Background and purpose:Metastatic colorectal cancer (mCRC) patients with K-ras mutation won’t benefit in the anti-epidermal growth factor receptor (EGFR) treatments. Thus K-ras mutation analysis is mandatory before this treatment. There is controversy that K-ras mutation analysis should be performed on primaries or related metastases. The aim of our study was to evaluate the concordance of K-ras status between primary and related metastases tumors, thus investigate the validity and rigorousness of clinical K-ras testing. Methods:Seventy-six patients with confirmed mCRC treated in Fudan University Shanghai Cancer Center were enrolled. After DNA extraction and PCR amplification, tumor specimens with paired primary tumors and related metastatic sites were put into sequencing analysis. And the K-ras mutation status in exon 2 was assessed. Results: K-ras mutation was detected in 31 out of 76 primary tumours (40.8%) and also 40.8%of the metastatic sites. But discordance was found between primary tumor and metastasis in 15 cases (19.7%):8 primary tumors had a K-ras mutation with a wild-type metastasis, meanwhile 7 primary tumors were wild type with a K-ras-mutated metastasis. Conclusion:Our study indicated that quite a few mCRC cases have different K-ras status between primary tumors and related metastatic sites, and it’s not very rigorous to choose the anti-EGFR treatments merely according to the primary tumor-K-ras mutation.Further study and consultation are needed on this problem.

Objective To explore the correlation between heart rate recovery after exercise test and disease severity in patients with chronic obstructive pulmonary disease(COPD)and assess its impact on the exercise capacity of COPD patients.Methods Arterial blood gas analysis, pulmonary lung function test and cardiopulmonary exercise testing were performed in 60 patients with stable COPD and 50 healthy volunteers.Based on the heart rate recovery after exercise test, COPD patients were divided into normal heart rate recovery group(n =41)and abnormal heart rate recovery group(n =19).Results The COPD patients had lower exercise capacity(peak oxygen uptake as percentage of predicted value, peak VO2％ pred)(66 ± 15vs.89±11, P＜0.01), peak heart rate [(134±21)vs.(149±13)beats/min, P＜0.01], heart rate recovery[(18 ± 9)vs.(27 ± 10)beats/min, P ＜ 0.01] and higher resting heart rate [(83 ± 13)vs.(77 ± 13)beats/min, P ＜0.01] than the controls.Compared with normal heart rate recovery group, forced expiratory volume in one second as percentage of predicted(FEV1 ％ pred)and exercise capacity decreased more significantly in abnormal heart rate recovery group(38 ± 15 vs.52 ± 16, P＜0.05 and 57 ± 12 vs.71 ±14, P ＜0.01).Heart rate recovery was significantly correlated with FEV1％ pred and peak V O2％ pred(r=0.42, P ＜ 0.01 and r =0.52, P ＜ 0.01).Multivariate regression analysis showed that heart rate recovery and FEV1 ％ pred could be used as independent predictors of exercise capacity in COPD patients.Conclusion In COPD patients, heart rate recovery is correlated with the degree of disease severity and it may be an independent predictor of exercise capacity.

Two γ-glutamyl-cysteine peptides (γ-GCPs ) , ( SC2 RC7 )-γ-L-glutamyl-S-allyl-L-cysteine ( 1 ) and ( SC2 RC7 )-γ-L-glutamyl-S-propyl-L-cysteine ( 2 ) have been isolated from fresh garlic scales using ion-exchange chromatography and pre-HPLC. Their molecular structures were identified by HPLC-MS, CD, 1 H NMR, 13 C NMR, specific rotation and confirmed by the corresponding standard compounds. The influence of exogenously adding 1 and 2 on the bioavailability of iron and zinc from food legume was examined with soybean and mung bean, in the level of 0. 01 mmol/5 g of legume respectively. The enhancing effect of the two γ-GCPs of compound 1 and 2 on bioaccessibility of iron was generally evidenced in the case of soybean ( from 1 . 88% to 6 . 73% and 4 . 42%) and mung bean ( from 2 . 52% to 12 . 04% and 9 . 38%) . The two γ-GCPs similarly enhanced the bioaccessibility of zinc from the food legume, in soybean ranging from 13. 37% to 23. 95% and 20. 58%, and in mung bean from 15. 98% to 28. 44% and 27. 05%. Thus, both compounds 1 and 2 obviously had a promoting influence on the bioavailability of iron and zinc from food legumes. These findings are of practical value in a food-based strategy to enhance the bioavailability of trace minerals for human health.

As a metabolic disorder during pregnancy,gestational diabetes mellitus (GDM) has an important effects on fetal development,neonatal health and maternal long-term health,and is one of the pregnancy complications with high incidence.It is of great significance that we have an accurate understanding of the etiology and risk factors of GDM for its prevention and control.GDM is a complex disease with multiple etiologies.Current studies have shown that the occurrence of GDM may be the result of combined effect of heredity and environment,but the exact etiology is still unclear.In this paper,we summarized the possible etiologies and risk factors of GDM,so as to understand the occurrence and development of GDM better and to provide possible references for prevention and further etiological studies of GDM.

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.

OBJECTIVETo evaluate the effect of different immune status on the incidence of hepatic lesions in patients with hepatitis B virus (HBV) infection undergoing anti-tuberculosis therapy.

METHODSThe PubMed (1966-2013), Embase (1966-2013), Wanfang (1998-2013), Chinese National Knowledge Infrastructure (CNKI; 1997-2013), and Chinese Biomedical (CBMdisc; 1860-2013) literature databases were searched for case-control studies of hepatic lesions in patients undergoing anti-tuberculosis therapy with or without concomitant HBV infection. The HBV patients were divided into subgroups according to hepatitis B e antigen (HBeAg) positivity or negativity, all members of the control group were HBsAg⁻. The data from all 7 studies included in the meta-analysis were extracted and analysed using RevMan5.2 soft-ware.

RESULTSPatients with HBV infection who were undergoing anti-tuberculosis therapy had a higher risk factor than the control patients (OR =5.81, 95% CI =[4.26, 7.39]). The HBV patients with HBeAg positivity who were undergoing anti-tuberculosis therapy had a high risk factor than the HBV patients with HBeAg negativity (OR =2.56, 95% CI=[1.90, 3.44]).

CONCLUSIONHBV infection is a risk factor for hepatic lesions when undergoing anti-tuberculosis therapy, and HBeAg-positive status may put a patient at higher risk.

Antitubercular Agents ; adverse effects ; therapeutic use ; Hepatitis B ; complications ; pathology ; Hepatitis B e Antigens ; blood ; Humans ; Liver ; drug effects ; pathology ; Tuberculosis ; complications ; drug therapy ; pathology

Objective To summarize the clinical features of 22 probands diagnosed with congenital muscular dystrophy (CMD),and to provide genetic counseling and prenatal diagnosis for 23 fetuses of these pedigrees.Methods Data of 22 CMD patients who were treated in the Pediatric Department of Peking University First Hospital during October 2006 to March 2016 were analyzed.Informed written consents for participation in this study were obtained from the parents or guardians.Prenatal diagnosis was performed using DNA samples extracted from fetal villus cells of 12 cases at 11-13 gestational weeks and amniotic fluid of 11 cases at 18-22 gestational weeks.Direct DNA sequencing by polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA) were used to detect CMD-related gene mutations.Linkage analysis of short tandem repeats (STRs) was used to identify maternal blood contamination and biological parents.Results Thirteen out of the 22 probands with CMD were diagnosed with congenital muscular dystrophy type 1 A (MDC1A),and all of them carried compound heterozygous mutations in LAMA2 gene.Prenatal diagnosis of 13 fetuses from these pedigrees found that four fetuses were wild-type,seven were heterozygotes and two carried the same mutations as their proband.Three probands with LMNA-related congenital muscular dystrophy (L-CMD) carried de novo mutations in LMNA gene.In these pedigrees,two fetuses were wild-type and one whose mother was mosaicism carried the same mutations as the proband.One proband with Ullrich congenital muscular dystrophy carried compound heterozygous mutations in COL6A2 gene and the fetus of the same pedigree was wild-type.Five probands were diagnosed with α-dystroglycanopathies.And among them,two cases of muscle-eye-brain disease (MEB) carried compound heterozygous mutations in POMGnT1 gene and the fetuses of the two peidgrees were heterozygotes;one case of congenital muscular dystrophy type 1C (MDC1C) had compound heterozygous mutations in FKRP gene and the fetus carried the same mutations;one patient diagnosed with POMGnT1-related congenital muscular dystrophy with mental retardation (CMD-MR) carried compound heterozygous mutations in POMGnT1 gene,and the fetus was positive for the same mutations;one proband with POMT1-related CMD-MR was positive for compound heterozygous mutations in POMT1 gene and the results of prenatal diagnosis for two fetuses of this pedigree showed that the first fetus had the same mutations as the proband,while the second was heterozygote.Conclusions No effective therapeutic method is available for CMD.Therefore,accurate genetic counseling and prenatal diagnosis are necessary to prevent CMD child from birth.

Objective To study the time extended for getting emergency intervention in different modes of transportation and factors influencing the modes of transportation of patients with ST elevation myocardial infarction (STEMI).Methods A total of 564 consecutive patients with STEMI admitted from September 2013 to June 2016 were enrolled in the study.The clinical data about time consumed for getting emergency intervention and modes of transportation were collected.Results According to the mode of transportation,patients were divided into three groups:emergency care system (EMS) transportation group (n =96),self-transportation group (n =206) and referral group in which the patients were sent in from other hospitals (n =262).EMS transportation group had significantly shorter total ischemic time before emergency treatment than self-transportation group (229 rin vs.418 min,P ＜ 0.05) and referral group (229 min vs.512 rin,P ＜ 0.05),and significantly shorter length of pre-hospital time than self-arrival group (55 min vs.110 min;P＜0.05) and referral group (55 min vs.372 min;P＜0,05).The referral group had longer pre-hospital time and the self-transportation group had longer door-to-balloon time,but there was no difference in total ischemic time between the self-arrival and referral group (Z =-1.882,P =0.068).Multivariate logistic regression was used to analyze influence factors in mode of transportation:(1) patients characterized with high school or university education,profession of civil service,and their transportation distance more than 30 km were greater in number than referral group (P ＜ 0.05);(2) patients identified with senior middle school education,staff member of public sectors or company,their transportation distance less than 30 km,and with killip grade above Ⅱ were more likely to have EMS transport (P ＜ 0.05);(3) patients defined as businessmen without taking out new rural cooperative medical insurance,taking up transportation distance less than 80 km,and subjecting to killip grade Ⅰ had a higher proportion of individuals of this kind taking self-transportation (P ＜ 0.05).Conclusion Mode of transportation is an important factor that affects the time extended to get emergency intervention.Education level,occupation,medical insurance type,transportation distance,killip grade are associated with modes of transport.

Mediation analysis is mainly used to explore the causal mechanism between independent variable X and dependent variable Y. It determines whether mediator M plays a role and evaluate the role’s degree in the causal path by decomposing the causal path between the independent variable X and the dependent variable Y. However, the classical mediation analysis is generally used for single mediator. This paper introduces a new mediation analysis method for multiple mediators.

Objective: To investigate the clinicopathological features and outcome of gastroenteropancreatic high-grade neuroendocrine tumors. Methods: A total of 60 gastroenteropancreatic high-grade neuroendocrine tumors were collected from January 1st, 2013 to December 31th, 2018 at Fudan University Shanghai Cancer Center, with available pathology databases and clinic follow-up information. At the same time, 157 cases of gastrointestinal pancreatic neuroendocrine neoplasm (NEN) diagnosed at the hospital in 2018 were collected and the incidence of NEN at all grades was compared. Results: There were 32 males and 28 females, aged 13-80 years (mean 54 years). Pancreas primary was the most common (48%, 29/60). Nodal metastatic rate was 9/16 and distant metastatic rate was 41%(18/44). Liver was the most common site of metastasis. Among all the gastroenteropancreatic neuroendocrine neoplasms diagnosed in the hospital in 2018, the incidence of high-grade neuroendocrine tumors was the lowest (7%, 11/157). High-grade neuroendocrine tumors had typical pathologic features of well-differentiated/moderate neuroendocrine tumors, but with significant differences in mitotic rates. By immunohistochemical staining, most of the tumors expressed neuroendocrine markers and somatostatin receptor 2 was positive in 60% (12/20) of the cases. The average Ki-67 index was 30%-40%, and there was significant difference between cases (18%-80%). The overall survival of high-grade neuroendocrine tumors was 43 months, and the disease-free survival was 12 months. Conclusions High-grade neuroendocrine tumor is a rare group of neuroendocrine tumors, with unique clinicopathological features and good prognosis. Pathological classification and grading of gastroenteropancreatic neuroendocrine neoplasms can help clinicians to select appropriate treatment and accurately evaluate prognosis.