groups (10 each): diabetes group (T2DM), bone marrow MSCs transplantation group (BMSC) and adipose tissue MSCs transplantation group (ADSC). Ten normal rats were set as control. MSCs were isolated from bone marrow or inguinal adipose tissue of normal rats. One week after STZ injection, 3×10 6 MSCs suspended in 1ml PBS were infused into rats via tail vein. The blood glucose was measured every day after MSCs transplantation, the intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) were performed the 7th day after transplantation to evaluate the effects of MSCs on diabetic rats. Pancreatic tissues were collected for insulin/glucagon immunofluorescence staining. Results After MSCs transplantation, the blood glucose decreased gradually and continuously in type 2 diabetic rats, with glucose tolerance and insulin sensitivity improved greatly. The improved insulin sensitivity was further confirmed by a decreased HOMA-IR (homeostasis model of assessment for insulin resistance) index and increased pancreas islet β-cells (P

Objective To evaluate the temporary hypoglycemic effect of adipose mesenchymal stem cells (AD-MSCs) on type 2 diabetic rats, and further discuss the mechanisms of AD-MSCs regulating blood glucose through hepatic glycometabolism. Methods The type 2 diabetic rat model was established by intraperitoneal injection of a single small dose of streptozotocin (STZ, 25mg/kg) after a high-fat diet for 8 weeks. The content of blood glucose was determined by tail vein bleeding at indicated time points (0h, 3h, 6h, 12h, 24h) after infusion of AD-MSCs, concurrently the rats were executed and the liver tissues were collected (diabetes group, n=5, normal group, n=3) for detecting the mRNA and protein expressions of glucokinase (GK), pyruvate kinase (PK) and phosphofructokinase (PFK) (the key enzyme of glycolysis) by real-time qPCR and Western blotting. Results The infusion of AD-MSCs significantly decreased blood glucose in a short period [30.55±1.49mmol/L(0h), 18.90±0.85mmol/ L(3h), 23.70±1.13mmol/L(6h), 21.90±1.00mmol/L(12h), respectively]. PCR results showed that the expressions of GK and PFK increased in the liver tissue of type 2 diabetic rats 3h after AD-MSCs infusion, and the expression of PK increased significantly 6h after AD-MSCs infusion (P

Background: Prolonged gonadal hormone deficiency in patients with idiopathic hypogonadotropic hypogonadism (IHH) may produce adverse effects on the endocrine homeostasis and metabolism. This study aimed to compare basal serum adrenocorticotropic hormone (ACTH) and cortisol levels between male IHH patients and healthy controls. Moreover, this study compared the basal hypothalamic-pituitary-adrenal (HPA) axis in patients with and without nonalcoholic fatty liver disease (NAFLD), and also evaluated the relationship between basal HPA axis and NAFLD in male IHH patients. Methods: This was a retrospective case-control study involving 75 Chinese male IHH patients (mean age 21.4 ± 3.8 years, range 17–30 years) and 135 healthy controls after matching for gender and age. All subjects underwent physical examination and blood testing for serum testosterone, luteinizing hormone, follicle-stimulating hormone, ACTH, and cortisol and biochemical tests. Results: Higher basal serum ACTH levels (8.25 ± 3.78 pmol/L vs. 6.97 ± 2.81 pmol/L) and lower cortisol levels (366.70 ± 142.48 nmol/L vs. 452.82 ± 141.53 nmol/L) were observed in male IHH patients than healthy subjects (all P

Objective To deepen the understanding of 45,X/46,XY mixed gonadal dysgenesis (45,X/46,XY MGD) by summarizing the respective clinical features of patients gathered from China, Brazil, Norway and Denmark suffering from the disease. Methods Comparative analysis was done with the clinical data of 7 patients suffering from 45,X/46,XY MGD diagnosed in the PLA General Hospital of China, and that of other domestic and foreign (Brazil, Norway and Denmark) cases summarized by Peking Union Medical College Hospital. Results Most of the patients of 45,X/46,XY MGD presented the Turner's syndrome-like clinical manifestations such as short stature, multiple naevi on face and lower hair line, etc. Cardiovascular and renal malformation could be found in some patients with 45,X/46,XY MGD. Regarding to the external genitalia, 42.9% (n=27) of the patients were considered to be ambiguous, with a variety of gonadal expression. Laboratory tests demonstrated elevation of follicle-stimulating and/or luteinizing hormone levels with decreased sex hormone levels in most of the patients with 45,X/46,XY MGD. Recombinant human growth hormone (RhGH), testosterone, artificial menstrual cycle and prophylactic gonadectomy were used as primary treatment. There were differences between the domestic and foreign patients in the reason to visit the hospital, and in the age for diagnosis. Chinese patients were always hospitalized for growth retardation, while the foreign patients might go to a doctor for consultation due to various reasons, such as abnormal genitalia, infertility, and fetal chromosomal abnormalities, and many of them might also be diagnosed as 45,X/46,XY MGD in prenatal period or at birth. That was why the average diagnostic age was 4.7 years younger in foreign patients than in Chinese patients. Conclusions No significant difference was found in the clinical characteristics of patients with 45,X/46,XY MGD among different countries and races. But the diagnostic age in Chinese patients is older, and the main reason to consult a doctor is growth retardation. DOI: 10.11855/j.issn.0577-7402.2016.01.14

Local inflammatory responses and alveolar epithelial cells (AECs) apoptosis are both important for the development of the acute lung injury (ALI), a clinically important complication causing high morbidity and mortality, but little is known about the molecular mechanisms underlying the pathogenesis. Herein, we showed for the first time that expression of Metastasis-associated protein 1 (MTA1), a master transcriptional regulator with the ability to regulate divergent cellular pathways by modifying the acetylation status of crucial target genes, was up-regulated in the alveolar cells of the Escherichia coli lipopolysaccharide (LPS)-induced murine ALI model. Inhibition of MTA1 expression by in vivo siRNA treatment exacerbated the pathology of LPS-induced ALI, by selectively promoting the expression of NF-κB-regulated inflammatory cytokines. Moreover, ablation of MTA1 expression promoted the LPS-induced apoptosis in AEC II cells, leaving AEC I cells unaffected. These data collectively underscore an alveolar facet of this important chromatin modifier, which may represent as a novel regulator and a new therapeutic target for the treatment of ALI.

Chemically defined media have been widely used in the biopharmaceutical industry to enhance cell culture productivities and ensure process robustness. These media, which are quite complex, often contain a mixture of many components such as vitamins, amino acids, metals and other chemicals. Some of these components are known to be sensitive to various stress factors including photodegradation. Previous work has shown that small changes in impurity concentrations induced by these potential stresses can have a large impact on the cell culture process including growth and product quality attributes. Furthermore, it has been shown to be difficult to detect these modifications analytically due to the complexity of the cell culture media and the trace level of the degradant products. Here, we describe work performed to identify the specific chemical(s) in photodegraded medium that affect cell culture performance. First, we developed a model system capable of detecting changes in cell culture performance. Second, we used these data and applied an LC-MS analytical technique to characterize the cell culture media and identify degradant products which affect cell culture performance. Riboflavin limitation and N-formylkynurenine (NFK), a tryptophan oxidation catabolite, were identified as chemicals which results in a reduction in cell culture performance.

Background Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a rare condition with untypical subclinical symptoms of Cushing's syndrome (CS). This study aimed to compare the clinical and pathological features of PBMAH with unilateral cortisol-secreting adrenal adenoma (UAA). Methods We prospectively included 46 PBMAH patients and 205 UAA patients from January 2000 to February 2014. Cortisol levels and 24 hours urine free cortisol (UFC) were determined at baseline and during dexamethasone suppression test (DST) using the chemiluminescence method. Computed tomography (CT) examination of the adrenal glands was performed in all patients. For patients treated with adrenalectomy, hematoxylin, and eosin, staining was performed for pathological examination. Results The proportion of patients with autonomous cortisol secretion was significantly higher in PBMAH patients (39.1%) than UAA patients (6.8%). The PBMAH patients showed significantly lower levels of basal cortisol, low dose dexamethasone suppressed cortisol, and high dose dexamethasone suppressed cortisol than the UAA patients (452.6±183.3 vs. 578.7±166.4 nmol/L, P=0.003; 394.5±298.9 vs. 549.2±217.7 nmol/L, P=0.002; 397.3±282.3 vs. 544.3±187.6 nmol/L, P=0.003). Similarly, the PBMAH patients had significantly lower levels of basal 24 hours UFC, low dose dexamethasone suppressed 24 hours UFC, and high dose dexamethasone suppressed 24 hours UFC than the UAA patients (1,144.4±1,048.1 vs. 1,674.9±1,520.4 nmol/24 h, P=0.032; 1,157.3±1,483.5 vs. 1,940.1±1,360.9 nmol/24 h, P=0.003; 1,256.4±1,767.0 vs. 1,969.9±1,361.7 nmol/24 h, P=0.011). Conclusions PBMAH is often associated with atypical CS symptoms. The clinical and imaging features of PBMAH are useful for the differential diagnosis of this disease.

We aimed to investigate the association between excess body mass index (BMI) and papillary thyroid cancer (PTC) in an operative population, and the impact of higher BMI on clinicopathological aggressiveness of PTC.Charts of 10,844 consecutive patients with thyroid nodules undergoing partial or total thyroidectomy between 1993 and 2015 were reviewed. Patients diagnosed with PTC were stratified in 4 groups: BMI < 18.5 (underweight), 18.5 ≤ BMI < 24 (normal-weight), 24 ≤ BMI < 28 (overweight) and BMI ≥ 28(obese). The impacts of high BMI on prevalence and clinicopathological parameters of PTC were retrospectively analyzed in both univariate and multivariate binary logistic regression analysis.For every 5-unit increase in body mass, the odds of risk-adjusted malignance increased by 36.6%. The individuals who were obese and overweight were associated with high risk of thyroid cancer [odds ratio (OR)= 1.982, P < .001; OR= 1.377, P < .001; respectively] compared to normal weight patients, and this positive association was found in both genders. Obesity was independent predictors for tumors larger than 1 cm (OR = 1.562, P < .001) and multifocality (OR = 1.616, P < .001). However, there was no difference in cervical lymph node (LN) metastasis among BMI groups. Crude analysis showed BMI was associated with advanced tumor-node-metastasis (TNM) stage (relative risk, approximately 1.23 per 5 BMI units, P < .001), but this association disappeared after adjusting for confounding factors.Obesity was significantly associated with the risk of PTC in a large, operative population. Higher BMI was significantly associated with larger tumor size and multifocal tumor.

Background and Aim: China PDS aimed to investigate the real-world effectiveness and tolerability of vildagliptin plus metformin (VM) in patients with type 2 diabetes mellitus (T2DM), compared with other oral dual agents (OD). Here, we present the results of prespecified baseline HbA1c subgroups. Materials and Methods: In China PDS, T2DM patients with poor glycemic control by monotherapy were assigned to either VM dual therapy or OD therapy according to local physician’s decision. In this subgroup study, patients were divided into three groups according to their baseline HbA1c levels (≤8%, 8-9%, >9%). The primary outcome was the proportion of patients with HbA1c Results: In total, 7(312 in VM vs. 394 in OD) patients in HbA1c≤8% group, 332 (151 in VM vs. 181 in OD) patients in HbA1c 8-9% group, and 236 (141 in VM vs. 95 in OD) patients in HbA1c>9% group were enrolled. Compared with OD, significantly higher proportion of patients reached primary outcome with VM in HbA1c ≤8% group (57.4% vs. 38.3%, P9% group (48.2% vs. 31.6%, P=0.011). The mean HbA1c changes from baseline to study endpoint in VM and OD were -0.61±0.932 and -0.32±0.874 (P9% group. Compared with OD, VM resulted in less tolerability findings (HbA1c≤8%: 7.7% vs. 16.8%; HbA1c 8-9%: 2.6% vs. 9.4%; HbA1c>9%: 5.0% vs. 16.8%; P Conclusion: In different baseline HbA1c groups, vildagliptin plus metformin dual therapy was associated with better glycemic control and good tolerability. Disclosure D. Hu: None. Y. Han: None. L. Chen: None. H. Jin: None. N. Yang: None. X. Shi: None. Q. Li: None. L. Liang: None. L. Zang: None. M. Liu: None. J. He: None. Y. Mu: None.

Background and Aim: The China PDS aims to investigate the effectiveness and safety of vildagliptin dual therapy in type 2 diabetes mellitus (T2DM) patients. Here, we compared the vildagliptin plus metformin (VM) and insulin secretagogue plus metformin (ISM). Materials and Methods: China PDS was a prospective, 1-year, real-world study conducted in 52 sites in patients with T2DM and inadequately controlled on monotherapy. Eligible patients were assigned either vildagliptin dual therapy or other dual therapy according to local physician’s decision. The proportions of patients with HbA1c Results: In total, 933 patients received vildagliptin dual therapy with 64.7% for VM, while 670 patients received other dual therapy with 48.7% for ISM (Table 1). Compared with ISM (31.6%), VM (50.8%) had higher proportion of patients reaching the primary outcome (P Conclusion: China PDS demonstrates that in a real-life setting, VM was effective in glycemic control and was well tolerated when compared with ISM. Disclosure L. Chen: None. Y. Han: None. D. Hu: None. H. Jin: None. N. Yang: None. X. Shi: None. Q. Li: None. L. Liang: None. L. Zang: None. M. Liu: None. J. He: None. Y. Mu: None.

Background and Aims: This real-world study aimed to assess the effectiveness and safety of vildagliptin plus metformin (VM) vs. other oral dual antidiabetes agents (OD) in type 2 diabetes mellitus (T2DM) patients in China. Materials and Methods: This prospective, 1-year, real-world study was conducted in 52 sites in patients inadequately controlled by monotherapy. Eligible patients were assigned either vildagliptin dual therapy or other OD according to local physician’s decision. The primary outcome was the proportion of patients with HbA1c Results: Totally 604 patients received VM and 670 patients received OD. After propensity score-matched, baseline HbA1c and BMI were similar in both groups. After 12-month treatment, 55.4% patients in VM and 36.2% in OD reached primary outcome (P Conclusion: China PDS demonstrates that in a real-life setting, vildagliptin plus metformin is effective in glycemic control and is well tolerated. Disclosure Y. Han: None. L. Chen: None. D. Hu: None. H. Jin: None. N. Yang: None. X. Shi: None. Q. Li: None. L. Liang: None. L. Zang: None. M. Liu: None. J. He: None. Y. Mu: None.