Seven drimane-type sesquiterpenoids from an earwig-associated Aspergillus sp / 中国天然药物

Drimane-type sesquiterpenoids are widely distributed in fungi. From the ethyl acetate extract of the earwig-derived Aspergillus sp. NF2396, seven new drimane-type sesquiterpenoids, named drimanenoids A-G (1-7), were isolated. Their structures were elucidated by diverse spectroscopic analysis including high-resolution ESI-MS, one- and two-dimensional NMR spectroscopy. Drimanenoids A-F (1-6) are new members of drimane-type sesquiterpenoid esterified with unsaturated fatty acid side chain at C-6. Drimanenoids C (3), D (4) and F (6) showed antibacterial activity against five types of bacteria with different inhibition diameters. Drimanenoid D (4) exhibited moderate cytotoxicity against human myelogenous leukemia cell line K562 with an IC50 value of 12.88 ± 0.11 μmol·L-1.

Clinical antitumor application and pharmacological mechanisms of Dahuang Zhechong Pill / 中草药·英文版

Cancer still has elevated morbidity and mortality, which undoubtedly impacts the life quality of affected individuals. Remarkable advances have been made in cancer therapy, although the toxicities of traditional therapies remain an obvious challenge. Dahuang Zhechong Pill (DHZCP), developed by Zhongjing Zhang in the Synopsis of the Golden Chamber, represents an effective anticancer traditional Chinese medicine (TCM). In this review, it was found that DHZCP is therapeutically utilized in liver, lung, gastric, pancreatic and other cancers in clinic. Pharmacological evidence showed that its anti-tumor mechanisms mainly involve induced cell cycle arrest, apoptosis and autophagy, as well as suppressed tumor cell proliferation, obstructed angiogenesis and metastasis, enhanced immunity, and reversal of multidrug resistance. The present review provides a solid basis for the clinical application of DHZCP and may promote the wide use of TCM in clinical antitumor application.

Infrequent gene mutations of KRAS, NRAS and BRAF in colorectal cancer and their clinical significance: a report of 1 513 cases / 中华消化外科杂志

Objective:To investigate the infrequent gene mutations of KRAS, NRAS and BRAF in colorectal cancer and their clinical significance.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 1 513 patients with colorectal cancer who were admitted to the Peking University Cancer Hospital from December 2013 to November 2018 were collected. There were 921 males and 592 females, aged from 15 to 97 years, with an average age of 59 years. The genomic DNA of tumor tissue was extracted, and the mutation status of KRAS (exon 2, 3), NRAS (exon 2, 3) and BRAF (exon 15) was detected by the Sanger sequencing. Observation indicators: (1) mutation status of KRAS, NRAS and BRAF; (2) relationship of different mutation status of KRAS, NRAS and BRAF with clinicopathological characteristics; (3) infrequent mutation status of single gene and its clinicopathological characteristics; (4) simultaneous mutations of two genes and their clinicopathological characteristics. Count data were expressed by absolute numbers or percentages, and comparison between groups was analyzed by the chi-square test.Results:(1) Mutation status of KRAS, NRAS and BRAF: the mutation rates of KRAS, NRAS and BRAF were 37.806%(572/1 513), 3.173%(48/1 513) and 5.486%(83/1 513) of the 1 513 patients with colorectal cancer, respectively. The mutation rates of exon 2 and exon 3 in KRAS were 35.889%(543/1 513) and 1.917%(29/1 513), respectively. The mutation rates of exon 2 and exon 3 in NRAS were 1.322%(20/1 513) and 1.851%(28/1 513), respectively. The mutation rate of exon 15 in BRAF was 5.486%(83/1 513). The mutation of KRAS mainly occurred in codon 12, 13 of exon 2 and codon 61 of exon 3, with a mutation rate of 27.759%(420/1 513), 7.733%(117/1 513), and 1.586%(24/1 513), respectively. Infrequent mutation in codon 14, 59, 60 of KRAS were found in 7 patients with colorectal cancer [0.463%(7/1 513)], including V14I mutation in 2 cases [0.132%(2/1 513)], A59T mutation in 2 cases [0.132%(2/1 513)], A59E mutation in 2 cases [0.132%(2/1 513)] and G60D mutation in 1 case [0.066%(1/1 513)]. The mutation of NRAS mainly occurred in codon 12, 13 of exon 2 and codon 61 of exon 3, including Q61K with a mutation rate of 0.925%(14/1 513), followed by G12D with a mutation rate of 0.727%(11/1 513). The mutation rates of Q61R, Q61H, Q61L, G13R, G12C, G12V, G12S, G13D, and G13C were relatively low. The mutation of BRAF mainly occurred in codon 600 of exon 15 as V600E mutation, with a mutation rate of 4.957%(75/1 513). Infrequent mutation in BRAF were found in 8 patients with colorectal cancer, with a mutation rate of 0.529%(8/1 513), including D594G mutation in 5 cases [0.330%(5/1 513)], D594H mutation in 1 case [0.066%(1/1 513)], S607T mutation in 1 case [0.066%(1/1 513)], and 599-600 codon insertion AGA in 1 case [0.066%(1/1 513)]. Of the 1 513 patients, 4 [0.264%(4/1 513)] had simultaneous mutations at codon 12 and 13 of KRAS, including 2 [0.132%(2/1 513)] with simultaneous mutations at G12V and G13D, 1 [0.066%(1/1 513)] with simultaneous mutations at G12D and G13A, and 1 [0.066%(1/1 513)] with simultaneous mutations at G12V and G13F. In addition, 1 patient [0.066%(1/1 513)] had simultaneous mutations at G13D of KRAS and G12S of NRAS, and 1 patient [0.066%(1/1 513)] had simultaneous mutations at G12C of KRAS and Q61H of NRAS. (2) Relationship of different mutation status of KRAS, NRAS and BRAF with clinicopathological characteristics: patients with different tumor location and tumor differentiation degree had significantly different KRAS mutation status ( χ2=25.317, 4.166, P<0.05); patients with different gender, tumor location, tumor differentiation degree, and lymph node metastasis had significantly different BRAF mutation status ( χ2= 11.290, 22.317, 38.035, 12.611, P<0.05). The proportion of Q61K mutation and Q61R mutation of NRAS in the patients with age of < 65 and ≥ 65 years was 12/18, 2/10 and 1/18, 5/10, respectively, showing significant differences between the two groups ( χ2=5.600, 7.542, P<0.05). (3) Infrequent mutation status of single gene and its clinicopathological characteristics: 15 of the 1 513 patients had single gene mutation. Of the 7 patients with infrequent mutations in codon 14, 59 and 60 of KRAS, 6 were males and 1 was female; 6 were < 65 years old and 1 was ≥ 65 years old; 3 had tumors located in the left colon, 3 in the right colon and 1 in the rectum; 6 had highly or moderately differentiated adenocarcinoma and 1 had poorly differentiated adenocarcinoma; 6 were in stage Ⅳ and 1 was in stage Ⅱ of TNM staging; 6 had distant metastasis and 1 had no distant metastasis; 3 had lymph node metastasis and 4 had no lymph node metastasis; there was no postoperative recurrence. Of the 8 patients with infrequent gene mutation of BRAF, 4 were males and 4 were females; 4 were < 65 years old and 4 were ≥ 65 years old; 5 had tumors located in the left colon, 1 in the right colon and 2 in the rectum; 7 had moderately differentiated adenocarcinoma and 1 had poorly differentiated adenocarcinoma; 5 were in stage Ⅳ, 2 in stage Ⅲ, and 1 in stage Ⅱ of TNM staging; 6 had distant metastasis and 2 had no distant metastasis; 3 had lymph node metastasis and 5 had no lymph node metastasis; 1 had postoperative recurrence. (4) Simultaneous mutations of two genes and their clinicopathological characteristics: 6 of the 1 513 patients had simultaneous mutations of two genes. Of 6 patients with simultaneous mutations of two genes, 5 were males and 1 was female; 2 were < 65 years old and 4 were ≥ 65 years old; 1 had tumor located in the left colon, 4 in the right colon and 1 in the rectum; 5 had highly or moderately differentiated adenocarcinoma and 1 had poorly differentiated adenocarcinoma; 5 were in stage Ⅳ and 1 was in stage Ⅱ of TNM staging; 4 had distant metastasis and 2 had no distant metastasis; 3 had lymph node metastasis and 3 had no lymph node metastasis; 1 had postoperative recurrence. Conclusions:The infrequent mutations of KRAS and BRAF in colorectal cancer often occur in the rare codon region and mainly are point mutations. Different mutations of KRAS, NRAS and BRAF are related to clinicopathological features, which provide an important basis for treatment of colorectal cancer.

Value of serum human epithelial growth factor receptor 2 extracellular domain and circulating tumor cells in evaluating therapeutic response in advanced gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To examine the correlation between serum human epithelial growth factor receptor 2 extracellular domain (HER2 ECD) and circulating tumor cells (CTC), as well as the dynamic variation of HER2 ECD and its correlation to the therapeutic efficacy.</p><p><b>METHODS</b>Fifty-three advanced gastric cancer (AGC) patients who treated in Peking University Cancer Hospital and ever enrolled into CTC study (ClinicalTrial gov. ID: NCT01625702) were retrospectively included in this study.</p><p><b>INCLUSION CRITERIA</b>the patients were histologically confirmed as locally advanced or recurrent and/or metastatic adencarcinoma; they received two or more cycles of fluorouracil-based chemotherapy or combination targeted therapy; serum CTC was counted before and after therapy; the clinical response was evaluated every 2 cycles of treatment by the presence of at least one measurable lesion according to RECIST version 1.1 criteria. This study was approved by Ethics Committee of Peking University Cancer Hospital, and informed consents were signed by patients. The sera before and after two cycles of treatment were collected for CTC enumeration and HER2 ECD detection, in which the levels of HER2 ECD were measured by chemiluminescence immunoassays method. The positive threshold value of HER2 ECD and CTC number were ≥15 μg/L and ≥3 CTCs/7.5 ml respectively. The progression-free survival (PFS) and overall survival (OS) were compared among different groups using Log-rank tests.</p><p><b>RESULTS</b>In 53 enrolled patients, 39 were histologically identified as negative HER2, 9 as positive HER2 and another 5 cases were unknown. All the patients received fluorouracil-based chemotherapy, and 9 positive HER2 patients received combined anti-HER2 targeted therapy. Before therapy, the median HER2 ECD concentration of 53 cases was 10.45 (8.0 to 83.2) μg/L. Seven patients exhibited positive HER2 ECD levels, in whom 4 were histologically HER2 positive, but 3 were histologically HER2 negative. The median CTC number of 53 cases was 2 (0 to 668) CTCs/7.5 ml, and the positive rate of CTC was 47.2%(25/53). Following 2 cycles of therapy, a total of 10 histologically HER2 negative patients exhibited positive HER2 ECD levels, in whom 2 also possessed positive HER2 ECD levels, 83.3 μg/L and 46.9 μg/L before therapy, and 22.4 μg/L and 20.4 μg/L after therapy respectively, whereas another 8 patients (10.3 to 14.5 μg/L before therapy) acquired the elevated expression of HER2 ECD following therapy (15.1 to 19.5 μg/L). It seems that the increased level of HER2 ECD after therapy was, though not statistically significant, correlated to low number of CTCs. In histologically HER2 negative patients, pretherapeutic HER2 ECD level (positive vs. negative) was not significantly correlated to PFS (7.6 months vs. 4.4 months, P=0.328) and OS (13.6 months vs. 10.9 months, P=0.679). However, in histologically HER2 positive patients, patients with positive HER2 ECD level before therapy exhibited longer PFS (10.7 months vs. 4.2 months, P=0.025) and OS (16.5 months vs. 8.9 months, P=0.015) compared to those with negative HER2 ECD level. Additionally, CTC number was significantly correlated to prognosis in histologically HER2 negative patients. Patients with positive pretherapeutic CTC number showed longer PFS (5.3 months vs. 3.3 months, P=0.049) and OS (14.3 months vs. 7.6 months, P=0.001) as well. While in histologically HER2 positive patients, CTC number was not obviously correlated to the PFS and OS. In above 8 negative HER2 patients acquiring elevated expression of HER2 ECD following therapy, the increased HER2 ECD level was not correlated to PFS and OS (all P>0.05). In 9 histologically HER2 positive patients, 4 patients who exhibited decreased HER2 ECD level and reduced or constant CTC number had longer PFS (7.5 to 15.3 months) and OS (11.0 to 26.3 months) compared with those 2 patients who suffered from acquired HER2 ECD level following therapy (PFS 3.0 to 4.8 months and OS 7.3 to 8.6 months).</p><p><b>CONCLUSIONS</b>In histologically HER2 positive patients, increased pretherapeutic HER2 ECD level predicts better prognosis. The acquired elevated HER2 ECD level following therapy is correlated to inefficient therapeutic response. The acquirement of elevated HER2 ECD level can also be found in histologically HER2 negative patients, which may be correlated to the corresponding variation of CTC number.</p>

Application of annular plane systolic excursion z-score in evaluation of heart systolic function of fetus with heart failure / 中华超声影像学杂志

Objective To establish z-score model for fetal tricuspid annular plane systolic excursion(FAM-TAPSE) and mitral annular plane systolic excursion(FAM-MAPSE) based on gestational age(GA),then to evaluate the ventricle systolic function of fetus with heart failure.Methods One thousand and twelve normal fetuses and 24 fetuses with heart failure were involved. FAM-TAPSE and FAM-MAPSE were measured by free angle M-mode echocardiography,and FAM-TAPSE and FAM-MAPSE z-score models of normal fetuses were constructed by using first standard regression analysis with GA as independent variable.The fetuses with heart failure were divided into left heart failure (LHF) group and right heart failure (RHF) group by Tei index.Subsequently,the two parameters between normal and fetuses with heart failure were compared. Results The models used to calculate z-score for FAM-TAPSE and FAM-MAPSE were constructed,and GA had close correlation with them. Compared with normal fetuses,the mean z-scores of FAM-TAPSE and FAM-MAPSE were statistically different in fetuses with heart failure(P<0.001). The FAM-MAPSE z-scores of LHF and the FAM-TAPSE z-scores of RHF were all less than-2 z-scores.Conclusions The FAM-TAPSE and FAM-MAPSE z-scores decline in fetuses with heart failure and they can provide quantitative evidence in evaluation of heart systolic function,FAM-TAPSE and FAM-MAPSE z-score would be markers for assessing heart systolic function in fetuses with heart failure.

Lipoic acid effects on electrophysiological changes of the sciatic nerve following ischemia/reperfusion injury / 中国组织工程研究

BACKGROUND:Lipoic acid, with a closed circle structure composed by sulphur and carbon atoms, exerts strong anti-oxidation, and has been extensively applied in the prevention and treatment of oxidative stress, diabetic cataract, diabetic neuropathy and cardiovascular diseases. OBJECTIVE:To investigate the protective effect of lipoic acid on peripheral nerve function during peripheral nerve ischemia/reperfusion injury. METHODS:Models of peripheral nerve ischemia/reperfusion injury were established in rabbits, and then rabbit models were then allotted to treatment and non-treatment groups. The treatment group was subdivided into experimental (injection of lippoic acid) and control groups according to the use of lipoic acid at 1, 3 and 6 hours after ischemia and before reperfusion. The ultrastructural changes of the sciatic nerve were observed under electron microscope, and the electrophysiological changes of the sciatic nerve were detected using evoked potential instrument. RESULTS AND CONCLUSION:With the ischemic time increasing, the number of vacuoles in the axon increased gradually, accompanied by axonal atrophy, and Waller's degeneration in the aggregated microfilaments. The myelin sheath thickening and dissolving were visible. All above phenomena became severest at 6 hours after ischemia. Compared with the control groups, lipoic acid reduced the number of the vacuoles in the axon and all eviated axonal atrophy, Waller's degeneration and demyelination. As the ischemic time increasing, the latency of sciatic nerve was significantly increased, and peaked at 6 hours of ischemia;while the amplitude was significantly decreased, and reached a minimum at 6 hours of ischemia. Compared with the control groups, in the experimental groups, the latency of sciatic nerve was significantly decreased, but the amplitude was significantly increased. These results suggest that lipoic acid provides neuroprotection against peripheral nerve ischemia/reperfusion injury.

Value of annular plane systolic excursion difference in evaluation of heart systolic function of normal fetuses in ;the second and late trimester with echocardiography / 中华超声影像学杂志

Objective To obtain the annular plane systolic excursion difference (APSED)of fetuses in second and late trimester by free angle M-mode (FAM)and tissue motion of annular displacement (TMAD)in order to assess the fetal ventricular function.Methods The mitral annular plane systolic excursion(MAPSE)and tricuspid annular plane systolic excursion(TAPSE)of four hundred and fifty five normal fetuses from 20 to 41 weeks were measured by FAM echocardiography,and the difference between them were calculated.Early diastolic velocities (Em)of the mitral annular and early diastolic velocities (Em')of the tricuspid annular were estimated by pulsed-wave tissue Doppler imaging (TDI),meanwhile systolic velocities (Sm)of the mitral annular and systolic velocities (Sm')of the tricuspid annular were also estimated by TDI.Fifty normal fetuses in the second and late trimester were choosed randomly,two-dimension imaging was obtained at the apical four-chamber view,then mitral annular plane and tricuspid annular plane displacement curve were acquired at the same time by using off-line QLab 8.1 software,and the differences in the peak time between them were compared.The trace of annular displacement were recorded by color tissue tracking technology.Results There was a significant difference between FAM-TAPSE and FAM-MAPSE in different gestational weeks (P 0.05).Conclusions The APSED existed in the second and late trimester continually.It was considering associated with fetal ventricular torsion.As the growth of gestational weeks,the increase of APSED reflected the enhanced reserve capacity of the fetal ventricular torsion.APSED can reflect the longitudinal motion and torsion movement of fetal ventricle quantitatively,and can be used as a new index to assess the fetal cardiac function.

Brief Talk about Standardization and Evaluation Criterion of Medical Experimental Records / 中华医学科研管理杂志

In view of the particularity of medical experiments,it's essential to improve the quality of medical university project and prevent academic misconduct for the authenticity and standardization of the experimental records.The paper discusses some solutions to these problems in standardization and management criterion of medical experimental records,and recommends the evaluation criterion of Capital Medical University for medical experimental records.

Z-score analysis of tricuspid annular plane systolic excursion in normal fetuses with fetal echocardiography / 中华超声影像学杂志

Objective To develop Z-score reference ranges for tricuspid annular plane systolic excursion(TAPSE) in normal fetuses from the measurements of gestational age(GA),biparietal diameter (BPD) or femur length(FL) using fetal echocardiography.Methods A retrospective cross sectional study of 1012 singleton normal fetuses were performed.The gestation age ranged from 20 to 41 weeks.Non-cardiac fetal biometric parameters included GA and BPD and FL were measured and calculated GA based on menstrual age.TAPSE was measured in a standard apical four-chamber view by free angle M-mode echocardiography.Normal Z-score ranges were developed for TAPSE using GA,BPD and FL as independent variables.These were accomplished by using first standard regression analysis and then weighted regression of absolute residual values for each parameter in order to adjust for inconstant variance.Results Linear regression model was the best description of the data in each case and correlations between TASPE and independent variables (GA,BPD,FL) were excellent.Heteroscedasticity of standard deviation (SD) with increasing independent variables also could be modeled with a simple linear regression.According to these equations,TAPSE Z-score =(the actual measurement of TAPSE-predicted TAPSE)/prediction SD.Conclusions Normal reference ranges and Z-scores for TAPSE have been provided.These normative data may be useful tools for assessment of fetal TAPSE,to evaluate fetal right ventricular function more accurately and effectively.