Objective:To study the survival and prognostic factors for the recurrent extracranial malignant germ cell tumors (MGCTs) in children, and to explore feasible salvage treatment.Methods:A retrospective study.Pediatric patients with recurrent extracranial MGCTs diagnosed in Shanghai Children′s Medical Center between January 2010 and January 2020 were retrospectively recruited.Comprehensive treatment regimens included surgery, chemotherapy and radiation.Kaplan-Meier survival analysis and Cox regression model were employed to analyze the survival and prognostic factors for children with recurrent extracranial MGCTs.Results:A total of 172 children with extracranial MGCTs were treated, including 21 (12.2%) recurrent cases.The median time of MGCT recurrence after the end of the first treatment was 11 months.Finally, 19 patients were recruited after excluding 2 non-eligible cases, including 10 boys and 9 girls with the age at recurrence of 26 (8-170) months.The follow-up time was 57 (13-122) months.Salvage chemotherapy, complete resection and radiotherapy were performed in 16, 14 and 4 patients, respectively.The 4-year overall survival (4yr-OS) rate was (82.5±9.2)%(19 cases). The 4yr-OS rate was significantly higher in patients managed with surgery but without adjuvant chemotherapy at the initial treatment (13 cases) than those managed with chemotherapy at the initial treatment (6 cases)[(92.3±7.4)% vs.(60.0%±21.9)%, P=0.002]. Univariant and Cox multivariant regression analyses showed that failure to achieve the normal range of alpha fetoprotein after 3 cycles of chemotherapy significantly influenced the survival of recurrent extracranial MGCTs. Conclusions:For patients with recurrent extracranial MGCTs, comprehensive treatment approaches like complete surgical resection, chemotherapy, and radiotherapy offer a favorable survival rate.Specifically, recurrent and re-treated patients who initially received surgery alone without adjuvant chemotherapy have a higher survival rate compared to those who received chemotherapy during the initial treatment.

Objective:To develop a preoperative CT image segmentation algorithm based on artificial intelligence deep learning technology for total hip arthroplasty (THA) revision surgery, and to verify and preliminarily apply it.Methods:A total of 706 revision cases with clear CT data from April 2019 to October 2022 in Chinese PLA General Hospital were retrospectively analyzed, including 520 males, aged 58.45±18.13 years, and 186 females, aged 52.23±16.23 years. All of them were unilateral, and there were 402 hips on the left and 304 hips on the right. The transformer_unet convolutional neural network was constructed and trained using Tensorflow 1.15 to achieve intelligent segmentation of the revision THA CT images. Based on the developed three-dimensional planning system of total hip arthroplasty, an intelligent planning system for revision hip arthroplasty was preliminarily constructed. Dice overlap coefficient (DOC), average surface distance (ASD) and Hausdorff distance (HD) parameters were used to evaluate the segmentation accuracy of transformer_unet, full convolution network (FCN), 2D U-shaped Net and Deeplab v3 +, and segmentation time was used to evaluate the segmentation efficiency of these networks.Results:Compared with the FCN, 2D U-Net, and Deeplab v3+ learning curves, the transformer_unet network could achieve better training effect with less training amount.The DOC of transformer_unet was 95%±4%, the HD was 3.35±1.03 mm, and the ASD was 1.38±0.02 mm; FCN was 94%±4%, 4.83±1.90 mm, 1.42±0.03 mm; 2D U-Net was 93%±5%, 5.27±2.20 mm, and 1.46±0.02 mm, respectively. Deeplab v3+ was 92%±4%, 6.12±1.84 mm, 1.52±0.03 mm, respectively. The transformer_unet coefficients were better than those of the other three convolutional neural networks, and the differences were statistically significant (all P<0.05). The segmentation time of transformer_unet was 0.031±0.001 s, FCN was 0.038±0.002 s, 2D U-Net was 0.042±0.001 s, Deeplab v3+ was 0.048±0.002 s. The segmentation time of transformer_unet was less than that of the other three convolutional neural networks, and the difference was statistically significant ( P<0.05). Based on the results of previous studies, an artificial intelligence assisted preoperative planning system for THA revision surgery was initially constructed. Conclusion:Compared with FCN, 2D U-Net and Deeplab v3+, the transformer_unet convolutional neural network can complete the segmentation of the revision THA CT image more accurately and efficiently, which is expected to provide technical support for preoperative planning and surgical robots.

Objective:To investigate the significance of serum fibroblast growth factor 19 (FGF19), Klotho and fibroblast growth factor receptor 4 (FGFR4) protein expression in patients with primary biliary cirrhosis (PBC).Methods:Sixty-three patients with PBC who received treatment in Ningbo Huamei Hospital, University of Chinese Academy of Sciences between August 2017 and July 2020 were included in the PBC group. An additional 51 healthy patients who concurrently received physical examination in the same hospital were included in the control group. Serum FGF19, Klotho and FGFR4 protein expression were determined by enzyme linked immunosorbent assay.Results:Serum FGF19 and FGFR4 protein in PBC group were (178.86 ± 21.28) ng/L and (2.96 ± 0.47) ng/L, respectively, which were significantly higher than those in the control group [(69.93 ± 12.12) ng/L, (1.21 ± 0.35) ng/L, t = 32.51, 27.98, both P < 0.05]. Klotho protein expression in the PBC group was significantly lower than that in the control group [(3.25 ± 0.89) μg/L vs. (9.67 ± 1.53) μg/L, t = 22.08, P < 0.05]. Serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase in the PBC group were (84.25 ± 13.24) U/L, (71.82 ± 10.35) U/L, (278.93 ± 32.45) U/L, respectively, which were significantly higher than those in the control group [(23.76 ± 3.42) U/L, (23.10 ± 4.53) U/L, (76.81 ± 16.36) U/L, t = 31.75, 31.26, 40.48, all P < 0.05]. The receiver operating characteristic curve analysis showed that the sensitivity and specificity of FGF19 in the diagnosis of PBC were 76.67% and 61.90%, respectively, they were 58.82% and 66.67% for Klotho protein diagnosis, 54.55% and 76.67% for FGFR4 protein. Pearson analysis revealed that there was a positive linear relationship between FGF19 and FGFR4 protein ( r = 0.78, P < 0.05), while there was a negative linear relationship between Klotho protein and FGFR4 protein ( r = -0.72, P < 0.05). Conclusion:In patients with PBC, serum FGF19 and FGFR4 protein levels are increased, while Klotho protein level is decreased. There is a positive linear relationship between FGF19 and FGFR4 protein, and there is a negative linear relationship between Klotho protein and FGFR4 protein. This study is highly innovative and scientific.

Objective:To investigate the clinical efficacy of dual growing rods (DGR) in the treatment of early onset scoliosis (EOS), and to evaluate the safety of its clinical application.Methods:From March 2015 to August 2021, a total of 20 EOS patients with onset age within 10 years old who were treated with dual growth rod technique were retrospectively analyzed, including 8 males and 12 females. The mean age of patients at first surgery was 9.0±1.4 years (range, 6.3-10.8 years); the preoperative Cobb angle was 59.0°±16.8° (range, 41.2°-103°). The Cobb angle, thoracic kyphosis angle, lumbar lordosis angle, T 1-T 12 height, T 1-S 1 height, coronal plane imbalance, sagittal vertical axis (SVA), apical vertebral translation (AVT) and Campbell's space available for lung ratio (SAL) were recorded and analyzed while surgery-related complications were also recorded. Results:The average follow-up time of 20 patients was 28.07±14.30 months. The average initial hospital stay was 20.56±8.28 days, the average initial operation time was 211.70±39.80 min, the average blood loss in the initial operation was 255.00±149.50 ml, and the average surgical distraction was 1.60±0.51 times per person. The Cobb angle of the main curve in the coronal plane decreased from 59.00°±16.80° before operation to 33.40°±11.80° after the initial operation, which was 29.67°±11.67° at 1 year and 29.40°±11.30° at the last follow-up. Preoperative thoracic kyphosis angle was 41.39°±6.06°, decreased to 31.72°±3.56° after the initial operation, was 30.32°±4.26° at 1-year and 30.24°±4.23° at the last follow-up; preoperative lumbar lordosis angle was 45.90°±8.03°, decreased to 42.65°±9.05° after initial operation, 41.55°±7.84° at 1-year follow-up, and 41.53°±8.21° at the last follow-up; preoperative T 1-S 1 height was 31.76±4.42 cm, initial after operation, it increased to 34.64±3.96 cm, 36.73±3.87 cm at 1 year, and 37.28±4.36 cm at the last follow-up; preoperative T 1-T 12 height was 17.38±2.76 cm. increased to 19.39±2.86 cm after the initial operation, 21.77±2.71 cm at 1 year, and 21.91±2.74 cm at the last follow-up; Preoperative coronal balance was 1.52±0.73 cm, and decreased to 0.87±0.38 cm after the initial operation, 0.81±0.38 cm at 1 year, and 0.77±0.37 cm at the last follow-up; preoperative sagittal balance was 1.94±0.78 cm, and 1.42±0.56 cm after operation, 1.28±0.55 cm at 1 year, and 1.26±0.57 cm at the last follow-up; The preoperative apical vertebra offset was 4.33±1.85 cm, and 2.16±1.47 cm after the initial operation, 1.63±1.17 cm at 1 year, and 1.61±1.23 cm at the last follow-up; SAL increased from preoperative 0.88±0.05 to 0.94±0.03 postoperatively, and 0.96±0.01 at 1-year follow-up, and 0.97±0.01 at the last follow-up. The differences between the above indicators before and after surgery were statistically significant ( P<0.05); there was a statistically significant difference in SAL between the 1-year follow-up and the last follow-up ( t=3.80, P=0.001), and other indicators were not statistically significant. Among the 20 cases, there were 5 cases of postoperative complications, including 2 cases of pedicle screw loosening and displacement, 2 cases of transverse process hook decoupling, and 1 case of proximal junctional kyphosis (PJK). The complication rate was 25% (5/20), all of them underwent revision treatment, and the prognosis was good after timely treatment. Conclusion:The dual growth bar technique can effectively control the progression of EOS deformity, preserve the longitudinal growth potential of the spine, and buy time for the development of the thorax in children, which has high safety.

Objective:To observe the efficacy of trigeminal nerve microvascular decompression in the treatment of elderly trigeminal neuralgia.Methods:A total of 96 elderly patients with trigeminal neuralgia admitted to our hospital from January 2015 to June 2016 were selected.48 patients were treated with percutaneous trigeminal semilunar ganglion radiofrequency thermocoagulation as a control group, and the other 48 patients were treated with trigeminal nerve microvascular decompression as the observation group.Efficacy indicators of post-operative pain severity scores, severity scores of post-operative complications, a sum of two categories of severity scores, which were compared between the two groups at one month and at 1, 3, 5 years after surgery.Results:One month after the operation, there was no significant differences in pain severity score, surgical complications severity scores, and a sum of two categories severity scores between the two groups of patients(all P>0.05). In the observation group versus the control group, pain severity scores were[(0.55±0.39)scores versus(0.94±0.61)scores, t=7.572, P=0.011 at 1 year after operation], [(0.81±0.61)versus(1.19±0.83)scores, t=7.513, P=0.012 at 3 years after operation]and[(1.13±0.65)and(1.55±0.91)scores, t=7.837, P=0.010 at 5 years after operation]respectively, showing more efficacy in observation group.In the observation group versus the control group, severity scores of surgical complications were[(0.39±0.28)and(0.67±0.49)scores, t=7.290, P=0.014, at 1 year after operation], [(0.65±0.37)and(0.94±0.55)scores, t=7.353, P=0.013 at 3 years after operation]and[(0.80±0.35)and(1.13±0.64)scores, t=7.475, P=0.012 at 5 years after operation], respectively, showing more efficacy in observation group.In the observation group versus the control group, overall efficacy from a sum of the two categories of severity scores were[(0.72±0.35)and(1.33±0.56)scorets, t=7.701, P=0.009 at 1 year after operation], [(1.21±0.49)and(1.78±0.70)scores, t=7.580, P=0.011 at 3 years after operation]and[(1.46±0.55)and(2.24±1.03)scores, t=8.026, P=0.007 at 5 years after operation], respectively, showing more efficacy in observation group.Overall, above three severity scores were lower than in the observation group than in the control group(all P<0.05). Conclusions:For elderly patients with trigeminal neuralgia, trigeminal nerve microvascular decompression has definite efficacy, long duration of pain relief, low incidence of surgical complications, and is safe and reliable, which is worthy of clinical application.

Objective:To analyze the clinical characteristics, therapeutic modalities and prognosis of desmoplastic small round cell tumor (DSRCT) in children, and to summarize the international research progress.Methods:A total of 8 children with DSRCT admitted to Shanghai Children′s Medical Center, Shanghai Jiaotong University, School of Medicine, from January 1999 to August 2019 were retrospectively studied.The clinical characteristics, consultation process and follow-up results were summarized, and the Kaplan-Meier survival analysis method was used to calculate the survival rate.Results:Among these 8 cases, there were 6 male children and 2 female children.Seven cases originated in the abdomen and pelvis, and 1 case originated in the sacral region.All cases had infiltrate surrounding tissues or viscera, and 4 cases(50%) had extra-peritoneal metastasis, including distant lymph node metastasis, liver, lung and bone metastasis.All patients received chemotherapy, among which 3 patients received radiotherapy, and 2 patients received autologous hematopoietic stem cell transplantation.The medical follow-up was continued to February 15, 2020, with the median follow-up period being 59 months.Three cases died and 5 cases survived (2 cases in complete remission, 1 case in recurrent relapse, 2 cases in partial remission still under treatment). The median relapse time was 14.5 months, the 3-year relapse-free survival rate was (30.0±17.5)%, and 3-year overall survival was (51.4±20.4)%.Conclusions:Half of DSRCT had distant metastasis; the prognosis was poor despite the aggressive multimodality therapeutic approaches, such as chemotherapy, cytoreductive surgery, and whole abdominopelvic radiotherapy and stem cell transplantation.

Objective:To compare the difference of epileptiform discharges detection in patients with epilepsy between the 25 electrodes electroencephalogram (EEG) system proposed by the International Federation of Clinical Neurophysiology in 2017 and the previous 19 electrodes EEG system.Methods:Patients suspected of epilepsy or with confirmed epilepsy who need a follow-up EEG were collected in Zhongshan Hospital, Fudan University from March 2018 to November 2019, and conventional video-EEG recording was performed on all patients for two hours with the standard 25 electrodes EEG system. Two neurophysiologists reviewed the recordings blindly using the 19 electrodes system and the 25 electrodes system, marking the epileptiform discharges and their amplitudes. Finally, the data were statistically analyzed.Results:A total of 403 patients were included in the study, in which 263 cases were diagnosed as epilepsy, including 129 cases of generalized epilepsy, 115 cases of temporal lobe epilepsy, 13 cases of frontal lobe epilepsy, two cases of parietal lobe epilepsy and four cases of occipital lobe epilepsy. In 115 temporal lobe epilepsy patients, 76 (66.09%) and 100 (86.96%) records were detected epileptiform discharges by the 19 or 25 electrodes EEG system respectively, and the difference was statistically significant (χ2=13.939, P<0.001). While in patients with non-temporal lobe epilepsy, there was not statistically significant difference between the two systems. In 76 patients whose temporal epileptiform discharges were detected by the two systems, the amplitudes of epileptiform discharges in the newly-added inferior temporal electrodes (F9/F10, T9/T10, P9/P10) and the original temporal electrodes (F7/F8, T7/T8, P7/P8) were (61.53±22.64) μV and (48.25±20.90) μV, respectively, with statistically significant difference between the two groups ( t=5.486, P<0.001). In patients with abnormal [79.59% (39/49) vs 61.22% (30/49), χ2=3.967, P=0.046] and normal [95.45% (42/44) vs 70.45% (31/44), χ2=9.724, P=0.003] imaging, the ability of the 25 electrodes EEG system to detect epileptiform discharges was higher than that of the 19 electrodes EEG system. Conclusion:The 25 electrodes EEG system can significantly improve the detection ability of temporal epileptiform discharges in patients with epilepsy, which is recommended for regular use to increase the detection ability of temporal area abnormal wave and assist the diagnosis and treatment of epilepsy.

Objective:To prepare primary cardiomyocyte (PCM) specific peptide-conjugated mesoporous silicon nanoparticles (MSN) with L-arginine (LA) as a core (PCM-MSN@LA), and evaluate its specific protective effect on septic myocardium.Methods:PCM-MSN@LA was prepared by condensation reaction, the characterization of PCM-MSN@LA, the amount of LA modification and release was detected, and the phagocytosis of PCM-MSN@LA and its affinity to myocardial tissue was observed. ① Experiment one: SD neonatal rat cardiomyocytes were divided into control group (Con group), lipopolysaccharide (LPS) group, MSN@LA/LPS group and PCM-MSN@LA/LPS group. The LPS group was stimulated with 5 mg/L LPS for 16 hours, while the MSN@LA/LPS group and PCM-MSN@LA/LPS group were treated with 5 mg/L LPS and 25 mg/L LA-containing nanoparticles (MSN@LA and PCM-MSN@LA) for 16 hours. Cell viability and reactive oxygen species (ROS) production levels were detected. Apoptosis was observed via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method (TUNEL). Western Blot was used to detect the changes in endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) proteins. ② Experiment two: 64 healthy male C57BL/6 mice were divided into Sham group, LPS group, MSN@LA/LPS group and PCM-MSN@LA/LPS group by random number table method, 16 mice in each group. LPS group were injected 50 mg/kg LPS intraperitoneally. MSN@LA/LPS group and PCM-MSN@LA/LPS group were injected with 0.5 mg/kg MSN@LA and PCM-MSN@LA via tail vein immediately after intraperitoneal injection of LPS. Eight animals in each group were used to observe the 24-hour survival rate, and the other 8 mice were used to detect cardiac function by echocardiography at 12 hours after operation; mRNA expressions of interleukin (IL-1, IL-6) and tumor necrosis factor-α (TNF-α) were measured by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR).Results:PCM-MSN@LA was spherical, with particle size of about 180 nm, Zeta potential of about -21 mV, with LA loaded. The amount of LA modification and release rate were 12.3% and 24.3%, respectively. Cell phagocytosis experiments showed that PCM-MSN@LA had the targeting ability of cardiomyocytes and myocardial tissue. Experiment one: after LPS stimulation of myocardial cells, cell viability decreased, while ROS generation, apoptosis, eNOS and iNOS protein expressions increased. Compared with LPS group, MSN@LA/LPS group and PCM-MSN@LA/LPS group had higher cell viability, reduced ROS levels and apoptosis, increased expressions of eNOS and iNOS. PCM-MSN@LA/LPS group changed the above effect further than MSN@LA/LPS group [cell viability ( A value): 0.51±0.08 vs. 0.41±0.03, ROS (relative fluorescence intensity): 28 450±1 941 vs. 35 628±2 551, TUNEL positive cells/total cells: 0.27±0.03 vs. 0.35±0.04, eNOS/β-Tubulin: 1.467±0.046 vs. 1.201±0.131, iNOS/β-Tubulin: 1.700±0.033 vs. 1.577±0.068, all P < 0.05]. Experiment two: the number of 24-hour survive in MSN@LA/LPS group and PCM-MSN@ LA/LPS group were higher than LPS group (number: 2, 4 vs. 1, P values were 0.36 and 0.03 respectively). Compared with Sham group, the cardiac function of LPS group was significantly inhibited and the mRNA expression of inflammatory factors increased. The PCM-MSN@LA/LPS group had higher left ventricular ejection fraction (LVEF) and left ventricular short-axis shortening rate (LVFS) than LPS group, and lower mRNA expressions of IL-1, IL-6, and TNF-α mRNA [LVEF: 0.456±0.019 vs. 0.337±0.017, LVFS: (21.97±1.78)% vs. (15.53±1.67)%, IL-1 mRNA (2 -ΔΔCT): 169.22±8.95 vs. 189.79±6.79, IL-6 mRNA (2 -ΔΔCT): 19.90±1.60 vs. 23.74±1.45, TNF-α mRNA (2 -ΔΔCT): 8.21±0.81 vs. 11.00±1.48, all P < 0.05]. There was no significant difference in each index between the MSN@LA/LPS group and LPS group. Conclusion:PCM-MSN@LA with myocardial targeting characteristic significantly increased the activity of myocardial cells, down-regulated the expression of inflammatory factors and the production of ROS, alleviated cardiac insufficiency in sepsis, and achieved the targeted treatment of myocardial injury in sepsis.

Objective:To describe our experiences in application of the 2019 revision of "CCCG-WT-2016" for the diagnosis of Wilms tumors.Methods:Ninety-one cases of Wilms tumor diagnosed at Shanghai Children′s Medical Center from January 2015 to December 2018 were collected. All cases were reviewed by two senior pathologists, including one from China and the other from Singapore, according to the 2019 revision of "CCCG-WT-2016."Results:The specimens were obtained by core biopsy ( n=21), primary nephrectomy ( n=41), post-chemotherapy nephrectomy/resection ( n=18), or biopsy/resection of metastatic/relapse/post-chemotherapy metastatic lesion(s) ( n=11). The specimens of core biopsy and primary nephrectomy ( n=62) all had favorable histology.Twelve post-chemotherapy nephrectomy cases were subdivided into three risk groups: low risk ( n=0), intermediate risk ( n=10) and high risk ( n=2). Six post-chemotherapy resection cases were subdivided into 3 risk groups:low risk ( n=0), intermediate risk ( n=5) and high risk ( n=1). The remaining 11 cases were comprised of metastatic, relapse, and post-chemotherapy metastatic lesions. The concordance rate of the two senior pathologists was 100%(91/91). Conclusions:The 2019 revision of "CCCG-WT-2016" is clearly written and easy to use. It can serve as the basis of accurate classification for clinical treatment.

Objective:To investigate the clinical and pathological features of pediatric NTRK-rearranged tumors.Methods:Four NTRK-rearranged soft tissue tumors and one renal tumor at Shanghai Children′s Medical Center, Shanghai Jiaotong University and Singapore KK Women′s and Children′s Hospital from January 2017 to September 2019 were identified. Pan-TRK immunohistochemistry, and the ALK and ETV6 gene break-apart fluorescence in situ hybridizations (FISH) were performed. NTRK gene rearrangement was detected using sequencing-based methods.Results:There were 3 males and 2 females in this study. The patients were between 3 months and 13 years of age. Histologically, the tumors were infiltrative spindle cell tumors with variable accompanying inflammatory cells. Immunohistochemistry showed positive reactivity for pan-TRK in all tumors, with nuclear staining for NTRK3 fusion, and cytoplasmic staining for NTRK1 fusion. The molecular testing revealed NTRK gene fusions (one each of TPM3-NTRK1, ETV6-NTRK3 and DCTN1-NTRK1, and two cases of LMNA-NTRK1). Two patients were receiving larotrectinib. The others were are well without disease, with follow-up durations of 9 to 29 months.Conclusions:NTRK-rearranged mesenchymal tumors from soft tissue sites and kidney are identified. A novel DCTN1-NTRK1 fusion is described. Pan-TRK immunohistochemistry is useful for diagnosis. NTRK-targeted therapy may be an option for unresectable, recurrent or metastatic cases.