Objective:To investigate the impact of immunosuppressive therapy on the severity of SARS-CoV-2 infection and cytokine levels in pediatric patients with kidney diseases.Methods:A retrospective analysis was conducted on the clinical data of 40 hospitalized pediatric patients who were diagnosed with SARS-CoV-2 infection at the 900th Hospital of PLA Joint Logistic Support Force from December 2022 to February 2023. Based on their immunosuppressive status prior to SARS-CoV-2 infection, these patients were categorized into immunosuppressive group and non-immunosuppressive group. Independent sample t-tests, Mann-Whitney U tests, and χ2 test were employed to compare the clinical baseline characteristics and laboratory data, the severity of SARS-CoV-2 infection, and the levels of cytokines between the 2 groups. Results:Among the 40 patients, 11 were in the immunosuppressive group (aged 13 (8, 14) years, 9 males and 2 females) and 29 in the non-immunosuppressive group (aged 2 (1, 4) years, 15 males and 14 females). In the immunosuppressive group, 2 were asymptomatic cases, 8 were mild cases, and 1 was moderate case, and there was no severe or critical cases. In the non-immunosuppressive group, 8 were mild cases, 5 were moderate, 15 were severe cases, 1 was critical case, and no asymptomatic cases. The underlying diseases in the immunosuppressive group included nephrotic syndrome (6 cases), IgA vasculitis nephritis (2 cases), lupus nephritis (1 case), post-renal transplantation (1 case), and renal failure (1 case), with a mean total immunosuppression score (TIS) of (3.6±1.4) points. In the non-immunosuppressive group, 2 patients had a history of epilepsy, and the remaining 27 cases had no underlying conditions, all with TIS scores of 0. Compared to the children in the non-immunosuppressive group, those in the immunosuppressive group were more likely to exhibit asymptomatic or mild infection, with lower risks of severe disease, cytokine storm, fever, and cough, but a higher risk of fatigue ( OR=1.22, 2.66, 0.48, 0.12, 0.12, 0.13, 1.22; 95% CI 0.93-1.62, 0.99-7.15, 0.33-0.70, 0.03-0.57, 0.03-0.57, 0.03-0.65, 0.93-1.62; all P<0.05). The levels of cytokine IL-6, interferon-α and interferon-γ in the immunosuppressive group were all lower than those in the non-immunosuppressive group ( Z=2.23, 2.51, 2.92, respectively; all P<0.05). Conclusion:Pediatric patients with kidney diseases receiving appropriate immunosuppressive therapy may mitigate the severity of SARS-CoV-2 infection by suppressing the expression of cytokines.

Objective:To investigate the feasibility of thigh muscles segmentation in patients with Duchenne muscular dystrophy (DMD) using the TransUNet deep learning model on MRI.Methods:This was a cross-sectional study. From April 2023 to September 2024, the axial T 1WI imagings of 60 DMD patients, confirmed by genetic analysis at Northwest Women′s and Children′s Hospital, were enrolled in this retrospective study. Patients were divided into a training set ( n=48) and a test set ( n=12) at a ratio of 8∶2 using random sampling. Fat infiltration scores were assigned to 11 thigh muscles, including the rectus femoris, vastus lateralis, vastus intermedius, vastus medialis, sartorius, adductor longus, adductor magnus, gracilis, semimembranosus, semitendinosus, and biceps femoris long head. A total of 1 078 images were included (884 for training, 194 for testing).The 12 DMD patients in the test set were divided into groups G1 to G4, with 2, 4, 2, and 4 cases respectively, according to the total score of muscle fat infiltration from low to high. A TransUNet model was trained on the T 1WI to perform automatic segmentation of the 11 thigh muscles in both thighs. The segmentation performance of the TransUNet automatic segmentation model was evaluated using the Dice similarity coefficient (DSC), intersection over union (IoU), and average symmetric surface distance (ASSD), with the results of manual delineation by physicians as the gold standard. And one-way analysis of variance or the Kruskal-Wallis H test was used to compare the segmentation effects of the automatic segmentation model on the thigh muscles of children among G1 to G4. Results:The mean processing time for the automatic segmentation of all 11 muscles in both thighs per patient was (8.3±1.5) s. The DSC, IoU and ASSD in training set and in test set were 0.971±0.011, 0.948±0.019, 0.69 (0.55, 0.96) and 0.944±0.021, 0.900±0.038, 0.58 (0.55, 0.91), respectively. In the training set, the semitendinosus muscle achieved the best segmentation results (DSC 0.99, IoU 0.97, ASSD 0.52). In the test set, the sartorius muscle showed the best segmentation performance (DSC 0.96, IoU 0.93, ASSD 0.50). There were no statistically significant differences in the overall DSC, IoU, or ASSD of the automatic segmentation model across groups G1 to G4 ( P>0.05). Conclusions:The TransUNet automatic segmentation model can rapidly and accurately segment the bilateral thigh muscles in patients with DMD, and the segmentation performance demonstrated consistent among patients with different degrees of muscle fat infiltration.

Objective:To investigate the feasibility of thigh muscles segmentation in patients with Duchenne muscular dystrophy (DMD) using the TransUNet deep learning model on MRI.Methods:This was a cross-sectional study. From April 2023 to September 2024, the axial T 1WI imagings of 60 DMD patients, confirmed by genetic analysis at Northwest Women′s and Children′s Hospital, were enrolled in this retrospective study. Patients were divided into a training set ( n=48) and a test set ( n=12) at a ratio of 8∶2 using random sampling. Fat infiltration scores were assigned to 11 thigh muscles, including the rectus femoris, vastus lateralis, vastus intermedius, vastus medialis, sartorius, adductor longus, adductor magnus, gracilis, semimembranosus, semitendinosus, and biceps femoris long head. A total of 1 078 images were included (884 for training, 194 for testing).The 12 DMD patients in the test set were divided into groups G1 to G4, with 2, 4, 2, and 4 cases respectively, according to the total score of muscle fat infiltration from low to high. A TransUNet model was trained on the T 1WI to perform automatic segmentation of the 11 thigh muscles in both thighs. The segmentation performance of the TransUNet automatic segmentation model was evaluated using the Dice similarity coefficient (DSC), intersection over union (IoU), and average symmetric surface distance (ASSD), with the results of manual delineation by physicians as the gold standard. And one-way analysis of variance or the Kruskal-Wallis H test was used to compare the segmentation effects of the automatic segmentation model on the thigh muscles of children among G1 to G4. Results:The mean processing time for the automatic segmentation of all 11 muscles in both thighs per patient was (8.3±1.5) s. The DSC, IoU and ASSD in training set and in test set were 0.971±0.011, 0.948±0.019, 0.69 (0.55, 0.96) and 0.944±0.021, 0.900±0.038, 0.58 (0.55, 0.91), respectively. In the training set, the semitendinosus muscle achieved the best segmentation results (DSC 0.99, IoU 0.97, ASSD 0.52). In the test set, the sartorius muscle showed the best segmentation performance (DSC 0.96, IoU 0.93, ASSD 0.50). There were no statistically significant differences in the overall DSC, IoU, or ASSD of the automatic segmentation model across groups G1 to G4 ( P>0.05). Conclusions:The TransUNet automatic segmentation model can rapidly and accurately segment the bilateral thigh muscles in patients with DMD, and the segmentation performance demonstrated consistent among patients with different degrees of muscle fat infiltration.

Objective:To investigate the impact of immunosuppressive therapy on the severity of SARS-CoV-2 infection and cytokine levels in pediatric patients with kidney diseases.Methods:A retrospective analysis was conducted on the clinical data of 40 hospitalized pediatric patients who were diagnosed with SARS-CoV-2 infection at the 900th Hospital of PLA Joint Logistic Support Force from December 2022 to February 2023. Based on their immunosuppressive status prior to SARS-CoV-2 infection, these patients were categorized into immunosuppressive group and non-immunosuppressive group. Independent sample t-tests, Mann-Whitney U tests, and χ2 test were employed to compare the clinical baseline characteristics and laboratory data, the severity of SARS-CoV-2 infection, and the levels of cytokines between the 2 groups. Results:Among the 40 patients, 11 were in the immunosuppressive group (aged 13 (8, 14) years, 9 males and 2 females) and 29 in the non-immunosuppressive group (aged 2 (1, 4) years, 15 males and 14 females). In the immunosuppressive group, 2 were asymptomatic cases, 8 were mild cases, and 1 was moderate case, and there was no severe or critical cases. In the non-immunosuppressive group, 8 were mild cases, 5 were moderate, 15 were severe cases, 1 was critical case, and no asymptomatic cases. The underlying diseases in the immunosuppressive group included nephrotic syndrome (6 cases), IgA vasculitis nephritis (2 cases), lupus nephritis (1 case), post-renal transplantation (1 case), and renal failure (1 case), with a mean total immunosuppression score (TIS) of (3.6±1.4) points. In the non-immunosuppressive group, 2 patients had a history of epilepsy, and the remaining 27 cases had no underlying conditions, all with TIS scores of 0. Compared to the children in the non-immunosuppressive group, those in the immunosuppressive group were more likely to exhibit asymptomatic or mild infection, with lower risks of severe disease, cytokine storm, fever, and cough, but a higher risk of fatigue ( OR=1.22, 2.66, 0.48, 0.12, 0.12, 0.13, 1.22; 95% CI 0.93-1.62, 0.99-7.15, 0.33-0.70, 0.03-0.57, 0.03-0.57, 0.03-0.65, 0.93-1.62; all P<0.05). The levels of cytokine IL-6, interferon-α and interferon-γ in the immunosuppressive group were all lower than those in the non-immunosuppressive group ( Z=2.23, 2.51, 2.92, respectively; all P<0.05). Conclusion:Pediatric patients with kidney diseases receiving appropriate immunosuppressive therapy may mitigate the severity of SARS-CoV-2 infection by suppressing the expression of cytokines.

Breast cancer is the most common cancer in women and one of the deadliest cancers worldwide.According to the distribution of tumor tissue,breast cancer can be divided into invasive and non-invasive forms.The cancer cells in invasive breast cancer pass through the breast and through the immune system or systemic circulation to different parts of the body,forming metastatic breast cancer.Drug resistance and distant metastasis are the main causes of death from breast cancer.Research on breast cancer has attracted extensive attention from researchers.In vitro construction of tumor models by tissue engineering methods is a common tool for studying cancer mechanisms and anticancer drug screening.The tumor microenvironment consists of cancer cells and various types of stromal cells,including fibroblasts,endothelial cells,mesenchymal cells,and immune cells embedded in the extracellular matrix.The extracellular matrix contains fibrin proteins(such as types Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅵ,and Ⅹcollagen and elastin)and glycoproteins(such as proteoglycan,laminin,and fibronectin),which are involved in cell signaling and binding of growth factors.The current traditional two-dimensional(2D)tumor models are limited by the growth environment and often cannot accurately reproduce the heterogeneity and complexity of tumor tissues in vivo.Therefore,in recent years,research on three-dimensional(3D)tumor models has gradually increased,especially 3D bioprinting models with high precision and repeatability.Compared with a 2D model,the 3D environment can better simulate the complex extracellular matrix components and structures in the tumor microenvironment.Three-dimensional models are often used as a bridge between 2D cellular level experiments and animal experiments.Acellular matrix,gelatin,sodium alginate,and other natural materials are widely used in the construction of tumor models because of their excellent biocompatibility and non-immune rejection.Here,we review various natural scaffold materials and construction methods involved in 3D tissue-engineered tumor models,as a reference for research in the field of breast cancer.

As non-invasive drug delivery systems,transdermal patches can deliver drugs through the intact skin at a fixed dose and a adjustable rate in order to product a systemic or local therapeutic effect.Focused on the key quality attributes of transdermal patches,the article illustrated the testing methods and how to control key points.It also briefly described the testing methods and standards of some other characteristics referring to pharmacopoeia,current policies and regulations in various countries,which provided a reference for pharmaceutical industries and relevant departments to improve the quality control methods and standards.

Background/Aims: We aimed to determine the association between blood urea level and incident cirrhosis, hepatic decompensation, and hepatocellular carcinoma in chronic liver disease (CLD) patients. Methods: The association between blood urea level and liver fibrosis/liver-related events were evaluated on continuous scale with restricted cubic spline curves based on generalized additive model or Cox proportional hazards models. Then, the above associations were evaluated by urea level within intervals. Results: Among 4,282 patients who had undergone liver stiffness measurement (LSM) by transient elastography, baseline urea level had a U-shaped association with LSM and hepatic decompensation development after a median follow-up of 5.5 years. Compared to patients with urea of 3.6–9.9 mmol/L, those with urea ≤3.5 mmol/L (adjusted hazard ratio [aHR], 4.15; 95% confidence interval [CI], 1.68–10.24) and ≥10 mmol/L (aHR, 5.22; 95% CI, 1.86–14.67) had higher risk of hepatic decompensation. Patients with urea ≤3.5 mmol/L also had higher risk of incident cirrhosis (aHR, 3.24; 95% CI, 1.50–6.98). The association between low urea level and incident cirrhosis and hepatic decompensation was consistently observed in subgroups by age, gender, albumin level, and comorbidities. The U-shaped relationship between urea level and LSM was validated in another population screening study (n=917). Likewise, urea ≤3.5 mmol/L was associated with a higher risk of incident cirrhosis in a territory-wide cohort of 12,476 patients with nonalcoholic fatty liver disease at a median follow-up of 9.9 years (aHR, 1.27; 95% CI, 1.03–1.57). Conclusions We identified a U-shaped relationship between the urea level and liver fibrosis/incident cirrhosis/hepatic decompensation in patients with CLD.

Cyclin-dependent kinase 9 (CDK9) activity is correlated with worse outcomes of triple-negative breast cancer (TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction (PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CˆN ligand and tested their activity against the CDK9-cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.

Reports of tuberculosis (TB) outbreaks among schoolchildren have increased in recent years in countries across the Western Pacific Region. Cases from China, Japan, Mongolia and the Republic of Korea were studied to derive lessons from the challenges and responses to TB outbreaks in schools. Despite differences in the TB burden and outbreak preparedness, the four countries reported similar challenges. These included delayed diagnosis of index cases, lack of experienced health professionals and sustained financial support, and difficulty in responding to intensified media and community attention. Early detection of outbreaks, established resource mobilization networks, coordination among stakeholders and proactive communication were highlights of successful outbreak responses. These principles could be adapted to each context for responses to future TB outbreaks in schools.

Background/Aims: Data on treatment efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) for chronic hepatitis C virus (HCV) infection in Asian patients with severe renal impairment are limited. This study aimed to study the treatment and side effects of GLE/PIB in these patients infected with non-1 genotype (GT) HCV. Methods: We prospectively recruited patients with Child’s A cirrhosis and eGFR <30 mL/min/1.73 m2 in Hong Kong and Taiwan during 2017–2018 to receive GLE/PIB treatment. Results: Twenty-one patients (GT2, n=7; GT3, n=6; and GT6, n=8) received GLE/PIB for 11.2±1.8 weeks. All except one were treatment-naïve. GLE/PIB was initiated in 16 patients while on dialysis (seven on peritoneal dialysis [PD] and nine on hemodialysis) and in five patients before dialysis. One patient died of PD-related peritonitis during treatment and two were lost to follow up. The SVR12 rate in the remaining 18 patients was 100%. All patients achieved undetectable levels at 4-, 12-, 24- and 48-week after treatment. Patients with deranged alanine aminotransferase showed normalization after 4 weeks and the response was sustained for 48 weeks. No significant adverse event was observed. Conclusions GLE/PIB treatment was associated with high efficacy and tolerability in HCV-infected patients with severe renal impairment.