AIM:To investigate the therapeutic effect of menstrual blood-derived endometrial stem cells(MenSCs)on chemotherapy-induced intestinal mucositis and flora disorders in mice,and to explore the potential mecha-nism.METHODS:The mice were randomly divided into 3 groups including normal treatment,cisplatin(Cis)treatment and Cis+MenSC treatment,with 10 mice in each group.To induce intestinal mucositis,the mice were treated with Cis(2 mg·kg-1·d-1)by intraperitoneal injection for 5 consecutive days.Control mice for normal group were received equal vol-umes of normal saline.For Cis+MenSC treatment,MenSCs(1×106)was transplanted into the mice of Cis treated mice through tail vein.The performances and weight changes of mice were examined during the experiment.After the treat-ment,the small intestine and colon were isolated for subsequent HE staining,the ratio of F4/80 and IL-6 positive cells in small intestine were detected by immunohistochemical staining,and the expression of tight junction,inflammation and apoptosis related proteins was detected by Western blot.16S rDNA amplicon sequencing was performed to detect the diver-sity and richness of intestinal flora in mice.RESULTS:Compared to the Cis group,the MenSCs-treated mice showed sig-nificantly increased body weight,relieved intestinal lymphocytes infiltration,alleviated intestinal villous edema,and or-derly arranged glands in intestinal tissues.Further analysis indicated that MenSCs transplantation significantly up-regulat-ed the expression of intestinal tight junction related proteins ZO-1 and occludin in Cis-treated mice(P＜0.05).Subse-quently,MenSCs transplantation significantly inhibited the macrophages infiltration in intestinal tissues(P＜0.01),down-regulated the expression of pro-inflammatory factors IL-1 and IL-6 and pro-apoptotic protein Bax(P＜0.01),while up-regu-lated anti-inflammatory factor IL-10 and anti-apoptotic protein Bcl-2(P＜0.01).Additionally,further microflora sequenc-ing indicated that MenSCs transplantation prevented mice from Cis-induced intestinal flora disorder,and significantly re-duced the abundance of harmful bacteria such as isenbergiella tayi and Anaerotruncus colihominis(P＜0.01).At the same time,the abundance of beneficial bacteria Lactobacillus apodemi was increased(P＜0.05),thereby restoring the composi-tion and function of healthy intestinal flora.CONCLUSION:MenSCs transplantation alleviates the chemotherapy-in-duced damage of intestinal structure,relieves the symptoms of chemotherapy-induced mucositis and restores the homeosta-sis of intestinal flora in mice.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective To study the effect of mitochondrial reactive oxygen species(ROS)on male fertility and its application value in assisted reproduction so as to provide a new method for fertility assessment and etiological treatment of male infertility.Methods The relationship between sperm ROS and male infertility,sperm nuclear DNA integrity and sperm membrane function was analyzed.Then the relationships of the ROS of sperms for fertiliza-tion with fertilization rate,cleavage rate,embryo rate and pregnancy outcome were analyzed.Results(1)The percentage of the high ROS in sperm membrane of the male infertility group was significantly higher than that of the normal fertility group(P<0.01),but there was no statistical difference in the percentage of the high ROS in the sperm mitochondria between the two groups.(2)The normal rate of sperm membrane function in the normal group was significantly higher than that in the abnormal group(P<0.01),but there was no significant difference in the sperm DNA fragmentation index(DFI)between the groups.(3)There was significant difference in the fertilization rate between the IVF control group and IVF observation group,but no significant difference was seen in the cleavage rate,excellent embryo rate and clinical pregnancy rate between the groups.Conclusion Sperm ROS is related to male fertility to some extent.Abnormal ROS may lead to impaired sperm membrane function and affect sperm fertilization ability,thus affecting male fertility.The detection of ROS in sperm can be used as a new method to evaluate male fertility and provide a basis for diagnosis or treatment of male infertility.For patients with ART or infertility,the appropriate time to conceive can be selected according to the sperm ROS level.

Objective:To investigate the feasibility of coronary CT angiography(CCTA)-feature tracking(FT) for assessing global and regional myocardial strain in patients with heart failure(HF).Methods:From July 2019 to December 2020, twenty-five patients diagnosed with HF from Peking Union Medical College Hospital were prospectively enrolled into the study. All patients underwent retrospective electrocardiogram-gated CCTA and cardiac MR (CMR) imaging within 7 days. CCTA-FT and CMR-FT were undertaken using cvi 42 dedicated commercial software to measure global and regional strain parameters, including global peak radial strain (GPRS), global peak circumferential strain (GPCS) and global peak longitudinal strain (GPLS), as well as peak radial strain (PRS), peak circumferential strain (PCS) and peak longitudinal strain (PLS) of left ventricular basal segment, middle segment and apical segment. Conventional left ventricular functional parameters were also calculated, including left ventricular ejection fraction (LVEF), left ventricular stroke volume (LVSV) and left ventricular mass index (LVMI). Paired t test or Wilcoxon signed-rank test was used to compare the differences of measurements between CCTA group and CMR group. Pearson or Spearman correlation analysis was used to analyze the correlation between the two groups. Inter-and intra-observer consistence in CCTA group was evaluated by intraclass correlation coefficient (ICC) analysis. Results:The effective radiation dose of CCTA examination was 6.00 (4.86,7.63) mSv. Inter-and intra-observer consistence in CCTA group was excellent, and the ICC value was 0.85-0.98. In the overall strain parameters, GPCS in CCTA group[-8.10%(-10.32%, -5.20%)] was significantly lower than that of CMR group[-8.49%(-13.79%, -5.95%)] ( Z=-2.15, P=0.031). There was no significant difference in GPRS and GPRS between the two measurement methods ( P>0.05). Strong correlations were observed between GPRS, GPCS and GPLS ( r=0.65, 0.63, 0.71,all P<0.001). For local strain parameters, PCS in the middle segment and apical segment of CCTA group were lower than those of CMR group ( Z=-2.17, -2.62, all P<0.05). There were no significant differences in PCS of basal segment, PRS and PLS of all segments between groups (all P>0.05). The PCS and PLS of basal segment, PRS of middle segment and PRS of apical segment were moderately correlated ( r=0.46, 0.52, 0.58, 0.53, P<0.05); The other local strain parameters were strongly correlated, the range of r value was from 0.64 to 0.70 (all P<0.001). For left ventricular functional parameters, LVEF, LVSV and LVMI showed no significant differences between groups ( P>0.05), and the correlation was extremely strong ( r=0.90, 0.89, 0.96, all P<0.001). Conclusions:The repeatability of CCTA-FT technique in measuring myocardial strain was good, and the correlation of parameters measured by CCTA-FT technique and CMR-FT technique was excellent. Therefore, CCTA-FT technique can be used as a new noninvasive and simple method to evaluate myocardial motor function.

Background::Pre-operative assessment with high-resolution magnetic resonance imaging (MRI) is useful for assessing the risk of local recurrence (LR) and survival in rectal cancer. However, few studies have explored the clinical importance of the morphology of the anterior mesorectum, especially in patients with anterior cancer. Hence, the study aimed to investigate the impact of the morphology of the anterior mesorectum on LR in patients with primary rectal cancer.Methods::A retrospective study was performed on 176 patients who underwent neoadjuvant treatment and curative-intent surgery. Patients were divided into two groups according to the morphology of the anterior mesorectum on sagittal MRI: (1) linear type: the anterior mesorectum was thin and linear; and (2) triangular type: the anterior mesorectum was thick and had a unique triangular shape. Clinicopathological and LR data were compared between patients with linear type anterior mesorectal morphology and patients with triangular type anterior mesorectal morphology.Results::Morphometric analysis showed that 90 (51.1%) patients had linear type anterior mesorectal morphology, while 86 (48.9%) had triangular type anterior mesorectal morphology. Compared to triangular type anterior mesorectal morphology, linear type anterior mesorectal morphology was more common in females and was associated with a higher risk of circumferential resection margin involvement measured by MRI (35.6% [32/90] vs. 16.3% [14/86], P = 0.004) and a higher 5-year LR rate (12.2% vs. 3.5%, P = 0.030). In addition, the combination of linear type anterior mesorectal morphology and anterior tumors was confirmed as an independent risk factor for LR (odds ratio = 4.283, P = 0.014). Conclusions::The classification established in this study was a simple way to describe morphological characteristics of the anterior mesorectum. The combination of linear type anterior mesorectal morphology and anterior tumors was an independent risk factor for LR and may act as a tool to assist with LR risk stratification and treatment selection.

Objective:To explore the feasibility in evaluating segmental extracellular volume (ECV) using dual-layer spectral detector CT in patients with heart failure with various percentages of delayed hyper-enhanced volume, using MRI as a reference.Methods:Twenty-seven patients with heart failure in Peking Union Medical College Hospital were prospectively enrolled in this study from July 2019 to January 2021. All the patients underwent both CT late iodine enhancement and MR late gadolinium enhancement imaging within a week. According to percentages of hyper-enhanced volume on cardiac MR image, myocardial segments were classified into 3 groups: 0-4% (group A), 5%-49% (group B) and 50%-100% (group C). ECV images were independently observed by 2 experienced radiologists. The correlation and agreement between CT-ECV and MRI-ECV for the whole myocardial assessment and for the segmental assessment were evaluated using Spearman correlation and Bland-Altman analysis. Inter-observer agreement was assessed using the ICC.Results:Of the 27 patients, 432 segments were analyzed, with 199 segments in group A, 151 segments in group B and 82 segments in group C. In the whole myocardial analysis, the CT-ECV and MRI-ECV were 32.25% (28.04%, 34.28%) and 32.27% (28.35%, 34.77%), respectively. A good correlation was found between CT-ECV and MRI-ECV ( r=0.969, P<0.001). Bland-Altman analysis between CT-ECV and MRI-ECV showed a small bias (0.4%), with 95% limits of agreement of -6.9% to 7.8%. as for the segmental myocardial assessment, the CT-ECV was 28.23% (26.18%, 29.92%) for group A, 33.29% (30.16%, 35.96%) for group B and 40.22% (34.06%, 46.70%) for group C. There was statistically significant difference in ECV among three groups (all P<0.001). Good correlations between CT-ECV and MRI-ECV were found in group A ( r=0.614, P<0.001), group B ( r=0.852, P<0.001) and group C ( r=0.953, P<0.001). Bland-Altman analysis between CT-ECV and MRI-ECV showed a small bias 2.0% (95% limits of agreement:-17.6%-21.6%) in group A, a small bias -0.4% (95% limits of agreement: -13.8%-12.9%) in group B and a small bias -1.8% (95% limits of agreement: -17.4%-13.9%) in group C. The ICC values between 2 observers were 0.877 and 0.945 on CT-ECV and MRI-ECV, respectively. Conclusions:The larger percentage of hyper-enhanced volume on cardiac MR image, the stronger correlation are between the CT-ECV and MRI-ECV. CT-ECV may be taken as an alternative tool for quantitative evaluation of myocardial tissue in patients with heart failure.

Objective:To explore and establish an artificial neural network (ANN) model for predicting the efficacy of first-line FOLFOX chemotherapy for metastatic colorectal cancer.Methods:A set of FOLFOX chemotherapy data from a group of patients with metastatic colorectal cancer (mCRC) (GSE104645) was downloaded from the GEO database as a training set. According to the FOLFOX protocol, the efficacy was divided into two groups: the chemo-sensitive group (including complete response and partial response) and the chemo-resistant group (including stable disease and progressive disease), including 31 cases in the sensitive group and 23 in the resistant group. Then, chip data (accessible number: GSE69657) from Fujian Medical University Union Hospital were chosen as a test set. A total of 30 patients were enrolled in the study, including 13 in the sensitive group and 17 in the resistant group. The batch effect correction was performed on the expression values of the two sets of matrices using the R 3.5.1 software Combat package. The gene expression difference of sensitive and resistant group in GSE104645 was analyzed by the GEO2R platform. P<0.05 and the absolute value of log 2FC>0.33 (FC abbreviation of fold change) were used as the threshold value to screen the drug resistance and sensitive genes of the FOLFOX regimen. An ANN was constructed using the multi-layer perceptron (MLP) to perform the FOLFOX regimen on the GSE104645 dataset. The GSE69657 expression matrix and clinical efficacy parameters were then used for retrospective verification. Receiver operating characteristic(ROC) curves were used to evaluate the test results and predictive power. Results:A total of 2, 076 differentially expressed genes in GSE104645 were selected, of which 822 genes were up-regulated and 1, 254 genes were down-regulated in the chemo-resistance group. The down-regulated genes were sensitive genes. GO analysis of the biological processes in which the differentially expressed genes were involved, revealed that they were mainly involved in the regulation of substance metabolism. A total of 39 genes were included in the final model construction. This was a neural network model with two hidden layers. The accuracy of predicting training samples and test samples was 75.7% and 76.5%, respectively, and the area under the ROC curve was 0.875. The chip data set of our department (GSE69657) was set as the test set, and the area under the ROC curve was 0.778.Conclusions:In this study, an artificial neural network model is successfully constructed to predict the efficacy of first-line FOLFOX regimen for metastatic colorectal cancer based on the microarray, and an independent external verification is also conducted. The model has good stability and well prediction efficiency. Besides, the results of this study suggest that the gene functions related to oxaliplatin resistance are mainly enriched in the regulation process of substance metabolism.

Objective:To explore and establish an artificial neural network (ANN) model for predicting the efficacy of first-line FOLFOX chemotherapy for metastatic colorectal cancer.Methods:A set of FOLFOX chemotherapy data from a group of patients with metastatic colorectal cancer (mCRC) (GSE104645) was downloaded from the GEO database as a training set. According to the FOLFOX protocol, the efficacy was divided into two groups: the chemo-sensitive group (including complete response and partial response) and the chemo-resistant group (including stable disease and progressive disease), including 31 cases in the sensitive group and 23 in the resistant group. Then, chip data (accessible number: GSE69657) from Fujian Medical University Union Hospital were chosen as a test set. A total of 30 patients were enrolled in the study, including 13 in the sensitive group and 17 in the resistant group. The batch effect correction was performed on the expression values of the two sets of matrices using the R 3.5.1 software Combat package. The gene expression difference of sensitive and resistant group in GSE104645 was analyzed by the GEO2R platform. P<0.05 and the absolute value of log 2FC>0.33 (FC abbreviation of fold change) were used as the threshold value to screen the drug resistance and sensitive genes of the FOLFOX regimen. An ANN was constructed using the multi-layer perceptron (MLP) to perform the FOLFOX regimen on the GSE104645 dataset. The GSE69657 expression matrix and clinical efficacy parameters were then used for retrospective verification. Receiver operating characteristic(ROC) curves were used to evaluate the test results and predictive power. Results:A total of 2, 076 differentially expressed genes in GSE104645 were selected, of which 822 genes were up-regulated and 1, 254 genes were down-regulated in the chemo-resistance group. The down-regulated genes were sensitive genes. GO analysis of the biological processes in which the differentially expressed genes were involved, revealed that they were mainly involved in the regulation of substance metabolism. A total of 39 genes were included in the final model construction. This was a neural network model with two hidden layers. The accuracy of predicting training samples and test samples was 75.7% and 76.5%, respectively, and the area under the ROC curve was 0.875. The chip data set of our department (GSE69657) was set as the test set, and the area under the ROC curve was 0.778.Conclusions:In this study, an artificial neural network model is successfully constructed to predict the efficacy of first-line FOLFOX regimen for metastatic colorectal cancer based on the microarray, and an independent external verification is also conducted. The model has good stability and well prediction efficiency. Besides, the results of this study suggest that the gene functions related to oxaliplatin resistance are mainly enriched in the regulation process of substance metabolism.

Objective:To evaluate the feasibility of high concentrated contrast media combined with monochromatic images to improve image quality with double low scanning in dual-layer spectral coronary CT angiography.Methods:Fifty-six patients with suspected coronary artery disease were enrolled and randomly separated into two groups. All patients were scanned at 120 kVp in step-and-shoot mode using a dual-layer detector CT (IQon spectral CT). Patients were either injected with 18 ml high concentration contrast medium(400 mgl/ml) at 2 ml/s (group A) or 45 ml contrast medium (370 mgl/ml) at 4 ml/s (group B). Forty to 80 keV monoenergetic images with 10 keV increment and conventional image (group A2) were reconstructed for group A, conventional poly-energetic image was reconstructed for group B. Region of interest was placed on aorta root (AO), middle segment of left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA) to measure the attenuation and noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Image quality was assessed by two reviewers independently with a 4-point scale on image quality (1-undiagnostic,4-excellent). The objective and subjective image evaluation were compared using the Kruskal-Wallis test. The Steel Dwass was used for multiple comparisons between monoenergetic images in Group A and conventional images in Group B, after the Kruskal-Wallis test.Results:There were significant differences among the attenuation, noise, SNR and CNR of group B, group A2, and monoenergetic images(all P<0.001).The CT value in the aortic root was significantly higher at 40-50 keV monoenergetic images than that in group B(all P<0.05), and similarly, the CT value in LAD,LCX and RCA at 40 keV were superior than that in group B(all P<0.001). There was no significant difference in the noise of the aortic root among 40 keV image, group A2 and group B(all P>0.05),while the noise in the 50-80 keV monoenergetic images were significantly lower than that in Group B(all P<0.001). The SNR and CNR in the aortic root were significantly higher at 40-60 keV monoenergetic images than that in group B(all P<0.001).The SNR in LAD and RCA at 40，50 keV and the CNR in LAD and RCA at 40-60 keV were higher than that in group B(all P<0.01).The SNR at 40-60 keV and CNR at 40-70 keV in LCX were superior than that in group B(all P<0.05). There were significant differences among the subjective image quality score of group B, group A2, and monoenergetic images(all P<0.001).The subjective image quality score of 40，50 keV images were not significantly different from that in group B (all P>0.05),while the score in 60-80 keV image and group A2 were lower than that of Group B(all P<0.001). Conclusion:40，50 keV low monochromatic images derived from dual-layer spectral detect CT combined with high concentrated contrast media can provide comparable or superior image quality with double low scanning in CCTA study.

Objective:To evaluate the clinical performance of postoperative deformity after the release of simple syndactyly, and to discuss the corresponding method for repair.Methods:Clinical data of 25 children with postoperative deformities after simple syndactyly releasing were reviewed retrospectively in the past 5 years, including 13 males and 12 females, with an average age of 3 years and 2 months. The possible causes leaded to postoperative deformity were analyzed by investigating the data of the first operation, including the age of the first operation, whether there was skin graft and whether there was postoperative infection. The common types of postoperative deformities were summarized through morphological observation, and the main methods of reoperation repair were reviewed. During follow-up, the improvement of postoperative deformities after repair was evaluated from the four aspects of webbed shape, finger shape, fingernail shape and skin color difference, so as to propose an effective repair plan for such postoperative deformities.Results:The average age of the first operation was 1 year and 5 months, 15 cases had no skin graft with tense skin, and 4 cases had a history of wound infection. The postoperative deformities of simple syndactyly can be summarized in four main categories: web deformity in 27 webs, finger deformity in 53 fingers, nail deformity in 46 nails and skin color difference in 15 fingers. During the revision surgery, for web deformity, Z-plasty technique were used to widen narrow webs, the flaps were used to reconstruct the recurred webs and the double wing flap were used in 13 webs. For finger deformity, in all cases, most of scar skin was reserved and released by multiple Z-plasty incisions to extend and straighten the fingers, while full-thickness skin grafting was employed if lacking of enough skin to close wound. For nail deformity, using the adjacent flap pushed forward to wrap the nail margin in 14 crooked nail cuticles and others remained untreated. For skin color difference, using z-plasty incision to break the large piece of dark skin into small one and remove the overly dark skin as much as possible. The average follow-up time after reoperation was 33 months, and all webs reached the normal depth and width. Except for the incomplete correction of the lateral deviation in 1 finger, the deformity of the other fingers hand was corrected completely. There was no improvement in other nail deformity except for 10 skew nail cuticle being improved. The skin color difference were improved in all cases.Conclusions:The occurrence of postoperative deformity of simple syndactyly may be related to the tight stitching (should have skin grafting) and the wound infection during primary surgery. The reconstructive operation should be performed about one year after the initial operation when the scar is softened. The flaps for construction of web space, especially double wing flap, can be used widely in all kinds of web deformities, which could result in excellent web shape. The area of skin grafting can be reduced dramatically by reserving softened scar skin. Multiple Z-plasty technique can make use of the transverse excess skin to extend the longitudinal skin and corrected enlarged finger bodies. When should be used to reduce the color difference. But the repair of most of nail deformity were too difficult to improve.