[Endoscopic full-thickness resection in near clinical complete response rectal cancer after neoadjuvant therapy].

Objective: To investigate the safety and feasibility of endoscopic full-thickness resection (EFTR) in the treatment of near-clinical complete response (near-cCR) rectal cancer after neoadjuvant therapy. Methods: A 74-year-old female patient with cT3N0M0 stage rectal adenocarcinoma who refused radical surgery for rectal cancer underwent neoadjuvant chemoradiotherapy (5 cycles of CapeOx chemotherapy and concurrent radiotherapy for 25 sessions) after multidisciplinary team discussion. One month after completing neoadjuvant treatment, reassessment including digital rectal examination, colonoscopy, and pelvic enhanced magnetic resonance imaging suggested near-cCR. Despite this, the patient requested rectal-preserving therapy. Subsequently, EFTR was performed five weeks after completion of neoadjuvant treatment. Postoperatively, supportive care including fasting, antimicrobial therapy, and nutritional support was provided. The patient started a liquid diet on the 6th day postoperatively and was discharged on the 13th day. Results: Pathological analysis revealed tubular adenoma with low-grade epithelial dysplasia, with negative margins and negative involvement of the base. During one-year follow-up, there were no signs of local regrowth or distant metastasis, and satisfactory anal function was observed. Conclusion: EFTR is safe and feasible in patients with near-cCR rectal cancer after neoadjuvant therapy. This approach should be considered after thorough evaluation of the patient's condition.

[Follow-up analysis of sex hormone levels and prognosis in women after hematopoietic stem cell transplantation].

Objective: To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT. Methods: Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results: The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions: The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.

[Exploration of phase angle used to construct PG-SGA nutritional assessment and prediction model for malignant tumor patients].

Objective: To explore the value of phase angle (PA) in constructing a predictive model of nutrition evaluation for tumor patients. Methods: A retrospective analysis was performed on 1 129 patients with malignant tumors hospitalized in the Cancer Center of Changzhi People's Hospital from June 2020 to February 2021. PA values of six parts of the body were measured by the body composition analyzer, including: left arm (LA), right arm (RA), left leg (LL), right leg (RL), the trunk (TR), and the whole body (WB). Patients' body mass index (BMI) was calculated and patient-generated subjective global assessment (PG-SGA) was assessed. The differences of PA values of six parts were compared and their correlations with BMI and PG-SGA in combination with age, gender and tumor disease types were analyzed, binary classification regression on BMI and PG-SGA was performed, and the functions of the best prediction model was fitted. Decision tree, random forest, Akaike information criterion in a Stepwise Algorithm (stepAIC) and generalized likelihood ratio test were used to select appropriate variables, and the logit logistic regression model was used to fit the data. Results: Comparing the PA values of six parts in pairs, it was found that the PA values of LA and RA, LL and RL, and TR and WB were linearly correlated and the coefficient was close to 1 (P<0.001). Binary classification regression was performed for BMI and PG-SGA, respectively. In order to make the data have clinical significance, 18.5 kg/m(2) was used as the classification point for BMI, 4 and 9 were used as the classification points for PG-SGA score, and the models of A, B and C were obtained. Suitable variables including PA-LA, PA-TR and tumor disease types were used as variables to fit BMI classification; BMI, PA-LA and age were used as variables to fit the PG-SGA model with 9 as the classification point. PA-LA, PA-TR, BMI, age and tumor disease types were used as variables to fit the PG-SGA model with 4 as the classification point. In this study, the predicted values of models A, B and C obtained by R-studio were imported into SPSS 26.0 software, and the cut-off values of classification were obtained by the receiver operating characteristic (ROC) curve. The ROC analytic results showed that the best cut-off values of Model A, B and C were 0.155, 0.793 and 0.295. Model A recommended when the probability is >0.155, a patient's nutritiond tatus should be classified as BMI < 18.5 kg/m(2) group. Model B recommended that PG-SGA<9 group be classified as the probability is >0.793. Model C recommended that PG-SGA < 4 group should be classified when probability is >0.295. Conclusions: The PG-SGA classification prediction model is simple to operate, and the nutritional status of patients can be roughly divided into three groups: normal or suspected malnutrition group (PG-SGA<4), moderate malnutrition group (4≤PG-SGA<9), and severe malnutrition group (PG-SGA≥9). This model can more efficiently predict the nutritional status of cancer patients, greatly simplify the nutritional assessment process, and better guide the standardized treatment of clinical malnutrition.

[Clinical and prognostic values of TP53 mutation in patients with B-lineage acute lymphoblastic leukemia].

Objective: To investigate the survival and prognosis of B-lineage acute lymphoblastic leukemia (B-ALL) patients with TP53 mutation. Methods: The clinical data of 479 newly diagnosed B-ALL patients treated in the First Affiliated Hospital of Soochow University from January 2016 to December 2019 were retrospectively analyzed. Results: Among 479 B-ALL patients, 34 cases (7.1%) were positive for TP53 gene mutation, and a total of 36 TP53 mutations were detected, including 10 frameshift gene mutations (27.8%) , 23 missense mutations (63.9%) and 3 nonsense mutations (8.3%) . A total of 34 (94.4%) mutations were located in the DNA binding domain (exons 5-8) .The average number of mutated genes in patients with TP53 gene mutation (2.3) and the group without TP53 gene mutation (1.1) were statistically different (P<0.001) . The proportion of Ph positive and Ph-like positive patients in the TP53 gene mutation negative group was significantly higher than that of the TP53 mutation positive group, and the difference was statistically significant (P<0.001) . The 3-year OS and EFS rates of the TP53 gene mutation negative group were significantly higher than those of the TP53 gene mutation positive group. The differences in OS and EFS rates between the two groups were statistically significant (χ(2)= 4.694, P = 0.030; χ(2)= 5.080, P= 0.024) . In the multivariate analysis, failure to achieve remission (CR) after one course of induction chemotherapy was an independent adverse prognostic factor affecting OS.Of the 34 patients with TP53 mutation, 16 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the CR(1) state, and 2 patients with recurrence after transplantation obtained CR(2) after infusion of donor-derived anti-CD19 chimeric antigen receptor T (CAR-T) cells. Among the 11 patients with TP53 gene mutation who relapsed during consolidation chemotherapy, 6 received anti-CD19 CAR T cell therapy, 4 patients achieved remission and minimal residual disease (MRD) turned negative, followed by bridging allo-HSCT, and 2 of them sustained CR. Conclusion: Missense mutations are the most common in B-ALL patients with TP53 gene mutation, and the majority of mutations were located in the DNA binding domain. B-ALL patients with TP53 gene mutation should undergo allo-HSCT as soon as possible after CAR-T cell therapy has cleared the MRD after recurrence. B-ALL patients with TP53 gene mutation still have a higher recurrence rate after allo-HSCT, and the infusion of donor-derived CAR-T cells can achieve better sustained remission.

SNHG3 silencing suppresses the malignant development of triple-negative breast cancer cells by regulating miRNA-326/integrin α5 axis and inactivating Vav2/Rac1 signaling pathway.

OBJECTIVE: Long non-coding RNA small nucleolar RNA host gene 3 (SNHG3) has been shown to participate in several tumorigenesis. Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer, which is the first leading cause of new cancer diagnoses in women globally. However, the role of SNHG3 remains little known in breast cancers, especially in TNBC. MATERIALS AND METHODS: Expression of SNHG3, miRNA-326-5p (miR-326) and integrin α5 (ITGA5) was detected using Real Time-PCR and Western blotting. Cell viability, apoptosis, migration, and invasion were measured by methyl thiazolyl tetrazolium assay, flow cytometry, and transwell assays, respectively. Vav2/Rac1 signaling pathway was evaluated by Western blotting by analyzing Vav2 and Rac1 levels. The interaction among miR-326, SNHG3 and ITGA5 was confirmed by Dual-Luciferase reporter assay. RESULTS: We found that the expression of SNHG3 and ITGA5 was upregulated and miR-326 was downregulated in TNBC tumors and cell lines (MDA-MB-231, BT-549, MDA-MB-468 and SUM159). Functionally, both SNHG3 silencing and miR-326 overexpression enhanced cell apoptosis, but depressed cell viability, migration and invasion in MDA-MB-231 and BT-549 cells, as well as inhibited Vav2 and Rac1 expression. Notably, miR-326 deletion could abolish the tumor-suppressive role of SNHG3 silencing; meanwhile, the similar anti-tumor effect of miR-326 overexpression was abrogated by ITGA5 restoration. Mechanically, SNHG3 silencing downregulated ITGA5 expression by functioning as a molecular "sponge" for miR-326. CONCLUSIONS: Silencing of SNHG3 suppressed the malignant development of TNBC cells, at least partially, through miR-326/ITGA5 axis and inhibiting Vav2/Rac1 signaling pathway.

[Dynamic alteration of microRNA in high phosphorus induced calcification of vascular smooth muscle cell].

OBJECTIVE: To study the change of microRNA during the early stage of high phosphorus induced vascular smooth muscle cell (VSMC) calcification and its related mechanism. METHODS: The in vitro calcification model was created through stimulating VSMC cell line A7r5 with high Pi (2.6 mmol/L) for 7 d. The calcification was validated through ocresolphthalein complexone colorimetry to detect the cellular calcium content, real-time PCR to measure the calcification-related gene expression and alizarin red staining to observe the formation of calcium nodules. Based on the cell calcification model, microRNA microarray array was applied to screen the profiles of microRNA expression in VSMC following high Pi stimulation for different periods (0, 3 and 12 h). The array data were analyzed by TAM tool to explore the activated signaling pathway. RESULTS: The calcium content of A7r5 cells induced by high Pi was increased 9.6 times high as cells without Pi treatment (P<0.05). VSMC contractile phenotype genes (SM-α actin, SM22) were down-regulated (P<0.05), while calcification-related genes (BMP2, MSX2, Runx2) were up-regulated (P<0.05) in VSMC stimulated by high Pi. The calcium nodules were obviously formed in cells after 7 d high Pi treatment. In microarray experiment, 680 individual microRNAs were detected in high Pi-treated VSMCs at different time points (0, 3 and 12 h). Among these genes, miR-183, miR-664 and miR-9* were increased whereas miR-542-5P, let-7f and miR-29a were decreased in time-dependent manners. Twenty-six kinds of signaling pathways, including cell apoptosis, differentiation and proliferation, were significantly activated. All these activated pathways were associated with calcification. CONCLUSION: This study implies that microRNA changed in high Pi-induced VSMCs may involve in the process of calcification.

Immuno-inflammatory regulation effect of mesenchymal stem cell transplantation in a rat model of myocardial infarction.

BACKGROUND: Mesenchymal stem cells (MSC) have recently been shown to possess immunomodulatory properties in vitro and in vivo. The present study aimed to investigate the regulatory effect of MSC transplantation on the immuno-inflammatory response in myocardial infarction (MI). METHODS: MI was induced in Sprague-Dawley rats by left anterior descending coronary artery ligation, and the animals were randomly assigned into the following three groups: sham ( n=8); phosphate-buffered saline (PBS) injected (MI+PBS, n=8); and MSC transplantation (MI+MSC, n=8). BrdU-labeled MSC or PBS was transplanted into peri-infarct myocardium by direct myocardial injection. At 1 and 28 days post-transplantation, cardiac function was evaluated by echocardiography. Transplanted cells were investigated through immunohistochemistry. Lymphocyte cytotoxic activity was evaluated with the crystal violet method. The activity of NF-kappaB and protein expression of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-10 in myocardium were assessed by immunohistochemistry and Western blot. RESULTS: Echocardiographic examination revealed that the MSC transplantation prevented left ventricular dilation and dysfunction at 28 days after the operation. BrdU-stained cells were found living in host heart 4 weeks after transplantation. MSC transplantation attenuated the cytotoxic activity of spleen lymphocytes. Transplantation of MSC inhibited the activity of NF-kappaB, attenuated the protein production of TNF-alpha and IL-6, and increased the expression of IL-10 in peri-infarct myocardium. DISCUSSION: MSC transplantation modulated the immuno-inflammatory response in MI. The immuno-inflammatory regulatory effect of MSC transplantation might partly account for the cardiac protection in myocardial infarction.