After years of development, Europe has accumulated extensive experience in the discipline development and global health degree education, laying a strong foundation for cultivating professionals with a global perspective and practical competencies. European universities have continuously explored and innovated in curriculum development and resource integration, offering valuable insights into establishing a comprehensive global health degree education system. This study reviews global health degree programs at 13 representative universities (ranked approximately among the top 100 medical schools in the QS World University Rankings) and two university alliances in Europe. The results of analysis reveals several key features of global health degree education in Europe, such as a wide variety of program types with shorter program durations, strong emphasis on interdisciplinary and cross-sectoral integration in teaching, resource sharing through university alliances, and extensive internship and employment opportunities. These findings offer the following implications for the development of global health degree education in China: providing diversified degree programs to meet the needs of different groups; strengthening interdisciplinary teaching to enhance the quality of practical education; and establishing platforms for shared teaching resources to promote international exchange and cooperation.

Objective:To investigate the genetic, clinical, and post-treatment characteristics of patients with glycogen storage disease type Ⅲ (GSD Ⅲ).Methods:A retrospective cohort analysis was performed on the genetic and clinical data of 26 cases with GSD Ⅲ who visited the Children's Hospital affiliated with Fudan University from June 2017 to December 2023. The patients were divided into non-missense variation and missense variation groups according to the types of mutation in the AGL gene.The correlation between genotype and phenotype was analyzed. All patients were treated with uncooked cornstarch after diagnosis. The changes before and after treatment were compared in patients who underwent more than twelve months of follow-up. A P value of <0.05 was used to denote statistical significance. Results:Among the 26 cases enrolled, 13 were female and 13 were male, and the median age of diagnosis was 28 (6 to 134) months. A total of thirty-five different types of AGL gene variation were detected, with c.1735+1G＞T (9/52, 17.3%) as the hotspot variation. The common clinical manifestations were elevated aminotransferases (26/26, 100%), hepatomegaly (25/26, 96.2%), fasting hypoglycemia (25/26, 96.2%), hyperketonemia (16/18, 88.9%), hypertriglyceridemia (TG) (20/26, 76.9%), elevated CK (16/25, 64.0%), and an abnormal electrocardiogram (12/16, 75.0%). Four cases (15.4%) had symptoms of myopathy at diagnosis. Liver biopsy was performed in eighteen cases, among whom 83.3% (15/18) had liver fibrosis≥S2. The number of cases with elevated levels of CK ( P＝0.031) and ALT ( P＝0.038)was pronounced in the non-missense variation group compared to that in the missense variation group. There were no statistically significant differences in age, height, liver size, degree of fibrosis, fasting blood glucose (Glu) and TG ( P>0.05). The median follow-up time of 14 cases was 40.5 (20-73) months, with improvement in body stature, reduced liver size, decreased ALT and TG, and improved Glu. However, four (28.6%) cases had new myopathy symptoms with raised CK ( P<0.05) and with advancing age, increased ALT diminished while CK level elevated ( P<0.05). Conclusions:The common clinical manifestations at the early stage of the GSD Ⅲdiagnosis are elevated aminotransferases, hepatomegaly, fasting hypoglycemia, hyperketonemia, high triglycerides, elevated CK, and fibrotic liver in China. Myopathy symptoms may arise following uncooked cornstarch treatment; however, there is significant improvement in height, liver-related, and metabolic parameters.

Background::The disease burdens for endometrial cancer (EC) vary across different countries and geographical regions and change every year. Herein, we reported the updated results of the Global Burden of Disease Study 2019 on EC with respect to age-standardized incidence and mortality from 1990 to 2019.Methods::The annual percentage change (APC) of incidence and mortality was evaluated using joinpoint regression analysis to examine the temporal trends during the same timeframe in terms of the global landscape, different sociodemographic indices (SDI), and geographic regions. The relationship between Human Development Index (HDI) and incidence and mortality was additionally explored.Results::The age-standardized incidence rates (ASIRs) revealed a significant average global elevation by 0.5% per year (95% confidence interval [CI], 0.3–0.7; P <0.001). The age-standardized mortality rates (ASMRs), in contrast, fell by an average of 0.8% per year (95% CI, ?1.0 to ?0.7; P <0.001) worldwide. The ASIRs and ASMRs for EC varied across different SDIs and geographical regions. We noted four temporal trends and a significant reduction by 0.5% per year since 2010 in the ASIR, whereas we detected six consecutively decreasing temporal trends in ASMR during the entire period. Notably, the estimated APCs were significantly positively correlated with HDIs (ρ = 0.22; 95% CI, 0.07–0.35; P = 0.003) with regard to incident cases in 2019. Conclusions::Incidence rates for EC reflected a significant increase overall (although we observed a decline since 2010), and the death rates declined consecutively from 1990 to 2019. We posit that more precise strategies can be tailored and then implemented based on the distinct age-standardized incidence and mortality burden in different geographical areas.

Objective:To summarize the genotype and clinical characteristics of chylomicron retention disease (CMRD) caused by secretion associated Ras related GTPase 1B (SAR1B) gene variations.Methods:Clinical data and genetic testing results of 2 children with CMRD treated at Children′s Hospital of Fudan University and Jiangxi Provincial Children′s Hospital from May 2022 to July 2023 were summarized. To provide an overview of the clinical and genetic characteristics of CMRD caused by SAR1B gene variations, all of the literature was searched and reviewed from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China VIP database, China Biology Medicine disc and PubMed database (up to January 2024) with "chylomicron retention disease" "Anderson disease" or "Anderson syndrome" as the search terms. All relevant literatures were reviewed to summarize the clinical and genetic features of CMRD caused by SAR1B gene variations.Results:One 11-year-old boy and one 4-month-old girl with CMRD. Both patients had lipid malabsorption, failure to thrive, decreased cholesterol, elevated transaminase and creatine kinase, and Vitamin E deficiency, with homozygous variations (c.224A>G) and compound heterozygous variations (c.224A>G and c.554G>T) in SAR1B gene, respectively. Case 1 was followed up for over a month, and he still occasionally experienced lower limb muscle pain. Case 2 was followed up for more than a year, and her had caught up to normal levels. Both patients had no other significant discomfort. Literature search retrieved 0 Chinese literature and 22 English literatures. In addition to the 2 cases reported in this study, a total of 51 patients were identified as CMRD caused by SAR1B gene variations. Twenty-one types of SAR1B variants 10 missense, 4 nonsense, 3 frameshift, 1 in-frame deletion, 1 splice, 1 gross deletion, and 1 gross insertion-deletion were found among the 51 CMRD cases. Among all the patients, 49 cases had lipid malabsorption (43 cases had diarrhea or fatty diarrhea, 17 cases had vomiting, and 12 cases had abdominal distension), 45 cases had lipid soluble Vitamin deficiency (43 cases had Vitamin E deficiency, 10 cases had Vitamin A deficiency, 9 case had Vitamin D deficiency, and 5 cases had Vitamin K deficiency), 35 cases had failure to thrive, 32 cases had liver involvement (32 cases had elevated transaminases, 5 cases had fatty liver, and 3 cases had hepatomegaly), 29 cases had white small intestinal mucosa under endoscopy, and 17 cases had elevated creatine kinase, 14 cases had neuropathy, 5 cases had ocular lesions, 2 cases had acanthocytosis, 1 case had decreased cardiac ejection fraction, and 1 case was symptom-free.Conclusions:Early infancy failure to thrive and lipid malabsorption are common issues for CMRD patients. The laboratory tests are characterized by hypocholesterolemia with or without fat-soluble Vitamin deficiency, elevated liver enzymes and (or) creatine kinase. Currently, missense variations are frequent among the primarily homozygous SAR1B genotypes that have been described.

Objective:To investigate the advantage of three dimensional(3D)-printed tissue compensators in radiotherapy for superficial tumors at irregular sites.Methods:A subcutaneous xenograft model of prostate cancer in nude mice was established. Mice were randomly divided into no tissue compensator group( n=6), common tissue compensator group( n=6), and 3D-printed tissue compensator group( n=6). Computed tomography (CT) images of nude mice in the 3D-printed tissue compensator group were acquired. Compensator models were made using polylactic acid, and material properties were evaluated by measuring electron density. CT positioning images of the three groups after covering the corresponding tissue compensators were acquired to delineate the gross tumor volume (GTV). Nude mice in the three groups were irradiated with 6 MV X-rays at the prescribed dose. The prescribed dose for the three groups was 1 500 cGy. The dose distribution in the GTV of the three groups was calculated and compared using the analytical anisotropic algorithm in the Eclipse 13.5 treatment planning system. The metal-oxide-semiconductor field-effect transistor was used to verify the actual dose received on the skin surface of nude mice. Results:The air gap in the 3D-printed tissue compensator group and the common tissue compensator group was 0.20±0.07 and 0.37±0.07 cm 3, respectively ( t=4.02, P<0.01). For the no tissue compensator group, common tissue compensator group, and 3D-printed tissue compensator group, the D95% in the target volume was (1 188.58±92.21), (1 369.90±146.23), and (1 440.29±45.78) cGy, respectively ( F=9.49, P<0.01). D98% was (1 080.13±88.30), (1 302.76±158.43), and (1 360.23±48.71) cGy, respectively ( F=11.17, P<0.01). Dmean was (1 549.08±44.22), (1 593.05±65.40), and (1 638.87±40.83) cGy, respectively ( F=4.59, P<0.05). The measured superficial dose was (626.03±26.75), (1 259.83±71.94), and (1 435.30±67.22) cGy, respectively ( F=263.20, P<0.001). The percentage variation in tumor volume growth after radiation was not significantly different between the common tissue compensator group and the 3D-printed tissue compensator group ( P>0.05). Conclusions:3D-printed tissue compensators fit well to the body surface, which reduces air gaps, effectively increases the dose on the body surface near the target volume, and provides ideas for radiotherapy for superficial tumors at some irregular sites.

Objective:To explore the clinicopathological characteristics, treatments and outcomes of posttransplant lymphoproliferative disorder(PTLD)in pediatric liver transplant recipients.Methods:From October 2016 to October 2021, retrospective data analysis was performed for 11 pediatric liver transplant recipients with PTLD. There were 5 males and 6 females with a diagnostic age of 1-8 years. Living donor liver transplantation(LDLT, n=9)and deceased donor liver transplantation(DDLT, n=2)were performed. All recipients received tacrolimus plus methylprednisolone. The major clinical manifestations included lymphadenopathy, splenomegaly, anemia, fever and digestive system symptoms(diarrhea, abdominal pain, ascites, hematochezia & intussusception, etc.). Laboratory tests hinted at hypoproteinemia, elevated transaminases and serum positivity of EBV-DNA. Positron emission tomography and computed tomography(PET-CT)revealed PTLD( n=9). Ten children were diagnosed by pathology, including lymphoid hyperplasia( n=3), plasmacytic hyperplasia PTLD( n=1), polymorphic PTLD( n=2), diffuse large B-cell lymphoma( n=2), infectious mononucleosis PTLD( n=1)and Burkitt lymphoma( n=1). Results:After a definite diagnosis of PTLD, tacrolimus was tapered or discontinued. And rituximab was prescribed. Two patients received chemotherapy(R-COP & R-CHOP)while 2 cases of local masses were operated. Up until February 2022, 10 cases survived and their conditions improved. One patient died of infection.Conclusions:PTLD is one of the most serious and fatal complications after liver transplantation in children. Clinical manifestations are diverse and an early diagnosis is difficult. The changes of EBV-DNA load should be closely monitored after liver transplantation. Imaging and pathological examinations may aid in an early diagnosis of PTLD. A treatment regimen based on immunosuppression reduction and rituximab improves the prognosis of PTLD in pediatric liver transplant recipients.

Objective:Partial stereotactic ablative boost radiotherapy(P-SABR)is a method to deliver SABR boost to the gross tumor boost volume(GTVb), followed by conventionally fractionated radiotherapy to the whole tumor area(GTV). GTVb is the max volume receiving SABR while ensuring the critical organ-at-risk(OAR)falloff to 3 GyE/f. We investigated the potential advantage of proton therapy in treating bulky non-small cell lung cancer(the tumor length greater than 8 cm).Methods:Nine patients with bulky NSCLC treated with photon P-SABR in our institute were selected. For the treatment planning of proton therapy, the GTVb target area was gradually outwardly expanded based on the photon GTVb target area until the dose to critical OARs reached 3 GyE/f. The GTV and CTV areas remained the same as photon plan. A proton intensity-modulated radiation treatment plan(proton-IMPT), a photon intensity-modulated radiation treatment plan(photon-IMRT)and a photon volumetric modulated arc therapy(photon-VMAT)were created for each patient, respectively. The dosimetric parameters of different treatment plans were compared.Results:The volume ratio of GTVb-photon and GTVb-proton to GTV was(25.4±13.4)% and(69.7±30.0)%,respectively( P<0.001). In photon-IMRT, photon-VMAT, and proton-IMPT plan groups, the mean dose of CTV was(76.1±4.9)Gy, (78.2±3.6)Gy, and(84.7±4.9)Gy, respectively; the ratio of tumor volume with Biologic Effective Dose(BED)≥ 90 Gy to GTV volume was(70.7±21.7)%, (76.8±22.1)%,and(97.9±4.0)%,respectively. The actual dose and BED to the tumor area of the proton-IMPT plan group were significantly higher than those of the photon plan group(both P<0.05). Besides, the OARs dose was significantly decreased in the proton-IMPT group, with(49.2±22.0)%, (56.8±19.0)% and(16.1±6.3)% of the whole lung V5 for photon-IMRT, photon-VMAT and proton-IMPT, respectively(all P<0.001). Conclusions:Larger GTV boost target volume, higher BED and reduced OARs dose can be achieved in proton plans compared with photon plans. Proton P-SABR is expected to further improve the local control rate of bulky NSCLC with fewer adverse effects.

ObjectiveTo investigate the clinical and genetic features of patients with glycogen storage disease type Ⅸa (GSD Ⅸa), and to improve the clinical understanding of the disease. MethodsA retrospective analysis was performed for the clinical data of 20 patients who were hospitalized and genetically diagnosed with GSD Ⅸa in Children’s Hospital of Fudan University from January 2015 to December 2018, and their clinical and genetic features were summarized. ResultsAll 20 patients with GSD Ⅸa were male, with a median age of 2.5 years at the time of confirmed diagnosis. All patients had hepatomegaly and elevated aminotransferases; of all patients, there were 5 patients (250%) with growth retardation, 19 (95.0%) with fasting hypoglycemia, 14 (70.0%) with hyperlactatemia, 9 (45.0%) with hypertriglyceridemia, and 5 (25.0%) with hypercholesterolemia. Fasting blood ketone was measured for 8 patients and all of these patients had an increase in blood ketone; all patients had normal uric acid, and 5 patients (25.0%) had positive urine ketone. Liver biopsy was performed for 18 patients, among whom 15 had mild to moderate liver fibrosis. A total of 16 mutations were detected in the PHKA2 gene, among which 5 were known pathogenic mutations and 11 were novel mutations, and most of the mutations were detected in the c.3614 locus. All patients were treated with uncooked cornstarch, and most patients achieved an improvement in clinical manifestations. ConclusionGSD Ⅸa is more common in male patients. This disease should be considered for patients with hepatomegaly, elevated aminotransferases, growth retardation, fasting hypoglycemia, elevated fasting blood ketone, and normal uric acid. Liver biopsy may help with the diagnosis of this disease, and clinical biochemical parameters and gene detection can be used to confirm diagnosis and classification. Most patients have mild clinical manifestations, while some patients may have liver fibrosis, and treatment with uncooked cornstarch can improve the condition of this disease.

Objective:To assess the transient elastography (TE) in assessing hepatic fibrosis in pediatric chronic liver disease.Methods:Children with chronic liver disease who were both examined with TE and percutaneous transhepatic puncture for grading Scheuer scores in the Children′s Hospital of Fudan University from January 2017 to September 2017 were recruited.Ordinal Logistic regression analysis was used to analyze the interfering factors for hepatic fibrosis.Receiver operating characteristic (ROC) curves were plotted to acquire the optimal cut-off value and to calculate the area under the curve (AUC). Results:Thirty-eight children were enrolled finally, including 28 boys and 10 girls with the mean age of 7.4 years old (1.1-16.0 years). The success rate of detecting hepatic fibrosis was 85%.Ordinal Logistic regression analysis discovered that only the value of liver stiffness measured by TE was correlated with the grade of hepatic fibrosis ( β=0.055, P<0.001). TE was effective to differentiate hepatic fibrosis[

Objective: To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance. Methods: Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children′s Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis. Results: A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (r=0.759, P<0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (P=0.011, P=0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (P=0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (P=0.006, P=0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (P>0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% vs. 94.7%, χ²=4.123, P=0.042) and PFS (5-year estimate, 66.7% vs. 94.7%, χ²=5.822, P=0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group (χ²=4.881, P=0.027); however, there was no statistical significance in 5-year PFS rate (P>0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% vs. 95.7%, χ²=6.285, P=0.012; PFS: 65.5% vs. 91.3%, χ²=5.405, P=0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL. Conclusion The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.