[Multicenter evaluation of minimal residual disease monitoring in early induction therapy for treatment of childhood acute lymphoblastic leukemia].

Objective: To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL). Methods: This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children's Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors. Results: Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×109/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively (χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant (χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively (χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%,χ2=4.13,P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%,χ2=4.06,P=0.044;(58.3±18.6)% vs. (85.7±3.2)%,χ2=9.44,P=0.002). Multivariate analysis showed that age (OR=0.58, 95%CI 0.35-0.97) and white blood cell count at first diagnosis (OR=0.43, 95%CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 (OR=0.55,95%CI 0.31-0.97), ETV6-RUNX1 fusion gene (OR=0.13,95%CI 0.03-0.54), MLL gene rearrangement (OR=2.55,95%CI 1.18-5.53) and white blood cell count at initial diagnosis (OR=0.52,95%CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions: The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

[Diagnostic and prognostic values of flow cytometry in diffuse large B-cell lymphoma with bone marrow involvement].

Objective: To analyze the diagnostic and prognostic values of flow cytometry (FC) in diffuse large B cell lymphoma (DLBCL) with bone marrow involvement (BMI). Methods: The clinical data of 412 patients with newly diagnosed DLBCL, including 243 males and 169 females, aged 64 (28-92) years old, in the Department of Hematology at Peking University Third Hospital from December 2012 to June 2022 were retrospectively analyzed. All patients underwent bone marrow biopsy (BMB) and bone marrow FC. The patients with BMI by FC were further detected by fluorescence in situ hybridization (FISH) for gene analysis. The positive rates and consistency of BMI detected by BMB and FC were evaluated. According to the results of BMB and FC examinations, all patients were divided into four groups: the BMB+FC+group (115 cases), the BMB-FC+group (50 cases), the BMB+FC-group (8 cases, the results did not include in statistical analysis because of small sample size), and the BMB-FC-group (239 cases). The clinical features, treatment response rates, 5-year survival rates, and immunophenotype characteristics by FC in different groups were analyzed. Results: Among the 412 patients with DLBCL, the positivity rates of BMB and FC for BMI detection were 29.9% (123/412) and 40.0% (165/412), respectively. Good consistency between BMB and FC was found (Kappa=0.841, P=0.001). The numbers of extranodal involvement≥2, splenomegaly, huge mass, higher Ki-67 score, higher international prognostic index (IPI) score, thrombocytopenia, and elevated lactate dehydrogenase level were more prevalent in the BMB+FC+group than those in the BMB-FC+group and the BMB-FC-group (all P<0.05). The treatment response rate in BMB+FC+group was 63.5% (73/115), which was lower than those in BMB-FC+group (88.0%, 44/50, P=0.048) and BMB-FC-group (90.0%, 215/239, P=0.032), respectively. The 5-year overall survival rates in three groups were (53.6±9.7) %, (72.5±8.6) %, and (75.2±7.6) %, respectively, with a statistically significant difference (P=0.037). According to the FISH results of bone marrow, 102 cases were diagnosed as not otherwise specified (NOS), 48 cases were diagnosed as double hit lymphoma (DHL), and 15 cases were diagnosed as triple hit lymphoma (THL). Compared with NOS subtypes, the tumor cells in DHL or THL subtypes had higher proportion of increased side scatter (SSC), higher positive rates of CD10 expression, CD38 strong expression and CD56 expression, and lower proportion of surface immunoglobulin light chain restriction (all P<0.05). Conclusions: FC is well consistent with BMB in diagnosing DLBCL with BMI. Combined with FISH detection, FC can contribute to the auxiliary diagnosis and risk stratification for DHL and THL, and provide reference for the prognostic evaluation in DLBCL with BMI.

Awareness, perceptions, and acceptance of human papillomavirus vaccination among parents in Hong Kong.

INTRODUCTION: This study investigated the awareness, perceptions, and acceptance of human papillomavirus (HPV) vaccination for children among parents in Hong Kong. It also explored factors associated with, and differences in, vaccine acceptance and hesitancy between parents of girls and boys. METHODS: Parents of boys or girls in Primary 5 to 6 were invited to participate in an online survey through an established health and lifestyle e-platform. RESULTS: Overall, 851 parents completed the survey: 419 (49.2%) had daughters, 348 (40.9%) had sons, and 84 (9.9%) had children of both genders. Parents who enrolled their children into the Childhood Immunisation Programme were more likely to accept HPV vaccination (79.7% vs 33.7%, odds ratio [OR]=7.70; 95% confidence interval [CI]=5.39-11.01; P<0.001); parents of girls were more likely to accept than parents of boys (86.0% vs 71.8%, OR=2.40; 95% CI=1.67-3.46; P<0.001). Among parents of girls and boys, the main reasons for HPV vaccination acceptance were prevention of cancers (girls: 68.8% and boys: 68.7%), prevention of sexually transmitted diseases (girls: 67.3% and boys: 68.3%), and optimal timing before initiation of sexual activity (girls: 62.8% and boys: 59.8%). Vaccine hesitancy was mainly associated with concerns about serious side-effects (girls: 66.7% and boys: 68.0%) and the belief that their children were too young (girls: 60.0% and boys: 54.0%). CONCLUSION: Parents in Hong Kong are hesitant about HPV vaccination for their sons. This barrier could be removed by providing information to correct vaccine safety misconceptions and offering a gender-neutral vaccination programme through the school-based Childhood Immunisation Programme.

[Clinical features of children with Cunninghamella spp. infection: a case report and literature review].

We report a case of mucormycosis induced by Cunninghamella spp. infection in a ten-year-old girl with acute lymphoblastic leukemia, who developed fever and respiratory symptoms after chemotherapy and was diagnosed with invasive fungal disease. Peripheral blood DNA sequences were analyzed using metagenomic next-generation sequencing (mNGS), and by comparison with the Pathogens Metagenomics Database (PMDB), we identified Cunninghamella spp. with sequence number 514 as the pathogen. The patient was treated with amphotericin B combined with posaconazole and showed a favorable response. We searched Pubmed, Embase, CNKI, and Wanfang database for reports of cases of Cunninghamella spp. infection in children and retrieved 22 reported cases (including 12 males) with a median age of 13.5 (3-18) years. In these 22 cases, hematological malignancy was the most common underlying condition (19/22), and most of patients experienced an acute onset and rapid progression with respiratory symptoms (14/20) and fever (16/20) as the most common symptoms. CT imaging often showed unilateral lesions with varying imaging findings, including pulmonary nodules or masses, infiltrative changes, and pleural effusion. Definite diagnoses were established in 18 of the cases, and 4 had probable diagnoses; the lungs and skin were the most frequent organs compromised by the infection. A definite diagnosis of Cunninghamella spp. infection still relied on histopathological examination and fungal culture, but the molecular techniques including PCR and mNGS had shown potentials in the diagnosis. Almost all the cases received antifungal treatment after diagnosis (21/22), and 13 patients also underwent surgeries. Death occurred in 9 (42%) of the cases at a median of 19 (4-54) days after onset of the signs or symptoms. The patients receiving antifungal therapy combined with surgery had a high survival rate (9/13, 69%) than those with antifungal therapy alone (3/8, 37%). Invasive fungal disease is a common complication in immunoco-mpromised patients, but Cunninghamella spp. infection is rare and has a high mortality rate. In cases highly suspected of this disease, active diagnosis and early treatment are critical to improve the survival outcomes of the patients.

[Expression of CD7 and its correlation with prognosis in patients with NK/T-cell lymphoma].

Objective: To analysis the expression of CD7 in NK/T-cell lymphoma as well as study the correlations between CD7 and clinical survival and prognosis. Methods: The clinical and pathological indicators of 112 NKTCL patients who were admitted to or consulted at the First Affiliated Hospital of Zhengzhou University between May 2008 and December 2019 were analyzed retrospectively. The CD7 expression in the tumor tissues was detected using immunohistochemistry staining, and the influence of CD7 expression on the survival and prognosis in the patients was analyzed. Results: The CD7 expression rate was 84.82% in 112 NKTCL patients, and its expression was not influenced by sex, age, and the primary site. An analysis of the complete clinical data of 72 patients showed that the CD7 expression was significantly correlated with the PINK score, tumor metastasis, and peripheral blood EBV-DNA level. However, the Ann Arbor stage, bone marrow involvement, B symptoms, IPI/aaIPI score, Ki-67, EBER, TIA-1, Granzyme B, LDH, and ß(2)-MG were not associated with the CD7 expression. The 1-year, 3-year, and 5-year overall survival (OS) rates of the 72 patients were 81.2%, 61.8%, and 58.8%, respectively, and the progression-free survival (PFS) rates were 53.5%, 29.4%, and 24.0%, respectively. The median overall survival (median-OS, mOS) was 81 mon, and the median progression-free survival (median-PFS, mPFS) was 14 mon. The 3-year OS rates in the CD7-positive group and the CD7-negative group were 58.1% and 83.9%, respectively, (P>0.05) . The 3-year PFS rates were 21.7% and 51.9%, respectively (P<0.05) . The univariate analysis showed that age, primary tumor site, Ann Arbor stage, IPI/aaIPI score, PINK score, LDH, ß(2)-microglobulin, EBV-DNA, Ki-67, and CD7 influenced patient prognosis. The multivariate analysis showed that Ann Arbor stage and CD7 were independent prognostic factors for PFS, while PINK score and Ki-67 were independent prognostic factors for OS. Conclusions: The expression rate of CD7 in NKTCL was high and was closely related to poor patient prognosis. The patients with high levels of EBV-DNA, metastatic disease, or high PINK score were more likely to express CD7.

[Analysis of clinical characteristics, treatment and survival of elderly patients with large diffuse B-cell lymphoma].

Objective: To analyze the clinical feature,treatment and survival outcome of elderly patients older than 80 years with large diffuse B-cell lymphoma. Methods: A total of 46 patients aged over 80 years with large diffuse B-cell lymphoma who were treated in Third Hospital of Peking University during the period from 2002 to 2018 were retrospectively analyzed, and the clinical features, laboratory data, survival and prognostic factors were included in Kaplan-Meier and prognostic analysis. Results: Patients older than 80 years old accounted for 15.7% (46/293) in all elderly patients, and the median age was 83 years old. There were 78.3% (36/46)patients who belonged to stage Ⅲ or Ⅳ, 63%(29/46) who had more than two extranodal organ involvement, and the higher proliferation index(Ki-67≥80%) was present in 53.7%(22/41) patients. Immunohistochemistry showed that 37% patients in 27 cases were double-expressed DLBCL. With a median follow-up of 25 months, the overall response rate (ORR) for the whole group was 63.0%, the complete response (CR) rate was 36.4%, the 2, 3-year progression-free survival (PFS) rate was 49.9% and 41.7%, the 2, 3-year overall survival (OS) rate was 54.6% and 43.6% respectively. The ORR for patients who received anthracycline-based therapies and non-anthracycline-based therapies were 81.8% and 55.0%, and the 3-year OS rate were 50.0% and 39.0%, respectively, but the difference was not statistically significant (P>0.05). 45.5% patients had hematologic toxicity of Grade Ⅲ or above, and 56.8% patients experienced infections during the treatment. Among the patients who died, the treatment-related mortality rate in group with high score of Charlson comorbidity index(CCI) was higher (43.8% vs 16.7%, P=0.03) . The National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score, nodal involvement area ≥3, 6 cycles of chemotherapy, CCI score, initial treatment outcome and refractory-relapsed were predictive of overall survival. Multivariate analysis indicated the CCI score (HR=6.463, P=0.008) and initial treatment outcome (HR=0.086, P=0.001) were independent prognostic risk factors. Conclusions: The clinical and pathological features of patients older than 80 years were highly aggressive with poor chemotherapy tolerance and high adverse reaction rate. Anthracycline-based therapies may be less important in the treatment of DLBCL patients aged over 80 years. Patients with high CCI score have higher treatment-related mortality and CCI can help identify elderly patients who are suitable for larger chemotherapy dose.

[A model to predict the recurrence of middle-high risk gastrointestinal stromal tumors based on preoperative fibrinogen and peripheral blood inflammatory indexes].

Objective: At present, the modified NIH classification commonly used in clinical practice is still insufficient for assessing the risk of postoperative recurrence in some patients with intermediate-high risk gastrointestinal stromal tumors (GIST). Through exploring risk factors for recurrence of intermediate-high risk GIST, this study establishes a predictive model for recurrence with more convenience and more precision in order to guide adjuvant therapy for intermediate-high risk GIST patients. Methods: A retrospective case-control study was carried out. Clinical and pathological data of 432 GIST patients who did not receive preoperative targeted treatment, underwent complete resection in the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2005 to June 2018, and were diagnosed as intermediate- or high-risk based on modified NIH classification by postopertive pathology, were retrospectively analyzed. Cox regression model was used to idenitify independent risk factors of recurrence, and a recurrence risk scoring model was established. The receiver operating characteristic curve (ROC curve), consistency index (C-index) and calibration curve were used to evaluate the accuracy of the scoring model in predicting the recurrence of moderate-risk and high-risk GIST patients. Results: Among 432 GIST patients, 332 were diagnosed as high-risk and 100 as moderate-risk; 237 were males and 195 females with average age of (57.4±12.4) years. Of 432 patients, 211 cases (48.8%) had fibrinogen (FIB) >3.5 g/L; 85 cases (19.7%) had platelet to lymphocyte ratio (PLR)>272.5; 122 cases (28.2%) had neutrophil to lymphocyte ratio (NLR) > 4.2; 102 cases (23.6%) had systemic inflammatory reaction index (SIRI)> 2.7; 198 cases (45.8%) had tumor long diameter >8 cm and 108 cases (25.0%) had mitotic counts > 8/50 HPF. Cox multivariable analysis showed that FIB (HR=1.789, 95% CI: 1.058-3.027, P=0.030), PLR (HR=1.862, 95% CI: 1.067-3.249, P=0.029), SIRI (HR=1.790, 95% CI: 1.039-3.084, P=0.036), tumor long diameter (HR=1.970, 95% CI: 1.105-2.925, P=0.017) and mitotic counts (HR=2.187, 95% CI:1.211-3.950, P=0.009) were independent risk factors for recurrence in patients with middle-risk and high-risk GIST. These 5 factors were included in the risk scoring model, which was given a weight score of 58 points, 62 points, 58 points, 63 points, and 78 points, respectively. Patients with a total score of ≤ 78 points were classified as moderate-risk recurrence (group I), those of 78 to 136 points as high-risk recurrence (group II) and those of >136 points as very high-risk recurrence (group III). ROC curve showed that the area under the curve (AUC) of the scoring model was 0.730 and the C-index was 0.724 (95% CI:0.687-0.787). The calibration curves and the Kaplan-Meier curves of patients in the three groups revealed that this model had a good predictive accuracy. Conclusions: For intermediate-risk and high-risk GIST patients, the preoperative FIB >3.5 g/L, PLR > 272.5 and SIRI > 2.7 are independent risk factors of recurrence after surgery. The recurrence risk scoring model established by combining tumor long diameter, mitotic counts, FIB, PLR and SIRI can effectively predict the risk of postoperative recurrence and metastasis in moderate-risk and high-risk GIST patients.

Knockdown of long noncoding RNA linc-ITGB1 inhibits tumor metastasis in colorectal cancer through suppressing BDNF.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Knockdown of long noncoding RNA linc-ITGB1 inhibits tumor metastasis in colorectal cancer through suppressing BDNF, by W.-B. Wan, Q.-L. Kong, published in Eur Rev Med Pharmacol Sci 2019; 23 (15): 6453-6458-DOI: 10.26355/eurrev_201908_18528-PMID: 31378884" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18528.

Low expression of miR-1 promotes osteogenic repair of bone marrow mesenchymal stem cells by targeting TLR1.

OBJECTIVE: Bone marrow mesenchymal stem cells (BMSCs) promote bone tissue repair. MiR-1 regulates myogenic and osteogenic differentiation of human adipose tissue stem cells. However, miR-1's effect on BMSCs osteogenesis is unclear. MATERIALS AND METHODS: Rat BMSCs were isolated and divided into control group, miR-1 group, and si-miR-1 group respectively transfected with miR-1 plasmid and miR-1 siRNA followed by analysis of cell proliferation by MTT assay and Caspase 3 activity. The expression of osteogenic genes Runx2 and OPN was measured by Real Time-PCR. Healthy male Sprague-Dawley rats were separated into fracture group, NC group, and si-miR-1 group followed by analysis of bone mineral density, miR-1 level by Real Time-PCR, type I collagen, and BMP-2 by enzyme-linked immunosorbent assay (ELISA), and TLR1 expression by Western blot. RESULTS: Transfection of miR-1 siRNA into BMSCs significantly downregulated miR-1 expression, promoted BMSCs cell proliferation, inhibited Caspase 3 activity, as well as promoted osteogenic genes Runx2 and OPN expression and decreased TLR1 expression (p<0.05). The upregulation of miR-1 expression significantly reversed the above changes. TLR1 is a target of miR-1. Downregulation of miR-1 expression in BMSCs of fractured rats significantly increased bone density and ALP activity, promoted type I collagen and BMP-2 expression, and decreased TLR1 expression (p<0.05). CONCLUSIONS: The downregulation of miR-1 promotes BMSCs osteogenic differentiation via targeting TLR1, which promotes osteogenic differentiation and bone healing.

[Analysis of imatinib trough concentration at steady state in adjuvant therapy of patients with high risk gastrointestinal stromal tumor].

Objective: To explore the features of imatinib mesylate (IM) plasma concentration during adjuvant therapy and clinical factors associated with IM plasma concentration in patients with high risk gastrointestinal stromal tumors (GIST), and to determine whether IM plasma concentration <1100 µg/L influences the efficacy of adjuvant therapy. Methods: A retrospective case control study method was used. Case inclusion criteria: (1) complete resection of lesion and GIST confirmed by pathology; (2) high risk classified according to modified National Institutes of Health classification system (2008); (3) administration of IM 400 mg/d for at least 1 month; (4) not taking the medication likely affecting IM pharmacokinetic, such as rifampicin, dilantin, and carbamazepine, within 1 month before blood collection. Data of GIST patients who visited GIST Disease - Oriented Outpatient, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 to December 2018 were retrospectively analyzed. After taking IM for 22-26 hours, 5 ml of peripheral venous blood was collected into EDTA anticoagulant tube. IM plasma concentration was detected by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Patients were divided into <1100 µg/L group and ≥1100 µg/L group according to plasma concentration. Linear regression was used to analyze the relevance between clinical features and IM plasma concentration. Parameters with normal distribution were analyzed by Pearson correlation coefficient, and parameters with non-normal distribution were analyzed by Spearman correlation. Kaplan-Meier survival curves and COX regression model were used for survival analysis. Results: Among the 85 patients enrolled in the study, 49 patients (57.6%) were male and 36 (42.4%) were female, with mean age of (51.9±11.0) years. The body mass index was (22.5±2.9) kg/m(2) and body surface area was (1.6±0.2) m(2). Thirty patients received gene test, including 23 patients with c-Kit exon 11 mutation, 4 with c-Kit exon 9 mutation, 1 with c-Kit exon 11 and 17 mutation and 2 without c-Kit or PDGFRA gene mutation. The mean IM plasma concentration was (1391.4±631.3) µg/L, and there were 32 patients with plasma concentration <1100 µg/L and 53 patients with plasma concentration ≥1100 µg/L. There were no statistically significant differences between the two groups in gender, age, body mass index, body surface area, hematological examination (white blood cells, albumin, alanine aminotransferase, aspartate aminotransferase and serum creatinine), tumor location, tumor size, mitotic counts, duration of adjuvant therapy and methods of operation (all P>0.05). Positive correlation between IM plasma concentration and serum creatinine was observed in linear regression analysis (r=0.297, P=0.007), but there were no correlations between IM plasma concentration and age (r=0.044, P=0.686), body mass index (r=0.066, P=0.547), body surface area (r=-0.010, P=0.924), white blood cells (r=-0.080, P=0.478), albumin (r=-0.065, P=0.563), alanine aminotransferase (r=0.114, P=0.308), aspartate aminotransferase (r=0.170, P=0.127) and duration of adjuvant therapy (ρ=0.060, P=0.586). There was no statistically significant difference in IM plasma concentration between patients with different genders (t=0.336, P=0.738) and patients with different surgical methods (F=0.888, P=0.451). Up to March 1, 2019. the median follow-up time was 30 (range 4-49) months. Tumor recurrence was detected in two patients with plasma concentration <1100 µg/L and two with plasma concentration ≥1100 µg/L. One recurrent patient with plasma concentration <1100 µg/L was detected to harbor c-Kit exon 11 and exon 17 mutations, and the other did not receive gene detection. Two recurrent patients with plasma concentration ≥1100 µg/L were both detected to harbor c-Kit exon 9 mutation. The 3-year relapse-free survival rate was 96.4% in the cohort, 96.2% in patients with plasma concentration <1100 µg/L, and 96.6% in patients with plasma concentration ≥1100 µg/L. No significant difference in relapse-free survival was observed between the two groups (P=0.204). Univariate Cox analysis showed that IM plasma concentration <1100 µg/L was not a risk factor for patients with high risk GIST (HR=0.238, 95% CI: 0.022-2.637, P=0.242). Conclusions: IM plasma concentration of adjuvant therapy in patients with high risk GIST varies with individual. Patients with higher level of serum creatinine are more likely to have a higher plasma concentration. A blood drug concentration standard of less than 1100 µg/L for advanced GIST patients may not influence the prognosis of patients with high risk GIST.

Knockdown of long noncoding RNA linc-ITGB1 inhibits tumor metastasis in colorectal cancer through suppressing BDNF.

OBJECTIVE: Recently, long noncoding RNA (lncRNAs) have got much attention for their role in the progression of cancers. In this research, lncRNA linc-ITGB1 was studied to identify whether it affects the development of colorectal cancer (CRC). PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was performed to detect the linc-ITGB1 expression of CRC cells and tissues. Moreover, the associations between linc-ITGB1 expression level and patients' overall survival rate were further analyzed. Furthermore, we conducted function assays, including wound healing assay and transwell assay, to explore the effect of linc-ITGB1 on CRC metastasis in vitro. In addition, the underlying mechanism was further studied. RESULTS: RT-qPCR results showed that linc-ITGB1 expression level was higher in CRC samples than that in adjacent tissues. Linc-ITGB1 expression was related closely to patients' overall survival time. Moreover, cell migration and cell invasion were inhibited after linc-ITGB1 was silenced in vitro. In addition, the mRNA and protein expression of BDNF was downregulated by the silence of linc-ITGB1. Furthermore, the expression level of BDNF was higher in CRC samples than that in adjacent tissues and was positively related to the expression of linc-ITGB. CONCLUSIONS: These results indicate that linc-ITGB1 could enhance CRC cell migration and invasion via upregulating BDNF. Linc-ITGB1 might be a potential therapeutic target for CRC patients.

[Laparoscopic versus open surgery for gastric gastrointestinal stromal tumors in unfavorable location: a propensity score-matching analysis].

Objective: To investigate the efficacy and feasibility of laparoscopic resection for gastric gastrointestinal stromal tumor (GIST) in unfavorable location by comparing with open surgery. Methods: Clinicopathological and follow-up data of 176 patients with gastric GIST in unfavorable location admitted at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2005 to December 2017 were analyzed retrospectively. There were 94 males and 82 females, aging of (57.4±12.7) years (range: 20-90 years). Of the 176 patients, 64 underwent laparoscopic surgery (laparoscopic group) and 112 underwent open surgery (open group). One-to-one propensity score matching (PSM) was performed to balance the covariance between laparoscopic group and open surgery group. Before PSM, the differences between the two group in tumor size and modified National Institutes of Health risk classification were significant. After PSM, there were 63 pairs (63 cases in laparoscopic group and 63 cases in open group) and the baseline characteristics were comparable between the two groups(P>0.05). The difference of short-term outcome between the two groups were compared using t test, χ(2) test or Wilcoxon rank-sum test. The survival curve was established by Kaplan-Meier method and the Log-rank test was used to compare the survival of the two groups. Results: The operation time of laparoscopic group was shorter ((141.6±100.6) minutes vs. (100.4±67.7) minutes, t=2.681, P=0.008), the hospitalization cost was higher ((5.2±0.7) ten thousand yuan vs. (4.2±0.8) ten thousand yuan, t=7.357, P=0.000) than open group. The time to first flatus ((49.1±8.2) hours vs. (71.0±4.6) hours, t=-18.482, P=0.000) and preoperative hospital stay ((10.3±6.0) days vs. (14.8±7.6) days, t=-3.717, P=0.000) was shorter in laparoscopic group. With a median follow-up time of 44 months (range: 10 to 154 months), the 1-, 3-, 5-year relapse-free survival rates in the laparoscopic group and open group were 98.3%, 92.1%, 92.1% and 100%, 86.3%, 83.2%, respectively (χ(2)=0.696, P=0.404). The 1-, 3-, 5-year overall survival rates in the laparoscopic group and open group were 96.6%, 94.7%, 94.7% and 100%, 91.1%, 81.4%, respectively (χ(2)=0.366, P=0.545). Conclusions: In experienced medical centers, laparoscopic resection is safe and feasible for GIST in unfavorable location. Compared to open surgery, laparoscopic resection achieves a faster postoperative recovery and a similar long-term prognosis.

[Efficacy of anti-CD19 CAR-T cell therapy in 10 refractory recurrent B cell malignancies].

Objective: To investigate the outcomes of anti-CD19 CAR-T cell for relapsed and refractory B cell malignancies. Method: Ten patients with relapsed and refractory B cell acute lymphocytic leukemia (B-ALL) and non-Hodgkin's lymphoma (NHL), diagnosed in the Department of Hematology of Peking University third Hospital from December 2015 to July 2017, were treated with anti-CD19 CAR-T cell therapy, and the efficacy and safety were analyzed. Results: Efficacy was assessed on the 28th day after cell infusion, including 66.7% (4/6) of complete remission (CR) for patients with ALL, 16.7% (1/6) of partial remission (PR), and 83.3% (5/6) of overall response rate (ORR). For NHL patients, CR was 33.3% (1/3) and most of the lesions disappeared in a patient with mantle cell lymphoma, but residual lesion presented persistent state. After infusion of anti-CD19 CAR-T cells, the main side effect was cytokine release syndrome (CRS) and fever. One patient presented with aphasia and the other one had multiple organ failure, which were improved after treatment. No patients died of CRS. Conclusion: anti-CD19 CAR-T cell for relapsed and refractory B cells hematological malignancies is safe, and the most problematic side effect is CRS, which can be controlled by therapy.

Correlation between elastic parameters and collagen fibre features in breast lesions.

AIM: To correlate elastic parameters with collagen fibre shape and arrangement features in breast lesions. MATERIALS AND METHODS: Shear-wave elastography (SWE) was used to measure the stiffness of breast lesions in 54 patients before surgical removal. The value of stiffness was expressed as the mean and maximum elasticity (Emean and Emax). Lesions were sliced and stained with picric acid-sirius red to display the extracellular matrix (ECM) collagen fibre. The categories of the collagen fibres were based on the shape and arrangement features, i.e., category 0, wavy collagen fibres similar to normal breast tissue; category 1, taut parallel collagen fibres around tumour nests; category 2, straightened and aligned collagen fibres tending to be perpendicular to the tumour boundary; category 3, collagen fibre in a honeycomb arrangement. Bivariate correlation analysis was used to analyse the relationship between elastic parameters and collagen fibre category. RESULTS: For all 54 lesions, the correlation coefficient between Emean and category was 0.693 (p < 0.001), and between Emax and category was 0.794 (p < 0.001). For 36 malignant lesions, the correlation coefficient between Emean and category was 0.658 (p < 0.001), and between Emax and category was 0.771 (p < 0.001). CONCLUSION: Emean and Emax of breast lesions evaluated by SWE were positively correlated with ECM collagen fibre shape and arrangement category. Changes of ECM collagen fibre shape and arrangement may account for the stiffness variations of breast lesions.