[The safety and efficacy of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia in children].

To explore the safety and efficacy of blinatumomab in the treatment of CD19 positive (CD19+) B-cell acute lymphoblastic leukemia (B-ALL) in children. A retrospective analysis was conducted on the clinical data of pediatric B-ALL patients who received blinatumomab treatment from Hematology & Blood Diseases Hospital of Chinese Academy of Medical Sciences from August 2021 to October 2023. Based on their disease status, the patients were divided into refractory/relapsed(RR) group, minimal residual disease clearance (MC) group, and chemotherapy intolerance (IC) group. Clinical data of the children were collected to evaluate the adverse drug reactions, therapeutic efficacy and survival of the children. In total, 35 patients were included, with 20 males and 15 females, aged from 0.6 to 16.4 (9.9±4.2) years old. There were 10 cases in the RR group, 20 cases in the MC group and 5 cases in the IC group. A total of 56 cycles of infusion were completed, with one cycle in 24 cases, two cycles in 5 cases, three cycles in 2 cases and four cycles in 4 cases. The median infusion time [M (Q1, Q3)] from the first to the fourth cycle was 14 (14, 28) days, 28 (28, 28) days, 28 (28, 28) days and 28 (26, 28) days, respectively. In terms of adverse reactions, the incidence of grade 1-2 cytokine release syndrome(CRS) was 57.1% (32/56), with grade 1 CRS accounting for 84.4% (27/32). The incidence rate of immune effector cell-associated neurotoxicity syndrome(ICANS) (grade 4) was 1.8% (1/56). In the RR group, 6 cases were treated effectively, and minimal residual disease(MRD) turned negative, before treatment, MRD levels were all less than 20%. Among them, 3 cases had MRD turning positive again 14 to 42 days after discontinuation of Belintoumab. Four cases were treated ineffectively, with MRD >20% before treatment. All MRD positive cases in MC group turned negative and all MRD negative cases in the IC group remained negative after treatment. The median follow-up time of RR group was 5.7 (3.8, 9.4) months, and 1 year median survival rate and event-free survival rate were 40.0%±21.9% and 33.3%±19.2%, respectively. The median follow-up time for MC and IC group patients was 6.7 (5.2, 12.5) months and 7.1 (5.1, 7.6) months, respectively, with an event free survival rate of 100%. The safety and efficacy of using belintoumab in partial RR, MRD clearance, and chemotherapy intolerance are good.

[Clinical and prognostic characteristics of pediatric acute myeloid leukemia with myelodysplasia-related changes under different diagnostic criteria].

Objective: To evaluate the clinical and prognostic differences in acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) children under different diagnostic criteria (World Health Organization (WHO) 2016 and WHO 2022 criteria). Methods: In this retrospective cohort study, clinical characteristics and prognosis information of 260 acute myeloid leukemia (AML) children admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from August 2017 to August 2021 were analyzed retrospectively. According to WHO 2016 and WHO 2022 diagnostic criteria, patients were divided into AML-MRC group and non-AML-MRC group, the prognostic and genetic differences between two groups were compared respectively. Meanwhile, the characteristics of children with 8 MRC-related genes defined in WHO 2022 diagnostic criteria were described. Mann-Whitney U test, chi-square test were used for comparison between groups. Survival curve was plotted by Kaplan-Meier method, and comparison between groups was performed by Log-Rank method. Results: Among the 260 children, there were 148 males and 112 females. The follow-up time was 26 (16, 38) months. A total of 28 children (10.8%) were diagnosed with AML-MRC according to the WHO 2016 diagnostic criteria. Compared with non-AML-MRC children, the frequency of PTPN11, RUNX11, SH2B3, MPL and STAG2 mutations was higher in AML-MRC children (25.0% (7/28) vs. 4.3% (10/232), 14.3% (4/28) vs. 3.9% (9/232), 10.7% (3/28) vs. 2.2% (5/232), 10.7% (3/28) vs. 2.2% (5/232), 10.7% (3/28) vs. 0.9% (2/232), all P<0.05). The 2-year overall survival (OS) and events free survival (EFS) rate of 28 AML-MRC children under WHO 2016 diagnostic criteria were worse than those of 232 non-AML-MRC children ((62.1±10.8)% vs. (94.5±1.6)%, χ2=22.1,P<0.001;(48.0±10.6)% vs. (70.9±3.2)%, χ2=6.33,P=0.012). Twenty-seven children (10.4%) were eventually diagnosed with AML-MRC according to WHO 2022 criteria, their 2-year OS rate were worse than 233 non-AML-MRC children ((60.8±11.1)% vs. (94.5±1.6)%, χ2=24.49,P<0.001), and there was no statistically significant difference in EFS rate between two groups at 2 years ((55.1±10.8)% vs. (70.1±3.2)%, χ2=2.44, P=0.119). Conclusions: Compared with the 2022 WHO diagnostic criteria, the survival rates of children with AML-MRC under the 2016 WHO diagnostic criteria were worse than that of children without MRC.The new version of the AML-MRC diagnostic criteria emphasizes the importance of genes.

[Clinical characteristics of programmed cell death-1 inhibitor-associated hypophysitis].

Objective: To explore the clinical features of programmed cell death-1 (PD-1) inhibitor-associated hypophysitis and improve the understanding of the disease. Methods: For the present retrospective case series study, the clinical data of patients with PD-1 inhibitor-associated hypophysitis who were treated at the Affiliated Hospital of Hebei University and the 3rd Hospital of Hebei Medical University from January 2020 to May 2023 were collected for analysis of clinical manifestations and prognosis. Results: Fifteen cases of PD-1 inhibitor-induced hypophysitis were included, with 13 males and 2 females. The mean age of onset was (62.1±7.5) years, and the median time of onset was 6.5 (4.7, 11.6) cycles of PD-1 inhibitor. At diagnosis, 14 patients complained of gastrointestinal symptoms, and 12 patients complained of fatigue. There were 12, 1, 1, 5, and 1 cases of hyponatremia, hypokalemia, hypoglycemia, hypotension, and fever, respectively. Secondary adrenocortical insufficiency occurred in all cases. Moreover, four patients had secondary hypothyroidism, and two patients had secondary hypogonadism. Posterior pituitary hypofunction was not found. Pituitary MRI showed one case each of vacuolar sella turcica, pituitary cystic lesion, pituitary stalk slightly shifted to the left, high metabolism in the sella turcica, and pituitary abnormal signal, while no abnormalities were found in 11 cases. The follow-up time was (47.66±11.93) weeks. At the last follow-up, one patient's serum levels of adrenocorticotropic hormone and cortisol returned to normal. Conclusions: Hypophysitis associated with PD-1 inhibitors occurs later, and gastrointestinal symptoms and fatigue are the most common clinical manifestations. PD-1 inhibitor-associated hypophysitis mainly manifests as adrenocortical hypofunction, and some cases manifest as hypothyroidism and hypogonadism. In addition, patients with PD-1 inhibitor-associated hypophysitis show no obvious imaging changes in the pituitary gland.

[Retrospective study of 70 cases with the head and neck non-parameningeal rhabdomyosarcoma].

Objective: To analyze the treatment outcomes and prognoses of children with head and neck non-parameningeal rhabdomyosarcoma (HNnPM RMS). Methods: A retrospective analysis was performed on the clinical data of children with HNnPM RMS admitted to Beijing Children's Hospital from September 2012 to September 2022. The clinical features, comprehensive treatment modes and prognoses of the patients were analyzed. The overall survival rate (OS) and event free survival rate (EFS) were calculated using the Kaplan-Meier method, and univariate analysis was performed using the Log-rank test. Results: A total of 70 children were included in this study, 38 males and 32 females, with a median age of 47 months (2-210 months). Pathological subtypes including the embryonal in 27 cases, the alveolar in 36 cases and the spindle cell and sclerosing in 7 cases. Thirty children (83.3%) with alveolar type were positive for FOXO1 gene fusion. All 70 children underwent chemotherapy, including 38 with neoadjuvant chemotherapy and 32 with adjuvant chemotherapy. Sixty of 70 children underwent surgery, of whom, 10 underwent two or more surgeries. There were 63 children underwent radiotherapy, including 54 with intensity-modulated radiation therapy, 4 with particle implantation and 5 with proton therapy. The median follow-up was 45 (5-113) months, the 5-year OS was 73.2%, and the 5-year EFS was 57.7%. Univariate analysis showed lymph node metastasis (χ2=5.022, P=0.025), distant metastasis (χ2=8.258, P=0.004), and high Intergroup Rhabdomyosarcoma Study (IRS) group (χ2=9.859, P=0.029) as risk factors for poor prognosis. Before June 2016, the 5-year OS based on BCH-RMS-2006 scheme was 63.6%, and after 2016, the 5-year OS based on CCCG-RMS-2016 scheme was 79.6%. Conclusion: Multidisciplinary combined standardized treatment can offer good treatment outcome and prognosis for children with HNnPM RMS. Local control is a key to the efficacy of comprehensive treatment.

Promotion of Plasma-Induced Deuterium Uptake in Ruthenium Films by Monolayer-Thick Tin Layers.

Surface impurities can have a significant influence on hydrogen uptake of materials. Examples such as the hydrogen spillover effect demonstrate that even very small surface impurity quantities can lead to order-of-magnitude changes in the total amount of hydrogen taken up by a material. In this work, we report the first experimental demonstration of promoted deuterium uptake in Ru thin films by Sn. Deuterium plasma exposures were carried out for Ru-capped targets covered by Sn up to a few atoms in thickness. After the exposure, the residual Sn content and the deuterium retention were measured to quantify the Sn etching and the deuterium uptake, respectively. By increasing the amount of Sn from zero to one atomic layer on Ru, we found after the exposure that the Sn content stays unchanged while the deuterium uptake rate severely increases with the Sn content by 2-3 orders of magnitude. These results can be understood by simulations using a reaction-diffusion model with multiple surface species and the lateral surface migration of deuterium. By contrast, as the as-deposited Sn content goes above one atomic layer, Sn removal takes place, and the deuterium uptake rate decreases with the as-deposited Sn content. Possible explanations are proposed by considering the interplay between Sn etching and deuterium uptake. In all, this work provides insights into interactions between multiple surface species in relation to plasma-induced hydrogen uptake. By further development, this could eventually lead to a potential mitigation method to circumvent the promoted hydrogen uptake in Ru-capped films.

[Efficacy and safety of endovascular therapy after 24 h from ischemic stroke onset in patients with acute anterior circulation ischemic stroke].

Objective: To explore the effectiveness and safety of endovascular treatment (EVT) for patients with acute anterior circulation ischemic stroke with symptom onset exceeding 24 h. Methods: In this retrospective cohort study, data were extracted from patients who underwent endovascular treatment for acute anterior circulation ischemic stroke at the First Hospital of Jilin University from February 2019 to April 2022. A total of 569 patients were included, with a mean age of 63 (54-70) years. Among them, 398 (69.9%) were male. The patients were divided into two groups based on symptom onset time:>24 h group and≤24 h group. Propensity score matching (PSM) was used to match the patients in a 1︰1 ratio between the>24 h group and the≤24 h group. Logistic regression was used to evaluate the impact of symptom onset time on outcome events. Results: Before PSM, compared with≤24 h group, the>24 h group had a younger age [56 (48, 64) vs. 64 (55, 70), Z=-3. 60, P<0.001]; lower proportion of prior atrial fibrillation [1.8% (1/57) vs. 21.1% (108/512), χ2=12.39, P<0.001]; lower proportion of wake-up stroke [7.0% (4/57) vs. 27.7% (142/512), χ2=11.54, P<0.001]; lower baseline NIHSS score [11.0 (7.5, 14.0) vs. 13.0 (10.0, 16.0), Z=-3.22, P<0.001]; and a higher American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology(ASITN/SIR) grading (P<0.001). After PSM, there were no significant differences in baseline characteristics between the two groups. There was no significant difference in the proportion of patients with a modified Rankin Scale (mRS) score≤2 at 90 days after surgery between the two groups (before matching: 42.0% vs. 40.4%, OR=0.745, 95%CI 0.407-1.362, P=0.339; after matching: 51.8% vs. 39.3%, OR=0.511, 95%CI 0.212-1.236, P=0.136). No significant differences were observed in the incidence of any safety outcomes between the>24 h group and the≤24 h group. Conclusion: For patients with acute anterior circulation ischemic stroke with symptom onset exceeding 24 h, EVT is feasible after strict radiological screening and has similar safety and effectiveness as for patients with symptom onset under 24 h.

[Response of the government and people in pandemics in the Tang Dynasty].

It was believed that the Tang Dynasty was a historical period with relatively few pandemics and little impact in the official history records. The reasons for this and the context and the living conditions of people during pandemics should be analysed in depth. This paper examined 49 pandemic outbreaks which seriously influenced on the society of the Tang Dynasty in terms of time and space distribution, historical features, correlation with other disasters, and regional distribution. The paper also analysed the measures taken by the government to deal with pandemics, including sending physicians and herbs, compensating the people, providing prescriptions, and burying dead bodies. This paper summarised the understanding of pandemics in the Tang Dynasty, such as the will of ghosts, the karma, the astrology and the contagion between the patients. It was found that the ways for the people at that time dealt with pandemics, included praying, offering sacrifices, asking for help from Monks and Taoist, and even moving to other safe places. It was also found the dead who were properly buried could give people psychological comfort.

Lung protection effect of EIT-based individualized protective ventilation strategy in patients with partial pulmonary resection.

OBJECTIVE: This study aimed to evaluate the lung protection effect of an individualized protective ventilation strategy based on lung impedance tomography (EIT) technology in patients with partial pulmonary resection. PATIENTS AND METHODS: Eighty patients of any gender, American Society of Anesthesiologists (ASA) classification I-II, age 30-64 years and body mass index (BMI) 18-28 kg/m2 who underwent elective thoracoscopic partial lung resection were selected and divided into 2 groups (n=40) using the random number table method: [positive end-expiratory pressure (PEEP) by electrical impedance tomography (EIT)] PEEPEIT group (experimental group) and control group. The PEEPEIT group used volume-controlled ventilation after one-lung ventilation, setting a tidal volume of 6 ml/kg and titrating the optimal PEEP value by EIT. Group C used volume-controlled ventilation after one-lung ventilation, setting a tidal volume of 6 ml/kg and a PEEP of 5 cm H2O. Clinical data were collected and recorded at 5 min after double lung ventilation (T0), single lung ventilation, 30 min after PEEP setting (T1), 60 min after PEEP setting (T2), the end of surgery, 10 min after resumption of double lung ventilation (T3) and 10 min after removal of the tracheal tube (T4), and serum surface active substance-associated protein-A (SP-A) concentrations were measured at T0, T3 and 1 d after surgery (T5). RESULTS: PEEP values were higher in the PEEPEIT group than in the control group at T1 and T2 (p-value <0.05); oxygenation index (OI) was higher in the PEEPEIT group compared to the control group at T2 and T3 (p-value <0.05); pulmonary dynamic compliance (Cdyn) was higher in the PEEPEIT group compared to the control group at T1 and T2 (p-value <0.05); intrapulmonary shunt rate (Qs/Qt) was lower in the PEEPEIT group compared to the control group at T1, T2 and at T3, the intrapulmonary shunt rate (Qs/Qt) was reduced in the PEEPEIT group compared to group C (p-value <0.05); at T5, the SP-A protein was reduced in the PEEPEIT group compared to group C. There was no statistically significant difference in the incidence of postoperative pulmonary complications between the two groups (p-value >0.05). CONCLUSIONS: The EIT-guided individualized protective ventilation strategy has a lung-protective effect in patients undergoing thoracoscopic partial lung resection.

[Genomics of next generation sequencing in pediatric B-acute lymphoblastic leukemia and its impact on minimal residual disease].

Objective: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.

Associations Between Primary Residence and Mental Health in Global Marginalized Populations.

Scholars suggest that marginalized people in non-urban areas experience higher distress levels and fewer psychosocial resources than in urban areas. Researchers have yet to test whether precise proximity to urban centers is associated with mental health for marginalized populations. We recruited 1733 people who reported living in 45 different countries. Participants entered their home locations and completed measures of anxiety, depression, social support, and resilience. Regression and thematic analyses were used to determine what role distance from legislative and urban centers may play in mental health when marginalized people were disaggregated. Greater distance from legislative center predicted higher anxiety and resilience. Greater distance from urban center also predicted more resilience. Thematic analyses yielded five categories (e.g., safety, connection) that further illustrated the impact of geographic location on health. Implications for community mental health are discussed including the need to better understand and further expand resilience in rural areas.

[Associations between multimorbidity patterns of 4 chronic diseases and physical activity with all-cause mortality].

Objective: To identify the prevalence of multimorbidity among a Chinese population, analyze the risk of all-cause mortality with different multimorbidity patterns, and the impact of exercise on the risk of multimorbidity-related mortality and life lost. Methods: The study was based on 437 408 MJ Health Management Center participants. The classification decision tree was used to explore multimorbidity patterns composed of hypertension, diabetes, chronic kidney disease (CKD), and chronic obstructive pulmonary disease (COPD). The Cox proportional hazards model was used to calculate the all-cause mortality hazard ratio (HR) for different multimorbidity patterns. Using Chiang's life table method, years of life lost were the difference in life expectancy for those with and without multimorbidity. Results: The prevalence rate of multimorbidity was 8.7%. Among multivariate patterns, the most common ones were "hypertension+CKD" (3.6%), "hypertension + diabetes + CKD" (1.1%) and "hypertension+diabetes+CKD+COPD" (0.1%). Compared with a healthy population, patterns with the highest mortality risk were "diabetes+CKD" (HR=3.80, 95%CI: 3.45-4.18), "diabetes+CKD+COPD" (HR=4.34, 95%CI: 3.43-5.49) and "hypertension+ diabetes+CKD+COPD" (HR=4.75,95%CI:4.15-5.43). Through low-intensity and moderate to high-intensity exercise, the increased HRs were attenuatedcompared with the inactive population. People with single disease and multimorbidity shortened life by 4.6 and 13.4 years, while exercise attenuated 2.3 and 4.6 years of life lost, of which low-intensity and moderate to high-intensity exercise saved 1.5 and 3.7 years of life lost due to chronic diseases. Conclusions: Multimorbidity patterns based on "diabetes + CKD" cause the highest mortality risk, and physical activity in reducing mortality was significant for either with or without multimorbidity. Higher exercise intensity leads to a greater relative reduction of mortality risk.

[Clinical characteristics and prognostic analyses of cervical neuroblastoma].

Objective: To determine the characteristics of cervical neuroblastoma and the effect of resection extent on survival and outcomes. Methods: We performed a retrospective review of 32 children with cervical neuroblastoma treated at Beijing Children's Hospital between April 2013 and August 2020. Data were collected from the medical record. The individualized therapy was designed based on staging and risk group. Based on the extent of resection, patients were divided into incomplete and complete resection groups. Event free and overall survival rates were compared between two groups using the Kaplan-Meier method. Results: The ages of patients ranged from 1 month to 81 months, with a median age of 11 months, including 7 males and 15 females. Twenty-nine patients (90.6%) presented with cervical painless mass. The average diameter of the primary tumors was (5.12±1.43) cm. Tumors were located in the parapharyngeal space in 25 cases (78.1%) and in the root of the neck in 7 cases (21.9%). None had MYCN amplification. According to International Neuroblastoma Staging System (INSS), 15 patients (46.9%) were identified as stage 1, 11 patients (34.3%) as stage 2B, 3 patients (9.4%) as stage 3 and 3 patients (9.4%) as stage 4. There were 12 patients (37.5%) at low risk, 17 patients (53.1%) at intermediate risk and 3 patients at high risk according to Children's Oncology Group (COG) risk classification system. All patients underwent tumor resection. Postoperatively Horner's syndrome occurred in 13 patients (40.6%), pneumonia in 9 patients (28.1%), pharyngeal dysfunction in 8 patients (25.0%) and transient hoarseness in 4 patients (12.5%). At a median follow-up of 36.5 months, the overall survival rate was 96.4%, with no significant difference between incomplete and complete resection groups (100.0% vs. 96.3%, χ2=0.19, P=0.667); the event free survival rate was 78.1%, with a significant difference between the two groups (40.0% vs. 85.2%, χ²=6.71, P=0.010). Conclusions: Primary cervical neuroblastoma has a young onset age, mostly in low and medium risk groups, and represents favorable lesions with good outcomes after multidisciplinary therapy. Less aggressive surgery with preservation of important structures is recommended. Complete resection should not be attempted if it would compromise vital structures.

Identification of Malus halliana R2R3-MYB gene family under iron deficiency stress and functional characteristics of MhR2R3-MYB4 in Arabidopsis thaliana.

Iron (Fe) is an essential element for plant growth and development. Fe deficiency can trigger leaf chlorosis and reduce fruit yield. Therefore, it is necessary to explore transcription factors in response to Fe deficiency stress. A total of 29 MhR2R3-MYB transcription factors were identified based on the transcriptome of Malus halliana under Fe deficiency stress. A comprehensive analysis of physical and chemical properties, gene structures, conserved motif composition, evolutionary relationship and chromosome distribution was performed. Subsequently, based on the transcriptome, 14 genes with the most significant expression under Fe deficiency stress were screened for qRT-PCR verification. Among them,the functional characteristics of MhR2R3-MYB4 (MD05G1089600) were further studied in Arabidopsis thaliana. Expression of 13 out of these 14 genes was upregulated, only one was downregulated. Maximum upregulation of MhR2R3-MYB4 under Fe deficiency was 36.39-fold and 58.21-fold compared with day 0 in leaves and roots, respectively. Overexpression of MhR2R3-MYB4 enhanced tolerance to Fe deficiency in A. thaliana and led to multiple biochemical changes: transgenic lines have higher chl a, chl b and Fe2+ content, higher enzyme activity (SOD, POD, CAT and FCR) and lower chlorosis than the wild type in Fe deficiency conditions. We suggest that MhR2R3-MYB4 plays an important part in Fe deficiency stress, which may contribute to improve Fe deficiency tolerance of apple in future.

[Efficacy and influencing factors of surgery combined with neoadjuvant chemoradiotherapy in the treatment of children with non-orbital head and neck rhabdomyosarcoma].

Objective: To evaluate the efficacy and influencing factors of surgery combined with neoadjuvant chemoradiotherapy in the treatment of children with non-orbital head and neck rhabdomyosarcoma (HNRMS). Methods: Information from 45 children diagnosed as non-orbital HNRMS and subjected to surgery combined with neoadjuvant chemoradiotherapy in Beijing Children's Hospital affiliated to Capital Medical University from August 2017 to July 2021 was analyzed. The patients included 25 males and 20 females, aged from 1 to 17 years old. The primary tumor site, pathological subtype, clinical stage, risk group, therapeutic regimen, resection range and outcome of all cases were also collected. The survival curves were made using the Kaplan-Meier method and the potential prognostic factors were investigated by Cox regression analysis. Results: Fifteen (33.3%) of 45 children achieved negative surgical margin under complete tumor resection. The postoperative pathological results showed that there were 20 cases of embryonic subtype, 19 cases of alveolar subtype and 6 cases of spindle sclerosis subtype. The postoperative follow-up time ranged from 4 to 71 months, with a median of 26 months. During the follow-up period, 13 children died, among whom brain metastasis was the most common cause of death, accounting for 7/13. The 3-year overall survival rate was 67.6%. Multivariate analysis showed that non-embryonic subtype (HR=6.26, 95%CI: 1.52-25.87, P=0.011) and failure to reach R0 resection (HR=9.37, 95%CI: 1.18-74.34, P=0.034) were independent risk factors affecting overall survival rate. Conclusion: Surgery combined with neoadjuvant chemoradiotherapy can offer a good efficacy for children with non-orbital HNRMS. Non-embryonic subtype and resection without negative operative microscopic margins are independent risk factors for poor prognosis, and brain metastasis is the main cause of death in these children.

[The diagnostic performance of 2020 Chinese Ultrasound Thyroid Imaging Reporting and Data System in thyroid nodules].

Objective: To evaluate the diagnostic performance of the Chinese Ultrasound Thyroid Imaging Reporting and Data System (C-TIRADS) in thyroid nodules,and to compare it with the TIRADS proposed by Kwak et al. (K-TIRADS) and the TIRADS proposed by the American College of Radiology (ACR-TIRADS). Methods: The data of 1 750 patients with 2 029 thyroid nodules in the Department of Thyroid Surgery, the Affiliated Hospital of Jining Medical University from January 2018 to November 2020 was retrospectively collected. Among them, there were 328 males and 1 422 females,aged from 6 to 86 with an average of (47±12) years. The nodules were divided into≤1.0 cm group(n=997) and>1.0 cm group(n=1 032)based on the size of the nodules. The stratification for malignant risk and the determination of benign or malignancy of the nodules was evaluated using the C-TIRADS, K-TIRADS and ACR-TIRADS, respectively. The receiver operating characteristic (ROC)curve analysis was performed to compare the diagnostic performance of the aforementioned three kinds of TIRADS using pathological results as the referent standard. Results: The optimal diagnosis points in the determination of malignant nodules of C-TIRADS, K-TIRADS and ACR-TIRADS in the two groups were 4A, 4b and 4 respectively according to ROC curve analysis. For the diagnosis of the malignant nodules, the C-TIRADS achieved with an AUC value of 0.772 and 0.892 in the ≤1.0 cm group and>1.0 cm group, respectively, which was significantly higher than K-TIRADS (AUC= 0.762 and 0.869, respectively) and ACR-TIRADS (AUC= 0.735 and 0.832, respectively) (P<0.05). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of C-TIRADS were 94.99%, 59.41%, 86.46%, 88.13%, 78.89% (≤1.0 cm group)and 88.34%, 90.05%, 89.34%, 86.33%, 91.57%(>1.0 cm group), respectively. C-TIRADS had the highest sensitivity, accuracy, and negative predictive value in the determination of malignant nodules in both groups compared to the other two kinds of TIRADS. Conclusions: The three kinds of TIRADS all have high diagnostic performance for the determination of the malignant nodules, and the C-TIRADS has the best overall efficacy, which can effectively assist clinicians for medical decision, and is worth to be popularized and applied in the clinical setting.

Accurate diagnosis of colorectal cancer based on histopathology images using artificial intelligence.

BACKGROUND: Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients' treatment. The current heavy workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses. METHODS: Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany. RESULTS: Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells. CONCLUSIONS: This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.