Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR+ ILC3 / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of composite Sophora colon-soluble Capsule (CSCC) on gut microbiota-mediated short-chain fatty acids (SCFAs) production and downstream group 3 innate lymphoid cells (ILC3s) of dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice model.@*METHODS@#The main components of CSCC were analyzed by hybrid ultra-high-performance liquid chromatography ion mobility spectromety quadrupole time-of-flight mass spectrometry (UHPLC-IM-QTOF/MS). Twenty-four male BALB/c mice were randomly divided into 4 groups (n=6) by using a computer algorithm-generated random digital, including control, DSS model, mesalazine, and CSCC groups. A DSS-induced colitis mice model was established to determine the effects of CSCC by recording colonic weight, colonic length, index of colonic weight, and histological colonic score. The variations in ILC3s were assessed by immunofluorescence and flow cytometry. The results of gut microbiota and SCFAs were acquired by 16s rDNA and gas chromatography-mass spectrometry (GC-MS) analysis. The expression levels of NCR+ ILC3-, CCR6+ Nkp46- (Lti) ILC3-, and ILCreg-specific markers were detected by enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction and Western blot, respectively.@*RESULTS@#The main components of CSCC were matrine, ammothamnine, Sophora flavescens neoalcohol J, and Sophora oxytol U. After 7 days of treatment, CSCC significantly alleviated colitis by promoting the reproduction of intestinal probiotics manifested as upregulation of the abundance of Bacteroidetes species and specifically the Bacteroidales_S24-7 genus (P<0.05). Among the SCFAs, the content of butyric acid increased the most after CSCC treatment. Meanwhile, compared with the model group, Lti ILC3s and its biomarkers were significantly downregulated and NCR+ ILC3s were significantly elevated in the CSCC group (P<0.01). Further experiments revealed that ILC3s were differentiated from Lti ILC3s to NCR+ ILC3s, resulting in interleukin-22 production which regulates gut epithelial barrier function.@*CONCLUSION@#CSCC may exert a therapeutic effect on UC by improving the gut microbiota, promoting metabolite butyric acid production, and managing the ratio between NCR+ ILC3s and Lti ILC3s.

Development and Application of Pharmacy Relevant Popular-science Video Courseware in Our Hospital / 中国药房

OBJECTIVE：To provide reference for the development and application of pharmacy popular-science video courseware. METHODS ：Combined with the problems existing in the medication of patients with chronic diseases at the present stage and the key points of medication management ，the theme ，content and form of this popular-science were determined ；the video shooting and production were completed ，and publicity and promotion were carried out. Questionnaire survey was conducted ， and the reception of pharmacy outpatient service in our hospital was counted ；the broadcasting effects of popular-science video were analyzed. RESULTS ：The theme of popular-science video courseware was determined to be self-medication management of patients with chronic diseases at home assisted by pharmacists. Combined with the “five moments ”of medication safety proposed by WHO ， the content included six units as knowing pharmacists ，understanding drugs ，taking drugs ，adding drugs ，checking drugs ，and discontinuing drugs. PPT video was used to explain the contents of each unit ，with an average duration of about 25 min. After the first unit was launched ，a total of 39 327 hits were received within two months. A total of 100 questionnaires were sent out ，97 questionnaires were collected （recovery rate of 97.0％）. Among them ，80（82.5％）thought it helpful to watch the video. Within two months after the broadcast of unit 1 video，the reception volume of pharmacy outpatient department of our hospital （1 160 person times ）increased by 104.2％ compared with the two months in the same period last year （568 person times ），and increased by 18.7％ compared with the two months before the broadcast （977 person times ）；99 patients came to the pharmacy outpatient department to consult because of watching the video ，and 55.6％ of the registered patients consulted the demonstration of video courseware and repeatedly mentioned related problems. CONCLUSIONS ：It is a beneficial exploration for pharmacists to develop popular-science video courseware with the theme of safe and rational drug use. It is the direction for future work to increase the scope of disease types ，target different groups of people or focus on different types of drugs and promot them in various forms.

Transcatheter arterial chemoembolization followed by surgical resection for hepatocellular carcinoma: a focus on its controversies and screening of patients most likely to benefit / 中华医学杂志(英文版)

Surgical resection (SR) is recommended as a radical procedure in the treatment of hepatocellular carcinoma (HCC). However, postoperative recurrence negatively affects the long-term efficacy of SR, and preoperative adjuvant therapy has therefore become a research hotspot. Some clinicians adopt transcatheter arterial chemoembolization (TACE) as a preoperative adjuvant therapy in patients undergoing SR to increase the resection rate, reduce tumor recurrence, and improve the prognosis. However, the findings of the most relevant studies remain controversial. Some studies have confirmed that preoperative TACE cannot improve the long-term survival rate of patients with HCC and might even negatively affect the resection rate. Which factors influence the efficacy of preoperative TACE combined with SR is a topic worthy of investigation. In this review, existing clinical studies were analyzed with a particular focus on several topics: screening of the subgroups of patients most likely to benefit from preoperative TACE, exploration of the optimal treatment regimen of preoperative TACE, and determination of the extent of tumor necrosis as the deciding prognostic factor.

Effects of scaffold microstructure and mechanical properties on regeneration of tubular dentin / 华西口腔医学杂志

Tubular dentin is of great significance in the process of tooth tissue and tooth regeneration, because it is not only the structural feature of primary dentin, but also can affect the tooth sensory function, affect the differentiation of dental pulp cells and provide strong mechanical support for teeth. Scaffold is one of the three elements of tissue engineering dentin regeneration. Most experiments on dentin regeneration involve the study of the microstructure and mechanical properties of the scaffold. The microstructure and mechanical characteristics of scaffold materials have important effects on the differentiation and adhesion of odontoblast, it can directly affect the tissue structure of regenerated dentin.

Alterations in the transmural gradient of ventricular repolarization with different pacing sites in normal and heart failure canines / 生理学报

Alterations of the transmural gradient of repolarization may contribute to the increase of transmural dispersion of repolarization and ventricular arrhythmias. The transmural gradient of repolarization may play an important role in sudden death associated with left ventricular epicardial pacing. To investigate the changes of transmural gradient dispersion of ventricular repolarization with different pacing sites in heart failure (HF) canines, 8 mongrel dogs were randomized into healthy group and HF group (n = 4). We mapped the monophasic action potential duration (MAPD) in the subendocardial, subepicardial and mid-myocardial layers of the left ventricle (LV) in canines of healthy and HF groups during right atrium (RA) pacing, right ventricular apical endocardial (RV) pacing, left ventricular lateral epicardial (LV) pacing and biventricular (Biv) pacing respectively. The results showed that in the healthy group, the MAPDs were significantly different among the three layers during RA pacing (all P 0.05). In the HF group, the MAPDs in all three layers were prolonged compared with those in the same locations in the healthy group (all P 0.05). By MAP recording with our new mapping electrode, we found a transmural MAPD gradient among the three layers of the LV during RA pacing and the gradient between the subendocardial and subepicardial layers vanished during RV, LV or Biv pacing in healthy dogs. In contrast, there was no transmural MAPD gradient during RA, RV, LV or Biv pacing in HF dogs. These results are helpful to understand the mechanism of ventricular arrhythmias in patients with HF.

Primitive Neuroectodermal Tumor as the Second Malignant Neoplasm in a Long-Term Survivor Child of Acute Lymphoblastic Leukemia: A Case Report / 中国医学科学杂志(英文版)

Acute lymphoblastic leukemia (ALL) is a common pediatric cancer. The second malignant neoplasms (SMNs) in long-term survivors of pediatric ALL are relatively rare. Herein we report a 10-year-old girl who was diagnosed as primitive neuroectodermal tumor (PNET) 5 years after the initial diagnosis of ALL with radiotherapy-free treatment. PNET is an exceedingly rare neoplasm in SMNs of survivors of childhood ALL. It is predisposed to be misdiagnosed and the pathogenesis is unclear. The outcome is poor. Long-term follow-up is necessary for the survival children of ALL.

Value of positive lymph node metastasis region in predicting postoperative recurrence for patients with esophageal squamous cell carcinoma after two-field esophagectomy / 中华放射肿瘤学杂志

Objective The recurrence rate is alarmingly high in patients with positive lymph node metastasis (pN+) esophageal squamous cell carcinoma (ESCC) after two-field surgery.This study aims to retrospectively evaluate the value of pN+ region in predicting postoperative recurrence in patients with pN+ thoracic ESCC after two-field radical esophagectomy.Methods A total of 329 patients with pN+ thoracic ESCC after two-field R0 esophagectomy were enrolled in this study.After surgery,pN+ region was located at the upper abdomen in 116 patients,mediastinum in 119 and upper abdomen plus mediastinum in 94,respectively.The enumeration data were analyzed by chi-square test.Logistic multivariate regression analysis was performed to evaluate the risk factors of postoperative recurrence.Cumulative recurrence rate was statistically analyzed by using Kaplan-Meier method,Log-rank test and Cox model multivariate analysis.Results The overall recurrence rate was 72.4％ (239/329).The overall locoregional recurrence (LR) rate was 58.1％(139/329) including 14.6％ in the neck,42.9％ in the mediastinum and 10.0％ in the upper abdomen.Multivariate logistic and Cox regression analyses demonstrated that pN + region was the only independent factor affecting the overall recurrence and LR rates (both P＜0.05).The overall recurrence and LR rates were 57.8％ and 44.0％ for patients with pN+ region in the upper abdomen,77.3％ and 62.3％ for those with pN+ region in the mediastinum and 85.1％ and 72.3％ for their counterparts with pN+ region in the upper abdomen and mediastinum,respectively.Additionally pN+ region was also the independent factor of the recurrence in the mediastinum or upper abdomen (both P＜0.05) rather than the neck (P＞0.05).The recurrence rates in the mediastimun and upper abomen were 27.6％ and 12.9％ for patients with pN+ region in upper abdomen,47.1％ and 4.2％ for those with pN+ region in the mediastinum,and 56.4％ and 13.8％ for patients with pN+ region in the upper-abdomen plus mediastinum,respectively.Conclusions LR is the main cause of failure in patients with pN + thoracic ESCC after two-field R0 surgery.pN + region can be utilized to predict the overall recurrence and LR rates,especially for patients with postoperative recurrence in the the mediastinum and upper abdomen.The findings in this investigation contribute to the design of the target volume of postoperative adjuvant radiotherapy.

Analysis of risk factors of recurrence of pT1-3N0M0 esophageal squamous cell carcinoma after two-field esophagectomy / 中华放射肿瘤学杂志

Objective To retrospectively analyze the factors of postoperative recurrence of stage pT1-3NoM0 esophageal squamous cell carcinoma.Methods A total of 488 patients who underwent two-field R0 esophagectomy,pathologically classified as stage pT1-3N0M0,without adjuvant radiotherapy and/or chemotherapy before or after surgery and postoperative survival time ≥ 3 months were enrolled in this study.Multivariate analysis was performed by using Cox model.Results At the end of follow-up,the overall recurrence rate was 36.9％(180/488);the local recurrence rate was 21.5％ (105/488),the distant metastasis rate was 6.8％ (33/488) and the local recurrence rate complicated with the distant metastasis rate was 8.6％ (42/488).Cox multivariate analysis demonstrated that tumor site and pT staging were the factors affecting the overall/local recurrence rate and distant metastasis.The recurrence rate in patients with the upper esophageal squamous cell carcinoma and stage pT3 was the highest,followed by those with the middle esophageal squamous cell carcinoma or stage pT2 and the lowest recurrence rate was observed in patients with the lower esophageal squamous cell carcinoma or stage pT1.Conclusions Tumor site and pT staging are the pivotal factors for postoperative recurrence of stage pT1-3 NoM0 esophageal squamous cell carcinoma after two-field R0 esophagectomy,which contributes to offer guidance to the selection of indications for postoperative adjuvant radiotherapy.

Impact factor of postoperative prognosis of esophageal cancer patients with stage pT2N0~1M0 / 中华肿瘤杂志

Objective@#To investigate the postoperative prognosis and the related factors of patients with stage pT2N0-1M0 of thoracic esophageal carcinoma(EC).@*Methods@#From 2008 to 2011, clinical data of 275 cases with stage pT2N0-1M0 of thoracic EC treated by esophagectomy were enrolled. These cases includ 180 male and 95 female. Among them, 32 cases were upper thoracic EC, 186 cases were middle thoracic EC and 57 cases were lower thoracic EC. Alternatively, 205 cases were stage pN0, 70 cases were stage pN1. 155 cases received esophagectomy alone and 120 cases received esophagectomy and postoperative adjuvant therapy.@*Results@#The end of follow-up time was on September 30th, 2014. The 1-, 3-, 5-year overall survival (OS) rates were 91.6%, 70.2% and 63.7%, respectively. The 1- 3-, 5-year progression-free survival (PFS) rates were 83.9%, 64.0% and 60.0%, respectively. The result of univariate analysis showed that the depth of tumor invasion, pathological type, pN stage and number of metastatic lymph nodes were significantly associated with OS (all of P<0.05). Moreover, the gender, the depth of tumor invasion, pathological type, pN stage and number of metastatic lymph nodes were significantly associated with PFS (all of P<0.05). Cox multivariate analysis showed that the location of primary tumor and pN stage were the independent factors of OS (both P<0.05). The gender, pN stage and postoperative adjuvant therapy were the independent factors of PFS (all of P<0.05).@*Conclusion@#Among the patients with pT2N0~1M0 stage of thoracic EC, patients with upper thoracic EC or pN1 stage have poorer postoperative prognosis compared with others, and postoperative adjuvant treatment is recommended for these patients.

Survival and the value of adjuvant chemotherapy in esophageal squamous cell carcinoma patients with lymphatic metastasis / 中华肿瘤杂志

Objective@#To investigate the prognosis and the value of adjuvant chemotherapy in esophageal squamous cell carcinoma (ESCC) patients with lymphatic metastasis.@*Methods@#From Jan, 2008 to Dec, 2011, 329 patients with ESCC who underwent two-field radical resection(R0), had lymphatic metastasis and survived over three months were enrolled in this study. There were 246 males and 83 females. The median age was 61 years-old. Site of lesion was located at upper- in 23, middle- in 226 and lower-thoracic segment in 80 patients. There were 114 patients treated with surgery alone and 215 patients with adjuvant chemotherapy. Prognostic factors including adjuvant chemotherapy were assessed in ESCC patients with lymphatic metastasis.@*Results@#In 329 ESCC patients with lymphatic metastasis, the 1-, 3-, 5-years overall survival (OS) rate and progress-free survival (PFS) rate were 74.5%, 31.7%, 24.5%, and 55.1%, 27.8%, 24.2%, respectively. Median OS and PFS were 22 and 15 months, respectively. Multivariate analysis showed that, site of lesion and disease stage were independent factors for OS and PFS (P<0.05). Adjuvant chemotherapy was also an independent prognostic factor for OS (P<0.05). Subgroup analysis showed that adjuvant chemotherapy could improve OS mainly in patients of males, ages≤60, tumor length <6 cm, well- or mediated differentiated squamous cell carcinoma, stage pT3, pN2 and ⅢB (P<0.05).@*Conclusions@#ESCC patients with lymphatic metastasis had poor prognosis. Site of lesion and disease stage were important prognositic factors for survival. Adjuvant chemotherapy could improve survival in specific patients.

Patterns of recurrence in patients with stage Ⅲ thoracic esophageal squamous cell carcinoma after radical resection / 中华肿瘤杂志

Objective@#To evaluate the patterns of recurrence and their value on target delineation for postoperative radiotherapy (RT) in patients with stage Ⅲ thoracic esophageal squamous cell carcinoma (ESCC) after esophagectomy.@*Methods@#395 patients (302 male and 93 female) of stage Ⅲ thoracic ESCC after radical resection were enrolled in this study. Among them, 375 patients were treated with two-field and other 20 with three-field esopahgectomy. 97 patients were treated with surgery alone, 212 with adjuvant postoperative chemotherapy (CT), 56 with radiotherapy (RT) and 30 with CT plus RT. Diagnosis of recurrence was primarily based on CT images, some of which were biopsy confirmed. The location and patterns of tumor recurrence were analyzed.@*Results@#The overall failure rates was 75.7% (299/395). Locoregional recurrence (LR) was found in 48.4% of the patients, distant metastasis (DM) in 16.2%, and LR plus DM in 4.3%. There were 208 patients occurred with LR, 26.9% (56) recurred in supraclavicular/neck (51 in supraclavicular), 69.7% (145) in mediastinum (88.7% in upper-mediastinum), and 19.7% (41) in upper abdomen (38 in para-aortic lymph node). Chi-square test and logistic multivariate regression analysis showed that TNM stage and adjuvant therapy were significantly associated with LR (P<0.05). Postoperative RT reduced LR (mainly LR in mediastinum), but postoperative CT did not decrease LR.@*Conclusions@#The recurrence rate is very high in stage Ⅲ thoracic ESCC patients, LR is the main pattern of failure. TNM stage is one of the most important factors for LR. Postoperative radiotherapy can reduce LR but postoperative chemotherapy does not decrease LR. Upper-mediastinum is the most common site of recurrence, followed by supraclavicular and para-aortic regions; these areas should be considered as the key target of postoperative radiotherapy.

Value of postoperative adjuvant threapy for patients of stage Ⅲ thoracic esophageal squamous cell carcinoma after radical resection / 中华放射肿瘤学杂志

Objective To retrospectively analyze the value of postoperative adjuvant therapy in the treatment of stageⅢthoracic esophageal squamous cell carcinoma ( ESCC) . Methods From 2008 to 2011, a total of 395 patients with stageⅢthoracic ESCC undergoing radical resection were enrolled as subjects. In those patients.97 received surgery alone (S).212 postoperative adjuvant chemotherapy (POCT),and 86 postoperative radiotherapy (PORT).Comparison of categorical data was made by chi?square test. The survival rates were calculated by the Kaplan?Meier method. The log?rank test was used for between?group comparison and univariate analysis. Results All patients were followed up for at least 3 years.125 cases were followed up for at least 5 years. The 5?year overall survival ( OS) rates in patients treated with S,POCT and PORT were 17. 1%,29. 2% and 36. 4%,respectively (P=0. 000).POCT and PORT could mainly increased OS in patients of males.upper?and middle?segment,severe ahhesion at surgery.well?or middle?differentiation,stageⅢa andⅢb(P=0. 000?0. 049);whenever ages.tumor lesion,two?/three field esophagectomy.and the number of removal lymph nodes. PORT could improved OS also (P=0. 001?0. 047).POCT could also improve OS in patients of ages≤60, tumor lesion<6 cm and removal lymph nodes<10 ( P=0. 002?0. 049 ) . The 5?year progression?free survival (PFS) were 19. 0% with S,28. 8% with POCT,36. 4% with PORT,respectively (P=0. 012).PORT could improve PFS (P=0. 012);especially for patients of males,ages ≤60,upper?and middle segment ESCC,tumor lesion ≥6 cm,severe ahhesion at surgery,removal lymph node<10 and ≥10,well or middle differentiation,stageⅢa andⅢb(P=0. 001?0. 042).But POCT could not increased PFS (P=0. 119) . Conclusions In the treatment of patients with stage Ⅲ thoracic ESCC undergoing radical resection,both POCT and PORT can improve the OS rate, particularly in patients with stage Ⅲa or Ⅲb middle and upper thoracic ESCC, severe adhesion formation during surgery. and moderately or well differentiated squamous cell carcinoma. The DFS rate is improved in patients treated with PORT,but not in those treated with POCT.

Impact of the Action Time of Inducers on Differentiation of 3T3-L1 Cells / 中国医学科学院学报

Objective To explore the effect of the action time of inducers on the differentiation of 3T3-L1 cells to adipocytes. Methods According to the "Cocktail" method,3T3-L1 cells were divided into three groups according to the action time of inducers,with the action time being 2,3 or 4 days,respectively. Cell morphology was observed using inverted microscope and adipose content were detected by Oil red "O" staining and detection of triglyceride. The cell viability was identified by trypan blue staining method. Results The proportion of samples (n=12) with differentiation rate above 80% in group A was 66% (12/18),while the differentiation rate of all the samples (n=18)in group B and group C were above 80%. For the Oil red "O",the OD value at 510 nm in group C was 2.59±0.17,which was significantly higher than that in group A (2.12±0.47;F=6.62,P=0.0001)and group B (2.20±0.17;F=5.15,P=0.0001),while no significant difference was found between group A and group B (F=1.14,P=0.74). As for the triglyceride,the value in group C was (1351.04±119.01)ng/ml,which was significantly higher than that in group A[ (1077.88±272.75)ng/ml;F=6.73,P=0.001] and group B [(1089.38±115.39)ng/ml;F=5.78,P=0.001],while no difference was found between group A and group B (F=0.27,P=0.64). The cell viability in group A,B,and C was (98.3±1.2)%,(98.5±1.8)%,and (98.9±2.1)%,respectively,showing no significant difference (F=0.18,P=0.83). Conclusions The modified procedure for the differentiation of 3T3-L1 cells to adipocytes can increase the differentiation rate and thus may be applied for establishing adipocyte models. The recommended action time is three days.

Patterns of recurrence in patients with stage pT3N0M0 thoracic esophageal squamous cell carcinoma after two-field esophagectomy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the patterns of recurrence and the related factors in patients with pT3N0M0 thoracic esophageal squamous cell carcinoma (ESCC) after two-field esophagectomy.</p><p><b>METHODS</b>From Jan 2008 to Dec 2009, 208 patients with stage pT3N0M0(2002, UICC) thoracic ESCC were treated with two-field esophagectomy in our hospital. There were 138 males and 70 females, and the median age was 60 years old (range 33-78). There were 33 patients in the upper-, 134 in the middle-, and 41 in the lower-thoracic esophagus, with a median length of lesion of 5 cm. There were 32 patients with no-, 78 with mild- and 98 patients with severe adhesions at surgery. The median number of dissected lymph nodes was 9 (range 1-27). 98 patients were treated with surgery alone and 110 with postoperative adjuvant chemotherapy. The statistical analysis was conducted using SPSS 13.0 software.</p><p><b>RESULTS</b>The follow-up was ended on July 2013. In the total group of 208 patients, the total recurrence rate was 41.8% (87/208). Among them, 52 patients had locoregional recurrence (LR), 15 had distant metastasis (DM) and 20 patients had both local recurrence and distant metastasis. 40.2% (35/87) of all recurrences were found within one year after operation, 67.8% (59/87) within 2 years, 86.2% (75/87) within 3 years, and 100% (87/87) within 4 years. The 1-, 3-, and 5-year progression-free survival (PFS) rate was 83.0%, 62.8% and 56.3%, respectively. The overall locoregional recurrence rate was 34.6% (72/208), among them, 9 cases had recurrence in the cervix (all were supraclavicular lymph node metastasis), 66 cases in the mediastinum and 4 cases had para-aortic lymph node metastasis. 83.3% (60/72) of the locoregional recurrence was located in the carinal region or upper area. The 1-, 3-, 5-year locoregional recurrence rate was 15.6%, 32.2%, and 36.8%, respectively, and the median time of recurrence was 15.5 months. The overall distant metastasis (DM) rate was 16.8% (35/208). The 1-, 3-, and 5-year DM rate was 4.4%, 15.3%, and 20.1%, respectively, and the median time of DM was 24 months. The most common site of DM was the lung and bone. The univariate analysis showed that age and tumor site were associated with PFS, tumor site and small lymph node in the mediastinum (diamter <1 cm) before surgery were related with LR (P<0.05 for all), and tumor site, histological differentiation and LR were related with distant metastasis after surgery (P<0.05). Multivariate analysis showed that the tumor site was an independent prognostic factor affecting the progression-free survival and locoregional recurrence (P<0.05), and histological differentiation and LR were independent factors associated with distant metastasis (P<0.05 for all).</p><p><b>CONCLUSIONS</b>The recurrence rate is very high in patients with pT3N0M0 thoracic ESCC after surgery, and most of them occur within 3 years after operation. Locoregional recurrence occurs more frequently and shortly than distant metastasis, and most of LR is located in the carinal region or upper-mediastinum. LR rate in upper-thoracic ESCC is very high, therefore, postoperative radiotherapy (PORT) is strongly suggested. LR rate in middle thoracic ESCC is also rather high and PORT is suggested. LR occur much less in the lower-thoracic ESCC, thus, PORT is not suggested routinely. Patients with poorly differentiated ESCC and LR have a high rate of distant metastasis.</p>

The role of galectin-4 in physiology and diseases

Galectin-4, a tandem repeat member of the β-galactoside-binding proteins, possesses two carbohydrate-recognition domains (CRD) in a single peptide chain. This lectin is mostly expressed in epithelial cells of the intestinal tract and secreted to the extracellular. The two domains have 40% similarity in amino acid sequence, but distinctly binding to various ligands. Just because the two domains bind to different ligands simultaneously, galectin-4 can be a crosslinker and crucial regulator in a large number of biological processes. Recent evidence shows that galectin-4 plays an important role in lipid raft stabilization, protein apical trafficking, cell adhesion, wound healing, intestinal inflammation, tumor progression, etc. This article reviews the physiological and pathological features of galectin-4 and its important role in such processes.

Positive End-expiratory Pressure Titration after Alveolar Recruitment Directed by Electrical Impedance Tomography / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Electrical impedance tomography (EIT) is a real-time bedside monitoring tool, which can reflect dynamic regional lung ventilation. The aim of the present study was to monitor regional gas distribution in patients with acute respiratory distress syndrome (ARDS) during positive-end-expiratory pressure (PEEP) titration using EIT.</p><p><b>METHODS</b>Eighteen ARDS patients under mechanical ventilation in Department of Critical Care Medicine of Peking Union Medical College Hospital from January to April in 2014 were included in this prospective observational study. After recruitment maneuvers (RMs), decremental PEEP titration was performed from 20 cmH 2 O to 5 cmH 2 O in steps of 3 cmH 2 O every 5-10 min. Regional over-distension and recruitment were monitored with EIT.</p><p><b>RESULTS</b>After RMs, patient with arterial blood oxygen partial pressure (PaO 2) + carbon dioxide partial pressure (PaCO 2 ) >400 mmHg with 100% of fractional inspired oxygen concentration were defined as RM responders. Thirteen ARDS patients was diagnosed as responders whose PaO 2 + PaCO 2 were higher than nonresponders (419 ± 44 mmHg vs. 170 ± 73 mmHg, P < 0.0001). In responders, PEEP mainly increased recruited pixels in dependent regions and over-distended pixels in nondependent regions. PEEP alleviated global inhomogeneity of tidal volume and end-expiratory lung volume. PEEP levels without significant alveolar derecruitment and over-distension were identified individually.</p><p><b>CONCLUSIONS</b>After RMs, PEEP titration significantly affected regional gas distribution in lung, which could be monitored with EIT. EIT has the potential to optimize PEEP titration.</p>

Identification of three novel frameshift mutations in the RUNX2 gene in three sporadic Chinese cases with cleidocranial dysplasia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the molecular etiology of three patients with sporadic cleidocranial dysplasia (CCD) and to provide genetic counseling and prenatal diagnosis for the family members based on the identified mutations.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood samples using a standard method. All 7 coding exons of the RUNX2 gene and their flanking intronic sequences were amplified by PCR and sequenced directly. The PCR products of the exons with mutations from the three patients were cloned into a T-vector. Positive clones were sequenced.</p><p><b>RESULTS</b>The three patients who have the typical CCD phenotypes involving clavicles, calvarium, stature, and teeth have carried various frameshift mutations in the RUNX2 gene. Patient 1 has a gross deletion of 80 nucleotides in exon 1 (c.227_306del), which caused a frameshift beginning at the Q/A repeat of the polypeptide and a premature termination (p.Ala76GlyfsX58). Patient 2 has a 2-bp duplication in exon 2 (c.471_472dupGG), which also caused a frameshift and a premature termination (p.Ala158GlyfsX19). Patient 3 has a T duplication in exon 7 (c.1321dupT), which caused a frameshift and a premature termination (p.Ser370PhefsX13) as well.</p><p><b>CONCLUSION</b>The three novel mutations in RUNX2 are the underlying molecular mechanism for the CCD phenotypes of three sporadic Chinese patients, respectively. These have broadened the mutation spectrum of RUNX2 gene and provided a molecular basis for the genetic counseling and prenatal diagnosis for the affected families.</p>

Children with idiopathic hypogonadotropic hypogonadism: clinical data analysis and mutations analysis of KAL1 and FGFR1 gene / 中华儿科杂志

<p><b>OBJECTIVE</b>To summarize the clinical features of idiopathic hypogonadotropic hypogonadism (IHH) diagnosed during childhood, and detect mutations in KAL1 and FGFR1, acting as key clues for diagnoses.</p><p><b>METHOD</b>We collected and analyzed clinical data of 21 cases (including demographic data, chief complaint, history of present illness, family history, physical examination, laboratory tests and imaging studies, etc.) diagnosed with IHH from December 2008 to February 2013. Polymerase chain reaction and gene sequencing was applied to detect mutations on KAL1 and FGFR1. Fifty healthy unrelated individuals were choosen as controls.</p><p><b>RESULT</b>Of 21 patients with IHH, 19 were males and 2 females, they visited us initially from 8-17 years old, with an average of (13.58 ± 2.38) years old. Sixteen cases were KS patients (76%). One boy reported abnormal sense of smelling but having olfactory perfect picture on MRI; 2/19 male cases had no puberty when they were over 13-14 years old without abnormal external genitalia. 8/19 cases only had small penis, 8/19 had both of cryptorchidism and small penis, and the Case 2 also had hypospadias. One boy had cryptorchidism combined with a normal penis. Only 2 girls diagnosed as IHH who visited us because of no puberty signs when they were 13 and 16 years old, respectively. Other clinical manifestations included: one with gynecomastia, 2 had mental retardation, and one was deaf; one with high palatal arch; one with mirror-movement and one with left renal agenesis but normal renal function respectively. Laboratory tests showed that the basic testosterone (T) is low and with inappropriately low or normal gonadotropin hormones. The results of cases of standard human chorionic gonadotropin (HCG) test of 7 cases out of 19 male children's were normal (testosterone>1 100 ng/L), and another nine cases continued to complete the extended HCG test, and the testosterone levels of two of them (cases 6, 8) were still lower than 1 000 ng/L. Family history: the parents in 9/21 family had delayed puberty, involving only one parent in 6 families, involving both in 2 families and the other one was an uncle having micropenis with a child. Among these 21 cases, only one boy's father had hyposmia and his first emission age was 14-15 years. Eleven patients accompanied abnormal sense of smelling and the olfactory organ abnormalities on MRI, 4 had olfactory organ abnormalities on MRI while they had good smelling function self-reportedly. We got 15 samples (12 KS and 3 nIHH cases) to screen the mutation of KAL1 (14 exons) and FGFR1 (18 exons). A splicing mutation c.1062+1G>A in KAL1 is identified in case 17 with IHH. One novel heterozygous FGFR1 mutation, a single base deletion mutation on the exon 1 c.27delC is identified in case 14. This mutation causes the premature termination codons.</p><p><b>CONCLUSION</b>This pilot research showed that IHH/KS diagnosis in children depends on clinical manifestation rather than gene analysis. Small penis or cryptorchidism, smelling abnormality and positive familial history may contribute to the KS/HH diagnosis. MRI of olfactory bulb acts as important proof for diagnosis of KS. Mutations in KAL1 and FGFR1 gene are not main causes of Kallmann syndrome.</p>

Establishment and functional identification of a stable cell line overexpression heme oxygenase-1 / 中国医学科学院学报

<p><b>OBJECTIVE</b>To establish a stable cell line overexpression heme oxygenase-1 (HO-1) mediated by a modified lentivirus system and identify its function.</p><p><b>METHODS</b>The HO-1 gene was amplified by polymerase chain reaction and cloned into the modified pLentiLox3.7 expression vectors. The recombinant plasmids were transfected into HEK293T cells and the HO-1 was detected by Western blot. The recombinant plasmids were transfected into HEK293T cells to produce the viruses, with the helping plasmids including plp1, plp2, and VSVG. HEK293T cells were infected by the viruses and the cells that can express HO-1 were identified by Western blot. The reactive oxygen species were detected in the HO-1-overexpression HEK293T cells and the normal cells after the adding of hydrogen peroxide. The same experiment was performed with human umbilical vein endothelial cells.</p><p><b>RESULTS</b>The stable cell line that can overexpress HO-1 was established, which was verified by Western blot. The reactive oxygen species in the HO-1-overexpression HEK293T cells and human umbilical vein endothelial cells decreased obviously after exposure to hydrogen peroxide.</p><p><b>CONCLUSIONS</b>The lentivirus-carrying HO-1 was successfully packaged and the stable cell line overexpression HO-1 was established. HO-1 can play a protective role in the course of oxidative damage.</p>