[Research status of the tumor stroma ratio in prognosis and treatment of pancreatic cancer].

An increasing number of studies suggested that the tumor microenvironment exerts a substantial influence on the pathophysiology of pancreatic cancer. As a crucial component of the tumor microenvironment,the tumor stroma plays a pivotal role in the occurrence,development,and chemotherapy resistance of pancreatic cancer. By serving as a proxy for the interaction between tumor cells and the microenvironment,the tumor stroma ratio(TSR) has emerged as a focal point of investigation in recent years. At present,numerous studies show that a low TSR is a protective factor for the prognosis of resectable pancreatic cancer. Additionally, patients with a low TSR are more suitable for the gemcitabine and albumin-bound paclitaxel chemotherapy regimen. But these researches are not conclusive, and there is still a gap between guiding precision treatment. Further research and exploration are required. Integration of artificial intelligence deep learning models into traditional pathological and imaging assessments facilitates precise evaluation of the TSR. It can also enable stratification and precision treatment of pancreatic cancer patients based on this index.

[circ_BACH2 affects the malignant biological behavior of papillary thyroid cancer by regulating miR-370-3p].

Objective: To investigate the influence of circ_BACH2 on the malignant biological behavior of papillary thyroid cancer and its molecular mechanism. Methods: Cancer tissues and paracancer tissues of 51 patients with papillary thyroid carcinoma from the Fourth Central Hospital of Tianjin between 2017 and 2019 were collected. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_BACH2, miR-370-3p and G protein coupled receptor kinase interacting factor 1 (GIT1) mRNA in tissues and cells; flow cytometry to detect cell apoptosis and cell cycle; plate clone formation experiment to detect the number of cell clones; cell counting kit 8 (CCK-8) to detect cell proliferation; Transwell array to detect cell migration and invasion; western blot to detect protein expressions; dual luciferase report experiment to detect the targeting relationship between circ_BACH2, miR-370-3p and GIT1; the nude mouse tumor formation experiment to detect the effect of circ_BACH2 on tumors in mice. Results: Compared with adjacent tissues, the expressions of circ_BACH2 and GIT1 in papillary thyroid cancer tissues was increased, while the expression of miR-370-3p was decreased. Compared with Nthy-ori3-1 cells, the expressions of circ_BACH2 in papillary thyroid cancer cells TPC-1 and SW579 were increased, the mRNA and protein levels of GIT1 were increased, miR-370-3p expression was decreased. The expression level of GIT1 mRNA was negatively correlated with that of miR-370-3p (r=-0.634), and the expression level of circ_BACH2 was positively correlated with that of GIT1 (r=0.635). The expression level of circ_BACH2 was negatively correlated with that of miR-370-3p (r=-0.394, P＜0.05). Circ_BACH2 and miR-370-3p has a binding site at the 3' UTR of GIT1. After knocking down circ_BACH2, the proportion of G0/G1 cells in papillary thyroid cancer cells TPC-1 and SW579 was increased, the proportion of S-phase cells was decreased and the proportion of G2/M-phase cells did not change significantly. The cell absorbance value was lower than that in si-NC group. The number of cell clone formation was decreased (43±5 vs 100±6, 54±8 vs 100±9); the cell apoptosis rate was increased [(19.60±2.40)% vs (4.30±0.20)%, (18.10±2.10)% vs (5.10±0.23)%]; cell migration number was decreased (61±7 vs 134±15, 58±6 vs 112±11), the invasion number was also decreased (45±6 vs 113±11, 47±4 vs 92±9); the expressions of Snail and Twist1 were decreased, and the expression of E-cadherin was increased (P＜0.000). Inhibition of miR-370-3p expression reversed the effect of circ_BACH2 knockdown on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Overexpression of GIT1 reversed the effects of overexpression of miR-370-3p on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Mice injected with TPC-1 cells stably transfected with sh-circ_BACH2 showed a reduction in tumor volume [(535±91) mm3 vs (857±114) mm3] after 35 days of culture; tumor weight was decreased [(0.62±0.13) mg vs (1.06±0.15) mg, P＜0.05]; the expressions of circ_BACH2 and GIT1 were decreased, and the expression of miR-370-3p was increased in nude mouse tumor tissue. Conclusion: Silencing circ_BACH2 may inhibit the proliferation, migration and invasion of papillary thyroid cancer cells in vitro, promote cell apoptosis, and inhibit tumor growth in vivo through targeted regulation of miR-370-3p/GIT1.

Pattern of relapse following three-field lymphadenectomy of esophageal carcinoma and related factors predictive of recurrence.

PURPOSE: For treatment of esophageal carcinoma, the optimal postoperative radiotherapy target volume after three-field lymph node dissection (3-FLD) had not been determined. We analyzed local recurrence pattern of thoracic esophageal carcinoma and risk factors of lymph node recurrence after 3-FLD without prophylactic radiotherapy. MATERIAL AND METHODS: We reviewed 1282 patients with thoracic esophageal squamous cell carcinoma (ESCC) who were treated with 3-FLD without radiotherapy from 2010 to 2018 and analysed local recurrence patterns and risk factors of lymph node recurrence, in order to provide a reference for determination of the radiotherapy target volume for thoracic ESCC. RESULTS: The lymph node recurrence accounted for 91.0% of treatment failures. The mediastinal, cervical and abdominal lymph node recurrence accounted for 84.92%, 36.07% and 22.30%, respectively (χ2=264.776, P=0.000). The superior, middle and inferior mediastinal lymph node recurrence rates were 67.54%, 27.87% and 0.98%, respectively (χ2=313.600, P=0.000). Cervical metastases were significantly associated with N stage and Preoperative cervical lymph node status. Abdominal metastases were significantly associated with the number of preoperative abdominal lymph node metastases (LNM), tumor location and N stage. CONCLUSIONS: The main pattern of local-regional recurrence might be lymph node metastasis after radical 3-FLD without radiotherapy in esophageal carcinoma. The dangerous lymph node recurrence regions included neck, superior and middle mediastinum. The abdominal areas might be irradiated for lower TEC patients with preoperative abdominal LNM.

[C1q or IgA deposition in glomeruli of children with primary membranous nephropathy].

Objective: To assess the correlation of glomerular C1q or IgA deposition with clinical and pathological features of primary membranous nephropathy (PMN) in children. Methods: The clinical and pathological manifestations including (phospholipase A2 receptor, PLA2R) and IgG subclasses staining in renal biopsies, serum anti-PLA2R antibody and therapeutic response of 33 children diagnosed with PMN in Peking University First Hospital from December 2012 to December 2020 were retrospectively summarized and analyzed. According to results of PLA2R test and findings renal pathological, the patients were divided into PLA2R-related group and non-PLA2R-related group, typical MN group and atypical MN group, C1q deposit group and non-C1q deposit group, as well as IgA deposit group and non-IgA deposit group respectively. T-test, Mann-Whitney U test and Fisher's exact probability test were used for comparison between the groups. Results: Among the 33 children with PMN, there were 20 males and 13 females, of that the age of onset was 11 (8, 13) years, and 32 patients had nephrotic level proteinuria. Renal biopsies were performed at 4.6 (2.1, 11.6) months after onset, and 28 patients (85%) received glucocorticoid or immunosuppressive therapy prior to renal biopsy. There were 20 cases (61%) with PLA2R-related MN and 13 cases (39%) with non-PLA2R-related MN. Compared with the non-PLA2R-related group, the PLA2R-related group had an older age of onset (12 (10, 13) vs. 7 (3, 12) years, Z=-2.52, P=0.011), a lower preceding infection rate (45% (9/20) vs. 11/13, P=0.032) and lower spontaneous remission rate (0 vs. 4/13, P=0.017). Renal PLA2R positivity was significantly associated with predominant or co-deposition of IgG4 (13/17 vs. 5/15, P=0.031) and low albumin levels at renal biopsy ((25±6) vs. (29±7) g/L, t=2.14, P=0.041). There were 12 patients with typical PMN and 21 patients with atypical PMN, and no significant difference in clinical and pathological manifestations was found between these 2 groups (all P>0.05). There were 10 cases (32.3%) with glomerular C1q deposition, and their disease course before renal biopsy was significantly shorter than those without C1q deposition (1.8 (0.8, 5.9) vs. 6.0 (2.5, 22.3) months, Z=-2.27, P=0.023). Twelve cases (36.4%) had glomerular IgA deposition, and their course of disease,clinical and pathological manifestations were not significantly different from those without IgA deposition (all P>0.05). Conclusion: Glomerular C1q or IgA deposition may not affect the clinical manifestations, glomerular PLA2R and IgG subclasses staining pattern, or the response to treatment of PMN in children.

[Tanshinone IIA alleviates lipopolysaccharide-induced renal tubular epithelial cell apoptosis by inhibiting RIP3/FUNDC1 signaling pathway].

OBJECTIVE: To investigate the effect of tanshinone IIA pretreatment on acute renal injury in lipopolysaccharide (LPS)-induced septic mice and explore the possible mechanism. METHODS: Thirty C57BL/6 mice were randomized for treatment with saline (control), 10 mg/kg LPS for 24 h, or 10 mg/kg tanshinone IIA 15 min before LPS treatment. After the treatments, serum creatinine and blood urea nitrogen levels of the mice were detected, renal pathologies were observed with PAS staining, and renal expressions of RIP3, cleaved caspase-3 and p18-FUNDC1 were detected with Western blotting. In the cell experiment, cultured normal human renal tubular epithelial cells (HK-2) were treated with LPS (10 mg/mL), LPS+ siNC, LPS+ siRIP3, or LPS+tanshinone IIA (10 mg/L), and the changes in cell apoptosis were examined with TUNEL staining; Western blotting was performed to detect the expression levels of RIP3, cleaved caspase-3 and p18-FUNDC1, and qRT-PCR was used to detect the expression of RIP3 mRNA. RESULTS: LPS challenge for 24 h significantly increased serum creatinine and blood urea nitrogen levels in the mice, caused obviously damages in the proximal renal tubules, and increased renal expressions of RIP3, cleaved caspase-3 and p18-FUNDC1 proteins. Tanshinone IIA pretreatment significantly improved LPS-induced renal injury in the mice, alleviated apoptosis of the renal cells, and inhibited the expressions of RIP3, cleaved caspase-3 and p18-FUNDC1 proteins. In HK-2 cells, LPS stimulation significantly increased the protein expressions of RIP3, cleaved caspase-3 and p18-FUNDC1 and induced obvious cell apoptosis. Pretreatment with tanshinone IIA strongly inhibited the expression of RIP3 and p18-FUNDC1 and reduced LPS-induced apoptosis of HK-2 cells. CONCLUSION: Tanshinone IIA can reduce LPS-induced apoptosis of renal tubular epithelial cells by inhibiting RIP3/FUNDC1 signal pathway.

Clinical and urodynamic features of secondary tethered cord syndrome: How can they be found longitudinally?

PURPOSE: Secondary tethered cord syndrome (TCS) can be diagnosed with signs of progressive deterioration in urological or neuro-orthopedic systems following primary untethering surgery. Though urological deterioration is a common secondary TCS manifestation, a paucity of diagnostic criteria makes diagnoses challenging. A detailed description of urological deterioration may help diagnose secondary TCS. Thus, the clinical and urodynamic features of the current secondary TCS cases were described. MATERIALS AND METHODS: Fifty-one patients who had undergone reuntethering for secondary TCS experienced improvement or stabilization of progressive problems. Moreover, their clinical and videourodynamic changes were longitudinally described. RESULTS: Loss of postoperative spontaneous voiding was the first urological secondary TCS sign for those who could void spontaneously. Urological problems mostly occurred during elementary school (6-12 years). Major urological presentations were recalcitrant urinary tract infection or urinary incontinence. Follow-up videourodynamic studies revealed typical changes, from acontractile bladder to overactive and low-complaint bladders. While detrusor overactivity did not always occur during the progression, detrusor sphincter dyssynergia was always present in all patients with urological deterioration. All patients postoperatively showed significant urodynamic improvement regardless of preoperative bladder dysfunction. This included four cases of restoring spontaneous voiding. Nine patients experienced newly appearing nonprogressive neuro-orthopedic complications despite their urological improvement. CONCLUSIONS: Urological deterioration should prompt secondary TCS suspicion, and changes in clinical patterns and videourodynamic studies helped diagnose it. However, reuntethering can effectively address urological problems at the cost of some neuro-orthopedic functions in some patients.

High expression level of interleukin-1ß is correlated with poor prognosis and PD-1 expression in patients with lung adenocarcinoma.

PURPOSE: Cytokines are vital pro-inflammatory factors and involved in tumor immune infiltration, and immune infiltration is closely related to PD-1/PD-L1 blockades immunotherapy. This study aims to explore the associations between cytokines and prognosis and also PD-1/PD-L1 expression in early lung adenocarcinoma, which is seldom reported. METHODS: 324 early lung adenocarcinoma patients with prior surgical resection were included and the associations between overall survival time and clinical factors and also cytokines including IL-1ß, IL-6 and TNF-α were analyzed by multivariate cox regression and Kaplan-Meier curve (log-rank test). Resected tumor samples were randomly obtained to detect the PD-1/PD-L1 expression by immunohistochemistry, and Chi square test was used for relations between cytokines and PD-1/PD-L1 expression. RESULTS: In this study group, 26.2% patients showed a high level of IL-1ß and patients with high IL-1ß level showed 19 months shortened mOS than those with normal IL-1 ß expression (mOS: 24.00, 95%CI 11.98-36.02 vs 43.00, 95% CI 37.37-48.63, p = 0.017). Among detected samples, the positive rate of PD-1 was 25.0% (13/52), and the positive rate of PD-L1 was 37.3% (19/52). The positive rate of PD-1 was 36.1% higher in high-IL-1 ß-level group as compared to normal-IL-1ß-level group (50.0% vs 13.9%, p = 0.012). No significant association was found between IL-1 ß and PD-L1 expression. CONCLUSION: High expression level of IL-1ß was correlated with poor prognosis and higher positive rate of PD-1 expression, which gave us insights into biomarkers of survival prediction and immunotherapy in lung adenocarcinoma. Further studies were still needed.

[The value of left ventricular longitudinal strain in the diagnosis and differential diagnosis of myocardial amyloidosis].

Objective: To investigate the characteristics of left ventricular longitudinal strain (LS) in myocardial amyloidosis (CA), hypertrophic cardiomyopathy (HCM) and Fabry disease (FD), as well as the correlation between left ventricular LS and these diseases. Methods: A total of 14 CA patients, 28 HCM patients and 5 FD patients who visited the Department of Cardiology of the First Affiliated Hospital of Suzhou University from June 2017 to November 2019 were retrospectively included. EchoPAC software was used to analyze left ventricular LS, and univariate logistic regression analysis was used to analyze the correlation between echocardiographic LS indexes and various myocardial hypertrophy diseases. The receiver operating characteristic (ROC) curve was used to assess the sensitivity and specificity of echocardiograph LS indexes in the diagnosis of various myocardial hypertrophy diseases. Results: There were significant differences in LS of left ventricular basal segment, inferior wall, posterior wall, lateral wall and posterior septum among the three groups (P<0.05). The absolute value of LS in the left ventricular basal segment decreased in the CA group; the absolute value of LS in left ventricular posterior wall and lateral wall decreased significantly in the FD group (P<0.05); the absolute values of LS in left ventricular basal segment, inferior wall, posterior septum, lateral wall and posterior wall increased significantly in the HCM group (P<0.05). The absolute value of LS < 7.9% in the left ventricular basal segment, or > 13.2% in the inferior wall and > 9.2% in the basal segment, or < 8.3% in the lateral wall and < 7.9% in the posterior wall were the indicators of high sensitivity and specificity in the diagnosis of CA, HCM and FD, respectively. Conclusions: Left ventricular LS was an important index to differentiate myocardial hypertrophy. Combined with their respective clinical characteristics, it could provide certain reference value for clinical practice.

[Analysis of comorbidity and polypharmacy in middle-aged and elderly patients].

Objective: To investigate the characteristics of comorbidities and polypharmacy in middle-aged and elderly patients and assess the potential risk of drug-drug interactions. Methods: Retrospective analysis was carried out among the outpatients aged ≥45 years in the Second Medical Center of the PLA General Hospital from January to December 2016. The patient's comorbidities and polypharmacy were collected from the electronic medical records and annual physical examination reports. The frequency and grade of drug-drug interactions (DDIs) were summarized and ranked by Lexicomp(®) Drug Interactions database. Results: A total of 1 340 patients were enrolled in the study, of which 930 patients (69.40%) used 5 or more drugs, and 660 patients (49.25%) used 10 or more drugs. Multivariate analysis showed that age and the number of comorbidities were independent factors of excessive polypharmacy. The total frequency of detecting clinically significant DDIs (C+D+X) was 857 cases, with 0.8 cases per person by Lexicomp(®) Drug Interactions database. Among them, medications for nervous system accounted for the highest proportion of X-level DDIs. Conclusions: The comorbidities and polypharmacy in middle-aged and elderly patients are very prominent. More attention should be paid to drug interactions, especially in patients with neurological medication.

Cystatin C alleviates H2O2-induced H9c2 cell injury.

OBJECTIVE: At present, the incidence of acute myocardial infarction is increasing year by year, and it has become one of the diseases with the highest mortality rate in humans. Myocardial ischemia-reperfusion injury (MIRI) is a major problem in the treatment of myocardial infarction, but clinically there is no effective way to treat MIRI. This study used Cystatin C (Cys C) to treat cardiomyocytes and rats to investigate the effect of Cys C on MIRI. MATERIALS AND METHODS: We used H2O2 to induce rat cardiomyocytes (H9c2 cells) injury and stimulated the cells with Cys C. Cell counting kit 8 (CCK8) assay was used to determine the optimal concentration of H2O2 and Cys C to stimulate H9c2 cells. We determined the effects of Cys C on oxidative stress and apoptosis levels in H9c2 cells by measuring the activity of dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA), and the expression of apoptosis-related molecules (caspase3/8/9, Bax and Bcl-2). Changes in the activity of the NF-κB signaling pathway in H9c2 cells were also detected. In addition, we made rat MIRI models by ligating the coronary arteries and used Cys C to treat rats to verify the effect of Cys C on MIRI. RESULTS: According to the results of the CCK8 assay, 1000 µM of H2O2 and 15 µM of Cys C were used to stimulate H9c2 cells. Cys C alleviated H2O2-induced H9c2 cell injury, manifested as a decrease in LDH and MDA activity and an increase in SOD activity. Cys C also reduced the apoptosis level in H9c2 cells. The activity of NF-κB signaling pathway in injured H9c2 cells was increased, and stimulation of Cys C could inhibit the NF-κB signaling pathway in H9c2 cells. The application of Cys C in MIRI rats also verified its therapeutic effect on MIRI. CONCLUSIONS: Cys C reduced the oxidative stress and apoptosis levels of cardiomyocytes by inhibiting the activity of NF-κB signaling pathway in cardiomyocytes, thereby reducing cardiomyocyte injury and treating MIRI.

Genomic profiling of the residual disease of advanced high-grade serous ovarian cancer after neoadjuvant chemotherapy.

The goal of our study was to demonstrate the spectrum of genomic alterations present in the residual disease of patients with advanced high-grade serous ovarian cancer (HGSOC) after neoadjuvant chemotherapy (NAC), including matched pretreatment biopsies. During the study period between 2006 and 2017, we collected pre-NAC and post-NAC tumor tissue samples from patients with advanced HGSOC. We performed combined next-generation sequencing and immunohistochemistry to identify actionable targets and pathway activation in post-NAC residual tumors. We also examined whether post-NAC profiling of residual HGSOC identified targetable molecular lesions in the chemotherapy-resistant component of tumors. Among 102 post-NAC samples, 41 (40%) of patients had mutations in homologous recombination repair (HRR) genes (HRR deficiency). Patients with HRR mutations had higher tumor mutation burdens (p < 0.001) and higher alterations in the PI3K-AKT-mTOR pathway (p = 0.004) than patients without these HRR mutations. Nevertheless, we found no significant differences in progression-free survival (p = 0.662) and overall survival (OS; p = 0.828) between the two groups. Most patients (91%) had alterations in at least one of the targetable pathways, and those patients with cell cycle (p = 0.004) and PI3K-AKT-mTOR signaling (p = 0.005) pathway alterations had poorer OS (Bonferroni-corrected threshold = 0.0083, 0.05/6). We showed the genomic landscape of tumor cells remaining in advanced HGSOC after NAC. Once validated, these data can help inform biomarker-driven adjuvant studies in targeting residual tumors to improve the outcomes of patients with advanced HGSOC after NAC.

[Expression of GTF2IP23 in breast cancer and it mediated regulation of GTF2I].

Objective: To investigate the expression level of antisense transcript of pseudogene, general transcription factor Ⅱi psedugen23 (GTF2IP23), in breast cancer and its effect on the host gene general transcription factor Ⅱi (GTF2I). Methods: The expressions of GTF2IP23 and GTF2I were detected in 40 cases of invasive breast cancer tumors and their counterparts by using quantitative real-time polymerase chain reaction (qRT-PCR). The effects of GTF2IP23 on the expression of GTF2I gene and cell proliferation and migration were analyzed by overexpression of GTF2IP23 in breast cancer cells. Results: The expression of GTF2IP23 mRNA in breast cancer tissues was significantly higher than that in adjacent tissues (P<0.001), while the expression of GTF2I mRNA was significantly lower than that in adjacent tissues (P=0.007). The expression of GTF2IP23 was negatively correlated with GTF2I (r=-0.335, P=0.025). The expression of GTF2IP23 in breast cancer cells was significantly higher than in normal breast cells (P<0.01), while GTF2I expression in breast cancer cells was significantly lower than that in normal breast cells (P<0.01). Overexpression of GTF2IP23 in ZR-75-30 cells significantly reduced the expression of GTF2I (P=0.034) and enhanced cell proliferation (P=0.017) and migration (P=0.026) capacity. Conclusions: GTF2IP23 is distinctly upregulated in breast cancer, it inhibits the expression of real gene GTF2I and promotes the proliferation of breast cancer cells.

[Cross-sectional study on clinic behavior and therapeutic status of patients with psoriatic arthritis in multi-center].

OBJECTIVE: To investigate and analyse the features of treatment behavior and standardized therapeutic status of patients with psoriatic arthritis (PsA). METHODS: Out patients diagnosed with PsA in People's Hospital of Peking University, Haidian Hospital, People's Hospital of Jianyang City, Central Hospital of Xinxiang City, Integrated Traditional Chinese and Western Medicine Hospital of Cangzhou City, The Third Hospital of Hebei Medical University from February to June 2018 were enrolled in this investigation. The data including gender, age of onset, course of disease, site of first consulting department, time of the first visit and definite diagnosis, follow-up interval, and use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and biological DMARDs (BioDMARDs) were collected and analyzed. RESULTS: In the cross-sectional study, 133 PsA patients were investigated. The mean age of onset was (47±11) years, the male to female ratio was 1.3:1, and mean disease duration was (16±8) years. Rheumatology department was the most common site of first hospital visit (37.6%, 50/133). Orthopedics department and dermatological department were visited by 24.1% (32/133) and 23.3% (31/133), respectively. Ratio of definite diagnosis was the highest in rheumatology department which was 78% (39/50). The ratio of definite diagnosis of dermatological department was the second highest, which was 19.4% (6/31). The mean definite diagnosed time was 7.6 months since the first visit of PsA patients, and diagnosed time was the shortest in rheumatology department, which had statistical significance. 37% PsA patients were treated appropriately in 3 months, 17.3% PsA patients were treated in 3-6 months and 40.2% patients with PsA visited their doctor more than once a year. 48.8% patients hadn't received standardized treatment before visit, and one third patients never received the therapy of DMARDs. Methotrexate was the most commonly used cDMARDs (58.3%), followed by leflunomide (20.5%) and BioDMARDs (19.7%), and biologicals were tumor necrosis factor antagonists. CONCLUSION: In this multi-center study, the first visit department of PsA patients was widely distributed, and most patients were definitely diagnosed in Rheumatology Department. The time of their first visit and definite diagnosis were delayed due to multi factors. Nearly half of the patients did not receive standardized treatment.

[Study on the application of oral magnesium sulfate solution in split doses as bowel preparation for colonoscopy in elderly patients].

Objective: To evaluate the efficacy and safety of oral magnesium sulfate solution in split doses as bowel preparation in elderly patients undergoing colonoscopy. Methods: A total of 368 elderly patients undergoing colonoscopy were enrolled at PLA General Hospital. The patients were randomly divided into magnesium sulfate solution orally in split doses group (group A, n=178) and single dose group (group B, n=190). Parameters including general information, defecation frequency, Boston bowel preparation score (BBPS), detection rate of lesions and adverse reactions. Results: The frequency of defecations in group A was (7.6±1.4), more than that in group B (6.6±1.5) with statistical significance (P<0.05). The duration of bowel preparation in group A was (128.6±25.3) min, shorter than that of group B (165.4±29.7) min (P<0.05). The BBPS in group A was (8.09±0.67), better than that of group B (7.34±0.58) (P<0.05). The detection rates of intestinal polyps and micropolyps (diameter<0.5 cm) in group A were 73/178 (41.0%) and 51/178 (28.7%) respectively, compared with 58/190 (30.5%) and 37/190 (19.5%) in group B (both P<0.05). In group A, 8 patients reported adverse reactions as abdominal distension and discomfort. One patient had ST-T abnormality of electrocardiogram (ECG). No nausea or vomiting occurred, yet 2 cases needed enema for inadequate bowel preparation. Twenty-one cases in group B reported adverse events including 7 with nausea and vomiting. There were 13 patients treated with enema. Abnormal ECG was found in 4 patients in group B. The satisfaction rate of group A was 97.8%, higher than that of group B (91.6%) (P<0.05). Conclusions: The effect of bowel preparation of elderly patients with magnesium sulfate solution in split dose has a better tolerance, good cleaning effect and low incidence of adverse reactions. It is an ideal choice for the elderly to prepare colonoscopy.

[Using of ¹8F-FDG to evaluate the effect of traumatic olfactory nerve injury on drug delivery through the nasal-brain pathway: a PET-MRI pilot study].

Objective:This study evaluated the effect of traumatic olfactory nerve injury on drug delivery through the nasal-brain pathway via the instillation of ¹8F-FDG at the olfactory cleft. Method:Seven healthy volunteers and 5 patients with traumatic dysosmia were enrolled in the study. Subjects were all instilled with ¹8F-FDG on each side of the olfactory cleft under endoscopy. After 12 hours, a PET/MR scan was performed to track the metabolism pathway of ¹8F-FDG. Then, we compared the diameter of the olfactory bulb and the olfactory bulb intake between normal volunteers and patients with traumatic olfactory disorders. Result:In healthy volunteers, there was a significant difference in ¹8F-FDG uptake between the regions of interest in which ¹8F-FDG was or was not in contact with the cribriform plate（P=0.012 7）; this difference also existed in patients with traumatic olfactory disorders（P=0.038 1）. Patients with traumatic olfactory disorders did not exhibit significant differences in ¹8F-FDG uptake in the region of interest compared with healthy volunteers（P=0.937 2）. Conclusion:The olfactory bulb is obviously atrophied in patients with traumatic olfactory dysfunction, and the uptake of ¹8F-FDG in the olfactory bulb region of interest is also reduced. The administration of ¹8F-FDG via olfactory fissure area can enter olfactory bulb and parafrontal tissues through the nasal brain pathway,¹8F-FDG can enter the central nervous system through the nasal-brain pathway, which is not affected by olfactory nerve transection injury.

[MicroPET-CT study of the association between odor stimulation and olfactory related brain activation in rats].

Objective: Using (18)F-fluorodeoxyglucose ((18)F-FDG) and microPET-CT to test the feasibility of (18)F-FDG PET-CT for validation of olfactory function of rats with standard phenethyl alcohol (PEA) and isovaleric acid (IVA) odors stimulation. To verify the possibility of (18)F-FDG PET-CT as a new objective examination method for olfactory function. Methods: Six healthy Sprague-Dawley (SD) male rats were selected with a weight of 250-300 g. First of all, buried food pellet test (BFT) was used to confirm the normal olfactory function of rats. Then in the next 3 days, after the intravenous injection of (18)F-FDG (18 MBq/100 g), awaken rats were placed in a ventilated plexiglas cage for 30 min. Subsequently, pure air (the first day), PEA (the second day) and IVA (the third day) were delivered. After odor stimulation for 30 min, rats were performed by a static PET-CT under anesthesia. Images reconstructed were assessed by SPM method and analyzed by VBM method. Data was analysied by paired t test. Results: Activation regions of rat's brain after PEA stimulation included bed nucleus and insula. Activation regions of rat's brain after IVA stimulation included olfactory bulb, anterior olfactory nucleus, amygdala, entorhinal cortex, olfactory cortex, piriform cortex, insula, prefrontal cortex, cingulate cortex and bed nucleus (P<0.005, Ke>20 voxels). Conclusions: Through microPET-CT, we can observe that olfactory stimulation with different odors can induce metabolic activation in different regions of rat's brain, which was in concordance with olfactory regions. The olfactory related brain regions of rats have strong responses to odor stimulation of IVA.

Cimetropium bromide does not improve polyp and adenoma detection during colonoscope withdrawal: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Endoscopic inspection of colonic mucosa is disturbed by colonic folds and peristalsis, which may result in missed polyps. Cimetropium bromide, an antispasmodic agent, inhibits peristalsis and colonic spasms, which may improve polyp detection. The purpose of this randomized, double-blind, placebo-controlled study was to investigate whether cimetropium bromide could improve polyp and adenoma detection in the colorectum and right colon. METHODS: Patients undergoing screening or diagnostic colonoscopy were randomized to receive intravenous cimetropium bromide (5 mg) or placebo after cecal intubation. The primary outcomes were the number of polyps per patient (PPP) and adenomas per patient (APP); secondary outcomes were the polyp detection rate (PDR), adenoma detection rate (ADR), and advanced neoplasm detection rate (ANDR). RESULTS: A total of 181 patients were analyzed; 91 patients received cimetropium bromide and 90 patients received placebo. Cimetropium bromide and placebo groups did not significantly differ in the PPP and APP for the colorectum (1.38 ±â€Š1.58 vs 1.69 ±â€Š2.28, P = .298; 0.96 ±â€Š1.27 vs 1.11 ±â€Š1.89, P = .517, respectively) and right colon (0.70 ±â€Š0.95 vs 0.78 ±â€Š1.21, P = .645; 0.47 ±â€Š0.81 vs 0.51 ±â€Š0.81, P = .757, respectively). Two groups also did not significantly differ in the PDR, ADR, and ANDR for the colorectum and right colon. Furthermore, there were no difference between groups in the PPP, APP, PDR, ADR, and ADNR in a sub-analysis of expert and non-expert endoscopists. CONCLUSIONS: Cimetropium bromide did not improve polyp and adenoma detection in the colorectum and right colon during colonoscope withdrawal, regardless of the expertness of the endoscopist. However, its use may be helpful in patients with active peristalsis or for beginning endoscopists during standard colonoscopy without a transparent cap.

Magnetic resonance imaging of tumor angiogenesis using dual-targeting RGD10-NGR9 ultrasmall superparamagnetic iron oxide nanoparticles.

OBJECTIVE: Using RGD10-NGR9 dual-targeting superparamagnetic iron oxide nanoparticles to evaluate their potential value in tumor angiogenesis magnetic resonance imaging (MRI) and the biodistribution in vitro and in vivo. MATERIALS AND METHODS: Dual-targeting RGD10-NGR9 ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles were designed and synthesized in our previous study. In vitro, prussian blue staining and phenanthroline colorimetry were conducted to evaluate binding affinity and adsorption of dual-targeting USPIO nanoparticles to αvß3-integrin/APN positive cells. In vivo, a xenograft mouse tumor model was used to evaluate the potential of the dual-targeting nanoparticles as an MRI contrast agent. After intravenous injection, the contrast-to-noise ratio (CNR) values of MR images obtained were calculated at predetermined time-points. The iron level was detected to access the biodistribution and plasma half-time. RESULTS: In vitro, dual-targeting USPIO nanoparticles bound to proliferating human umbilical vein endothelia cells with high specificity. In vivo, contrast MRI of xenograft mice using dual-targeting nanoparticles demonstrated a significant decrease in signal intensity and a greater increase in CNR than standard MRI and facilitated the imaging of tumor angiogenesis in T2*WI. In terms of biodistribution, dual-targeting USPIO nanoparticles increased to 1.83 times in tumor lesions as compared to the control. And the plasma half-time was about 6.2 h. CONCLUSION: A novel RGD10-NGR9 dual-targeting USPIO has a great potential value as a contrast agent for the identification of tumor angiogenesis on MRI, according to the high specific affinity in vitro and in vivo.

Predictive factors to diagnosis undifferentiated early gastric cancer after endoscopic submucosal dissection.

It is difficult to predict precisely whether the lesion corresponds to endoscopic resection indication. Furthermore, discrepancy may occur between endoscopic forceps biopsy (EFB) and finally resected specimen, which may be diagnosed as undifferentiated cancer and additional surgery may be required. Our study aimed to evaluate predictive factors to diagnose undifferentiated cancer after endoscopic submucosal dissection (ESD).Among the 532 patients diagnosed by ESD between January 2009 and December 2015, 557 early gastric cancer (EGC) cases were studied. Factors predicting diagnosis of undifferentiated cancer and clinical outcomes of the lesions were retrospectively analyzed.Among the 557 cases with EGC, 535 (96.1%) were diagnosed as differentiated cancer and 22 (3.9%) as the undifferentiated type with ESD. Tumor size was larger (mean size 20.67 vs 13.59 mm, P < .001) and age was lower (60.24 vs 64.50 years, P < .001) in the group with undifferentiated cancer. En bloc resection rate was similar (95.5% vs 95.9%, P = .886), but the complete resection rate was lower (72.7% vs 92.4%, P < .001) in the group with undifferentiated cancer. On multivariate analysis, tumor size ≥10 mm (OR = 11.340, P = .032), age <55 years (OR = 5.972, P = .004), surface redness (OR = 11.562, P = .024), and whitish discoloration (OR = 35.368, P < .001) were predominantly associated with undifferentiated cancer.Young age (<55 years), large tumor size (≥10 mm), surface redness, and whitish discoloration are predictors of undifferentiated cancer, and lesions with these features detected need to be treated cautiously.

[Clinical phenotypes of hepatocyte nuclear factor 1 homeobox b-associated disease].

Objective: Hepatocyte nuclear factor 1 homeobox b (HNF1B) -associated disease is an autosomal dominant inherited disorder with a variable, multi-systemic phenotype. In China, five adult probands and one child proband with HNF1B-associated disease had been reported, whereas few fetuses are described. The aims of this retrospective study were to understand about the clinical manifestations of HNF1B-associated disease and to further improve the recognition of this disorder. Method: Four patients (3 males, 1 female) and three fetuses with HNF1B mutations were included in this study. They were admitted to our hospital from January 2013 to March 2017. HNF1B mutations were detected using targeted next generation sequencing and quantitative real-time PCR or Sanger sequencing. HNF1B heterozygous deletion of exons 1-9 was found in 4 patients and 2 fetuses, and HNF1B heterozygous missense mutation in 1 fetus. These two mutations had been reported. Two patients and 1 fetus had de novo mutations. Results of renal ultrasonography with or without magnetic resonance imaging, biochemical investigations, urine routine examination and other necessary investigations in 7 cases were analyzed. Result: Three patients were Han Chinese ethnicity, and one patient was Mongolian. In patients 1 and 4, abnormal fetal kidneys were discovered by routine ultrasonography, and the age at first feature identified in Patients 2 and 3 were 13 years and 28 years. Patient 3 had normal renal function and the remainder had reduced glomerular filtration rate. In addition, patient 4 presented with nephrotic syndrome and glycosuria, patient 2 with early onset hyperparathyroidism and renal osteodystrophy, and patient 3 with diabetes mellitus. All the 4 patients had renal structural abnormalities including bilateral multiple renal cysts, dysplasia and hyperechogenic kidneys. Only patient 3 had a positive family history of renal diseases, the remainder had a negative family history of renal diseases. In 3 fetuses, prenatal ultrasound anomalies were detected during the second trimester. These 3 fetuses had hyperechogenic kidneys with or without renal cysts. Polyhydramnios was detected in only one of the 3 fetuses. Two of the 3 fetuses had a positive family history of renal diseases. Conclusion: Clinical phenotypes of HNF1B-related disease are heterogeneous, renal malformations clearly appear to be the most common manifestation, multiple renal cysts are characteristic, and patients can progress to impaired kidney function during childhood; HNF1B mutation is a differential diagnosis of fetal hyperechogenic kidneys or multiple renal cysts.