Objective:To investigate the occurrence rate and distribution pattern of three-rooted mandibular molars in children using CBCT.Methods:CBCT images of 206 children aged 4-11 years were retrospectively analyzed.The root numbers of the bilateral man-dibular first and second deciduous molars,and the permanent mandibular first molars were recorded.A chi-square test was used to de-tect the gender and side difference.Spearman correlation test was used to analyze the relation between the bilateral homologous teeth and the mandibular first and second deciduous molars on each side.Results:The occurrence rate of three-rooted mandibular first and second deciduous molars and mandibular permanent first molars was 10.9％(19/175),25.1％(46/183)and 28.4％(57/201)for individuals,respectively(x2=18.543,P＜0.01),and 8.7％(32/366),19.0％(73/384)and 23.6％(95/402)for teeth(x2=30.692,P＜0.01),re-spectively.Gender difference was not detected for each tooth type(all P＞0.05),while side differences were detected in mandibular sec-ond deciduous molars and the frequency of three-rooted molar on the right and left side was 23.7％and 14.2％(P＜0.05),respectively.The concurrence rate of bilateral three-rooted mandibular deciduous first and second molars and mandibular permanent first molars was 57.9％(11/19),47.8％(22/46)and 66.7％(38/57),respectively,and the rho was 0.710,0.597 and 0.745,respectively(all P＜0.01);between the three-rooted deciduous first and second molars on the left side,rho=0.188(P＜0.05)and on the right side,rho=0.304(P＜0.01).Conclusion:The occurrence rate of three-rooted mandibular molars in children increases in the following sequence:first deciduous molars＜second deciduous molars＜first permanent molars.They frequently occur bilaterally and exhibit a moderate to high degree of correlation.However,the correlation was very weak between the mandibular deciduous first and second molars.

Background::Sentinel lymph node (SLN) biopsy is gradually accepted as the standard of care in breast cancer patients with down-staged axillary disease after neoadjuvant chemotherapy (NAC). However, it is still difficult to precisely define pre-NAC clinical node-positive (cN1) and post-NAC clinical node-negative (ycN0). This prospective single-center trial was designed to evaluate the feasibility and accuracy of standard targeted axillary dissection (TAD) after NAC in highly selective pre-NAC cN1 patients (not considering ultrasound-based axillary ycN staging).Methods::This prospective trial included patients with initial pre-NAC cT1–3N1M0 invasive breast cancer but with a rigorous definition of cN1 from the Affiliated Cancer Hospital of Zhengzhou University. When NAC was effective (including complete and partial responses) and preoperative axillary palpation was negative, preoperative ultrasound-based axillary staging was not considered, and all patients underwent TAD followed by axillary lymph node (LN) dissection. The detection rate (DR) and false-negative rate (FNR) of TAD were calculated.Results::A total of 82 patients were included, and 77 of them were eligible for data analysis. The DR for TAD was 94.8% (73/77). There were 26 patients with one abnormal LN at the time of diagnosis based on ultrasound, 45 patients with two, and 2 patients with three. One patient had one TAD LN, four patients had two TAD LNs, and 68 patients had three or more TAD LNs. Preoperative axillary palpation yielded negative results for all 73 patients who successfully underwent TAD. Preoperative ultrasound-based ycN0 and ycN+ conditions were detected for 52 and 21 cases, respectively. The FNR was 7.4% (2/27) for standard TAD (≥3 SLNs), which was lower than that of all successful TAD (≥1 SLN; 10.0%, 3/30).Conclusions::In rigorously defined pre-NAC cN1 breast cancer patients, standard TAD is feasible for those with negative axillary palpation after NAC, and FNR is also less than 10%.Registration::chictr.org.cn, ChiCTR2100049093

Objective:To evaluate the value of preoperative prediction of vessel invasion (VI) of locally advanced gastric cancer by machine learning model based on the venous phase enhanced CT radiomics features.Methods:A retrospective analysis of 296 patients with locally advanced gastric cancer confirmed by pathology in the First Affiliated Hospital of Zhengzhou University from July 2011 to December 2020 was performed. The patients were divided into VI positive group ( n=213) and VI negative group ( n=83) based on pathological results. The data were divided into training set ( n=207) and test set ( n=89) according to the ratio of 7∶3 with stratification sampling. The clinical characteristics of patients were recorded, and the independent risk factors of gastric cancer VI were screened by multivariate logistic regression. Pyradiomics software was used to extract radiomic features from the venous phase enhanced CT images, and the minimum absolute shrinkage and selection algorithm (LASSO) was used to screen the features, obtain the optimal feature subset, and establish the radiomics signature. Four machine learning algorithms, including extreme gradient boosting (XGBoost), logistic, naive Bayes (GNB), and support vector machine (SVM) models, were used to build prediction models for the radiomics signature and the screened clinical independent risk factors. The efficacy of the model in predicting gastric cancer VI was evaluated by the receiver operating characteristic curve. Results:The degree of differentiation (OR=13.651, 95%CI 7.265-25.650, P=0.003), Lauren′s classification (OR=1.349, 95%CI 1.011-1.799, P=0.042) and CA199 (OR=1.796, 95%CI 1.406-2.186, P=0.044) were independent risk factors for predicting the VI of locally advanced gastric cancer. Based on the venous phase enhanced CT images, 864 quantitative features were extracted, and 18 best constructed radiomics signature were selected by LASSO. In the training set, the area under the curve (AUC) of XGBoost, logistic, GNB and SVM models for predicting gastric cancer VI were 0.914 (95%CI 0.875-0.953), 0.897 (95%CI 0.853-0.940), 0.880 (95%CI 0.832-0.928) and 0.814 (95%CI 0.755-0.873), respectively, and in the test set were 0.870 (95%CI 0.769-0.971), 0.877 (95%CI 0.788-0.964), 0.859 (95%CI 0.755-0.961) and 0.773 (95%CI 0.647-0.898). The logistic model had the largest AUC in the test set. Conclusions:The machine learning model based on the venous phase enhanced CT radiomics features has high efficacy in predicting the VI of locally advanced gastric cancer before the operation, and the logistic model demonstrates the best diagnostic efficacy.

Purpose: Patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer can benefit from trastuzumab deruxtecan. Given the unclear prognostic characteristics of HER2-low breast cancer, we investigated the prognostic characteristics of HER2-low expression from primary tumor to residual disease after neoadjuvant chemotherapy (NACT). Materials and Methods: The data of HER2-negative patients receiving NACT at our center were collected. Pathological complete response (pCR) rate were compared between HER2-0 and HER2-low patients. The evolution of HER2 expression from primary tumor to residual disease and its impact on disease-free survival (DFS) were examined. Results: Of the 690 patients, 494 patients had HER2-low status, of which 72.3% were hormone receptor (HR)–positive (p < 0.001). The pCR rates of HER2-low and HER2-0 patients (14.2% vs. 23.0%) showed no difference in multivariate analysis regardless of HR status. No association was observed between DFS and HER2 status. Of the 564 non-pCR patients, 57 (10.1%) changed to HER2-positive, and 64 of the 150 patients (42.7%) with HER2-0 tumors changed to HER2-low. HER2-low (p=0.004) and HR-positive (p=0.010) tumors before NACT were prone to HER2 gain. HER2 gain patients had a better DFS compared with HER2-negative maintained patients (87.9% vs. 79.5%, p=0.048), and the DFS of targeted therapy group was better than that of no targeted therapy group (92.4% vs. 66.7%, p=0.016). Conclusion Although HER2-low did not affect the pCR rate and DFS, significant evolution of HER2-low expression after NACT creates opportunities for targeted therapy including trastuzumab.

Objective:To investigate the effect of CHI3L1 on the biological function of chondrocytes and its role in lumbar facet joint degeneration.Methods:The human lumbar facet joint articular cartilage were collected, and the relative mRNA expression of CHI3L1 gene detected by quantitative fluorescence PCR. Then explored the correlation between joint degeneration and gender, age and relative mRNA expression of CHI3L1. Human chondrocytes were cultured in vitro. The effects of CHI3L1 on chondrocyte proliferation, cycling, and apoptosis, as well as expression of related inflammatory factors, were investigated. The mechanism by which CHI3L1 regulates the degeneration of articular cartilage was investigated using the signal transduction pathway protein chip.Results:There was a positive correlation between the grade of degeneration in lumbar facet joint and the relative expression of CHI3L1 gene mRNA ( r=0.76, P<0.001). There was no correlation with the patient's gender ( r=-0.12, P=0.500). A positive correlation between the age of patients and the relative expression of CHI3L1 gene mRNA was found ( r=0.47, P=0.005). Compared with the non-degenerative group, the expression of CHI3L1 gene mRNA significantly increased in the degenerative group, and the expression of CHI3L1 gradually increased with the aggravation in the grade of degeneration ( F=18.90, P<0.001). Compared with the non-degenerative group, the chondrocytes in the CHI3L1 group had significantly lower proliferation at 48 h (OD 490/fold=7.132), 72 h (OD 490/fold=4.803), 96 h (OD 490/fold=2.431) and 120 h (OD 490/fold=0.009). The ratio of chondrocytes in G1 phase, S phase and G2/M phase were 85.03%±3.05%, 12.78%±2.29% and 0.90%±0.76% in the CHI3L1 group, and 73.93%±2.73%, 22.81%±1.93% and 0.99%±0.87% in control group, respectively. There were significant differences in the percentage of chondrocytes in G1 phase ( t=4.70, P<0.001) and S phase ( t=5.80, P<0.001) between the two groups. The percentages of apoptosis in chondrocyte in CHI3L1 group and control group were 8.64%±0.76% and 5.68%±1.13%, which has a statistically difference ( t=4.47, P<0.001). The expression of IL-6 in chondrocytes of CHI3L1 group was 49.60±0.01 pg/ml, which was higher than that of 47.88±0.01 pg/ml in the control group ( t=132.70, P<0.001). The expression of TNF-α was 95.93±0.02 pg/ml, which was higher than 90.69±0.02 pg/ml in the control group ( t=376.10, P<0.001). There was significant difference in expression of IL-6 in chondrocytes between the CHI3L1 group and the control group ( t=132.72, P<0.001). The expression of TNF-α ( t=376.10, P<0.001) was statistically difference. Protein chip detected 53 proteins with significant differences in expression and 43 proteins with significant differences in protein phosphorylation levels. Bioinformatics analysis was used to identify 16 signaling pathways in which the above different proteins might be involved, including ErbB, PI3K, Akt, Ras, JAK, STAT3, MAPK pathway. In the MAPK pathway, the expression of MAPK1 and RAF1 proteins was higher in the chondrocytes of the CHI3L1 group than in the control group (1.094±0.00 vs. 0.814±0.00, 0.988±0.00 vs. 0.786±0.00; t=103.16, P<0.001; t=54.32, P<0.001). Compared with the control group, the expression of MAPK1 and RAF1 proteins was significantly increased in the chondrocytes of the CHI3L1 group. Conclusion:The expression of CHI3L1 is corrected to articular cartilage degeneration. CHI3L1 is able to inhibit the proliferation of articular chondrocytes, which regulated the cycling of chondrocytes from G1 phase to S phase, promote the apoptosis of chondrocytes, and promote the expression of IL-6 and TNF-α in chondrocytes. Regulation of chondrocytes biological function through the MAPK pathway, which is a potential biomarker for the clinical diagnosis and treatment of lumbar joint degeneration.

Objective:To investigate the prognostic value of molecular subtypes in patients with resected invasive breast cancer.Methods:Between 2015 and 2018 7 869 patients with invasive breast cancer after undergoing surgery were included in this analysis. Breast cancer was classified into four subtypes according to the status of hormone receptor (HR) and HER2: HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. Kaplan-Meier curves and COX regression were used to compare disease-free survival (DFS) and overall survival (OS) among different subtypes.Results:The 5-year DFS and OS were 86.30% and 94.29%, respectively. Proportions of HR+/HER2-、HR+/HER2+、HR-/HER2+ and HR-/HER2- were 52.9%、17.5%、14.1%和15.5%, respectively. The 5-year DFS of HR+/HER2- subtype (88.12%) was higher than HR+/HER2+ (84.67%, P=0.026), HR-/HER2+ (84.19%, P<0.001) and HR-/HER2- (83.70%, P<0.001). The 5-year OS of HR+/HER2- (95.38%) was not different from HR+/HER2+ (95.17%, P=0.187), while it was higher than that of HR-/HER2+ (92.26%, P<0.001) and HR-/HER2- (91.69%, P<0.001). Subtype was still a significant factor regarding DFS and OS in multivariable analyses adjusting for age, sex, stage, Ki67, types and time of surgery. The DFS ( P=0.257) and OS ( P=0.511) was not different between HR-/HER2+与HR+/HER2- subtypes, while HR-/HER2+ and HR-/HER2- patients had worse DFS ( P<0.05) and OS ( P<0.05) than that with HR+/HER2-. Conclusions:Molecular subtype is a significant independent prognostic factor for DFS and OS in operable invasive breast cancer. HR+ subtypes have better prognosis compared with HR- subtypes. The DFS and OS were not different between HR+/HER2- and HR+/HER2+, or between HR-/HER2+ and HR-/HER2-.

Objective: To develop and evaluate an automatic intensity-modulated radiation therapy (IMRT) program for cervical cancer based on a database of overlap volume histogram (OVH) and high-quality cervical IMRT plans for previously-treated patients. Methods: A database consisting of high-quality IMRT plans and OVHs from 200 cervical cancer patients was established. OVHs of another 26 cervical cancer patients were converted into gray level images to calculate the image similarity compared with those from the database. The planning optimization function of the patients from the database with the highest image similarity was selected and inherent Pinnacle³ scripts were utilized to automatically generate IMRT plan. Finally, the dosimetric parameters, plan quality and design time were statistically compared between the automatic and manual plans. Results: The target coverage, conformity index and homogeneity index did not significantly differ between two plans (all P>0.05). The V₄₀, V₄₅ and mean dose for the rectum in the automatic plans were significantly decreased by 6.1%, 1.3% and 50.7 cGy than those in the manual plans (all P<0.05). Compared with the manual plans, the mean dose for the intestine and femur in the automatic plans were significantly reduced by 31.7 cGy and 188.9 cGy (both P<0.05), whereas the mean dose for the ilium was slightly decreased by 92.3 cGy in the automatic plans (P>0.05). The plan design time was shortened by 71% in the automatic plans. Conclusions The automatic IMRT plans based on a database of OVH and high-quality IMRT plans can not only significantly shorten the plan design time, but also reduce the irradiated dose of normal tissues without compromising the target coverage and conformity index.

Objective:To explore the method and curative effect evaluation of repairing and rebuilding the long segmental bone defect after resection of long bone malignant tumors in adolescents.Methods:Reviewed our experience in 10 patients. Among them, 4 were male and 6 were female. The age was 10.2 years old (range, 6-16 years old). Including 7 cases of osteosarcoma, 3 cases of Ewing's sarcoma; 2 cases of humerus tumors, 7 cases of femoral tumors, and 1 case of tibial tumors-who presented between April 2015 and October 2019, in which the proportion of bone defect account for 71.4%-89.3% of the total length of diseased bone after tumor resection, with an average value of 80.9%. Considering the epiphyseal growth of young people, on the premise of ensuring enlarged tumor resection, we use traditional fibula autograft and prosthesis combined with steel plate, 3D printing design to retain the super-prosthesis of the epiphysis, and 3D printing bone trabecular was processed for the sake of making it grow successfully into the binding part of prosthesis and bone as we expect, simultaneously, the design of the short-force arm retaining the bilateral epiphysis can assit the steel plate and interlocking screws to enhance the stability.Results:The operation was completed successfully, and there were no complications such as nerve and blood vessel injury during the operation. After follow-up of 4-8 months, with an average follow-up of 22.9 months. One patient's review of X-ray film after 2 years of the operation showed that the transplanted fibula had a sign of bone resorption, and the internal fixation was in it's original position without obvious abnormalities. Two cases' auxiliary steel plates had fractured within one and a half to two years after surgery. With replacing the fractured steel plates, the internal fixation was good until now. According to the evaluation standards of the International Society of Limb Salvation: 2 cases of humerus osteosarcoma were respectively scored 23 points, 26 points, an average of 24.5 points; 4 cases of femoral osteosarcoma and 3 cases of femoral Ewing's sarcoma respectively scored 26 points and 25 points, 19 points, 30 points, 27 points, 24 points, 28 points (average, 25.6 points); 1 case of tibial osteosarcoma scored 26 points; all obtained relative satisfying treatment results.Conclusion:The combination of 3D printing and traditional machining techniques to produce an individualized long segmental prosthesis that preserves the epiphysis which applicated in the limb salvage treatment of bone malignant tumors can achieve excellent therapeutic effect.

Objective To analyze clinical efficacy of artificial prosthesis in giant cell tumor in distal femur,and to investigate risk factors affecting prosthesis failure and functional outcomes.Methods 42 patients with giant cell tumor of bone in distal femur,who had undergo prosthesis replacement from January 2002 to May 2015,were enrolled in this study.There were 24 males and 18 females,with an average age of 38.53± 12.87 years.There were 28 primary patients and 14 relapsed patients,including 11 cases of recurrence once and 3 cases of twice.Three-dimensional finite element model was used to analyze the effect of different angles of deviation of the spinal needle on the deformation of the bone wall.The correlations between the factors such as age,sex,occupation,prosthesis type,and other factors on prosthesis loosening were compared.Biomechanical effect of lower limbs caused by prosthesis offset angle was analyzed through gait analysis.Analyzed the effects of primary tumor or recurrence,prosthesis service status,and length of surgical osteotomy on joint function.Results A total of 42 patients were followed up by 20-158 months,with an average of 68.7 months.The 3 year survival rate of prosthesis was 83.33％ for 3 years and 57.14％ for 5 years.The major reason of prosthesis failure was loose (18/42,42.8％).X-ray films showed 19 cases of prosthetic intramedullary nail and sagittal bias of medullary force line angle ＞ 3° in the first follow-up.Osteotomy length (OR=0.132,P=0.0027) and offset angle of needle (OR=25.000,P=0.000) were significantly correlated to prosthesis loose.A length more than 12 cm and angle more than 3° were easier to result in prosthesis loose.There were no significant correlation between prosthesis failure and patients age,gender,occupation and prosthesis type.Gait analysis shows that the unsuitable bias angle of the prosthesis can significantly change the joint force of the prosthesis.The average score of MSTS 93 function evaluation was 25.43±4.256,excellent in 33 cases,good in 7 cases and poor in 2 cases.Function of patients with primary GCT were better than that of recurrent ones.Patients with one 1 times recurrence were better than that of recurrence twice (P=0.003).Patients without prosthesis loosening and revision were better than that with loosening (P=0.001).Patients with an osteotomy length less than 12 cm had a poorer function than that with more than 12 cm (P=0.002).Conclusion The main factors affecting distal femoral prosthesis replacement therapy of GCT is loosening,which was caused by broach and medullary cavity mismatch,osteotomy length,prosthesis rotation,prosthesis position.The function of the prosthesis is mainly affected by operation times,prosthesis status,osteotomy length and low patella.

Objective To analyze the efficacy of total claviculectomy in the treatment of Ewing's sarcoma and to discuss the impact of clavicular reconstruction on the outcome.Methods The clinical records of a 13-year-old male patient with left clavicular Ewing's sarcoma were reviewed.The subject received 2 cycles (at an interval of 2 weeks) of neoadjuvant chemotherapy comprising cisplatin 120 mg/m2 (1 d),adriomycin 30 mg/m2 (3 d),and ifosfamide 2.0 g/m2 (5 d).Total claviculectomy was carried out without clavicular reconstruction and the patient underwent 9 cycles of subsequent chemotherapy.The appearance and function of the operated limb,radiological examinations of the surgical site,ECT bone scans and pulmonary CT were followed up.The literatures regarding the total and subtotal excision of the clavicle were reviewed to investigate the importance of clavicular reconstruction.Results After 23-months of follow-up,the patient was subjectively free of limb function compromise.Physical examinations indicated drooping of the operated shoulder by 2 cm,whereas the appearance was similar between both shoulders.Functionality of the operated limb was recovered.The motion of the left shoulder:abduction 90°,adduction 40°,anterior flexion 90°,extension 45°,internal rotation 80°,external rotation 60°,and no restriction of limb elevation.Manual muscle strength tests showed V/V muscle strength of the operated limb.American Shoulder and Elbow Surgeons' form (ASES) and Musculoskeletal Tumor Society (MSTS) score were 96 and 30,respectively.Postoperative X-ray films demonstrated mild thoracic scoliosis.The patient did not appear recurrence and metastasis.Conclusion Total claviculectomy is efficacious for treating clavicular Ewing's sarcoma.Clavicular reconstruction may not be imperative for treatment of clavicular malignancy because of the increased technical difficulty and great risk of complications.