Objective:To explore the patterns of failure after postoperative intensity-modulated radiotherapy for gastric cancer.Methods:Clinical data of patients diagnosed with gastric cancer or gastroesophageal junction carcinoma with pathological stages T 3-4N 0 or T xN 1-3 admitted to Cancer Hospital of Chinese Academy of Medical Sciences from May 2009 to December 2018 were retrospectively analyzed. All patients received postoperative radiotherapy. During the follow-up, tumor recurrence was confirmed by imaging or endoscopic or pathological data, etc. According to the location of tumor recurrence, recurrence patterns were divided into local, regional and distant recurrence. Differences in recurrence patterns among different groups were compared using t-test and Chi-square test. Patient survival was assessed through Kaplan-Meier method. Results:A total of 76 patients were enrolled, with a median age of 49 years old (27-67 years old), 34 cases (45%) were classified as T 3 stage, 40 cases (53%) of T 4 stage, and 75 cases (99%) of N 1-3 stage, respectively. Seventy-three patients (92%) were classified as stage Ⅲ, and 38 patients (50%) underwent D2 dissection. The median follow-up time was 32.8 months (7.1-138.5 months). The median time of recurrence was 17.6 months (2.9-113.6 months). The median survival time after recurrence was 8.19 months (0.6-91.9 months). There were 13 cases (17%) of local recurrence, 6 cases (8%) of regional recurrence, and 72 cases (95%) of distant metastasis in patients. Peritoneal metastasis (33 cases, 43%) and distant lymph node metastasis (12 cases, 16%) were the main patterns of distant recurrence. Conclusions:By intensity-modulated radiotherapy technology, adjuvant radiotherapy yields favorable local and regional control for gastric cancer. Distant metastasis is still the main pattern of recurrence.

Objective:To analyze clinical efficacy of intensity-modulated chemoradiotherapy for patients with anal squamous cell carcinoma and identify prognostic factors.Methods:Clinical data of patients with anal squamous cell carcinoma who received intensity-modulated chemoradiotherapy in the Cancer Hospital of Chinese Academy of Medical Sciences from January 1, 2010 to January 1, 2022 were retrospectively analyzed. Regular follow-up was carried out. The main indexes included disease-free survival (DFS), locoregional failure-free survival (LRFFS) and overall survival (OS), and adverse reactions were recorded. The survival curve was delineated by Kaplan-Meier method and the influencing factors of survival were analyzed by Cox regression models.Results:A total of 65 patients were enrolled with 19 (29%) males and 46 (71%) females. According to the American Joint Committee on Cancer (AJCC) 7 th edition staging, there were 7 (11%), 28 (43%), 10 (15%), and 20 (31%) patients with stage I, II, IIIa, and IIIb, respectively. Before the chemoradiotherapy, 2 (3%) patients received chemotherapy and 12 (18%) patients received local resection. The median dose of radiotherapy was 54 Gy (range: 45-64 Gy) and the main concurrent chemotherapy regimen was capecitabine combined with cisplatin ( n=34, 52%). The completion rate of radiotherapy during concurrent chemoradiotherapy was 100%, and the chemotherapy completion rate was 88%. During the therapy, 5 patients (8%) were interrupted but completed concurrent chemoradiotherapy in full dose, and 8 patients (12%) reduced the dose of concurrent chemotherapy due to the toxicities. During the chemoradiotherapy, 15 cases (23%) experienced grade 3-4 leukopenia, and 17 cases (26%) experienced grade 3-4 radiation dermatitis. No treatment-related death occurred during the treatment. The median follow-up time was 50.4 months (range: 4.4-142.2 months), local recurrence occurred in 7 cases (11%), distant metastasis occurred in 3 cases (5%), and the 5-year DFS, LRFFS and OS rates were 78.8%, 86.5% and 85.1%, respectively. Cox univariate analysis indicated that T stage was significantly associated with DFS ( P=0.006), and tended to be associated with OS ( P=0.054). Conclusions:Intensity-modulated radiotherapy combined with concurrent chemotherapy is an effective treatment for anal squamous cell carcinoma, with tolerable acute toxicities. T stage is an influencing factor of DFS in anal squamous cell carcinoma patients.

Cancer immunotherapy is impaired by the intrinsic and adaptive immune resistance. Herein, a bispecific prodrug nanoparticle was engineered for circumventing immune evasion of the tumor cells by targeting multiple immune resistance mechanisms. A disulfide bond-linked bispecific prodrug of NLG919 and JQ1 (namely NJ) was synthesized and self-assembled into a prodrug nanoparticle, which was subsequently coated with a photosensitizer-modified and tumor acidity-activatable diblock copolymer PHP for tumor-specific delivery of NJ. Upon tumor accumulation via passive tumor targeting, the polymeric shell was detached for facilitating intracellular uptake of the bispecific prodrug. NJ was then activated inside the tumor cells for releasing JQ1 and NLG919 via glutathione-mediated cleavage of the disulfide bond. JQ1 is a bromodomain-containing protein 4 inhibitor for abolishing interferon gamma-triggered expression of programmed death ligand 1. In contrast, NLG919 suppresses indoleamine-2,3-dioxygenase 1-mediated tryptophan consumption in the tumor microenvironment, which thus restores robust antitumor immune responses. Photodynamic therapy (PDT) was performed to elicit antitumor immunogenicity by triggering immunogenic cell death of the tumor cells. The combination of PDT and the bispecific prodrug nanoparticle might represent a novel strategy for blockading multiple immune evasion pathways and improving cancer immunotherapy.

Objective:To evaluate the effectiveness of deep learning (DL)-based radiomic features extracted from pre-treatment diffusion-weighted magnetic resonance images (DWI) for predicting neoadjuvant chemoradiation treatment (nCRT) response in patients with locally advanced rectal cancer (LARC).Methods:Forty-three patients receiving nCRT from 2016 to 2017 were included. All patients received DWI before nCRT and total mesorectal excision surgery 6-12 weeks after completion of nCRT. The patient-cohort was split into the responder group ( n=22) and the non-responder group ( n=21) based on the post-nCRT response assessed by postoperative pathology, MRI or colonoscopy. DL-based radiomic features were extracted from the apparent diffusion coefficient map of the DWI using a pre-trained convolution neural network, respectively. Least absolute shrinkage and selection operator-Logistic regression models were constructed using extracted radiomic features for predicting treatment response. The model performance was evaluated with repeated 20 times stratified 4-fold cross-validation using receiver operating characteristic (ROC) curves. Results:The model established with DL-based radiomic features achieved the mean area under the ROC curve of 0.73(SE, 0.58-0.80).Conclusion:DL-based radiomic features extracted from pre-treatment DWI achieve high accuracy for predicting nCRT response in patients with LARC.

Objective To investigate the effects of downstaging and neoadjuvant reetal(NAR) score on the prognosis of patients with clinical stage Ⅲ middle-low rectal cancer undergoing preoperative concurrent chemoradiotherapy.Methods From 2006 to 2014,195 patients who were admitted to our hospital and diagnosed with clinical stage Ⅲ middle-low rectal cancer by pelvic magnetic resonance imaging or computed tomography were enrolled.All patients received preoperative radiotherapy with doses of 42-50.4 Gy (median:50 Gy,93.8％ of patients received doses of ≥ 50 Gy) and concurrent chemotherapy with capecitabine ± oxaliplatin.Total mesorectal (R0) excision surgery was performed at 4-15 weeks (median:7 weeks) after concurrent chemoradiotherapy.The effects of downstaging (stage yp0-Ⅱ) and NAR score (calculated based on cT staging and ypT/N staging) on the prognosis were evaluated.The 3-year disease-free survival (DFS) rate was calculated using the Kaplan-Meier method and analyzed by log-rank test.Results In all the patients,the median follow-up time was 44 months (6.7-125.5 months);the 3-year DFS rate was 76.8％.Downstaging after preoperative chemoradiotherapy was a significant prognostic factor for the 3-year DFS (92.2％ vs.56.8％,P=0.000).The median NAR score was 15.0(0-65.0) in all the patients.Patients with NAR scores of ≤ 15.0 had significantly improved 3-year DFS than those with NAR scores of＞15.0(90.1％ vs.57.0％,P=0.001).In patients with downstaging,those with NAR scores of ≤8.4 had significantly improved prognosis compared with those with NAR scores of＞ 8.4(95.1％ vs.87.5％,P=0.022).Conclusions Patients with downstaging after preoperative concurrent chemoradiotherapy for stage c Ⅲ middle-low rectal cancer have satisfactory prognosis.The NAR score is an effective prognostic predictor.

Objective To evaluate the clinical outcome associated with the core decompression in combination with the nano-hydroxyapatite/collagen composite rod combined with decalcified bone matrix in a consecutive series of patients with osteonecrosis of femoral head,especially the prevention of collapse of femoral head and its predisposing factors.Methods From August,2012 to May,2013,46 pationts (50 hips) who had undergone core decompression in combination with nano-hydroxyapatite/collagen composite rod insertion in corporated with decalcified bone matrix in our hospital were involved in this study.Postoperative care consisted of prophylactic intravenous antibiotic and anticoagulation therapy.Patients were instructed to be non-weight-bearing for 3 weeks,to partial weight-bear for the next 3 weeks,and to weight bear as tolerated thereafter.All patients were evaluated both clinically and radiographically.The primary clinical outcome of this study was functional improvement assessed with the Harris hip score.Serial radiograms of the pelvis were taken at 1,3,6,12 months post-operatively to analyze the process of osteonecrosis.Results All patients followed up for 12 months,no one suffer complications.The mean Harris score pre-operation was 65.6 ± 10.6,post-operation score was 87.5 ± 15.3,with a mean improvement of 21.8 ± 13.2 (P ＜ 0.05).According to Harris hip score system,excellent for 30 hips,good for 14 hips,fair for 2 hip and poor for 4 hips.Refer to the Kaplan-Meier survivorship curve,the success rate at 12 months post-operatively was 92％.Radiological changes coincided with clinical changes.Conclusion Core decompressionin combination with nano-hydroxyapatite/ collagen composite rod insertion in corporated with decalcified bone matrix provided a minimally invasive surgical treatment option to treat early stage osteonecrotic hips(stage Ⅰ and Ⅱ) and to prevent femoral heads from collapsing,with clinical outcomes and success rates priorto other commonly used surgical procedures.

Osteoarthritis is a common cause of functional deterioration in older adults and is an immense burden on the aging population. Altered chondrogenesis is the most important pathophysiological process involved in the development of osteoarthritis. However, the molecular mechanism underlying the regulation of chondrogenesis in patients with osteoarthritis requires further elucidation, particularly with respect to the role of microRNAs. MiR-21 expression in cartilage specimens was examined in 10 patients with knee osteoarthritis and 10 traumatic amputees. The effect of miR-21 on chondrogenesis was also investigated in a chondrocyte cell line. The effect of miR-21 on the expression of growth differentiation factor 5 (GDF-5) was further assessed by luciferase reporter assay and western blot. We found that endogenous miR-21 is upregulated in osteoarthritis patients, and overexpression of miR-21 could attenuate the process of chondrogenesis. Furthermore, we identified GDF-5 as the direct target of miR-21 during the regulation of chondrogenesis. Our data suggest that miR-21 has an important role in the pathogenesis of osteoarthritis and is a potential therapeutic target.
Cartilage/metabolism/pathology ; Case-Control Studies ; Cell Line ; Chondrocytes/*metabolism/pathology ; Growth Differentiation Factor 5/genetics/*metabolism ; Humans ; MicroRNAs/genetics/*metabolism ; Osteoarthritis/*metabolism/pathology ; Up-Regulation

Objective To evaluate the clinical effects and experiences of short stem ceramic-on-ceramic total hip arthroplasty in the treatment of young and middle-aged patients with femoral head necrosis.Methods From December 2009 to March 2011,40 patients with femoral head necrosis were treated primarily with short stem ceramic-on-ceramic hip arthroplasty (43 hips) through posterior-lateral or anterior-lateral approach.There were 23 males,17 females； with the mean age of 40.5 years (range,27-55 years).All cases were stage Ⅳ or more according Steinberg stage.The patients were followed up at the 3,6,12 months after operation,and then once each year.Standard X-ray films were taken at the follow-ups.Femoral prosthesis subsidence was assessed through X-ray films.Harris scores system and WOMAC Osteoarthritis Index were recorded before and after operation to evaluate clinical effects of surgery.Results Thirty-eight patients (41 hips) were followed up for 21-36 months,with an average of 31.3 months.The femoral stem subsided 0.68±2.90 mm at the last follow-up.After operation,hip pain of patients was relieved obviously.The Harris score improved from 38.7±12.1 (15-66) preoperatively to 95.2±4.49 (83-100) postoperatively,WOMAC Index from 66.7±12.0 (49-94) to 12.8±5.6 (0-24).During follow-up period,there was no serious complication such as femoral neck fracture,infection of wound,pulmonary embolism,et al.No dislocation,implant prosthesis failure and infection were observed.Conclusion The short stem hip arthroplasty preserves bone stock to a great extent.The short stem implant showed a good stability and osseous integration.The wear rate of ceramic-on-ceramic bearing surface is extremely low.Short stem hip arthroplasty plus ceramic-on-ceramic bearing surface might be a good option for the young and middle-aged patients with femoral head necrosis.

Objective To evaluate the clinical indications and outcomes of dynesys neutralization system in the treatment of degenerative lumbar diseases.Methods From January 2007 to December 2011,102 consecutive patients with degenerative lumbar spine diseases underwent posterior decompression and internal fixation with the Dynesys dynamic neutralization system.Among them,69 patients were followed up,including 39 males and 30 females,aged from 30 to 62 years (average,44 years).The series of cases were composed of 24 cases of lumber disc herniation,35 cases of degenerative spinal stenosis,10 cases of degenerative changes of lumbar discs.Results The mean follow-up period was 35 months (range,6-44 months).The visual analogue scale (VAS) score decreased from preoperative 8.6 (range,6-9) to postoperative 2.8 (range,0-5),and the Oswestry disability index (ODI) improved from preoperative 73％ (range,30％-91％) to postoperative 30％ (range,0-61％).There were no implant failure or infection.According to the evaluation criteria of surgical treatment for low back pain,which was established by the Chinese Orthopaedic Association,the result was excellent in 53 patients,good in 12 patients,fair in 4 patients and poor in 1 patient.Conclusion The Dynesys dynamic neutralization system is effective in the treatment of degenerative lumbar spine disease,which can reserve the range of motion of stabilized segments,prevent degeneration of adjacent segments and improve clinical outcomes.

Objective To evaluate the clinical efficacy of total hip arthroplasty with subtrochanteric femoral shortening osteotomy for Crowe Ⅳ developmental dysplasia of the hip.Methods From September 2003 to September 2012,21 patients (24 hips) underwent total hip arthroplasty with subtrochanteric femoral shortening osteotomy for Crowe Ⅳ developmental dysplasia of the hip in our hospital.There were 3 males and 18 females,aged from 28 to 71 years (average,54±10 years).The ceramicpolyethylene articulation was used in 17 patients (20 hips),and metal-polyethylene articulation in 4 patients (4 hips).The osteotomy site was treated with autologous bone graft in 18 patients (21 hips) and allogeneic bone graft in 3 patients (3 hips).The Harris hip score was used to assess the clinical results.Results A total of 18 patients were followed up for 0.5 to 9 years (average,3.5 years).The Harris hip score was improved from preoperative 47.9±9.1 to 88.4±3.5 at 6 months postoperatively.For most patients,hip pain relieved significantly; range of motion of the hip was improved,and the gait returned to normal.Sciatic nerve palsy occurred in 1 patient.There was no wound infection.X-rays 6 months after operation showed that the position of prostheses was satisfactory,without loosening of prostheses and bone block resorption.Conclusion Total hip arthroplasty with subtrochanteric femoral shortening osteotomy can achieve good clinical effect in Crowe Ⅳ developmental dysplasia of the hip.Moreover,it can improve leg length discrepancy and decrease the risk of sciatic nerve injury.