Résumé
Objective To investigate the mechanism of morin-induced autophagy in non-small cell lung cancer A549 cells based on mTOR/STAT3 signaling axis.Methods A549 cells were divided into blank group and 30,60,90,120 and 150 μg·mL-1 of morin groups.After 24,48 and 72 hours of culture,the cell proliferation activity was detected by CCK-8 method,and the cell inhibition rate was calculated.A549 cells were divided into blank group and 30,90,150 μg·mL-1 morin groups.After 14 days of culture,the cell proliferation was detected by colony formation assay.After 24 hours of culture,the cell proliferation ability was detected by BeyoClickTM EdU-488.Apoptosis was detected by flow cytometry;acridine orange staining was used to detect cell autophagy;the formation of autophagosomes was observed by transmission electron microscopy.Western Blot was used to detect the expression levels of apoptosis,autophagy and mTOR/STAT3 signaling axis-related proteins in cells.A549 cells were divided into blank group,blank group + chloroquine(10 μg·mL-1)group,morin(30,150 μg·mL-1)group,morin(30,150 μg·mL-1)+ chloroquine(10 μg·mL-1)group.After 48 hours of intervention,the cell activity was detected by CCK-8 method,and the cell survival rate was calculated.Results Compared with the blank group,the inhibition rate of A549 cells in 60,90,120,150 μ g·mL-1 of morin group was significantly increased after 24 hours of intervention(P＜0.05,P＜0.001).The inhibition rates of A549 cells in 30,60,90,120 and 150 μg·mL-1 of morin groups were significantly increased after 48 and 72 hours of intervention(P＜0.001).The number of A549 cell colonies and the number of green fluorescent proliferation positive cells in the 30,90,150 μg·mL-1 of morin groups were significantly decreased(P＜0.01,P＜0.001),the apoptosis rate was significantly increased(P＜0.01,P＜0.001),and the protein expression level of cleaved-PARP was significantly increased(P＜0.001).The protein expression levels of p-P38/P38 MAPK in A549 cells of 90 and 150 μg·mL-1 of morin groups were significantly increased(P＜0.01,P＜0.001).Different degrees of orange fluorescence appeared in A549 cells of 30,90 and 150 μg·mL-1 of morin groups,and the orange fluorescence of 90 and 150 μg·mL-1 of morin groups was significant.Autophagosomes and autolysosomes appeared in the cytoplasm of A549 cells in 150 μg·mL-1 of morin group,respectively.The protein expression of LC3-Ⅱ in A549 cells of 150 μg·mL-1 of morin group was significantly up-regulated(P＜0.05).The protein expression of Atg16L1-Ⅱ in A549 cells of 90,150 μg·mL-1 of morin group was significantly up-regulated(P＜0.001),and the protein expressions of p-mTOR/mTOR and p-STAT3/STAT3 were significantly down-regulated(P＜0.001).Compared with the morin(150 μg·mL-1)group,the survival rate of A549 cells in the morin(150 μg·mL-1)+chloroquine(10 μg·mL-1)group was significantly increased(P＜0.05).Conclusion Morin can promote the apoptosis of A549 cells and induce autophagy in A549 cells,and the mechanism may be related to mTOR/STAT3 axis.
Résumé
ObjectiveTo investigate the structural and functional characteristics of gut microbiota in common traditional Chinese medicine （TCM） syndromes of irritable bowel syndrome with diarrhea （IBS-D）. MethodsIBS-D patients who visited the Hospital of Chengdu University of Traditional Chinese Medicine， and healthy participants from the Physical Examination Centre of the same hospital were recruited from 1st January 2020 to 31st March 2021.The IBS-D patients were classified into syndrome of liver constraint and spleen deficiency， and syndrome of spleen deficiency and dampness exuberance； together with the recruited healthy participants， there were liver-constraint group， dampness-exuberance group， and healthy group. General information， including age， gender and body mass index （BMI）， were collected， and Irritable Bowel Syndrome Symptom Severity Scale （IBS-SSS） as well as Irritable Bowel Syndrome Quality of Life Scale （IBS-QOL） scores were additionally collected from IBS-D patients. Fresh fecal samples were also collected and tested by macro-genome sequencing technology for abundance statistical display， PCoA， Anosim， LEfSe bioinformatic analysis of the annotated gut microbiota structure and function. ResultsThere was no statistically significant difference in the general information of the participants in the three groups （P＞0.05）； the difference in the IBS-SSS and IBS-QOL scores between liver-constraint group and dampness-exuberance group were not statistically significant （P＞0.05）. The study included 28 cases each in liver-constraint group， dampness-exuberance group， and healthy group. The number of specific genes to patients in liver-constraint group was 269 135， with 216 156 in dampness-exuberance group and 249 759 in healthy group， accounting of total 1 784 036 in the three groups. There were differences in the relative abundance distribution of the top ten species of gut microbiota among the three groups， with smaller differences at the phylum， class and order levels， and larger differences at the family， genus and species levels. There were differences in the relative abundance of structure and function of the gut microbiota among the three groups. Species PCoA and Anosim analyses at the species level showed significant differences in the composition of the microbiota among the three groups. Further LEfSe analyses showed that patients in liver-constraint group were screened for 14 dominant strains， of which Clostridium sp. CAG 217， Lachnospira pectinoschiza， Anaerotruncus sp. CAG 528， Paeniclostridium sordellii， Eubecterium sp. CAG 76， Bacillus cereus were affected to a greater extent in abundance differences； dampness-exuberance group screened 24 species of dominant bacteria， of which Roseburia inulinivorans， Eubacterium sp. CAG 251， Roseburia hominis， Unclassified Eubacterium rectale， Roseburia intestinalis， and Megamonas funiformis were affected to a greater extent in abundance differences； no dominant functional genes were screened for patients in liver-constraint group， and dampness-exuberance group was screened for flagellum assembly （ko02040）， porphyrin metabolism （ ko00860）， salmonella infection （ko05132）， and benzoic acid degradation （ko00362）. The differentially dominant functional genes in liver-constraint group and dampness-exuberance group may mainly focus on metabolism （including biodegradation and metabolism of exogenous substances， energy metabolism， lipid metabolism， etc.）. ConclusionIBS-D with syndrome of liver constraint and spleen deficiency is characterized by the enrichment of 14 gut microbiota， such as Clostridium sp. CAG 217， while IBS-D with syndrome of spleen deficiency and dampness exuberance is characterized by the enrichment of 24 gut microbiota， such as Roseburia inulinivorans， and 4 functional enrichments， such as flagellum assembly. Clostridium sp. CAG 217 and Roseburia inulinivorans are expected to be biomarkers for IBS-D patients in the two syndromes， respectively.
Résumé
Objective To investigate the relationship between combined plasma ferritin and triglyceride (TG) concentrations in early pregnancy and the risk of gestational diabetes mellitus (GDM). Methods A total of 1 000 pregnant women who had antenatal care at the Sixth Hospital of Wuhan from January 2021 to January 2023 were selected as the research subjects. The cut-offs of ferritin and TG were analyzed by using unrestricted cube splines. All participants were divided into 4 groups according to the cut‐off values of ferritin and TG. Associations between combined ferritin and TG concentrations and GDM risk were estimated using multivariable logistic regression models. Results A total of 158 (15.8%) participants were diagnosed with GDM. The ferritin and TG levels in early pregnancy of pregnant women in the GDM group were significantly higher than those in the non-GDM group (P<0.05). After adjusting for potential confounders, the OR for the risk of developing GDM after combining ferritin with TG was 2.35 (1.65, 3.35). Couclusion The increase in plasma ferritin and TG concentrations in early pregnancy is positively correlated with the increased risk of GDM. Pregnant women with high plasma ferritin (˃65.7 ng/mL) and high TG (˃1.9mmoL/L) have the greatest risk of GDM.
Résumé
A combined epidemic prediction method based on multi-source data fusion is presented to address the common problems of low accuracy,weak generalization,single structure,poor nonlinear processing ability,and long prediction time in traditional epidemic prediction models.The collected multi-source epidemic data are normalized and subjected to feature selection using principal component analysis.An ARIMA-GM-BPNN model for pandemic prediction is constructed by combining ARIMA model,grey GM model and BPNN.The fitting values of the first two prediction models are used as inputs to BPNN for model training.After sufficiently integrating the data and combining the advantages of different prediction models,the optimal combined model is obtained and used for forecasting the incidence and trend of epidemics.Experimental results show that the combined model exhibits excellent fitting performance,with predicted incidences and trends consistent with the real conditions.The proposed approach improves prediction accuracy and generalization capabilities,and it can provide reliable data support for epidemic prediction and control.
Résumé
Objective:To compare and explore the clinical efficacy and safety of endoscopic thyroidectomy by gasless unilateral axillary approach for the treatment of papillary thyroid microcar cinoma (PTMC) .Methods:One hundred and ten patients with unilateral PTMC admitted to the Department of Thyroid and Breast Surgery, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, from Jan.3 2019 to Mar. 2022 were used as clinical study subjects, and according to the patients' choice of surgical modality, they were divided into 30 cases in the endoscopic thyroidectomy by gasless unilateral axillary approach (ETGUA) group and 80 cases in the minimally invasive video-assisted thyroidectomy (MIVAT) group. We retrospectively compared and analyzed the differences in the surgery-related indexes, aesthetic satisfaction rate at 3 months postoperatively and functional status of the anterior cervical region between the 2 groups. SPSS 26.0 statistical software was used to process the data, analyze and draw conclusions. P<0.05 was considered a statistically significant difference. Results:The number of lymph nodes cleared in the study group (6.60±4.41) was less than that in the control group (9.63±6.25) ( P<0.05) ; the total operative time (169.83±28.76) min, postoperative drainage (173.60±94.33) ml, and time to remove drainage tubes after surgery (5.73±1.86 ) d was significantly higher than the total operative time (145.56±33.89) min, postoperative drainage (107.28±53.82) ml, and time to remove drainage tubes after surgery (2.88±1.07) d in the control group ( P<0.01) ;the intraoperative bleeding, number of positive lymph nodes, and postoperative hospital stay were not statistically significant between the two groups ( P>0.05) .The aesthetic satisfaction rate of the study group had a significant advantage over the control group (90% vs 70%) ( P<0.01) .Comparing the functional status of the anterior cervical region between the two groups after surgery,the occurrence of swallowing discomfort or with pulling sensation was better in the study group than in the control group 1 week after surgery ( P<0.05), and there was no statistically significant difference between the two groups in the occurrence of neck pain score, abnormal sensory function (neck pressure, foreign body sensation, numbness and pins and needles) and vocal difficulty ( P>0.05) ; 3 months after surgery, abnormal sensory function of the neck in the study group (at 3 months postoperatively, the occurrence of abnormal neck sensory function (neck pressure, foreign body sensation, numbness and pins and needles sensation) and swallowing discomfort or pulling sensation were better in the study group than those in the control group ( P<0.05). There were no signs of local recurrence or distant metastasis in both groups at follow-up to date. Conclusions:Both minimally endoscopic thyroidectomy procedures were safe, feasible, and effective in the treatment of unilateral PTMC. Among them, the ETGUA is more suitable for patients with strong cosmetic needs within the indications because of its concealed incision and its ability to protect the function of the anterior cervical region, and can be the preferred option.
Résumé
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.
Sujets)
Humains , Sesquiterpènes polycycliques , Sesquiterpènes/composition chimique , Aspergillus/composition chimique , Spectroscopie par résonance magnétique , Structure moléculaireRésumé
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.
Résumé
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.
Résumé
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.
Résumé
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.
Résumé
<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>
Résumé
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.
Résumé
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.
Résumé
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.