[Clinical analysis of 18 children with aggressive mature B-cell lymphoma after liver transplantation].

Objective: To summarize the clinical characteristics, prognostic factors and treatment outcomes of childhood aggressive mature B-cell lymphoma after liver transplantation. Methods: This retrospective study included 18 children with newly diagnosed aggressive mature B-cell lymphoma after liver transplantation and treated from June 2018 to June 2022 in the Department of Hematology and Oncology of Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine. Clinical characteristics, treatment and outcomes of patients at last evaluation were analyzed. Overall survival (OS) and event free survival (EFS) rates were calculated by Kaplan-Meier method and Log-Rank analysis was performed to find factors of poor prognosis. Results: Among all 18 patients, there were 6 males and 12 females, and the age of onset was 40 (35, 54) months. The interval from transplant to tumor diagnosis was 21 (17, 35) months and 5 patients had early onset disease (<1 year since transplant). Seventeen patients had abdominal lesions. Diarrhea, vomiting and abdominal masses were the main clinical manifestations. All patients were Epstein-Barr virus (EBV) related posttransplant lymphoproliferative disorders (PTLD). One patient received individualized therapy due to critical sick at diagnosis, and the remaining 17 patients received CP (cyclophosphamide, methylprednisolone plus rituximab) and (or) modified EPOCH (prednisone, etoposide, doxorubicin, vincristine, cyclophosphamide plus rituximab) regimens. Of all 18 patients, 15 cases got complete response, 2 cases got partial response, 1 patient died of severe infection. The 2-year OS and EFS rates of 18 patients were (94±5)% and (83±8)%, respectively. None of age, gender or early onset disease had effect on OS and EFS rates in univariate analysis (all P>0.05). Conclusions: The symptoms of PTLD were atypical. Close surveillance of EBV-DNA for patients after liver transplantation was crucial to early stage PTLD diagnosis. CP or modified EPOCH regimen was efficient for pediatric patients with aggressive mature B cell lymphoma after liver transplantation.

Radiomics model and clinical scale for the preoperative diagnosis of silent corticotroph adenomas.

OBJECTIVE: Silent corticotroph adenomas (SCAs) are a subtype of nonfunctioning pituitary adenomas that exhibit more aggressive behavior. However, rapid and accurate preoperative diagnostic methods are currently lacking. DESIGN: The purpose of this study was to examine the differences between SCA and non-SCA features and to establish radiomics models and a clinical scale for rapid and accurate prediction. METHODS: A total of 260 patients (72 SCAs vs. 188 NSCAs) with nonfunctioning adenomas from Peking Union Medical College Hospital were enrolled in the study as the internal dataset. Thirty-five patients (6 SCAs vs. 29 NSCAs) from Fuzhou General Hospital were enrolled as the external dataset. Radiomics models and an SCA scale to preoperatively diagnose SCAs were established based on MR images and clinical features. RESULTS: There were more female patients (internal dataset: p < 0.001; external dataset: p = 0.028) and more multiple microcystic changes (internal dataset: p < 0.001; external dataset: p = 0.012) in the SCA group. MRI showed more invasiveness (higher Knosp grades, p ≤ 0.001). The radiomics model achieved AUCs of 0.931 and 0.937 in the internal and external datasets, respectively. The clinical scale achieved an AUC of 0.877 and a sensitivity of 0.952 in the internal dataset and an AUC of 0.899 and a sensitivity of 1.0 in the external dataset. CONCLUSIONS: Based on clinical information and imaging characteristics, the constructed radiomics model achieved high preoperative diagnostic ability. The SCA scale achieved the purpose of rapidity and practicality while ensuring sensitivity, which is conducive to simplifying clinical work.

[Estradiol regulates the expression of plasma membrane Ca2+-ATPase isoform 2 in inner ear of rats].

Objective: To observe the effects of estradiol on expression of plasma membrane Ca2+-ATPase isoform 2 in inner ear of rats. Methods: Twenty-five Three-months-old female Sprague-Dawley rats were randomly and equally divided into five groups by random number table mathod,with five rats in each group. Animals in Sham group were sham-operated while others were bilateral ovariactmized. One month after modeling, the OVX groups were supplemented with estradiol (E2 group), progesterone (P group), estradiol and progesterone (E2+P group)and vehicle sesame oil (Veh group), while the Sham operation group (Sham group) was supplemented with vehicle sesame oil.All rats were sacrificed and otocysts were obtained immediately. Enzyme-linked immunosorbent assay was used to detect the changes in serum estradiol and progesterone levels of each group of rats before operation, before treatment and before sacrifice. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of total PMCA2 protein and mRNA in the inner ear of each group. Results: There was no significant difference in serum estradiol and progesterone levels among the five groups before operated(P>0.05). Before treatment, the serum estradiol and progesterone levels of rats in each group were significantly lower than those in Sham group (P<0.05). The serum estradiol level in E2 group and E2+P group was not significantly different from that in Sham group (P>0.05), while the serum estradiol level in P group and Veh group was significantly different from that in Sham group (P<0.05). The level of progesterone in P group and E2+P group was higher than that in Sham group (P<0.05), while the level of progesterone in Veh group and E2 group was lower than that in Sham group (P<0.05). Protein and mRNA expression of PMCA2 in P and Veh groups were significantly decreased compared with that of Sham group (P<0.05) while the expression levels underwent no significantly change in E2 and E2+P groups (P<0.05). Conclusion: The decrease of serum estradiol level can reduce the expression of otolith regulatory protein PMCA2 in rats, and then affect otolith metabolism, which may be an important link of estrogen affecting otolith metabolism.

[Diffusion-weighted magnetic resonance imaging instead of contrast-enhanced imaging for evaluating immediate therapeutic efficacy of high-intensity focused ultrasound ablation of adenomyosis].

OBJECTIVE: To explore the feasibility of diffusion-weighted magnetic resonance imaging (DWI) instead of contrast-enhanced (CE) imaging for evaluation of the immediate therapeutic efficacy of high-intensity focused ultrasound (HIFU) ablation for treatment of adenomyosis. METHODS: We retrospectively analyzed the data of 29 patients aged 40.5 ± 5.4 years under going HIFU treatment for adenomyosis in our hospital between December, 2017 and July, 2020. The patients received MRI examination both before and within 24 h after the operation. Two observers analyzed the morphology of the ablation area on DWI and classified the lesions into type 1 (spot-like or no obvious signal intensity changes), type 2 (patchy signal intensity changes) and type 3 (ring-like signal intensity changes). The inter- and intra-observer reliability of morphological assessment was assessed using kappa test. The volume of necrotic tissues following the ablation was measured with both DWI and CE imaging, and the consistency of the measurements and the inter- and intra-observer reliability of DWI-based measurements were evaluated using Bland-Altman plot tests. RESULTS: The median volume of necrotic tissues was 36.9 cm3 (range 16.4-65.5 cm3) following ablation of the 29 lesions. DWI findings identified 24-25 (82.8%-86.2%) lesions with type 2 or 3 signal changes following the ablation with measurable necrotic tissue volume. On DW images, the Kappa value of intra- and inter-observer reliability for morphological classification of the ablation area reached 0.798 (P=0.000) and 0.933 (P= 0.000), respectively. Bland-Altman plots showed a good consistency of the necrotic volumes measured by CE and at DWI with a strong inter- and intra-observer reliability of DWI-based volume measurements (with only one point outside the range of 95% limits of agreement). The remaining 4 or 5 lesions, which presented with type 1 signal changes following ablation, were all small in size (the largest was only 18.61 cm3) and showed poor therapeutic responses to the ablation. CONCLUSION: DWI-based morphological assessment and necrotic tissue volume measurement can replace CE imaging for assessment of the immediate therapeutic efficacy of HIFU ablation for treatment of adenomyosis.

[Research progress of three-dimensional printed guides in unicompartmental knee arthroplasty].

Unicompartmental knee arthroplasty(UKA) is an important surgical technique for the treatment of end-stage knee osteoarthritis, which has high requirement for the position and angle of the prosthesis. The application of three-dimensional(3D) printed in UKA reflects several characteristics such as accuracy,efficiency and safety,but the current research results show that there is still lack of consistency in the design of 3D printed guides and the standard of prosthetic position parameters. This article reviews the history, manufacturing requirements and process of 3D printed guides during UKA surgery, as well as the results of current clinical research. Whether 3D printed guides can safely and effectively improve the placement accuracy of inexperienced doctors during UKA surgery,and whether the long-term results are worthy of clinical promotion need further verification.

[Effects of hnRNP E1 on expression of early genes E2, E6 of HPV16 and biological function in cervical cancer cells].

Objective: To explore the effects of hnRNP E1 on the expression of early genes E2, E6 of HPV16 and the biological function in cervical cancer SiHa cell lines. Methods: The cell experiments in vitro were carried out in cervical cancer cell lines SiHa. The expression levels of E2, E6 mRNA and protein of HPV16 were detected by Real-time PCR and Western blot, respectively, before and after up-regulating hnRNP E1. Meanwhile, the cell proliferation, cycle and apoptosis were evaluated by CCK-8 and flow cytometry. Data analyses were performed using SPSS 22.0 and Graphpad Prism 7.0 software. Results: Compared with the blank and the blank plasmid group, the cells activity and proliferation decreased at 24, 48 and 72 h after up-regulating hnRNP E1 (P<0.05), while the percentage of cells in G0/G1 phase increased and the percentage in S and G2/M phase and proliferation index decreased (P<0.05). Moreover, the late apoptotic rate and the total apoptotic rate increased (P<0.05). The expression levels of E6 mRNA and protein of HPV16 in hnRNP E1 up-regulated group were significantly lower than that in both blank group and blank plasmid group, the differences were significant (P<0.05), showing the tendency of cells proliferation index decrease and total apoptotic rate increase with decreased HPV16 E6 expression. There were no significant differences in the expression of E2 mRNA of HPV16 among the three groups (P=0.427), and no E2 protein of HPV16 was detected. Conclusions: hnRNP E1 could inhibit the transcription and translation of E6 oncogene of HPV16 and further inhibit the proliferation and promote apoptosis of cervical cancer cells, suggesting that hnRNP E1 might be a potential target marker to prevent cervical lesions. But no association between hnRNP E1 and HPV16 E2 was found in SiHa cells.

Long-chain non-coding RNA LOC554202 promotes proliferation, migration, and invasion of nasopharyngeal carcinoma cells by binding to microRNA-31 expression and regulating RhoA expression.

OBJECTIVE: Long-chain non-coding LOC554202, as a host gene for microRNA-31, has been shown to play a crucial role in a variety of diseases, especially tumors. However, its biological function in nasopharyngeal carcinoma (NPC) has not been reported. PATIENTS AND METHODS: The expression levels of LOC554202 and microRNA-31 in NPC tumor tissue samples and cell lines were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The impacts of LOC554202 and microRNA-31 on the biological functions of NPC cells were examined by Cell Counting Kit-8 (CCK-8) and transwell assays. In addition, the modulation of LOC554202 on the expressions of microRNA-31 and RhoA was further confirmed by qRT-PCR and Western blot analysis. RESULTS: The data of this study indicated that LOC554202 expression in NPC tissues and cell lines was remarkably upregulated, while microRNA-31 level showed an opposite tendency. Increasing LOC554202 expression remarkably enhanced the growth and metastasis of NPC cells, which was inhibited by overexpression of microRNA-31. Overexpression of LOC554202 downregulated microRNA-31 expression but upregulated that of RhoA, which may be a potential mechanism for the implication of LOC554202 in NPC. CONCLUSIONS: As a host gene of microRNA-31, LOC554202 enhances RhoA expression and thus promotes the proliferative capacity and invasiveness of NPC cells.

[The influence of patellofemoral joint degeneration on outcome of Oxford medial unicompartmental knee arthroplasty].

Objective: To explore the influence of lateral patellofemoral joint degeneration on the treatment of anteromedial osteoarthritis of knee joint by Oxford medial unicompartmental knee arthroplasty. Methods: The clinical data of 73 patients (73 knees) with knee osteoarthritis underwent unicompartmental knee arthroplasty at Department of Orthopaedic Surgery, Xuanwu Hospital, Capital Medical University from March 2016 to December 2017 were analysed respectively.There were 18 males and 55 females, aged (68.6±7.5) years(range: 53 to 89 years).The lateral patellofemoral joints of patients were evaluated by Ahlback grading system. Patients with Ahlback 0 andⅠ were in the non degenerative group (37 cases), and those with Ahlback Ⅱ and above were in the degenerative group (36 cases). Hospital for special surgery knee score(HSS) and the Western Ontario and McMaster Universities(WOMAC) osteoarthritis index, as well as the condition of kneeling, sit to stand movement, up stair and down stair were recorded. The data before and after operation were compared by paired sample t test, and the data between groups were compared by independent sample t test. χ(2) test was used for counting data. Pearson correlation analysis was used to compare the correlation between ahlback score, HSS and WOMAC osteoarthritis index. Results: The follow-up time was (35.1±6.6) months (range: 25 to 47 months).The knee function of the patients improved significantly after operation.The HSS score increased from 57.7±11.8 preoperative to 81.8±7.8 postoperative (t=16.64, P=0.00) and WOMAC osteoarthritis index decreased from 48.9±13.4 preoperative to 15.6±8.8 postoperative (t=20.48, P=0.00). There was no statistical difference in the change of HSS between the degenerative group and the non-degenerative group before and after surgery(27.5±12.2 vs. 22.5±12.3, t=-1.65, P=0.10) as well as the change of WOMAC osteoarthritis index(31.8±14.0 vs. 36.4±13.7, t=-1.35, P=0.18), but the lateral patellofemoral joint degeneration was related to inability to complete squats (χ(2)=5.17, P=0.04) and sitting up (χ(2)=7.22, P=0.01). Conclusion: The degeneration of lateral patellofemoral joint has no effect on the early functional recovery of patients with anteromedial knee osteoarthritis after Oxford medial unicompartmental knee arthroplasty.

[The role of human papillomavirus 16 early genes E2 and E6 and heterogeneous nuclear ribonucleoprotein E2 in cervical carcinogenesis and their interaction effect].

Objective: To investigate the role of human papillomavirus (HPV) 16 early genes E2 and E6 and heterogeneous nuclear ribonucleoprotein (hnRNP) E2 and their interaction effects in the progression of the cervical cancer. Methods: Women with normal cervix (NC), low cervical intraepithelial neoplasia (CIN Ⅰ) and high cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ) from the cervical lesions cohort in Jiexiu County of Shanxi Province from June 2014 to September 2014, and patients with cervical squamous cell carcinoma (SCC) treated at the Second Hospital of Shanxi Medical University in the same period were enrolled in this study. There were 257 participants, about 67 NC cases (26.07%), 69 CIN Ⅰ cases (26.85%), 68 CIN Ⅱ/Ⅲ cases (26.46%), and 53 SCC cases (20.62%), respectively. The information of demographic characteristics, life health habits and cervical lesions were collected by using the structured questionnaire. Cervical exfoliated cells and cervical biopsy tissues were collected to detect the infection of HPV16 and the protein expression levels of hnRNP E2, HPV16 E2 and E6. According to the median-value of the protein expression levels of hnRNP E2, HPV16 E2 and E6 and E2/E6 ratio in the NC group, the study participants were divided into the high and low expression groups/ratio groups. The multivariate logistic regression model was used to analyze the correlation between HPV16 early gene E2 and E6, hnRNP E2 and cervical cancer. The interaction effect was analyzed by using the generalized multifactor dimensionality reduction (GMDR) model. Results: The ages of NC, CIN Ⅰ, CIN Ⅱ/Ⅲ and SCC groups were (47.00±9.07), (47.64±7.35), (46.37±8.67) and (51.26±8.03) years old, respectively. The multivariate logistic regression model analysis showed that the HPV16 E2 low expression, E6 high expression and E2/E6 low ratio could increase the risk of CIN Ⅱ/Ⅲ, about OR (95%CI) values 11.11 (1.63-75.56), 8.00 (1.28-50.04), and 9.75 (1.22-77.72), respectively and SCC, about OR (95%CI) values 14.22 (2.11-95.88), 10.33 (1.67-64.00), and 12.38 (1.56-97.91), respectively. The hnRNP E2 low expression could increase the risk of CIN Ⅱ/Ⅲ and SCC, about OR (95%CI) values 3.35 (1.39-8.10) and 5.53 (1.54-19.88). The result of GMDR showed that there were interaction effects of the hnRNP E2 low expression, HPV16 E2 low expression and HPV16 E6 high expression in both CIN Ⅱ/Ⅲ and SCC groups. Conclusion: The HPV16 E2 low expression, HPV16 E6 high expression and hnRNP E2 low expression could increase the risk of high-grade cervical intraepithelial neoplasia and cervical cancer, and they might have an important interaction effect in the progression of the cervical cancer.

Non-invasive and real-time proliferative activity estimation based on a quantitative radiomics approach for patients with acromegaly: a multicenter study.

BACKGROUND: Proliferative activity prediction is important for determining individual treatment strategies for patients with acromegaly, and tumor proliferative activity is usually measured by the expression of Ki-67. OBJECTIVE: This study aimed to assess the value of a magnetic resonance imaging (MRI)-based radiomics approach in predicting the Ki-67 index of acromegaly patients. METHODS: A total of 138 patients with acromegaly were retrospectively reviewed and randomly assigned to primary and validation cohorts. Radiomics features were extracted from MR images, and then the elastic net and recursive feature elimination algorithms were applied to determine critical radiomics features for constructing a radiomics signature. Subsequently, multivariable logistic regression analysis was used to select the most informative clinical features, and a radiomics nomogram incorporating a radiomics signature and selected clinical features was constructed for individual predictions. Twenty-five acromegaly patients were enrolled for multicenter model validation. RESULTS: Seventeen radiomics features were selected to construct a radiomics signature that achieved an area under the curve (AUC) value of 0.96 and 0.89 in the primary cohort and the validation cohort, respectively. A radiomics nomogram that incorporated the radiomics signature and eight selected clinical features was constructed and showed good discrimination and calibration, with an AUC of 0.94 in the primary cohort and 0.91 in the validation cohort. The radiomics signature in the multicenter validation achieved an accuracy of 88.2%. The analysis of the decision curve showed that the radiomics signature and radiomics nomogram were clinically useful for patients with acromegaly. CONCLUSIONS: The radiomics signature developed in this study could aid neurosurgeons in predicting the Ki-67 index of patients with acromegaly and could contribute to non-invasive measurement of proliferative activity, affecting individual treatment strategies.

[The long coding RNA GSTM3TV2 acts an oncogene to promote chemoresistance in pancreatic cancer].

Objectives: To examine the expression of the long coding RNA GSTM3TV2 in pancreatic cancer tissues and to examine its role and mechanism in chemoresistance of pancreatic cancer cells. Methods: The expression of lncRNA GSTM3TV2 in 15 pancreatic cancer specimens and corresponding adjacent to cancer tissue samples diagnosed by Department of Pathology, Peking Union Medical College Hospital was detected by real-time PCR.And the expressions of GSTM3TV2 in pancreatic cancer cell AsPC-1, BxPC-3, MIAPaCa-2, PanC-1, SU86.86, T3M4, and chemoresistant cells AsPC-1/GR and MIAPaCa-2/GR, and human pancreatic nestin-expressing cells hTERT-HPNE were detected. Pancreatic cancer cell lines were transfected with GSTM3TV2-pcDNA3.1(+)in order to get cells with GSTM3TV2 overexpression.GSTM3TV2-siRNA was transfected into pancreatic cancer cells to knock down GSTM3TV2. The cell chemoresistance was measured by CCK-8 and flow cytometry assay when incubated with nab-paclitaxel. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of GSTM3TV2 on chemoresistance of tumor growth in nude mice.Western blot assay was also performed to detect the molecular mechanism of chemoresistance of GSTM3TV2. Results: Comparing toadjacent tissues(0.084±0.019), GSTM3TV2 expression was significantly upregulated in the pancreatic cancer tissues(0.493±0.084) (t=5.146, P<0.05). GSTM3TV2 expression were higher in the chemotherapy resistance pancreatic cancer cells AsPC-1/GR(210.799±19.788) and MIAPaCa-2/GR(122.408±23.419) than that in the AsPC-1(3.793±0.615) and the MIAPaCa-2(5.179±1.095)(t=21.800,P<0.05;t=-18.490,P<0.05). The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing GSTM3TV2 group ((1 059.609±102.498)mm(3)) was significantly larger than that in the control group((566.414±81.087) mm(3)) by treated with nab-paclitaxel(t=4.230,P<0.05).Meanwhile, GSTM3TV2 could promote the expression of Cyclin D1, CDK6, Cyclin E1, Vimentin, N-cadherin, ZEB1, Snail and Slug; but decrease cleaved caspase-3, cleaved PARP in pancreatic cancer cells. Conclusions: The expression level of GSTM3TV2 in pancreatic canceris higher than that in paired adjacent tissues. GSTM3TV2 may act as an oncogene to promote chemoresistance in pancreatic cancer through regulation of cell proliferation, apoptosis, and epithelial-mesenchymal transition.

A mid-treatment break and reassessment maintains tumor control and reduces toxicity in patients with hepatocellular carcinoma treated with stereotactic body radiation therapy.

BACKGROUND AND PURPOSE: Patients with hepatocellular carcinoma (HCC) commonly have underlying liver dysfunction with variable tolerance to liver stereotactic body radiation therapy (SBRT). We hypothesized that insertion of a 1-month mid-treatment break would allow us to adapt treatment to the individual patient response, thereby reducing toxicity without compromising local control (LC). MATERIALS AND METHODS: We analyzed HCC patients receiving 3-5 fraction SBRT at our institution from 2005 to 2017. Over this time, patients were offered enrollment on prospective trials assessing individualized adaptive SBRT. Based on normal tissue complication probability and modeling of changes in liver function following a 1-month treatment break between fractions 3 and 4, patients could receive a total of 3 or 5 fractions. Patients not on trial received 3 or 5 fractions without a break. Toxicity was defined as a ≥2 point rise in Child-Pugh (CP) score within 6 months of SBRT. RESULTS: 178 patients were treated with SBRT to 263 HCCs. Median follow-up was 23 months. 86 treatments had a 1-month break. 1-Year LC was 95.4%; this was not different between patients treated with or without a break (p = 0.14). Controlling for tumor size and dose a break was not associated with inferior LC (HR: 0.58, 95%CI: 0.1-3.34, p = 0.54). 54 patients experienced a ≥2 point rise in CP score. Controlling for the number of prior liver directed therapies and mean liver dose, a treatment break reduced the odds of toxicity (OR: 0.42, 95% CI: 0.17-1.03, p = 0.06). CONCLUSION: A one-month mid-treatment break and reassessment may reduce the odds of treatment related toxicity without compromising LC.

[Risk factor analysis on anastomotic leakage after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy and establishment of a nomogram prediction model].

Objective: To investigate the risk factors of anastomotic leakage (AL) after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy and construct a nomogram prediction model. Methods: This study was a retrospective case-control study that collected and reviewed the clinicopathological data of 359 patients who underwent laparoscopic surgery from January 2012 to January 2018, including 202 patients from the Department of General Surgery, Nanfang Hospital of Southern Medical University and 157 patients from the Department of Gastrointestinal Surgery of Fujian Provincial Cancer Hospital. Inclusion criteria: (1) age ≥ 18 years old; (2) diagnosis as rectal cancer by biopsy before treatment; (3) distance from tumor to anus within 12 cm; (4) locally advanced stage (T3-T4 or N+) diagnosed by imaging (CT, MRI, PET or ultrasound); (5) standardized neoadjuvant therapy followed by laparoscopic radical operation. Exclusion criteria: (1) previous history of colorectal cancer surgery; (2) short-term or incomplete standardized neoadjuvant therapy; (3) Miles, Hartmann, emergency surgery, palliative resection; (4) conversion to open surgery. Clinicopathological data, including age, gender, body mass index (BMI), preoperative albumin, distance from tumor to anus, operation hospital, American Society of Anesthesiologists score (ASA score), operation time, T stage, N stage, M stage, TNM stage, pathological complete response (pCR) were analyzed with univariate analysis to identify predictors for AL after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy. Then, incorporated predictors of AL, which were screened by multivariate logistic regression, were plotted by the "rms" package in R software to establish a nomogram model. According to the scale of the nomogram of each risk factor, the total score could be obtained by adding each single score, then the corresponding probability of postoperative AL could be acquired. The area under ROC curve (AUC) was used to evaluate the predictive ability of each risk factor and nomogram on model. AUC > 0.75 indicated that the model had good predictive ability. The Bootstrap method (1000 bootstrapping resamples) was applied as internal verification to show the robustness of the model. The discrimination of the nomogram was determined by calculating the average consistency index (C-index) whose rage was 0.5 to 1.0. Higher C-index indicated better consistency with actual risk. The calibration curve was used to assess the calibration of prediction model. The Hosmer-Lemeshow test yielding a non-significant statistic (P>0.05) suggested no departure from the perfect fit. Results: Of 359 cases, 224 were male, 135 were female, 189 were ≥ 55 years old, 98 had a BMI > 24 kg/m(2), 176 had preoperative albumin ≤ 40 g/L, 128 had distance from tumor to anus ≤ 5 cm, 257 were TNM 0-II stage, 102 were TNM III-IV stage, and 84 achieved pCR after neoadjuvant therapy. The incidence of postoperative AL was 9.5% (34/359). Univariate analysis showed that gender, preoperative albumin and distance from tumor to the anus were associated with postoperative AL (All P<0.05). Multivariate logistic regression analysis revealed that male (OR=2.480, 95% CI: 1.012-6.077, P=0.047), preoperative albumin ≤40 g/L (OR=5.319, 95% CI: 2.106-13.433, P<0.001) and distance from tumor to anus ≤ 5 cm (OR=4.339, 95% CI: 1.990-9.458, P<0.001) were significant independent risk factors for postoperative AL. According to these results, a nomogram prediction model was constructed. The male was for 55 points, the preoperative albumin ≤ 40 g/L was for 100 points, and the distance from tumor to the anus ≤ 5 cm was for 88 points. Adding all the points of each risk factor, the corresponding probability of total score would indicated the morbidity of postoperative AL predicted by this nomogram modal. The AUC of the nomogram was 0.792 (95% CI: 0.729-0.856), and the C-index was 0.792 after internal verification. The calibration curve showed that the predictive results were well correlated with the actual results (P=0.562). Conclusions: Male, preoperative albumin ≤ 40 g/L and distance from tumor to the anus ≤ 5 cm are independent risk factors for AL after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy. The nomogram prediction model is helpful to predict the probability of AL after surgery.

Pharmacological inhibition of ß-catenin/BCL9 interaction overcomes resistance to immune checkpoint blockades by modulating Treg cells.

The Wnt/ß-catenin (ß-cat) pathway plays a critical role in cancer. Using hydrocarbon-stapled peptide technologies, we aim to develop potent, selective inhibitors targeting this pathway by disrupting the interaction of ß-cat with its coactivators B-cell lymphoma 9 (BCL9) and B-cell lymphoma 9-like (B9L). We identified a set of peptides, including hsBCL9CT-24, that robustly inhibits the activity of ß-cat and suppresses cancer cell growth. In animal models, these peptides exhibit potent anti-tumor effects, favorable pharmacokinetic profiles, and minimal toxicities. Markedly, these peptides promote intratumoral infiltration of cytotoxic T cells by reducing regulatory T cells (Treg) and increasing dendritic cells (DCs), therefore sensitizing cancer cells to PD-1 inhibitors. Given the strong correlation between Treg infiltration and APC mutation in colorectal cancers, it indicates our peptides can reactivate anti-cancer immune response suppressed by the oncogenic Wnt pathway. In summary, we report a promising strategy for cancer therapy by pharmacological inhibition of the Wnt/ß-cat signaling.

[The role and mechanism of 2-deoxyglucose in reversing osimertinib-acquired resistance of non-small cell lung cancer cell line].

Objective: To explore the role and mechanism of 2-deoxyglucose (2-dg) in reversing osimertinib- acquired resistance of non-small cell lung cancer(NSCLC)cell line. Methods: The NSCLC line H1975 (purchased from the American Type Culture Collection) was conducted by induction method in vitro to construct the osimertinib-resistance NSCLC cell line H1975-OR. The osimertinib-resistance of H1975-OR cell line was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony-formation assay, Ki67 incorporation assay and the expression of apoptosis-related protein. The glycolysis level was assayed by the lactic acid production measured in the culture medium supernatant of H1975 and H1975-OR. The expression of glycolysis key enzymes (HK2, GLUT1, P-PKM2) and apoptosis-related protein (BIM, Bcl-2) were detected by Western blot. The cells were divided into control group, 2-deoxyglucose (4 mmol/L) monotherapy group, osimertinib (3 µmol/L) monotherapy group and 2-deoxyglucose (4 mmol/L)+ osimertinib (3 µmol/L) combination therapy group, then the apoptosis rate of cells was measured by flow cytometry to evaluate the pro-apoptotic ability of drugs. Date were analyzed by Independent-Samples t-test using SPSS 16.0 statistical software. Results: The glycolysis level of osimertinib-sensitive cell line H1975 was lower than that of osimertinib-resistance cell line H1975-OR [the yield of lactic acid, respectively, was (21.0±0.9) and (26.5±2.8) mmol·L(-1)·10(4)cells(-1), P<0.05]. The osimertinib- acquired resistance of H1975-OR could be reversed by 4 mmol/L 2-deoxyglucose(the IC(50) value of osimertinib in H1975-OR cell line decreased from (7.0±1.9) µmol/L to (1.4±0.1) µmol/L, which was close to the IC(50) value of osimertinib in H1975 cell line (1.0±0.2) µmol/L. The apoptosis rate of H1975-OR was significantly higher in 2-deoxyglucose + osimertinib combination therapy group (26.7±2.4)%, compared to control group (5.1±0.7)%, 2-deoxyglucose monotherapy group (6.1±2.5)% and osimertinib monotherapy group (11.4±2.7)%(all P<0.05). The expression of pro-apoptotic protein BIM in H1975-OR was significantly higher in 2-deoxyglucose+ osimertinib combination therapy group (177.8±28.1)% and the expression of anti-apoptotic protein Bcl-2 in H1975-OR was significantly lower in 2-deoxyglucose+ osimertinib combination therapy group (24.6±5.2)%, compared to control group (100±0)%, all P<0.05. Conclusion: 2-deoxyglucose can reverse the acquired resistance of NSCLC cell line to osimertinib, which may be related to the inhibition of cell glycolysis and the induction of apoptosis.

[The correlation of ganglion cell layer thickness with visual field defect in non-functional pituitary adenoma with chiasm compression].

Objective: To investigate the consequences of the thickness of ganglion cell layer (GCL) and visual field defect of non-functional pituitary adenoma with chiasm compression. Methods: A case control study. The study included 40 (80 eyes) non-functional pituitary adenoma patients in Peking Union Medical College Hospital from March 2015 to February 2017. Twenty patients (no visual field defect group, 40 eyes) of them were detected to be chiasm compressed or touched by the adenoma with no visual field defect detected, and the other 20 patients (visual field defect group, 40 eyes) were the sex-and-age matched pituitary adenoma patients with bitemporal heminopsia. This study also included 20 (control group, 40 eyes) sex-and-age matched healthy controls. The para-papillary retinal nerve fiber layer (RNFL) thickness in 6 quadrants including nasal, temporal, nasal superior, temporal superior, nasal inferior and temporal inferior as well as the macular GCL thickness and ganglion cell-inner plexiform layer (GCIPL) thickness in 4 quadrants including nasal superior, nasal inferior, temporal superior and temporal inferior were measured. The non-parametric test was used to compare the RNFL, GCL and GCIPL thickness among the three groups. Results: The mean age among the three groups was (46±10) years and the difference among the three groups was not significant (P=0.88). The sex ratio of the three groups was 9∶11 (male∶female) and the difference among the three groups was not significant. The mean axial length among the three groups was (23.22±0.90) mm and the difference among the three groups was not significant (P=0.51). The thickness of para-papillary RNFL of temporal superior, temporal, nasal superior, nasal, nasal inferior quadrants and whole circumference was significantly thinner in the visual field defect group than the control group [(129.88±28.64) µm, (63.63±26.84) µm, (88.08±32.16) µm, (50.68±19.99) µm, (92.48±25.06) µm, and (85.00±20.65) µm vs. (141.10±18.95) µm, (79.12±16.78) µm, (113.68±21.28) µm, (69.67±14.23) µm, (117.80±31.32) µm, and (102.80±9.68) µm, t=2.26, 3.06, 4.14, 4.84, 4.25, 4.88, all P<0.05]. In the nasal quadrant, the para-papillary RNFL of the no visual field defect group was significantly thinner compared with the control group [(61.45±9.83) µm vs. (69.67±14.23) µm, t=2.97, P<0.05]. The total GCL thickness was (30.48±5.42) µm in the visual field defect group, (31.35±2.77) µm in the no visual field defect group, thinner than that in the control group [(33.32±2.92) µm, t=2.92, 3.62; both P<0.05]. The total GCIPL thickness showed no significant difference among the three groups (P=0.07). In the superior and inferior temporal quadrants, the GCL and GCIPL thickness showed no significant difference among the three groups (all P>0.05). In the superior and inferior nasal quadrants, the GCL thickness was (29.41±5.97) µm, and (28.47±5.13) µm in the visual field defect group, (31.15±3.27) µm and (30.61±2.96) µm in the no visual field defect group, and (34.23±3.16) µm and (32.97±2.78) µm in the control group. The GCL thickness in the nasal quadrant was thinner in the visual field defect group (t=4.45, 4.82)and the no visual field defect group(t=4.23, 3.63) than in the control group (all P<0.01). However, no significant difference in GCL thickness was detected between the visual field defect group and the no visual field defect group (both P>0.05). In the superior and inferior nasal quadrants, the GCIPL thickness was (54.06±10.50) µm and (51.77±9.18) µm in the visual field defect group, (58.03±4.00) µm and (56.23±5.37) µm in the no visual field defect group, and (62.26±7.11) µm and (59.39±6.64) µm in the control group. The GCIPL thickness was thinner in the nasal quadrant in the visual field defect group than in the control group (t=3.95, 4.20, both P<0.01). Only in the Superior nasal quadrant, the GCIPL was significantly thinner in the no visual field defect group than the control group (t=3.25, P<0.01). Conclusion: The optic GCL may get thinner in pituitary nonfunctional adenoma with chiasm compression patients without the RNFL layer thinning and visual field defect. (Chin J Ophthalmol, 2019, 55: 186-194).