Cervical and endometrial cancers of intestinal origin diagnosed 18 years after vaginal replacement with a sigmoid colon segment: a case report and review of the literature.

Background: Sigmoid colpoplasty is a surgical method for the treatment of vagina agenesis. Malignant tumors of neovaginas derived from sigmoid colons are rare. Case presentation: We report a 33-year-old woman who underwent sigmoid colpoplasty for vaginal agenesis and presented 18 years later with vaginal bleeding. Examination revealed cancer of the neovagina with involvement of the cervix and endometrium. The patient was administered four cycles of chemotherapy because she refused surgery. Conclusions: Patients with a history of colpoplasty should undergo long-term comprehensive testing after reconstruction, including regular gynecological, colposcopic, and gastrointestinal examinations. In patients with cancer of the neovagina, a comprehensive treatment plan should be developed in consultation with gynecologists and surgeons. There is no standard treatment, although surgery plus chemotherapy or radiotherapy appears to be effective.

MSPEDTI: Prediction of Drug-Target Interactions via Molecular Structure with Protein Evolutionary Information.

The key to new drug discovery and development is first and foremost the search for molecular targets of drugs, thus advancing drug discovery and drug repositioning. However, traditional drug-target interactions (DTIs) is a costly, lengthy, high-risk, and low-success-rate system project. Therefore, more and more pharmaceutical companies are trying to use computational technologies to screen existing drug molecules and mine new drugs, leading to accelerating new drug development. In the current study, we designed a deep learning computational model MSPEDTI based on Molecular Structure and Protein Evolutionary to predict the potential DTIs. The model first fuses protein evolutionary information and drug structure information, then a deep learning convolutional neural network (CNN) to mine its hidden features, and finally accurately predicts the associated DTIs by extreme learning machine (ELM). In cross-validation experiments, MSPEDTI achieved 94.19%, 90.95%, 87.95%, and 86.11% prediction accuracy in the gold-standard datasets enzymes, ion channels, G-protein-coupled receptors (GPCRs), and nuclear receptors, respectively. MSPEDTI showed its competitive ability in ablation experiments and comparison with previous excellent methods. Additionally, 7 of 10 potential DTIs predicted by MSPEDTI were substantiated by the classical database. These excellent outcomes demonstrate the ability of MSPEDTI to provide reliable drug candidate targets and strongly facilitate the development of drug repositioning and drug development.

A Nomogram for Predicting Event-Free Survival in Childhood Acute Lymphoblastic Leukemia: A Multicenter Retrospective Study.

Objective: Even though childhood acute lymphoblastic leukemia (ALL) has an encouraging survival rate in recent years, some patients are still at risk of relapse or even death. Therefore, we aimed to construct a nomogram to predict event-free survival (EFS) in patients with ALL. Method: Children with newly diagnosed ALL between October 2016 and July 2021 from 18 hospitals participating in the South China children's leukemia Group (SCCLG) were recruited and randomly classified into two subsets in a 7:3 ratio (training set, n=1187; validation set, n=506). Least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were adopted to screen independent prognostic factors. Then, a nomogram can be build based on these prognostic factors to predict 1-, 2-, and 3-year EFS. Concordance index (C-index), area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance and clinical utility of nomogram. Result: The parameters that predicted EFS were age at diagnosis, white blood cell at diagnosis, immunophenotype, ETV6-RUNX1/TEL-AML1 gene fusion, bone marrow remission at day 15, and minimal residual disease at day 15. The nomogram incorporated the six factors and provided C-index values of 0.811 [95% confidence interval (CI) = 0.792-0.830] and 0.797 (95% CI = 0.769-0.825) in the training and validation set, respectively. The calibration curve and AUC revealed that the nomogram had good ability to predict 1-, 2-, and 3-year EFS. DCA also indicated that our nomogram had good clinical utility. Kaplan-Meier analysis showed that EFS in the different risk groups stratified by the nomogram scores was significant differentiated. Conclusion: The nomogram for predicting EFS of children with ALL has good performance and clinical utility. The model could help clinical decision-making.

New anterior controllable antedisplacement and fusion surgery for cervical ossification of the posterior longitudinal ligament: a biomechanical study.

OBJECTIVE: The traditional anterior approach for multilevel severe cervical ossification of the posterior longitudinal ligament (OPLL) is demanding and risky. Recently, a novel surgical procedure-anterior controllable antedisplacement and fusion (ACAF)-was introduced by the authors to deal with these problems and achieve better clinical outcomes. However, to the authors' knowledge, the immediate and long-term biomechanical stability obtained after this procedure has never been evaluated. Therefore, the authors compared the postoperative biomechanical stability of ACAF with those of more traditional approaches: anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF). METHODS: To determine and assess pre- and postsurgical range of motion (ROM) (2 Nm torque) in flexion-extension, lateral bending, and axial rotation in the cervical spine, the authors collected cervical areas (C1-T1) from 18 cadaveric spines. The cyclic fatigue loading test was set up with a 3-Nm cycled load (2 Hz, 3000 cycles). All samples used in this study were randomly divided into three groups according to surgical procedures: ACDF, ACAF, and ACCF. The spines were tested under the following conditions: 1) intact state flexibility test; 2) postoperative model (ACDF, ACAF, ACCF) flexibility test; 3) cyclic loading (n = 3000); and 4) fatigue model flexibility test. RESULTS: After operations were performed on the cadaveric spines, the segmental and total postoperative ROM values in all directions showed significant reductions for all groups. Then, the ROMs tended to increase during the fatigue test. No significant crossover effect was detected between evaluation time and operation method. Therefore, segmental and total ROM change trends were parallel among the three groups. However, the postoperative and fatigue ROMs in the ACCF group tended to be larger in all directions. No significant differences between these ROMs were detected in the ACDF and ACAF groups. CONCLUSIONS: This in vitro biomechanical study demonstrated that the biomechanical stability levels for ACAF and ACDF were similar and were both significantly greater than that of ACCF. The clinical superiority of ACAF combined with our current results showed that this procedure is likely to be an acceptable alternative method for multilevel cervical OPLL treatment.

Anatomical Evaluation of Spinal Nerve and Cervical Intervertebral Foramina in Anterior Controllable Antedisplacement and Fusion Surgery: A Cadaveric and Radiologic Study.

OBJECTIVE: To achieve the anatomical evaluation of spinal nerve and cervical intervertebral foramina in anterior controllable antedisplacement and fusion (ACAF) surgery, a novel surgical technique with the wider decompression, through a cadaveric and radiologic study. METHODS: Radiographic data of consecutive 47 patients (21 by ACAF and 26 by anterior cervical corpectomy and fusion [ACCF]) who have accepted surgery for treatment of cervical ossification of the posterior longitudinal ligament(OPLL) and stenosis from March 2017 to March 2018 were retrospectively reviewed and compared between an ACAF group and ACCF group. Three postoperative radiographic parameters were evaluated: the decompression width and the satisfaction rate of decompression at the entrance zone of intervertebral foramina on computed tomography (CT), and the transverse diameter of spinal cord in the decompression levels on magnetic resonance imaging (MRI). In the anatomic study, three fresh cadaveric spines (death within 3 months) undergoing ACAF surgery were also studied. Four anatomic parameters were evaluated: the width of groove, the distance between the bilateral origins of ventral rootlets, the length of ventral rootlet from their origin to the intervertebral foramina, the descending angle of ventral rootlet. RESULTS: The groove created in ACAF surgery included the bilateral origins of ventral rootlets. The rootlets tended to be vertical from the rostral to the caudal direction as their takeoff points from the central thecal sac became higher and farther away from their corresponding intervertebral foramina gradually. No differences were identified between left and right in terms of the length of ventral rootlet from the origin to the intervertebral foramina and the descending angle of ventral rootlet. The decompression width was significantly greater in ACAF group (19.2 ± 1.2 vs 14.7 ± 1.2, 21.3 ± 2.2 vs 15.4 ± 0.9, 21.5 ± 2.1 vs 15.7 ± 1.0, 21.9 ± 1.6 vs 15.9 ± 0.8, from C3 to C6 ). The satisfactory rate of decompression at the entrance zone of intervertebral foramina tended to be better in the left side in ACAF group (significant differences were identified in the left side at C3/4 , C4/5 , C6/7 level, and in the right side at C4/5 level when compared with ACCF). And decompression width was significantly greater than the transverse diameter of spinal cord in ACAF group. Comparatively, there existed no significant difference in the ACCF group besides the C5 level. CONCLUSION: ACAF can decompress the entrance zone of intervertebral foramina effectively and its decompression width includes the origins and massive running part of bilateral ventral rootlets. Due to its wider decompression range, ACAF can be used as a revision strategy for the patients with failed ACCF.

Quality of life and related demographic factors in long-term survivors of childhood non-Hodgkin's lymphoma. / å„¿ç«¥éžéœå¥‡é‡‘æ·‹å·´ç˜¤é•¿æœŸç”Ÿå­˜è€ ç”Ÿæ´»è´¨é‡åŠç›¸å ³äººå£å­¦å› ç´ ç ”ç©¶.

OBJECTIVES: To evaluate the quality of life and related demographic factors in long-term survivors of childhood non-Hodgkin's lymphoma (NHL). METHODS: A retrospective analysis was performed on the medical and demographic data of the NHL patients who received treatment in the Sun Yat-sen University Cancer Center and achieved long-term survival at follow-up, with an age of <18 years at initial diagnosis and a present age of ≥18 years. A questionnaire survey was performed using 36-Item Short-Form Health Survey (SF-36) and the symptom subscale of the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30). The health status of long-term survivors of NHL was evaluated by comparing the scores of various dimensions of the SF-36 scale of general adult population in the United States (American norm) and those of the SF-36 scale of general adult population in Hong Kong, China (Hong Kong norm). The correlation between the score of each dimension of the scale and demographic characteristics was evaluated. The symptoms of long-term NHL survivors were evaluated according to the score of QLQ-C30 scale. RESULTS: A total of 23 patients with NHL with complete follow-up data were enrolled. The pathological types included diffuse large B-cell lymphoma in 10 patients, Burkitt lymphoma in 4 patients, T-cell lymphoblastoma in 5 patients, B-cell lymphoblastoma in 3 patients, and natural killer/T cell lymphoma in 1 patient. All patients received the chemotherapy regimen containing anthracyclines and alkylating agents. The median present age was 26.2 years (range: 16.9-55.8 years), and the median age at initial diagnosis was 10.4 years (range: 2.4-17.6 years). Among the 23 patients, 6 were married and had children and 2 had chronic diseases. There was no significant difference between the long-term survivors and the US norm in role physical, general health, role-emotional, and mental health (P>0.05), while the long-term survivors had significantly better scores of the other dimensions than the US norm (P<0.05). Similar results were obtained for the comparison between the long-term survivors and the China Hong Kong norm. Age at initial diagnosis was negatively correlated with the scores of social functioning, role physical, and general health in the SF-36 scale (P<0.05), and the present age of patients was positively correlated with the score of physical functioning and was negatively correlated with the score of general health (P<0.05). The urban and rural distribution of patients was related to the general health status (P<0.05). In addition, the long-term survivors of childhood NHL had relatively low scores of the symptom domain of QLQ-C30, and few moderate or severe symptoms were found. CONCLUSIONS: Long-term survivors of childhood NHL tend to have a good overall health status, with no significant differences compared with the general population. Age at initial diagnosis is the main demographic factor that affects patients' quality of life. Citation.

Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - a multi-centric clinical study of GD-2008-ALL protocol.

BACKGROUND: The prognosis of childhood acute lymphoblastic leukemia (ALL) is optimistic with a 5-year event-free survival (EFS) rate of 70-85%. However, the major causes of mortality are chemotherapy toxicity, infection and relapse. The Guangdong (GD)-2008-ALL collaborative protocol was carried out to study the effect of reduced intensity on treatment related mortality (TRM) based on Berlin-Frankfurt-Münster (BFM) 2002 backbone treatment. The study was designed to elucidate whether the reduced intensity is effective and safe for children with ALL. METHODS: The clinical data were obtained from February 28, 2008 to June 30, 2016. A total of 1765 childhood ALL cases from 9 medical centers were collected and data were retrospectively analyzed. Patients were stratified into 3 groups according to bone marrow morphology, prednisone response, age, genotype, and karyotype information: standard risk (SR), intermediate risk (IR) and high risk (HR). For SR group, daunorubicin was decreased in induction IA while duration was reduced in Induction Ib (2 weeks in place of 4 weeks). Doses for CAM were same in all risk groups - SR patients received one CAM, others got two CAMs. RESULTS: The 5-year and 8-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 83.5±0.9% and 83.1±1.0%, 71.9±1.1% and 70.9±1.2%, and 19.5±1.0% and 20.5±1.1%, respectively. The 2-year treatment-related mortality (TRM) was 5.2±0.5%. The 5-year and 8-year OS were 90.7±1.4% and 89.6±1.6% in the SR group, while the 5-year and 8-year EFS were 81.5±1.8% and 80.0±2.0%. In the SR group, 74 (15.2%) patients measured minimal residual disease (MRD) on Day 15 and Day 33 of induction therapy. Among them, 7 patients (9.46%) were MRD positive (≥ 0.01%) on Day 33. The incidence of relapse in the MRD Day 33 positive group (n=7) was 28.6%, while in the MRD Day 33 negative group (n=67) was 7.5% (p=0.129). CONCLUSIONS: The results of GD-2008-ALL protocol are outstanding for reducing TRM in childhood ALL in China with excellent long term EFS. This protocol provided the evidence for further reducing intensity of induction therapy in the SR group according to the risk stratification. MRD levels on Day 15 and Day 33 are appropriate indexes for stratification.

Prognostic Value and Outcome for ETV6/RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Report From the South China Children's Leukemia Group.

PURPOSE: To analyzed the outcome of ETV6/RUNX1-positive pediatric acute B lymphoblastic leukemia (B-ALL) with the aim of identifying prognostic value. METHOD: A total of 2,530 pediatric patients who were diagnosed with B-ALL were classified into two groups based on the ETV6/RUNX1 status by using a retrospective cohort study method from February 28, 2008, to June 30, 2020, at 22 participating ALL centers. RESULTS: In total, 461 (18.2%) cases were ETV6/RUNX1-positive. The proportion of patients with risk factors (age <1 year or ≥10 years, WB≥50×109/L) in ETV6/RUNX1-positive group was significantly lower than that in negative group (P<0.001), while the proportion of patients with good early response (good response to prednisone, D15 MRD < 0.1%, and D33 MRD < 0.01%) in ETV6/RUNX1-positive group was higher than that in the negative group (P<0.001, 0.788 and 0.004, respectively). Multivariate analysis of 2,530 patients found that age <1 or ≥10 years, SCCLG-ALL-2016 protocol, and MLL were independent predictor of outcome but not ETV6/RUNX1. The EFS and OS of the ETV6/RUNX1-positive group were significantly higher than those of the negative group (3-year EFS: 90.11 ± 4.21% vs 82 ± 2.36%, P<0.0001, 3-year OS: 91.99 ± 3.92% vs 88.79 ± 1.87%, P=0.017). Subgroup analysis showed that chemotherapy protocol, age, prednisone response, and D15 MRD were important factors affecting the prognosis of ETV6/RUNX1-positive children. CONCLUSIONS: ETV6/RUNX1-positive pediatric ALL showed an excellent outcome but lack of independent prognostic significance in South China. However, for older patients who have the ETV6/RUNX1 fusion and slow response to therapy, to opt for more intensive treatment.

Elevated Expression of T-Cell Immunoglobulin and Mucin Domain 3 on T Cells from Peripheral Blood in Patients with Cervical Carcinoma.

OBJECTIVE: To investigate the expression of T-cell immunoglobulin and mucin domain 3 (TIM-3) on peripheral T cells of cervical carcinoma patients. METHODS: Peripheral blood samples from 15 high-grade cervical squamous intraepithelial lesion (HSIL) patients, 24 cervical carcinoma patients, and 21 healthy controls were collected. TIM-3 expressions on the surface of peripheral CD4+ T cells and CD8+ T cells were analyzed with flow cytometry. RESULTS: There was significantly lower expression of CD4+ T cells and CD8+ T cells in HSIL patients and cervical carcinoma patients compared with healthy controls. We also found that TIM-3 expression on peripheral CD4+ T and CD8+ T cells of both HSIL patients and cervical carcinoma patients was significantly increased compared to the control group. Further analyses revealed that the expression of TIM-3 on peripheral CD4+ T and CD8+ T cells significantly increased in stage III-IV cervical carcinoma patients compared to stages I-II. CONCLUSION: The increased expression of TIM-3 on CD4+ T cells and CD8+ T cells of patients with cervical carcinoma and HSIL suggests the potential role of TIM-3 in the development and progression of cervical carcinoma, which may be a novel therapy target for cervical carcinoma.

Consensus statement on diagnosis and treatment of cervical ossification of posterior longitudinal ligament from Asia Pacific Spine Society (APSS) 2020.

PURPOSE: The study aimed to develop an evidence-based expert consensus statement on diagnosis and treatment of cervical ossification posterior longitudinal ligament (OPLL). METHOD: Delphi method was used to perform such survey, and the panel members from Asia Pacific Spine Society (APSS) 2020 were invited to answer the open-ended questions in rounds 1 and 2. Then the results were summarized and developed into a Likert-style questionnaire for voting in round 3, and the level of agreement was defined as 80%. In the whole process, we conducted a systematic literature search on evidence for each statement. RESULTS: Cervical OPLL can cause various degrees of neurological symptoms, an it's thought to be more common in Asia population. CT reconstruction is an important imaging examination to assist diagnosis and guide surgical choice. Segmental, continuous, mixed, and focal type is the most widely used classification system. The non-surgical treatment is recommended for patients with no or mild clinical symptoms, or irreversible neurological damage, or failed surgical decompression, or condition cannot tolerant surgery, or refusing surgery. As OPLL may continue to develop gradually, surgical treatment would be considered in their course inevitably. The surgical choice should depend on various conditions, such as involved levels, thickness, and type of OPLL, skill-experiences of surgeons, which are listed and discussed in the article. CONCLUSION: In this statement, we describe the clinical features, classifications, and diagnostic criteria of cervical OPLL, and review various surgical methods (such as their indications, complications), and provide a guideline on their choice strategy.

The Significance of Galectin-1 and Galectin-9 Expression in Endometrial Carcinoma.

OBJECTIVES: To explore the expression of Galectin-1 and -9 and clinicopathological features in endometrial carcinoma (EC). METHODS: Normal endometrium (NE), atypical endometrial hyperplasia (AH), and endometrial cancer were collected, and immunohistochemistry was used to detect the expression of Galectin-1 and -9 in all specimens in the same condition. RESULTS: The positive rate of Galectin-1 expression in NE, AH, and endometrial cancer was 30, 70, and 90.2%. The positive rate of Galectin-9 expression in them was 20, 75, and 78.4%, respectively. The expression of Galectin-1 and -9 in the EC and AH was significantly higher than that in the NE (p< 0.05). However, there was no significant difference between the EC and the AH (p > 0.05). The expression of Galectin-1 in endometrial adenocarcinoma was significantly different among tissues of different histological grades, pathological stages, degrees of myometrial infiltration, or lymph node metastasis (p > 0.05). The expression of Galectin-9 in endometrial adenocarcinoma was significantly different among different historical grades, pathological stages, degrees of myometrial infiltration, and lymph node metastasis (p < 0.05). The expression of Galectin-9 in tissues at an early stage, with the degree of myometrial infiltration <1/2, and without lymph node metastasis, was significantly stronger than in those in the late stage, with a degree of myometrial infiltration ≥1/2 and lymph node metastasis. CONCLUSION: Both Galectin-1 and -9 were associated with the occurrence of EC and its pathological behavior. High expression of Galectin-1 suggests a poor prognosis, whereas high expression of Galectin-9 was associated with early pathological changes. Galectin-1 and -9 can provide references for early screening and indicate the prognosis of endometrial lesions, which are of great significance for patients' quality of life.

Comparison of Long-Term Outcomes and Sequelae Between Children and Adult Nasopharyngeal Carcinoma Treated With Intensity Modulated Radiation Therapy.

PURPOSE: Our purpose was to compare long-term survival outcomes and sequelae between child and adult nasopharyngeal carcinoma (NPC) in the era of intensity modulated radiation therapy. METHODS AND MATERIALS: Data on 285 patients with NPC aged ≤18 years at diagnosis and treated with intensity modulated radiation therapy between January 2004 and November 2016 were retrospectively reviewed. A propensity score matching method was adopted to screen matched adult patients with NPC at a ratio of 1:3. Survival outcomes and treatment-related toxicities between child and adult groups were compared. RESULTS: In total, 159 children and 477 adult patients with NPC were included in this study. The 5-year overall survival, distant metastasis-free survival, locoregional relapse-free survival, and disease-free survival between children and adults were 89.2% versus 83.6% (P = .144), 88.7% versus 83.5% (P = .124), 96.4% versus 89.1% (P = .013), and 86.5% versus 77.3% (P = .021), respectively. Subgroup analyses revealed that the young age was an independent prognostic factor of overall survival, distant metastasis-free survival, and locoregional relapse-free survival in the advanced N stage (N2-3) group and disease-free survival in the advanced T stage (T3-4) group and N2-3 and stage III-IVA groups. The most common sequela was ototoxicity (68.9%) in child patients and xerostomia (70.8%) in adult patients. Adult survivors had a significantly higher incidence of grade 3 to 4 late toxicities in xerostomia (17.6% vs 8.9%; P = .004), skin dystrophy (9.3% vs 3.7%; P = .022), neck fibrosis (8.3% vs 4.4%; P < .001), and radiation encephalopathy (0.8% vs 0; P = .006). Child survivors were more likely to develop grade 3 to 4 growth retardation and endocrine insufficiency (3.0% vs 0.3%; P = .014). CONCLUSIONS: Child patients with NPC achieved significantly better survival outcomes but fewer late toxicities than adult patients. However, we should pay great attention to growth problems of child survivors.

Risk assessment of vertebral artery injury in anterior controllable antedisplacement and fusion (ACAF) surgery: a cadaveric and radiologic study.

PURPOSE: We have introduced a novel surgery technique named anterior controllable antedisplacement and fusion (ACAF) for the treatment of ossification of the posterior longitudinal ligament. As reported, the satisfactory postoperative outcome can be attributed to the larger decompression width. However, it may associate with high prevalence of vertebral artery injury (VAI) theoretically. Thus, assessment of the vulnerability of vertebral artery in ACAF is of great importance. METHODS: Computed tomographic scan data of 28 patients were retrospectively studied. Seven radiographic parameters were evaluated: uncinate process (UP) tips distance, transverse foramen (TF)-UP tips distance, TF-LWL (the ipsilateral limited wedging line) distance, the limited distance of lateral decompression, the maximum oblique angle of LWL, TF-LWG (the lateral wall of groove) distance, and width of groove. Eleven fresh cadaveric spines undergoing ACAF surgery were also studied. Two anatomic parameters were evaluated: width of groove and LWG-TF distance. RESULTS: The UP tips distance increased from C3 to C6 and tended to be larger in males. The UP tip-TF distance and LWL-TF distance were smallest at C4, but both were larger than 2 mm. Maximum oblique angle decreased from C3 to C6. Postoperatively, both radiographic and cadaveric measurements showed the width of groove was larger than UP tips distance, but LWG-TF distance was larger than 2 mm in all levels. CONCLUSION: UP can be used as anatomical landmarks to avoid VAI during ACAF surgery. Radiographic and cadaveric measurements verified the safety of ACAF surgery, even for those cases with wedging and lateral slotting.

Prediction of RNA-protein interactions by combining deep convolutional neural network with feature selection ensemble method.

RNA-protein interaction (RPI) plays an important role in the basic cellular processes of organisms. Unfortunately, due to time and cost constraints, it is difficult for biological experiments to determine the relationship between RNA and protein to a large extent. So there is an urgent need for reliable computational methods to quickly and accurately predict RNA-protein interaction. In this study, we propose a novel computational method RPIFSE (predicting RPI with Feature Selection Ensemble method) based on RNA and protein sequence information to predict RPI. Firstly, RPIFSE disturbs the features extracted by the convolution neural network (CNN) and generates multiple data sets according to the weight of the feature, and then use extreme learning machine (ELM) classifier to classify these data sets. Finally, the results of each classifier are combined, and the highest score is chosen as the final prediction result by weighting voting method. In 5-fold cross-validation experiments, RPIFSE achieved 91.87%, 89.74%, 97.76% and 98.98% accuracy on RPI369, RPI2241, RPI488 and RPI1807 data sets, respectively. To further evaluate the performance of RPIFSE, we compare it with the state-of-the-art support vector machine (SVM) classifier and other exiting methods on those data sets. Furthermore, we also predicted the RPI on the independent data set NPInter2.0 and drew the network graph based on the prediction results. These promising comparison results demonstrated the effectiveness of RPIFSE and indicated that RPIFSE could be a useful tool for predicting RPI.

Multicenter randomized trial of arsenic trioxide and Realgar-Indigo naturalis formula in pediatric patients with acute promyelocytic leukemia: Interim results of the SCCLG-APL clinical study.

Intravenous arsenic trioxide (ATO) has been adopted as the first-line treatment for acute promyelocytic leukemia (APL). Another arsenic compound named the Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine containing As4 S4 , has been shown to be highly effective in treating adult APL. In the treatment of pediatric APL, the safety and efficacy of RIF remains to be confirmed. This randomized, multicenter, and noninferiority trial was conducted to determine whether intravenous ATO can be substituted by oral RIF in the treatment of pediatric APL. From September 2011 to January 2017, among 92 patients who were 16 years old or younger with newly diagnosed PML-RARa positive APL, 82 met eligible criteria and were randomly assigned to ATO (n = 42) or RIF (n = 40) group. The remaining 10 patients did not fulfilled eligible criteria because five did not accept randomization, four died and one had hemiplegia prior to arsenic randomization due to intracranial hemorrhage or cerebral thrombosis. Induction and consolidation treatment contained ATO or RIF, all-trans-retinoic acid and low intensity chemotherapy. End points included event-free survival (EFS), adverse events and hospital days. After a median 3-year follow-up, the estimated 5-year EFS was 100% in both groups, and adverse events were mild. However, patients in the RIF group had significantly less hospital stay than those in the ATO group. This interim analysis shows that oral RIF is as effective and safe as intravenous ATO for the treatment of pediatric APL, with the advantage of reducing hospital stay. Final trial analysis will reveal mature outcome data.

Can K-Line Predict the Clinical Outcome of Anterior Controllable Antedisplacement and Fusion Surgery for Cervical Myelopathy Caused by Multisegmental Ossification of the Posterior Longitudinal Ligament?

OBJECTIVE: To analyze the correlation between the K-line-based classification of patients with ossification of the posterior longitudinal ligament (OPLL) and their outcome after anterior controllable antedisplacement and fusion (ACAF) surgery. METHODS: A series of 24 patients with multisegmental OPLL were enrolled. All patients underwent ACAF surgery. First, the patients were classified into 2 groups according to their K-line classification. Then, we separated the patients into subgroups according to their OPLL thickness. The Japanese Orthopaedic Association scores before and 6 months after surgery were studied, and the recovery rate (RR) was calculated. The preoperative and postoperative radiologic parameters were also investigated. RESULTS: Clinical and radiographic assessments showed no significant correlation between the K-line-based classification of patients with OPLL and their outcome of ACAF surgery (P > 0.05). When the OPLL was ≤6 mm thick, K-line-based classification groups had a similar change of occupation ratio and RR (P > 0.05). However, when the OPLL was >6 mm thick, the mean RR was 61.8% ± 14.0% in the K-line (+) group and 78.3% ± 9.7% in the K-line (-) group (P < 0.05), and the mean was 16.0% ± 4.2% in the K-line (+) group and 28.0% ± 7.1% in the K-line (-) group (P < 0.05). CONCLUSIONS: This study shows that K-line can predict the clinical outcome of ACAF surgery for multisegmental OPLL in a different way from posterior decompression surgery. When the OPLL was thin, the outcome was satisfactory and there was no correlation with K-line-based classification of patients with OPLL. When the OPLL was >6 mm thick, the K-line (-) group patients had a better outcome than did K-line (+) group patients.

Evaluating the Rotation Correction of the Main Thoracic Curve in Severe Adolescent Idiopathic Scoliosis: Bending and Traction vs. Fulcrum - A Preliminary Report.

BACKGROUND Flexibility evaluation methods were only used to assess the changes of coronal Cobb angle in patients with adolescent idiopathic scoliosis (AIS). Little attention was attached to the vertebral rotation in these methods. MATERIAL AND METHODS 21 patients with severe adolescent idiopathic scoliosis were enrolled in this study. Coronal flexibility and rotation correction were compared on the supine bending, traction and fulcrum bending radiographs. The apical vertebral body rib ratio (AVB-R), and Perdriolle rotation angles were used to measure the rotation of the main thoracic curve. Statistical analysis was performed with one-way Analysis of Variance(ANOVA). Correlations between postoperative AVB-R and AVB-R in supine bending, traction and fulcrum bending radiographs were assessed utilizing the Linear Regression. RESULTS There were trends towards increased coronal flexibility in fulcrum bending versus traction versus supine bending, but there were no significant differences due to the limited sample size. And all were significantly lower than postoperative correction. The correction of AVB-R at traction and supine bending radiographs were significantly better than fulcrum bending, however, all were significantly lower than postoperative correction. Correction of Perdriolle rotation angle at traction radiograph was best among these methods. A univariant linear regression analysis showed a strong linear correlation between the postoperative AVB-R and the AVB-R in the traction radiograph. CONCLUSIONS As to patients with severe AIS, the coronal plane flexibility evaluated at the fulcrum bending radiograph is superior to that at the traction radiograph. This may be explained by the measurement errors induced by the better derotation capacity at the traction radiograph. Rotation correction evaluated at the traction radiograph proves better than the fulcrum bending radiographs, showing a linear correlation with the postoperative correction.

Neuroprotective Effects of Valproic Acid in a Rat Model of Cauda Equina Injury.

BACKGROUND: Histone deacetylase inhibitors, including valproic acid (VPA), are promising therapeutic interventions in neurological disorders and play an important role in synaptic activity and neuronal function. METHODS: A total of 30 rats were randomly allocated to 3 groups: sham, control, and VPA. The rats in the VPA and control groups received laminectomy at the L4 level of the vertebrae and silicone gel implantation into the epidural spaces L5 and L6. Rats in the sham group only received laminectomy at the L4 level of vertebrae without any implantation. VPA (300 mg/kg in saline) was administered 2 hours before the surgery. After the surgery, the VPA group received further VPA injections at 300 mg/kg twice a day for 1 week. The same volume of saline was injected in the control group. Neurobehavioral tests using the Basso, Beattie, Bresnahan scale and the oblique board test were performed for 1 week starting at 2 hours before surgery up to day 7 after surgery. At day 7 after surgery, tissues from the compressed cauda equina (L5-L6) were subjected to hematoxylin and eosin, luxol fast blue, or immunofluorescence staining, whereas the terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end label assay staining was performed on the tissue from the dorsal root ganglions and the lumbar segment of the spinal cord proximal to the compressed cauda equina (L5-L6). RESULTS: The behavioral results suggested a significant improvement in the lower limb motor function in the VPA group compared with controls (P < 0.05). Furthermore, histologic assessment revealed a significant reduction in nerve fibers showing Wallerian degeneration and demyelinating lesions in the VPA group, in addition to an increased myelination compared with the control group (P < 0.05). The terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end label assay staining revealed a significant decrease in the number of apoptotic neurons in the spinal cord anterior horn and dorsal root ganglions in the VPA group compared with controls (P < 0.05). CONCLUSIONS: Our data demonstrated that VPA could alleviate cauda equina injury, reduce apoptotic cells, and improve motor recovery, suggesting a neuroprotective effect in acute cauda equina syndrome.

Rapamycin ameliorates CCl4-induced liver fibrosis in mice through reciprocal regulation of the Th17/Treg cell balance.

Previous investigations have suggested that the activation of Th17 cells and/or deficiency of regulatory T cells (Tregs) are involved in the pathogenesis of liver fibrosis. The aim of the present study was to investigate the effect of rapamycin on immune responses in a carbon tetrachloride (CCl4)-induced murine liver fibrosis model. Liver fibrosis was induced by intraperitoneal administration with CCl4. Following injection of CCl4, the mice were treated intraperitoneally with rapamycin (1.25 mg/kg/day) for 8 weeks. Hematoxylin and eosin staining and Masson's trichrome staining were used for histological examination. The protein levels of forkhead/winged helix transcription factor P3, retinoic-acid-related orphan receptor (ROR)­Î³t in liver tissue were determined by western blotting, the frequency of Th17 and Treg cells in the liver was evaluated by flow cytometry, and a suppression assay was measured by incorporating [3H]­thymidine. In addition, to explore the effect of Tregs expanded with rapamycin on hepatic stellate cells (HSC), HSCs were co­cultured with Tregs from rapamycin or phosphate­buffered saline­treated mice. It was found that rapamycin treatment led to a significant reduction in the number of Th17 cells and in the expression levels of ROR­Î³t in the liver tissues. Simultaneously, the results of the present study showed a significant increase in the frequency of Tregs and a marked enhancement in the expression of forkhead/winged helix transcription factor P3 in the rapamycin­treated mice. Furthermore, the Tregs in rapamycin­treated mice had significantly higher suppressive effects, compared with the cells from mice treated with phospphate­buffered saline. Consequently, rapamycin treatment prevented the development of CCl4-induced hepatic fibrosis, which was shown by its histological appearances. These results suggested that the immunosuppressive effect of rapamycin on liver fibrosis was associated with the suppression of hepatic fibrogenesis and regulation of the Th17/Treg cell balance.