[Clinical analysis of 18 children with aggressive mature B-cell lymphoma after liver transplantation].

Objective: To summarize the clinical characteristics, prognostic factors and treatment outcomes of childhood aggressive mature B-cell lymphoma after liver transplantation. Methods: This retrospective study included 18 children with newly diagnosed aggressive mature B-cell lymphoma after liver transplantation and treated from June 2018 to June 2022 in the Department of Hematology and Oncology of Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine. Clinical characteristics, treatment and outcomes of patients at last evaluation were analyzed. Overall survival (OS) and event free survival (EFS) rates were calculated by Kaplan-Meier method and Log-Rank analysis was performed to find factors of poor prognosis. Results: Among all 18 patients, there were 6 males and 12 females, and the age of onset was 40 (35, 54) months. The interval from transplant to tumor diagnosis was 21 (17, 35) months and 5 patients had early onset disease (<1 year since transplant). Seventeen patients had abdominal lesions. Diarrhea, vomiting and abdominal masses were the main clinical manifestations. All patients were Epstein-Barr virus (EBV) related posttransplant lymphoproliferative disorders (PTLD). One patient received individualized therapy due to critical sick at diagnosis, and the remaining 17 patients received CP (cyclophosphamide, methylprednisolone plus rituximab) and/or modified EPOCH (prednisone, etoposide, doxorubicin, vincristine, cyclophosphamide plus rituximab) regimens. Of all 18 patients, 15 cases got complete response, 2 cases got partial response, 1 patient died of severe infection. The 2-year OS and EFS rates of 18 patients were (94±5)% and (83±8)%, respectively. None of age, gender or early onset disease had effect on OS and EFS rates in univariate analysis (all P>0.05). Conclusions: The symptoms of PTLD were atypical. Close surveillance of EBV-DNA for patients after liver transplantation was crucial to early stage PTLD diagnosis. CP or modified EPOCH regimen was efficient for pediatric patients with aggressive mature B cell lymphoma after liver transplantation.

[Clinical features of patients with metastatic pheochromocytoma/paraganglioma].

Objective: To analyze the clinical features of patients with metastatic pheochromocytoma/paraganglioma (PPGL). Methods: A follow-up study. The clinical data of 250 patients with metastatic PPGL treated at Peking Union Medical College Hospital from January 2018 to August 2023 were retrospectively analyzed, including 124 males and 126 females. The clinical features and treatment status of patients with metastatic PPGL were summarized and analyzed. Kaplan-Meier survival curve was used to evaluate patients' prognosis. Results: The age of onset, age of diagnosis, and age of tumor metastasis in patients with metastatic PPGL were (33.1±14.2) years, (35.4±15.2) years, and (40.7±15.3) years, respectively. Metastasis occurred in 26.4%(66/250) of patients at the time of initial diagnosis. Among patients without metastases at the time of initial diagnosis, the time from primary tumor resection to metastasis[M(Q1, Q3)] was 5.0 (3.0, 9.0) years, among which 20.1%(37/184) of patients had metastases more than 10 years after surgery. Most patients showed increased 24-hour urinary norepinephrine and plasma normetanephrine, accounting for 78.2%(176/225) and 78.7%(85/108), respectively. 42.3%(69/163) of patients had increased neuron specific enolase (NSE)levels. Germline mutations were screened in 201 patients, of which 55.2%(111/201) had germline pathogenic mutations. In patients with gene mutations, 76.5%(85/111) had SDHB mutations. 52.0%(130/250) of metastatic PPGL patients had primary sites outside the adrenal gland, with the Ki-67 index of 5% (3%, 8%). There were 85.6%(214/250) patients had multisystem metastasis, with bone metastasis being the most common site of metastasis, accounting for 60.8%(152/250). In terms of treatment, 32.8%(75/229) of patients underwent two treatment regimens and 8.7%(20/229) of patients underwent three treatment regimens. Most patients had a good prognosis, with a 5-year and 10-year survival rate of 88.0% and 84.0%, respectively. However, some patients had rapid disease progression, and as of August 2023, 30 patients died, and the time from diagnosis to death in deceased patients was 2.0 (1.0, 4.0) years. Conclusions: Patients with metastatic PPGL have a high rate of germline mutations, especially those with SDHB mutations. The metastatic PPGL is usually multisystem metastasis with the characteristics of mostly paraganglioma, large lesion diameter and high Ki-67 index.

[Analysis of clinical characteristic of children with progressive familial intrahepatic cholestasis type 3].

Objective: To analyze the clinical manifestations, pathology, and gene variant characteristics in children with progressive familial intrahepatic cholestasis type 3 (PFIC3). Methods: This retrospective study assessed the clinical manifestations, pathological features, gene variants, and prognosis data of 11 children with PFIC3 hospitalized in the Department of Hepatology, Fifth Medical Center, PLA General Hospital, from January 2015 to December 2022. Panel or whole exome sequencing was performed on the probands, followed by Sanger sequencing for verification within the family. Detected pathogenic variants were compared with known disease databases. Additionally, the new variants were predicted the deleteriousness and protein structure using relevant software to evaluate their pathogenicity. Results: Among the 11 PFIC3 children, 8 were boys and 3 were girls. The age of onset was 3.1 (0.2, 15.6) years. The main complaint of onset was different in the 11 patients;5 of them were abnormal liver function, 3 of them were liver and spleen enlargement, 2 of them were abdominal distension, and 1 of them was jaundice. Alanine aminotransferase, asparate aminotransferase and γ-glutamyltransferase increased in all the patients, which were(113±40), (150±44) and (270±156) U/L respectively. Moreover, direct bilirubin increased in 9 patients, and cholestasis was showed in 8 patients. All patients showed liver fibrosis on imaging, and 8 patients had cirrhosis. The pathological features of 8 cases by liver biopsy were as follows: 8 cases of fibrosis in the portal area, 7 cases of small bile duct hyperplasia, 4 cases of positive copper staining, and 5 cases of cirrhosis. A total of 17 ABCB4 gene variants were detected, including 9 new variants: c.589C>T(p.Q197X), c.1230+1G>A(Splicing), c.2914G>A(P.D972N), c.1058G>A(p.C353Y), c.956G>T(p.G319V), c.473T>A(p.L158Q), c.164T>C(p.L55S), c.2493G>C(p.R831S), and c.1150G>C(p.G384R). All 11 patients were treated with ursodeoxycholic acid and followed up for 5.1(0.6, 7.4) years. Among them, 4 cases of cirrhosis progressed continuously, 3 cases had liver transplantations, and the remaining 4 cases were stable after medical treatment. Conclusions: Children with PFIC3 have early onset, diverse clinical manifestations, rapid progression of fibrotic and cholestasis, as well as poor prognosis. Genetic testing helps to confirm the diagnosis.

[Clinical characteristics and prognostic factors of patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis associated interstitial lung disease].

Objective: To analyze the clinical characteristics and prognostic factors of patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5)-positive dermatomyositis associated interstitial lung disease (DM-ILD). Methods: The patients with MDA5+DM-ILD who were admitted to Department of Respiratory Medicine, Nanjing Drum Tower Hospital from January 2017 to March 2021 were enrolled. The clinical data and survival information were analyzed retrospectively. Patients were divided into survival group or death group, and rapid progressive ILD (RP-ILD) group or non-rapid progressive ILD group, according to their survival status and clinical progression. Results: A total of 105 patients with anti-MDA5+DM-ILD (median age of onset 54 years) were enrolled, 58% being female (61 cases). The main sub-type of dermatomyositis was amyopathic dermatomyositis (n=74, 70%), followed by dermatomyositis (n=31, 30%). The main extrapulmonary manifestations were skin lesions (n=60, 57.1%), muscle manifestations(n=20, 19%) and arthralgia/arthritis (n=20, 19%). 15.4% of the patients had positive ANA (antibody titer≥1∶320), and 61.9% of the patients had anti-RO-52 kDa antibody. A total of 66 patients (62.8%) developed RP-ILD, and 58 patients (56.3%) died. Lower oxygenation index (OR=0.974, 95%CI:0.954-0.994, P=0.012) and no joint pain (OR=0.032, 95%CI: 0.002-0.663 P=0.026) were independent risk factors for RP-ILD. Cox regression analysis showed that RP-ILD (HR=3.194, 95%CI:1.025-9.954, P=0.045), older than 53 years (HR=3.450, 95%CI: 1.388-8.577, P=0.008), ferritin level more than 1 330.5 ng/ml (HR=3.032, 95%CI 1.208-7.610, P=0.018) and C-reactive protein (CRP) above 16.95 mg/L (HR=2.794, 95%CI:1.102-7.084, P=0.030) were independent predictors of mortality. Conclusions: The clinical manifestations of patients with anti-MDA5+DM-ILD presenting to the respiratory department were heterogeneous, with most being amyopathic dermatomyositis, and both the incidence of RP-ILD and the risk of death were high. Even in the absence of associated rash, joint, or muscle manifestations, anti-MDA5 antibody screening should be considered in patients with rapidly progressive ILD who were negative on baseline autoantibody screening but positive for anti-RO52kDa antibody.

[Relationship between plasma levels of thrombin activatable fibrinolysis inhibitor, plasminogen activator inhibitor-1 and tissue-type plasminogen activator and deep venous thrombosis in patients with systemic lupus erythematosus].

Objective: To investigate the plasma levels of thrombin activatable fibrinolysis inhibitor (TAFI), plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) in patients with systemic lupus erythematosus (SLE), and their relationship with deep venous thrombosis of the lower limbs. Methods: A case-control study was conducted to retrospectively select 32 SLE patients with deep venous thrombosis of the lower extremities (thrombus group) admitted to Liaocheng People's Hospital in Shandong Province from June 2018 to June 2021, including 4 males and 28 females, with a mean age of (49.7±5.5) years. Meanwhile, 64 SLE patients without deep venous thrombosis of the lower extremities (control group) were also selected, including 11 males and 53 females, with a mean age of (50.8±5.5) years. The plasma levels of TAFI, PAI-1 and t-PA of the two groups were compared. A logistic regression model was used to analyze the correlation of TAFI, PAI-1 and t-PA with SLE in patients. Results: The plasma levels of TAFI, PAI-1 and t-PA were (32.77±5.17) mg/L, (29.43±5.51) µg/L and (6.58±1.40) µg/L in the thrombotic group, while the plasma levels of TAFI, PAI-1 and t-PA in the control group were (23.56±4.40) mg/L, (19.00±4.40) µg/L and (9.40±2.23) µg/L. The levels of TAFI and PAI-1 in the thrombotic group were higher than those in the control group, while the level of t-PA was lower than that in the control group (all P<0.05). The results of logistic regression model showed that higher TAFI levels (OR=1.75, 95%CI: 1.05-2.90, P=0.043), higher PAI-1 levels (OR=1.85, 95%CI: 1.04-3.29, P=0.046), and lower t-PA levels (OR=0.72, 95%CI: 0.52-0.99, P=0.048) were related factors for the occurrence of deep venous thrombosis of the lower limbs in SLE patients. Conclusion: The plasma levels of TAFI and PAI-1 in SLE patients with deep venous thrombosis of the lower extremities increase, while the t-PA level decreases, which are related factors for the occurrence of deep venous thrombosis of the lower extremities in SLE patients.

[Preliminary study on the ability of 68Ga-Pentixafor PET/CT to differentiate between adrenal aldosterone-producing adenoma and nonfunctional adenoma].

Objective: To evaluate the ability of 68Ga-Pentixafor (nuclide ligand imaging agents for chemokine receptor 4) PET/CT to differentiate between aldosterone-producing adenoma (APA) and adrenal nonfunctional adenoma (NFA), and to assess how well this imaging method correlates with clinical features and postoperative outcomes. Methods: This was a cross-sectional study involving 73 APA and 12 NFA patients who received 68Ga-Pentixafor PET/CT imaging at Peking Union Medical College Hospital from August 2018 to October 2021. The receiver operating characteristic (ROC) curve was used to evaluate the differential value of visual analysis and the maximum standard uptake value (SUVmax) of the focus on APA and NFA. The related factors of SUVmax, and its predictive effect on postoperative outcomes were analyzed using Pearson or Spearman analysis and χ2 text. Results: 68Ga-Pentixafor PET/CT imaging was positive in 64 APA patients (sensitivity=87.7%) and negative in all 12 NFA patients (specificity=100%). The area under the ROC curve with SUVmax differentiating APA and NFA was 0.932 (P<0.001). When the SUVmax cut-off point was 6.23, the sensitivity was 80.8% and the specificity was 100%. The SUVmax correlated positively with lesion size (r=0.598) and aldosterone/renin activity ratio (r=0.313) and correlated negatively with potassium level (r=-0.286), renin activity (r=-0.240) and age of diagnosis (r=-0.273) (all P<0.05). Of the patients who underwent adrenalectomy and received more than 6 months of post-surgical follow-up, the clinical complete remission rate was higher for 68Ga-Pentixafor PET/CT imaging-positive patients than imaging-negative patients (24/39 vs. 0/4, P=0.031). Conclusions: 68Ga-Pentixafor PET/CT is effective at differentiating between APA and NFA. The SUVmax of 68Ga-Pentixafor PET/CT correlates with age at onset, lesion size, and the severity of clinical manifestations, and is able to predict postoperative outcomes.

[A multicenter study on childhood Hodgkin lymphoma treated with HL-2013 regimen in China].

Objective: To evaluate the efficacy of the Hodgkin lymphoma (HL)-2013 regimen in the treatment of children with HL, and to investigate the prognostic factors of childhood HL. Methods: Clinical data of 145 children (aged ≤18 years) with newly diagnosed HL, treated with HL-2013 regimen in 8 tertiary referral centers for childhood cancer from August 2011 to April 2021 were analyzed retrospectively. All the diagnosis were confirmed by histopathological morphology and immunohistochemical examination. The clinical characteristics and treatment outcomes were summarized, and the patients were divided into different groups according to clinical characteristics. Kaplan-Meier method was used for survival analysis, and the comparison of survival rates between groups was performed with Log-rank test. Results: Of the 145 cases, there were 115 males and 30 females, the age at diagnosis was 7.9 (5.8, 10.6) years. Cervical lymph node enlargement (114 cases, 78.6%) was the common symptom of the disease, and 57 patients (39.3%) were accompanied by large masses. The most common pathological classification was mixed cell type (93 cases, 64.1%). According to the Ann Arbor staging system, there were 9 cases of stage Ⅰ, 62 cases of stage Ⅱ, 45 cases of stage Ⅲ, 29 cases of stage Ⅳ. According to the risk stratification: there were 14 cases of low-risk group, 76 cases of medium-risk group and 55 cases of high-risk group. Of all patients, 68 cases (46.9%) achieved an early complete remission (CR) after 2 courses of chemotherapy, and the CR rate was 93.8% (136/145) after first-line treatment. Disease recurrence or progression occurred in 22 cases (15.2%). Of all patients, 125 cases survived, 6 cases died and 14 cases were lost to follow-up. Among the survived cases, 123 cases were continuously at CR state,and the follow-up time was 55 (40, 76) months. The 5-year overall survival (OS) and event free survival (EFS) rates were (95.3±1.9)% and (84.2±3.0)% for the entire group, respectively. 5-year OS and EFS rates for patients with stage Ⅲ-Ⅳ were both lower than those for patients with stage Ⅰ-Ⅱ (χ2=6.28 and 7.58, both P<0.05), the 5-year OS and EFS rates for patients in high-risk group were both lower than those for patients in low-risk and medium-risk group (χ2=10.93, 7.79, both P<0.05). The 5-year OS rates for the patient with early CR and without early CR were 100.0% and (90.9±3.6)% (χ2=5.77, P=0.016). EFS rates for the patient with early CR (68 cases) and without early CR (77 cases) were (93.8±3.0)% and (75.8±5.0)% (χ2=8.78, P=0.003). Conclusions: HL-2013 regimen is significantly effective in the treatment of pediatric HL. However, the patients in high-risk group and those without early CR are prone to disease recurrence or progression. Stage Ⅲ-Ⅳ and without early CR were associated with worse prognosis.

[Epidural photobiomodulation accelerates the drainage of brain interstitial fluid and its mechanism].

OBJECTIVE: To evaluate the effect of photobiomodulation (PBM) on the drainage of brain interstitial fluid (ISF) and to investigate the possible mechanism of the positive effect of PBM on Alzheimer's disease (AD). METHODS: Twenty-four SD male rats were randomly divided into PBM group (n=12), sham PBM group (n=6), and negative control group (n=6). According to the injection site of tracer, the PBM group was further divided into PBM-ipsilateral traced group (n=6) and PBM-contralateral traced group (n=6). Rats in the PBM group and the sham PBM group were exposed to the dura minimally invasively on the skull corresponding to the frontal cortical area reached by ISF drainage from caudate nucleus region. The PBM group was irradiated by using 630 nm red light (5-6 mW/cm2), following an irradiation of 5 min with a 2 min pause, and a total of 5 times; the sham PBM group was kept in the same position for the same time using the light without power. The negative control group was kept without any measure. After PBM, tracer was injected into caudate nucleus of each group. The changes of ISF drainage in caudate nucleus were observed according to the diffusion and distribution of tracer molecule by tracer-based magnetic resonance imaging, and the structural changes of brain extracellular space (ECS) were analyzed by diffusion rate in ECS-mapping (DECS-mapping) technique. Finally, parameters reflecting the structure of brain ECS and the drainage of ISF were obtained: volume fraction (α), tortuo-sity (λ), half-life (T1/2), and DECS. The differences of parameters among different groups were compared to analyze the effect of PBM on brain ECS and ISF. One-Way ANOVA post hoc tests and independent sample t test were used for statistical analysis. RESULTS: The parameters including T1/2, DECS, and λ were significantly different among the PBM-ipsilateral traced group, the PBM-contralateral traced group, and the sham PBM group (F=79.286, P < 0.001; F=13.458, P < 0.001; F=10.948, P=0.001), while there was no difference in the parameter α of brain ECS among the three groups (F=1.217, P=0.324). Compared with the sham PBM group and the PBM-contralateral traced group, the PBM-ipsilateral traced group had a significant decrease in the parameter T1/2 [(45.45±6.76) min vs. (76.01±3.44) min, P < 0.001; (45.45±6.76) min vs. (78.07±4.27) min, P < 0.001], representing a significant acceleration of ISF drainage; the PBM-ipsilateral traced group had a significant increase in the parameter DECS [(4.51±0.77)×10-4 mm2/s vs. (3.15±0.44)×10-4 mm2/s, P < 0.001; (4.51±0.77)×10-4 mm2/s vs. (3.01±0.38)×10-4 mm2/s, P < 0.001], representing a significantly increased molecular diffusion rate of in the brain ECS; the PBM-ipsilateral traced group had a significant decrease in the parameter λ (1.51±0.21 vs. 1.85±0.12, P=0.001; 1.51±0.21 vs. 1.89±0.11, P=0.001), representing a significant decrease in the degree of tortuosity in the brain ECS. CONCLUSION: PBM can regulate the brain ISF drainage actively, which may be one of the potential mechanisms of the effect of PBM therapy on AD. This study provides a new method for enhancing the brain function via ECS pathway.

[Analysis of 42 cases of childhood superior vena cava syndrome associated with mediastinal malignancy].

Objective: To summarize the clinical features, management and outcome of superior vena cava syndrome (SVCS) associated with mediastinal malignancy in children. Methods: Clinical data of 42 children of SVSC associated with mediastinal malignancy in Shanghai Children's Medical Center from January 2015 to December 2021 were collected and analyzed retrospectively. The clinical manifestations, pathological diagnosis, disease diagnosis process, and prognosis were summarized. Results: Among 42 children of SVCS associated with mediastinal malignancy, there were 31 males and 11 females. The age at diagnosis was 8.5 (1.9, 14.9) years. Cough and wheezing (33 cases, 79%), orthopnea (19 cases, 45%) and facial edema (18 cases, 43%) occurred most commonly. T-cell lymphoblastic lymphoma (T-LBL) was the most frequent pathological diagnosis (25 cases, 60%), followed by T-cell acute lymphoblastic leukemia (T-ALL) (7 cases, 17%), anaplastic large cell lymphoma (4 cases, 10%) and diffuse large B-cell lymphoma (2 cases, 5%), peripheral T-lymphoma, Hodgkin lymphoma, Ewing's sarcoma and germ cell tumor (1 case each). Pathological diagnosis was confirmed by bone marrow aspiration or thoracentesis in 14 cases, peripheral lymph node biopsy in 6 cases, and mediastinal biopsy in 22 cases. Twenty-seven cases (64%) had local anesthesia. Respiratory complications due to mediastinal mass developed in 3 of 15 cases who received general anesthesia. Of the 42 cases, 27 cases had sustained remission, 1 case survived with second-line therapy after recurrence, and 14 cases died (2 cases died of perioperative complications and 12 cases died of recurrence or progression of primary disease). The follow-up time was 36.7 (1.2, 76.1) months for 27 cases in continuous complete remission. The 3-year overall survival (OS) and events free survival (EFS) rates of 42 children were 59% (95%CI 44%-79%) and 58% (95%CI 44%-77%) respectively. Conclusions: SVCS associated with mediastinal malignancy in children is a life-threatening tumor emergency with high mortality. The most common primary disease is T-LBL. The most common clinical symptoms and signs are cough, wheezing, orthopnea and facial edema. Clinical management should be based on the premise of stable critical condition and confirm the pathological diagnosis through minimal invasive operation.

[Prognostic value of translocation t(11;14) in primary light-chain amyloidosis treated with bortezomib-based regimen].

Objective: To investigate the prognostic value of translocation t(11;14) in newly-diagnosed primary light-chain (AL) amyloidosis patients treated with bortezomib-based regimen. Method: Clinical information of newly-diagnosed AL amyloidosis patients in Peking Union Medical College Hospital who had baseline t(11;14) data and accepted bortezomib-combined therapies from September, 2015 to September, 2021 was collected. The relationships between t(11;14) status and baseline characteristics, hematological response, organ response and prognosis were analyzed. Results: A total of 152 patients were included, aged (59.5±9.1) years and 93 cases were male (61.2%). Forty-six patients carried t(11;14) (30.3%). There was no statistical difference in the proportion of organ involved, distribution of Mayo 2004 and 2012 stages and laboratory indexes between patients with and without t(11;14) (all P>0.05). For hematological response, the difference in the rates of ≥very good partial response (VGPR) between those with t(11;14) and without after the first cycle [28.2%(11/39) vs 37.4%(34/91), P>0.05] was not statistically significant. After 3 cycles, the difference in the rates of ≥VGPR between two groups was not statistically significant [35.9%(14/39) vs 51.1%(46/90), P>0.05]. The difference in the ratio of the best hematological response reaching ≥VGPR between two groups during the first-line treatment was not statistically significant [52.2%(24/46) vs 64.2%(68/106), P>0.05]. But patients with t(11;14) had lower cardiac response rate at 3 months [15.2%(5/33) vs 34.6%(28/81), P=0.038] and 6 months [19.4%(6/31) vs 50.6%(42/83),P=0.003] than those without, but the difference in cardiac response rates at 12 months was not statistically significant [41.7%(10/24) vs 53.5%(38/71),P>0.05]. For survival, the differences in overall survival (not reached vs 50.1 months, P>0.05) and hematological event-free survival (36.2 months vs 39.9 months, P>0.05) between patients carrying t(11;14) and those without were not statistically significant. Conclusion: Patients with t(11;14) had lower cardiac response rate than those without, but their hematological response and survival are not significantly different from those free from t(11;14).

[Recurrence and metastasis of pheochromocytoma/paraganglioma after tumor resection and clinical characteristics analysis].

Objective: The purpose of this study is to investigate the incidence of recurrence or metastasis of pheochromocytoma/paraganglioma (PPGL) patients after primary tumor resection, and to compare the differences of clinical indicators between patients with or without recurrence or metastasis. Methods: This study is a retrospective study. All 157 patients were followed up after tumor resection in Peking Union Medical College Hospital from 2008 to 2016. We obtained the basic information [age of diagnosis, gender, height, weight and body mass index (BMI)], the onset status of PPGL (age of onset, course of disease, family history, tumor location, whether the tumor is bilateral or multiple, and preoperative blood pressure), clinical and pathological features of PPGL tumor (tumor size, whether it could adhere, invade or infiltrate during operation, whether the tumor capsule is smooth and complete on the postoperative pathological diagnosis, whether there is infiltration growth and cystic necrosis on tumor pathology and Ki-67 index), and laboratory examination results [24 hours urinary norepinephrine (NE), epinephrine (E), dopamine (DA) before operation]. According to the outpatient or telephone follow-up, the postoperative incidences of recurrence and metastasis were explored, and the basic information, status of onset, clinical and pathological characteristics of tumors, and laboratory test results of patients were compared. Results: A total of 157 patients, 69 males and 88 females, were with an average age of (42.4±13.4) years old. There were 103 patients with PCC and 54 with PGL. The average follow-up time was (9.5±2.0) years. Of the 103 patients with PCC, 13 (12.6%) had postoperative recurrence and 9 (8.7%) had distant metastasis. Compared with the patients without recurrence and metastasis, the onset age of the 13 patients with recurrence was younger [(27.3±15.7) years vs (39.3±12.2) years, P=0.003], the course of disease was longer [48.0 (23.0, 141.0) months vs 12.0 (4.0, 60.0) months, P=0.010]. The tumor size of 9 patients with distant metastasis was larger [8.0 (6.1, 12.8) cm vs 5.0 (4.0, 7.0) cm, P=0.027]. Of the 54 patients with PGL, 8 (14.8%) had postoperative recurrence and 5 (9.3%) had distant metastasis. Compared with the patients without recurrence and metastasis, the course of disease of the 8 patients with recurrence was longer [90.0 (36.3, 165.0) months vs 24.0 (8.0, 72.0) months, P=0.009], and the proportion of primary tumors with multiple lesions was higher (4/8 vs 4.4%, P=0.003). The preoperative diastolic blood pressure was higher in 5 patients with distant metastasis [(146.0±32.1) mmHg vs (120.6±25.3) mmHg, P=0.043] (1 mmHg=0.133 kPa), and the proportion of primary tumors with multiple lesions was higher (2/4 vs 4.4%, P=0.029). Conclusion: PPGL patients are prone to have recurrence or metastasis. PPGL patients with postoperative recurrence or distant metastasis had younger onset age, longer course of disease, larger tumor size and higher proportion of multiple lesions.

[Efficacy and safety of daratumumab in the treatment of advanced light chain amyloidosis].

Objective: The study investigated the efficacy and safety of daratumumab in the treatment of cardiac light chain (AL) amyloidosis. Methods: We retrospectively analyzed the clinical characteristics, hematologic response, organ response, long-term survival, and adverse events of 20 patients with newly diagnosed or relapsed/refractory cardiac AL amyloidosis treated with daratumumab in Peking Union Medical College Hospitalo from January 2017 to March 2021. Results: The overall median age of 20 patients was 62 (range, 45-73) yeas, with a male to female ratio of 2.3:1. Nine patients were newly diagnosed, while 11 patients had relapsed or refractory disease. Based on Mayo 2004 cardiac AL staging system, stages Ⅱ and Ⅲ diseases were present in 20 patients respectively. Four patients died during the first cycle of daratumumab, and the remaining 16 patients completed a median of 3 (range, 1-10) cycles of treatment. Overall hematologic response rates were 80% each at 1, 3, and 6 months after treatment initiation, and 45% , 60% , and 60% of the patients achieved at least a very good partial response at 1, 3, and 6 months respectively. The median duration to hematologic response was 13 (range, 6-28) days. At 3, 6, and 12 months, 20% , 30% , and 40% of the patients respectively achieved a cardiac response, and the median days to response was 91 (range, 30-216) days. As of the last follow-up, 9 (45% ) patients died. The 1-month mortality rate of all the patients and stage IIIb patients was 25% and 40% , respectively. The 1-year overall survival rate was 48.4% . Lymphocytopenia was the most common hematological adverse event (above grade 3) . Non-hematological adverse events were mainly infusion-related reactions and infections. Conclusion: Daratumumab could induce deep and rapid hematologic response in newly diagnosed and previously treated cardiac AL amyloidosis patients. However, daratumumab was not effective in preventing the high and early mortality rate in stage Ⅲb patients.

[The 491st case: thrombocytosis, gastrointestinal hemorrhage, intestinal perforation].

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) featured by clonal proliferation of platelets, thrombosis and hemorrhage. Portal hypertension is a serious complication of ET associated with poor prognosis. We report a patient with ET complicated with acute upper gastrointestinal hemorrhage and intestinal perforation due to portal hypertension. She had an uneventful recovery after surgical and endoscopic treatment.

[The mechanism of circ_0023990/miR-873-5p/ANXA2 axis regulating radiosensitivity and development of thyroid carcinoma].

Objective: To explore the effect and possible mechanism of circ_0023990 on the radiosensitivity of thyroid cancer cells. Methods: qRT-PCR was used to detect the expression of circ_0023990 in the cancer tissues of 55 patients with thyroid cancer and thyroid cancer cell lines (TPC-1, KTC-1, FTC-133 and CAL-62), and the relationship between the expression of circ_0023990 in cancer tissues and the clinical characteristics of the patients were analyzed. Thyroid cancer cells TPC-1 and KTC-1 were divided into sh-circ_0023990 group, sh-NC group, sh-circ_0023990+anti-miR-873-5p group, sh-circ_0023990+anti-miR-NC group, miR-873-5p group, miR-NC group, miR-873-5p+pcDNA-ANXA2 group and miR-873-5p+pcDNA group, and then clone formation experiment was used to detect cell radiosensitivity. After each group of cells was irradiated with 4Gy radiation, the expression of γH2AX protein in the cells was detected by Western Blot. The dual luciferase reporter gene experiment verified the targeting relationship between circ_0023990 and miR-873-5p or miR-873-5p and ANXA2. Results: The expression of circ_0023990 in thyroid cancer tissues was higher than that in normal tissues (2.15±0.09 vs. 0.97±0.05, P<0.05), and its expression was closely related to tumor size, lymph node metastasis and TNM staging of patients with thyroid cancer (P<0.05). The expression of circ_0023990 in thyroid cancer cell lines (TPC-1, KTC-1, FTC-133 and CAL-62) were higher than that of normal thyroid cells HTori-3 (3.16±0.38, 2.63±0.28, 1.82±0.24, 1.71±0.22 vs. 1.00±0.10, all P<0.05). The survival scores of TPC-1 and KTC-1 cells in the sh-circ_0023990 group were significantly lower than those in the sh-NC group (P<0.05), and the sensitization ratios were 2.482, 1.643; The survival scores of TPC-1 and KTC-1 cells in the sh-circ_0023990+anti-miR-873-5p group were higher than those in the sh-circ_0023990+anti-miR-NC group (P<0.05), and the sensitization ratios were 0.305, 0.441, respectively. The survival scores of TPC-1 and KTC-1 cells in the miR-873-5p group were lower than those in the miR-NC group (P<0.05), and the sensitization ratios were 2.044, 1.653 respectively. The survival scores of TPC-1 and KTC-1 cells in the miR-873-5p+pcDNA-ANXA2 group was higher than that in the miR-873-5p+pcDNA group (P<0.05), and the sensitization ratios were 0.496, 0.686, respectively. The expression of γH2AX protein in TPC-1 and KTC-1 cells of the 4 Gy+sh-circ_0023990 group were higher than that in the 4 Gy+sh-NC group (2.68±0.27 vs. 1.87±0.25, 2.46±0.19 vs. 1.77±0.14; all P<0.05), but the expression of γH2AX protein in TPC-1 and KTC-1 cells of the 4 Gy+sh-circ_0023990+anti-miR-873-5p group were lower than that in the 4 Gy+sh-circ_0023990+anti-miR-NC group (1.13±0.09 vs. 1.69±0.09, 1.11±0.08 vs. 1.60±0.08; both P<0.05). The expression of γH2AX protein in TPC-1 and KTC-1 cells in the 4 Gy+miR-873-5p group were higher than that in the 4 Gy+miR-NC group (2.35±0.16 vs. 1.84±0.14, 2.26±0.12 vs. 1.77±0.13; both P<0.05), but the expression of γH2AX protein in TPC-1 and KTC-1 cells of the 4 Gy+miR-873-5p+pcDNA-ANXA2 group were lower than that in the 4 Gy+miR-873-5p+pcDNA group (1.96±0.12 vs. 2.41±0.12, 1.92±0.07 vs. 2.28±0.12; both P<0.05). circ_0023990 targeted the negative regulation of miR-873-5p, and ANXA2 was the target gene of miR-873-5p. Conclusion: circ_0023990 was highly expressed in thyroid cancer tissues and cell lines, and it may promote the radiotherapy resistance of thyroid cancer cells in vivo through regulating miR-873-5p/ANXA2 axis.

[Analysis of differences in clinical and biochemical characteristics and treatment effects in patients with different genotypes of Prader-Willi syndrome].

Objective: To analyze the differences in clinical and biochemical characteristics and treatment effects in patients with different genotypes of Prader-Willi syndrome (PWS). Methods: A total of 35 patients with PWS, 20 males and 15 females aged from 0.8 to 10.0 years with an average age of 3.0 years, were retrospectively included in this study. All of them were treated in the Department of Endocrinology of Peking Union Medical College Hospital from May 2017 to December 2018. The clinical material, biochemical data, and peripheral blood samples of the patients were collected. Genomic DNA was extracted from peripheral blood leukocytes of patients, and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was used to detect gene deletion or abnormal methylation. According to the results of detection, 35 patients were divided into two groups: paternal deletion group(n=27) and methylation abnormal group(n=8). The biochemical test results and the effect of growth hormone (GH) treatment of the two groups were analyzed. Results: MS-MLPA showed that 77% (27/35) of the patients were confirmed paternal deletion and 23% (8/35) were abnormal methylation. In terms of biochemical test results, the plasma concentrations of uric acid(UA) in the paternal deletion group were higher than that in the abnormal methylation group [(363±101) µmol/L vs (259±74) µ mol/L, P=0.019 ]. There is a linear relationship between body weight and uric acid level. After adjustment for weight., there was no significant difference in UA level between the two groups (P=0.101). Patients in both groups were treated with GH ((0.14±0.03) U/kg, QD). In paternal deletion group, patients were followed up for (26.0±13.6) months, and their height increased from (99.0±31.5) cm [(-0.3±1.1) SDS] to (107.5±27.0) cm [(0.7±0.9) SDS] (P=0.037). In the abnormal methylation group, patients were followed up for (25.8±11.6) months, and their height increased from (86.4±31.2) cm [(-0.7±1.8) SDS] to (95.6±26.5) cm [(0.0±1.6) SDS] (P=0.557). There was no significant difference in body mass index (BMI) between paternal deletion group and abnormal methylation group before and after treatment [(22.0±7.1) vs (22.4±6.8)] kg/m2, P=0.890;(17.0±3.1) vs (16.4±2.7) kg/m2, P=0.754]. Conclusions: There were no significant differences in biochemical test results between patients with paternal deletion and those with abnormal methylation. Early treatment with GH in PWS patients can effectively improve the increasing height and reduce excessive weight gain.

[Clinical analysis of 60 children with anaplastic large cell lymphoma in a single center].

Objective: To summarize the clinical features, treatment outcome and prognostic factors of childhood anaplastic large cell lymphoma (ALCL). Methods: Clinical data of 60 newly diagnosed and biopsy-proven ALCL pediatric patients (≤18 years of age) at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2018 were collected. All patients were treated with the Chinese Children Cancer Group-B cell-non-Hodgkin Lymphoma 2010 (CCCG-BNHL-2010) regimen. Overall survival (OS), event free survival (EFS) and progression free survival (PFS) rates were calculated by the Kaplan-Meier method. Univariate analysis was performed with Log-Rank test to find factors of poor prognosis. Results: Among 60 ALCL patients included in the current study, 39 were males and 21 females, the age of onset was 7.9 (1.2-16.7) years. Among all cases, 43 (72%) had B syndrome (any of the following: fever, drenching, weight loss). Forty-nine (82%) cases had lactate dehydrogenase (LDH) levels<2 times upper limit of normal (ULN) and 11 (18%) cases had LDH levels 2-<4 times ULN. The distribution of stages was stage Ⅰ,Ⅱ,Ⅲ, and Ⅳ in 2% (1/60), 5% (3/60), 92% (55/60), and 2% (1/60) of patients, respectively. Of 58 cases who had results of anaplastic lymphoma kinase (ALK) immunohistochemical staining, 53 (91%, 53/58) cases were positive. Visceral involvement was observed in 12 patients (20%). The 4-year OS and EFS rates were (88±4)% and (76±6)% for the entire group, respectively. Univariate analysis for gender, B symptoms, LDH level, ALK expression, clinical stage and visceral involvement showed that only LDH level correlated with an inferior OS rate (χ²=6.571, P=0.010) while not correlated with EFS rate. No independent risk factor for disease progression or recurrence was found by Logistic regression. Up to the last follow-up, 44 cases were continuously at complete remission state, and their follow-up time was 50 (13-119) months. Of 13 (23%) cases experienced disease progression or relapse, 3 cases abandoned treatment, 2 cases progressed to death, 8 cases received second line or salvage treatment (6 survived at last follow-up). For post progression or relapse cases, the 2-year OS and PFS rates were (60±16)% and (16±14)%, respectively. The treatment related death occurred in 3 cases (5%) and all of them were due to severe infection during the chemotherapy. Conclusions: The efficacy of CCCG-BNHL-2010 regimen in the treatment of children with ALCL was good. However, the safety needs to be improved as the treatment-related mortality in the present study was slightly higher. Efficient second line or salvage treatment can achieve cure in pediatric patients post progression or recurrence. LDH ≥2 times ULN was associated with worse prognosis.

[Timing of food introduction to the infant diet and risk of food allergy: a systematic review and Meta-analysis].

Objective: To evaluate the relationship between the timing of complementary feeding for infants and the occurrence of food allergy. Methods: The PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang Data database were searched for randomized controlled trials (RCTs) about the effects of early introduction of complementary foods in infants on the occurrence of food allergy. Papers published from the establishment of the databases to December 31, 2019 were extracted. The quality of the selected literature was evaluated using the risk-of-bias (ROB) tools in the Cochrane Handbook, and the RevMan 5.3 software was used for meta-analysis. For the complementary food analyzed in a few reports in literature, a systematic review was conducted. Results: A total of 8 RCTs were extracted, and the systematic review and Meta-analysis were carried out according to food types. The results of Meta-analysis showed that compared with late introduction (after 6 months of age), early introduction (before 6 months of age) of eggs (RR=0.60, 95%CI 0.46-0.79) could reduce the risk of egg allergy in infants. The subgroup analysis of the six studies about eggs demonstrated that in infants with a prior or family history of allergic diseases, the introduction of eggs before 6 months of age was associated with reduced risk of egg allergy (RR=0.55, 95%CI 0.40-0.75), and the introduction of raw eggs (RR=0.67, 95%CI 0.49-0.93) and small amount of eggs (equivalent to weekly protein 0-4 g) (RR=0.55, 95%CI 0.36-0.85) before 6 months of age were also associated with reduced risk of egg allergy. In addition, egg supplementation during 4-6 months of age reduced the occurrence of egg allergy compared with supplementation before 4 months of age (RR=0.58, 95%CI 0.43-0.78). The systematic review found no conclusive relationship between early peanut introduction and peanut allergy, nor the correlation between early cow's milk protein introduction and cow's milk protein allergy (P>0.05). Conclusion: Early introduction (before 6 months of age) of eggs in infants' complementary foods can prevent infant egg allergy, but the limitations of the study need to be considered.