Genetic spectrum of CAKUT and risk factors for kidney failure: a pediatric multicenter cohort study.

BACKGROUND: Congenital anomalies of the kidney and urinary tracts (CAKUT) are the leading cause of kidney failure in children with phenotypic and genotypic heterogeneity. Our objective was to describe the genetic spectrum and identify the risk factors for kidney failure in children with CAKUT. METHODS: Clinical and genetic data were derived from a multicenter network (Chinese Children Genetic Kidney Disease Database, CCGKDD) and the Chigene database. A total of 925 children with CAKUT who underwent genetic testing from 2014 to 2020 across China were studied. Data for a total of 584 children wereobtained from the CCGKDD, including longitudinal data regarding kidney function. The risk factors for kidney failure were determined by the Kaplan-Meier method and Cox proportional hazards models. RESULTS: A genetic diagnosis was established in 96 out of 925 (10.3%) children, including 72 (8%) with monogenic variants, 20 (2%) with copy number variants (CNVs), and 4 (0.4%)with major chromosomal anomalies. Patients with skeletal abnormalities were more likely to have large CNVs or abnormal karyotypes than monogenic variants. Eighty-two patients from the CCGKDD progressed to kidney failure at a median age of 13.0 (95% confidence interval, 12.4-13.6) years, and twenty-four were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48, XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors. CONCLUSIONS: The genetic spectrum of CAKUT varies among different subphenotypes. The identified factors indicate areas that require special attention.

Real-world data on breast pathologic complete response and disease-free survival after neoadjuvant chemotherapy for hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer: a multicenter, retrospective study in China.

BACKGROUND: The data in the real-world setting on breast pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for hormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+, HER2-) breast cancer (BC) is limited. The present study aims to screen for some predictors and investigate the prognostic significance of breast pCR after NAC in HR+, HER2- BC in China. METHODS: This was a multicenter, retrospective study. In this study, three hundred eighty-four HR+, HER2- BC patients who received NAC were enrolled between 2010 and 2016 from Shanghai Jiaotong University Breast Cancer Database (SJTU-BCDB). These patients were dichotomized according to the presence of breast pCR after NAC. Logistic analysis was used to screen for predictors associated with breast pCR. Kaplan-Meier (K-M) curve and a propensity score matching (PSM) analysis were performed to compare the disease-free survival (DFS) between the two groups. Cox regression was used to analyze the prognostic significance of breast pCR on DFS in HR+, HER2- BC. A nomogram model was established to predict the probability of DFS at 1, 3, and 5 years after NAC. RESULTS: Fifty-seven patients (14.8%) achieved breast pCR. Univariate analysis showed that tumor size, estrogen receptor (ER), progesterone receptor (PR), and Ki67 were associated with breast pCR. Further, multivariate analysis showed that tumor size, PR, and Ki67 remained statistically significant. K-M curves showed a statistical difference between the breast pCR and non-pCR groups before PSM (p = 0.047), and a more significant difference was shown after PSM (p = 0.033). Cox regression after PSM suggested that breast pCR, adjuvant ET, clinical T stage, and Ki67 status were the significant predictive factors for DFS in HR+, HER2- BC patients. The adjusted hazards ratio (aHR) for breast pCR was 0.228 (95% CI, 0.070~0.739; p = 0.014), for adjuvant endocrine therapy was 0.217 (95% CI, 0.059~0.801; p = 0.022), for Ki67 was 1.027 (95% CI, 1.003~1.052; p = 0.027), for cT stages 2 and 3 compared with 1, the values were 1.331 (95% CI, 0.170~10.389), and 4.699 (95% CI, 0.537~41.142), respectively (p = 0.043). A nomogram was built based on these significant predictors, providing an integrated probability of DFS at 1, 3, and 5 years. The values of area under the receiver operating characteristic (ROC) curve (AUC) were 0.967, 0.991, and 0.787, at 1 year, 3 years, and 5 years, respectively, demonstrating the ability of the nomogram to predict the DFS. CONCLUSIONS: This real-world study demonstrates that tumor size, PR, and Ki67 were independent predictive factors for breast pCR in HR+, HER2- BC. Breast pCR after NAC was an independent predictor for DFS in HR+, HER2- patients, regardless of a change in nodes. Furthermore, the nomogram built in our study could predict the probability of individualized DFS in HR+, HER2- BC patients.

New strategy of color and power doppler sonography combined with DMSA in the assessment of acute pyelonephritis in infants.

BACKGROUND: The purpose of this study was to evaluate the clinical value of color and power doppler sonography (CPDS) when combined it with 99mTc-dimercaptosuccinic acid scintigraphy (DMSA) in assessment of acute pyelonephritis (APN) in infants. METHODS: A total of 79 children with APN admitted to our hospital from June 2016 to Jan 2019 were enrolled, including 52 boys and 27 girls, age range 1 month to 3 years old. All cases followed the diagnostic criteria for acute pyelonephritis and excluded anatomical abnormalities of urinary system. All 79 patients were examined by urinary ultrasonography (US), CPDS, and DMSA within 48 h of fever and analyzed the clinical value of combining the two methods in the assessment of APN in infants. RESULTS: Among 79 children, urinary ultrasonography revealed 2 cases of renal cortical echo changes, both located in the upper pole of the kidney, 24 cases of kidney enlargement, and 1 case of left kidney shrinkage. Ninety-five kidneys were shown to be diseased with DMSA, while 105 kidneys abnormal by CPDS. The sensitivity of CPDS was 69.4%, and the specificity was 38.1%. In children younger than 6 months, the sensitivity of CPDS was 56.9%, which was 84.2% in childeren between 6 months to 1 year, and 94.4% from 1 to 3 years old, respectively. The corresponding specificity of CPDS was 44.1, 26.7, and 35.7%. There was no significant correlation between CPDS levels and DMSA positive results. The abnormal rate of intermediate part in the kidneys was significantly lower than that in the upper and lower poles. Children with abnormal CPDS have a greater risk of renal scarring(p < 0.05). CONCLUSION: Abnormalities detected by CPDS in a cohort of infants with APN poorly correlated with DMSA findings. But the sensitivity of CPDS is highly age-related, it can be used as a non-invasive helpful tool for early diagnosis of acute pyelonephritis in infants older than 6 months old.

[Clinical features of neurogenic bladder with vesicoureteral reflux in children].

OBJECTIVE: To study the clinical features of vesicoureteral reflux (VUR) in children with neurogenic bladder (NB), and to provide a reference for its early diagnosis and treatment. METHODS: Clinical data were collected from 26 children with NB and urinary tract infection who were admitted to the Department of Pediatric Nephrology from January 2014 to December 2019. According to the presence or absence of VUR, the children were divided into a VUR group with 11 children and a non-VUR group with 15 children. Clinical features were compared between the two groups. RESULTS: Compared with the non-VUR group, the VUR group had a significantly higher proportion of children with non-Escherichia coli urinary tract infection, hydronephrosis (the severity of hydronephrosis increased with the grade of VUR), abnormal 99mTc-DMSA renal scanning findings, elevated ratios of urinary albumin, urinary IgG and urinary transferrin to creatinine, increased residual urine volume, and increased detrusor leak point pressure (P < 0.05). CONCLUSIONS: When NB children have the clinical manifestations of non-Escherichia coli urinary tract infection, hydronephrosis, abnormal 99mTc-DMSA renal scanning findings, glomerular proteinuria, increased bladder residual urine volume, and high detrusor leak point pressure, such children may already have VUR, and so diagnosis and intervention should be performed as early as possible.

[Long-term prognosis of vesicoureteral reflux: a follow-up observation of 138 children].

OBJECTIVE: To study the long-term prognosis of vesicoureteral reflux in children. METHODS: A retrospective analysis was performed for the clinical data of 138 children (218 ureters with reflux) who were diagnosed with vesicoureteral reflux for the first time from November 2005 to March 2017 and received medical treatment and regular follow-up. According to the initial grade of reflux, the ureters with reflux were divided into a low-grade group (141 ureters, grade I-III) and a high-grade group (77 ureters, grade IV-V), and the two groups were compared in terms of clinical data and follow-up results. RESULTS: Among the 138 children, there were 82 boys and 56 girls. Their age ranged from 31 days to 10 years at the time of confirmed diagnosis, with a median age of 8 months. The follow-up time ranged from 8 months to 7 years, with a median follow-up time of 1.4 years. At the time of confirmed diagnosis, the high-grade group had significantly higher levels of urinary N-acetyl-ß-D-glucosaminidase, urinary microalbumin and urinary immunoglobulin G than the low-grade group (P<0.05). Among the 218 ureters with reflux, 132 (60.6%) achieved a reduction in the grade of reflux (among which 74 achieved complete disappearance of reflux), 43 had no change in the grade of reflux, and 43 had an increase in the grade of reflux. Compared with the high-grade group, the low-grade group had a significantly higher complete remission rate (41.1% vs 19.5%, P=0.001) and a significantly shorter time to complete remission of reflux (P=0.002). CONCLUSIONS: Most children with vesicoureteral reflux can achieve a reduction in the grade of reflux or even complete disappearance of reflux during follow-up, and the children with low-grade reflux have better prognosis than those with high-grade reflux.

Multi-granularity prior networks for uncertainty-informed patient-specific quality assurance.

Deep Learning Automated Patient-Specific Quality Assurance (PSQA) aims to reduce clinical resource requirements. It is vital to ensure the safety and effectiveness of radiation therapy by predicting the dose difference metric (Gamma passing rate) and its distribution. However, current research overlooks uncertainty quantification in model predictions, limiting their trustworthiness in real clinical environments. This paper proposes a Multi-granularity Uncertainty Quantification (MGUQ) framework. A Bayesian framework that quantifies uncertainties at multiple granularities for multi-task PSQA, specifically Gamma Passing Rate (GPR) prediction and Dose Difference Prediction (DDP), integrates visualization-based interactive components. Using Bayesian theory, we derive a comprehensive multi-granularity loss function that comprises granularity-specific loss and coherence loss components. Additionally, we proposed Multi-granularity Prior Networks, a dual-stream network architecture, to infer the distributions of DDP (modeled as t-distributions) and GPR (modeled as Gaussian distributions) under specific statistical assumptions. Comprehensive evaluations are conducted on a dataset from ''Peeking Union Medical College Hospital'', and results show that our proposed method achieves a minimum MAE loss of 0.864 with a 2%/3 mm criterion and realizes the uncertainty visualization of dose difference. Further, it also achieves 100% Clinical Accuracy (CA) with a workload of 67.2%. Experiments demonstrate that the proposed framework can enhance the trustworthiness of deep learning applications in PSQA.

Pancreatic agenesis and altered m6A methylation in the pancreas of PDX1-mutant cynomolgus macaques.

As an essential transcriptional activator, PDX1 plays a crucial role in pancreatic development and ß-cell function. Mutations in the PDX1 gene may lead to type 4 maturity-onset diabetes of the young (MODY4) and neonatal diabetes mellitus. However, the precise mechanisms underlying MODY4 remain elusive due to the paucity of clinical samples and pronounced differences in pancreatic architecture and genomic composition between humans and existing animal models. In this study, three PDX1-mutant cynomolgus macaques were generated using CRISPR/Cas9 technology, all of which succumbed shortly postpartum, exhibiting pancreatic agenesis. Notably, one tri-allelic PDX1-mutant cynomolgus macaque (designated as M4) developed a pancreas, whereas the two mono-allelic PDX1-mutant cynomolgus macaques displayed no anatomical evidence of pancreatic formation. RNA sequencing of the M4 pancreas revealed substantial molecular changes in both endocrine and exocrine functions, indicating developmental delay and PDX1 haploinsufficiency. A marked change in m6A methylation was identified in the M4 pancreas, confirmed through cultured PDX1-mutant islet organoids. Notably, overexpression of the m6A modulator METTL3 restored function in heterozygous PDX1-mutant islet organoids. This study highlights a novel role of m6A methylation modification in the progression of MODY4 and provides valuable molecular insights for preclinical research.

Rediscovery of Angiopteris tonkinensis (Marattiaceae) after 100 years, and its revision.

The border area between south-eastern Yunnan, China and northern Vietnam is one of the regions with richest biological diversity including that of the fern genus Angiopteris (Marattiaceae). Based on the analysis of morphology and DNA sequences of multiple chloroplast regions (atpB, rbcL, rps4-trnS spacer and trnL-F spacer), we revised Angiopteris tonkinensis (Hayata) J.M.Camus and proposed a new combination Angiopteris tamdaoensis (Hayata) J.Y.Xiang & T.Wang, comb. nov., which was previously regarded as a synonym of A. tonkinensis. We found support for a monophyletic Angiopteris including Protomarattia. This discovery adds two new distribution sites of A. tonkinensis, one in China (Malipo, Yunnan) and one in Vietnam (Quan Ba, Ha Giang). We suggest A. tonkinensis should be categorised as Critically Endangered (CR) species according to the criteria of IUCN.

Study on the dosimetry effect of rotational errors of a multi-channel cylinder applicator of vagina / 中国医学装备

Objective:To investigate the dosimetry effect of rotational errors of multi-channel cylinder vaginal applicator of intravaginal irradiation after surgery of endometrial cancer.Methods:A total of 18 patients who underwent surgery of endometrial cancer at Peking Union Medical College Hospital from June to December 2022 were selected.The plans of patients who adopted the treatment of multi-channel cylinder applicator of vagina were retrospectively analyzed,which maintained the same retained mode with clinical plan.The applicator was rotated clockwise by 22.5? and 45.0?,respectively,simulating the rotational errors that occurred in placing the applicator among clinical inter-fractions.And then,the changes of dosimetry of target area and organs at risk(OAR)under two kinds of rotation amplitudes were further analyzed.Results:When the applicator was rotated as 22.5?,the minimum doses to 90%volumes of CTV by 2.03%than that of clinical plan,which was significantly different(t=5.86,P<0.05),and the maximal doses to 2cc of OARs of bladder and rectum respectively increased 2.35%and 2.71%,and the differences of them were statistically significant(t=-3.49,-2.40,P<0.05),respectively.When the applicator was rotated as 45?,the D90 of the target area decreased by 5.75%than that of clinical plan,which was statistically significant(t=14.07,P<0.05).The D2cc values of the bladder and rectum increased respectively by 6.50%and 9.49%than that of clinical plan,which were statistically significant(t=-7.72,-6.9,P<0.05).The differences of the exposed doses of sigmoid colon and small intestine after the applicator was rotated by 22.5? and 45.0? between the plan and original plan were respectively less,which were not statistical significance.Conclusion:The multi-channel cylinder applicator can provide individualized dose distribution in intravaginal irradiation.However,attention should be paid to the placement of the applicator when patients undergo inter-fractional treatment,in order to avoid deviations in the angular alignment from the original plan.This can impact the dosages of the target area and OARs.

Analysis of risk factors and their warning effectiveness for postoperative intestinal barrier dysfunction in patients with severe traumatic brain injury / 中华创伤杂志

Objective:To investigate the risk factors and their warning effectiveness for postoperative intestinal barrier dysfunction (IBD) in patients with severe traumatic brain injury (sTBI).Methods:A retrospective cohort study was conducted to analyze the clinical data of 101 patients with sTBI admitted to Wuxi Branch of Zhongda Hospital Affiliated to Southeast University from May 2020 to February 2023, including 63 males and 38 females, aged 21-81 years [(53.4±14.2)years]. All the patients underwent emergency surgery. The patients were divided into IBD group ( n=67) and non-IBD group ( n=34) according to whether or not they had IBD after surgery. The gender, age, basic diseases (hypertension and diabetes), types of intracranial hematoma (subdural, epidural, and intracerebral hematoma), preoperative Glasgow Coma Scale (GCS), cerebral hernia, intraoperative initial intracranial pressure (iICP), operation time, removal of bone flap, treatment time in ICU, initiation time of enteral nutrition, and use of broad-spectrum antibiotics were recorded in the two groups. Univariate and multivariate binary Logistic regression analyses were conducted to assess the correlations between above-mentioned indicators and incidence of postoperative IBD in sTBI patients and determine the independent risk factors for sTBI. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the warning effectiveness of each risk factor for IBD. Results:The results of the univariate analysis showed that preoperative GCS, cerebral hernia, intraoperative iICP, removal of bone flap, treatment time in ICU, initiation time of enteral nutrition, and use of broad-spectrum antibiotics were significantly correlated with the incidence of IBD in sTBI patients ( P<0.05 or 0.01), while there were no correlations of IBD with gender, age, basic diseases, types of intracranial hematoma and operation time ( P>0.05). The results of the multivariate binary Logistic regression analysis showed that preoperative GCS≤5 points ( OR=2.49, 95% CI 1.17, 5.32, P<0.05), intraoperative iICP>23 mmHg (1 mmHg=0.133 kPa)( OR=1.20, 95% CI 1.03, 1.39, P<0.05), and initiation time of enteral nutrition>24 hours ( OR=10.03, 95% CI 1.26, 80.21, P<0.05) were highly correlated with postoperative IBD in sTBI patients. The results of the ROC curve analysis showed that intraoperative iICP had the highest warning value (AUC=0.91, 95% CI 0.85, 0.96), followed by preoperative GCS (AUC=0.88, 95% CI 0.82, 0.95), and initiation time of enteral nutrition had the lowest warning value (AUC=0.78, 95% CI 0.69, 0.87). Conclusions:Preoperative GCS≤5 points, intraoperative iICP>23 mmHg, and initiation time of enteral nutrition>24 hours are independent risk factors for postoperative IBD in sTBI patients. The warning value of intraoperative iICP ranks the highest for postoperative IBD in sTBI patients, followed by preoperative GCS, with initiation time of enteral nutrition having the lowest warning value.

Research on the robustness of Ethos cervical cancer online fully automatic generation of adaptive plans / 中华放射肿瘤学杂志

Objective:To evaluate the robustness of fully automated adaptive planning for Ethos online adaptive radiotherapy (ART) based on the intelligent optimization engine (IOE).Methods:Clinical data of 11 stage ⅠB cervical cancer patients admitted to Peking Union Medical College Hospital between June 2021 and June 2022 were retrospectively analyzed. Original planning images and iterative cone-beam computed tomography (iCBCT) images of each radiotherapy treatment were acquired, and all patient data were imported into the Ethos simulator. IOE-based 9-field automatic plan generation was performed for 11 patients using Ethos, and the generated plans were sent to online adaptive radiotherapy simulation to obtain each online adaptive radiotherapy plan (273 fractions in total) and complete the simulated treatment. For comparison, manual plan design was performed based on the images and contoured structures used for online adaptive radiotherapy planning, and the manually plans created with evenly divided 9 fields. Dosimetric parameters, plan complexity parameters, and Mobius quality assurance (QA) pass rates were collected to compare and evaluate the robustness of the online adaptive radiotherapy plan in terms of organs at risk (OAR), target volume dosimetric parameters, and plan complexity by using paired t-test or rank sum test. Results:The online adaptive plan of cervical cancer had comparable planning target volume (PTV) coverage compared to the manual plan. For the clinical target volume (CTV) D 99%, online adaptive plan was significantly higher than the manual plan [(45.93±0.36) vs. (45.32±0.31) Gy, P<0.001]. For hot dose area, the maximum point dose (PTV D max) of adaptive plan was significantly higher than the manual plan [(49.89±1.25) vs. (48.48±0.77) Gy, P<0.001], but the PTV D 1% of adaptive plan was significantly lower than the manual plan [(47.22±0.29) vs. (47.59±0.48) Gy, P<0.001]. There was no statistical difference in the conformal index ( P=0.967). And there was significant difference in the homogeneity index, with same medians and less dispersion in adaptive plan ( P<0.001). For OAR dose, bladder D mean, rectal V 40 Gy, small intestine D mean of adaptive plan was slightly higher than that of the manual plan; the rectal D mean, small intestine D 2 cm3 of the adaptive plan was slightly lower than that of manual plan; dosimetric parameters of right and left femoral heads, spinal cord and bone marrow of the adaptive plan were better than those of manual plan. The adaptive plan had more monitor units (MU) than the manual plan, but the complexity of the adaptive plan was significantly lower than that of the manual plan (0.135±0.012 vs. 0.151±0.015, P<0.001). For Mobius γ pass rate (5%/3 mm), both adaptive and manual plans met clinical requirements. Conclusion:Ethos cervical cancer online adaptive plan, which is based on the IOE engine, demonstrates good robustness and ensures the quality of online adaptive plans generated for each treatment fraction.

Performance evaluation of Ethos intelligent optimization engine in automatic plan generation / 中华放射肿瘤学杂志

Objective:To evaluate the automatic optimization performance and clinical feasibility of the intelligent optimization engine (IOE) in the Ethos online adaptive radiotherapy platform.Methods:Clinical data of 11 patients with postoperative cervical cancer treated with Halcyon accelerator were retrospectively analyzed. Manual planning was performed for all patients using the 4 full arc volumetric modulated arc therapy (VMAT) (Manual-4Arc) in Eclipse, with a prescription dose of 45 Gy/25F. Patient images and structures were imported into the Ethos simulator, and appropriate clinical goals were added based on clinical requirements. The target coverage was normalized to 95%. Automatic plan generation was conducted using IOE, resulting in 7, 9, and 12 field intensity modulated radiotherapy (IMRT) plans (IMRT-7F、IMRT-9F、IMRT-12F), as well as 2 and 3 arc VMAT plans (VMAT-2Arc、VMAT-3Arc). Dosimetric index comparisons were made between the Manual-4Arc plans and the 5 groups of IOE-generated plans through one-way analysis of variance. Based on the analysis results, Turky post hoc multiple comparisons were performed to evaluate the automatic optimization performance of IOE.Results:In terms of the high dose area, the IMRT-12F plans showed the lowest D 1% for the planning target volume (PTV), and there were significant differences compared to the Manual-4Arc plans ( P=0.004). Regarding target coverage, all groups produced clinical target volume (CTV) plans that met the clinical requirements. Although the Ethos online adaptive plans were normalized during planning, the PTV coverage was slightly insufficient. For organs at risk (OAR) close to the target, such as the bladder, there were significant differences in V 30 Gy, V 40 Gy, and D mean among the 6 groups of plans. The dose ranking for the bladder was generally as follows: IMRT-12F<IMRT-9F<Manual-4Arc<IMRT-7F<VMAT-3Arc<VMAT-2Arc. There were significant statistical differences in V 30 Gy and D mean for the rectum, and the dose ranking was generally consistent with that of the bladder, except for a switch between the IMRT-7F and Manual-4Arc plans. There were no significant differences in rectal V 40 Gy, small intestine D max, and D mean among the 6 groups of plans. For OAR distant from the target, such as the left and right femoral heads, spinal cord, and bone marrow, the dose ranking was generally as follows: IMRT-12F<IMRT-9F<IMRT-7F<VMAT-2Arc<VMAT-3Arc<Manual-4Arc. Conclusion:The plans automatically generated by Ethos IOE in postoperative patients with cervical cancer can achieve similar performance to manual plans, and the automatically generated IMRT-12F and IMRT-9F plans are recommended for clinical use.

Progress of microglial efferocytosis in neonatal hypoxic ischemic encephalopathy / 国际儿科学杂志

Neonatal hypoxic ischemic encephalopathy(HIE)is a hypoxic ischemic brain injury caused by perinatal asphyxia.It is the major cause of neonatal death and neurological damage of infant and children, and its characteristic pathophysiological alteration is massive neuronal apoptosis.Microglia, one of the central nervous system phagocytes, play an important role in development of neonatal HIE.In recent years, efferocytosis has been discovered to be a specific phagocytosis of phagocytes.In neonatal HIE, microglia are able to remove apoptotic cells through efferocytosis, preventing further necrosis of apoptotic cells, which can trigger inflammatory responses and brain damage.Understanding the role of microglial efferocytosis in neonatal HIE may aid in elucidating its pathogenesis and exploring potential therapeutic approaches.This article is a review of the progress of microglial efferocytosis in neonatal HIE.

Effect of different doses of vitamin D supplementation on preterm infants - an updated meta-analysis.

OBJECTIVE: Vitamin D deficiency (VDD) is common among infants, especially in preterm babies. There are some controversies over its use on body development, immune function and incidence of bronchopulmonary dysplasia (BPD). METHODS: We systematically reviewed PubMed, Embase, and Cochrane databases for studies in English, and in Wanfang, VIP, and Cnki databases for Chinese studies (databases were last launched on 1 August 2016). RESULTS: Twelve original random controlled studies (seven in English and five in Chinese) were included (1). There are no differences between high-dose (800-1000 IU/d) and low-dose (400 IU/d) groups on calcium, phosphorus, and 25(OH)D concentrations (p > .05). However, length gain and head circumference gain are significantly increased in the high-dose group (p < .05) (2). IL-2, Ig-A, and Ig-G levels are significant increased in the vitamin D supplementation group compared with the control group (p < .05) (3). With respect to BPD, there is no significant difference between the vitamin D supplementation group and the control group (p > .05). CONCLUSIONS: In preterm infants, daily supplementation of vitamin D in doses of 800-1000 IU compared with 400 IU appears to be better not only in development but also in immune function. But clinical trials with a larger sample size are still needed.

Assessment of the safety and efficacy of combination chemotherapy and PD-1/PD-L1 inhibitor treatment of breast cancer: A meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#As the efficacy of programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors combined with chemotherapy in curing breast cancer is still controversial, this meta-analysis compares the efficacy and safety of PD-1/PD-L1 inhibitors combined with chemotherapy and chemotherapy alone in the treatment of breast cancer, which provides guidance for the clinical treatment.@*METHODS@#Relevant studies published as of April 2022 in the various databases including EMBASE, PubMed, and Cochrane Library were selected. Randomized controlled trials (RCTs) in which control patients underwent chemotherapy alone and experimental group patients underwent combination chemotherapy and PD-1/PD-L1 inhibitor treatment were included in this investigation. Investigations without complete information, researches from which information could not be extracted, duplicate articles, animal studies, review articles, and systematic reviews were excluded. STATA 15.1 was employed for all statistical analyses.@*RESULTS@#In total, eight eligible studies were identified, revealing that combination chemotherapy and PD-1/PD-L1 inhibitor treatment was linked to significant increases in progression-free survival (PFS) relative to chemotherapy alone (hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0.70-0.99, P = 0.032) but not overall survival (HR = 0.92, 95% CI: 0.80-1.06, P = 0.273). Pooled adverse event rates were also increased within the group of combination treatment relative to the chemotherapy group (risk ratio [RR] = 1.08, 95% CI: 1.03-1.14, P = 0.002). Specifically, nausea rates were lesser within the group of combination treatment relative to the group of chemotherapy (RR = 0.48, 95% CI: 0.25-0.92, P = 0.026). Subgroup analyses indicated that the PFS of patients who underwent combination atezolizumab or pembrolizumab and chemotherapy treatment were substantially longer than those of patients who underwent chemotherapy alone (HR = 0.79, 95% CI: 0.69-0.89, P ≤0.001; HR = 0.79, 95% CI: 0.67-0.92, P = 0.002).@*CONCLUSIONS@#The pooled results suggest that combination chemotherapy and PD-1/PD-L1 inhibitor treatment approaches help prolong PFS in breast cancer patients, but have no statistically significant effect on overall survival (OS). Additionally, combination therapy can significantly improve complete response rate (CRR) compared with chemotherapy alone. However, combination therapy was associated with greater rates of adverse events.

The effects of a novel brain-derived peptide HIBDAP regulating the pyroptosis of oxygen-glucose deprived microglia / 中国新生儿科杂志

Objective:To study the role of a novel brain-derived peptide hypoxic-ischemic brain damage associated peptide (HIBDAP) in regulating pyroptosis of oxygen-glucose deprived (OGD) microglia.Methods:The sequence of HIBDAP was coupled with the sequence of cell-penetrating peptide transactivator of transcription (TAT) to form TAT-HIBDAP. Fluorescein isothiocyanate (FITC) labeled TAT-HIBDAP was added to microglia cells and observed under fluorescence microscope. Microglia cells were treated with different concentrations of TAT-HIBDAP (1, 5, 10, 20 μmol/L) and then OGD process. Cell pyroptosis was analyzed using lactate dehydrogenase (LDH) assay. The concentration of TAT-HIBDAP with the most prominent inhibiting effects was determined and selected for subsequent experiments. The pyroptosis morphology of the control group, the OGD group and the HIBDAP group (5 μmol/L TAT-HIBDAP+OGD) was observed using transmission electron microscope. The mRNA and protein expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes were examined using real-time quantitative PCR and Western Blot analysis.Results:Fluorescence microscope showed FITC-labeled TAT-HIBDAP could successfully enter microglia cells. Compared with the OGD group, low concentrations of TAT-HIBDAP (1, 5, 10 μmol/L) could significantly reduce microglia pyroptosis and the concentration of 5 μmol/L showed the most prominent effects. Compared with the control group, OGD group showed typical pyroptosis morphology and HIBDAP group showed significantly improved morphology. The mRNA and protein expression of NLRP3 inflammasomes in the OGD group were significantly higher than the control group and also the HIBDAP group.Conclusions:The novel brain-derived peptide HIBDAP may reduce the expression of NLRP3 inflammasomes and inhibit the pyroptosis of OGD microglia.

Clinical commissioning of the Flexitron afterloader / 中华放射医学与防护杂志

Objective:To formulate clinical commissioning procedures, items, and testing method for Flexitron afterloader hardware and software and establish relevant quality control procedures in order to meet national standards and clinical requirements.Methods:Clinical commissioning included hardware, treatment planning system (TPS), and end-to-end (ETE) full-process testing. The radioactive source positioning accuracy was measured using a source position check ruler. The accuracy and linearity of dwell time were evaluated using three method: stopwatch timing, ion chamber measurement, and video analysis. The accuracy of source position simulator, connecting tubes, source position check ruler, and other measuring tools was tested using a high-precision ruler. Films were used for calibration of marker lines and applicators. The electrometer and well chamber were used to calibrate the radioactive source activity. The display and reconstruction accuracies of the TPS were evaluated using physical image data. ETE testing was conducted using a custom-made phantom for scanning, planning, and dose measurement.Results:The accuracy testing result of the commissioning items were within acceptable limits. The deviation in source activity measurements was 0.21%, and the ETE point dose measurement deviation was 2.32%, both of which met the clinical requirements. However, there was a 2 mm difference between the nominal and measured values of the magnetic resonance marker line in the accuracy testing items. Therefore, adjustments were required when using marker line for catheter reconstruction based on magnetic resonance images.Conclusions:By summarizing the clinical commissioning experience of the Flexitron afterloader, this study has developed quality control method and baseline levels of result of afterloader and TPS items, which provides a reference for the commissioning before clinical use.

Application of stereotactic body radiotherapy planning verification phantom in HyperArc technique for brain metastases / 中华放射医学与防护杂志

Objective:To explore the feasibility of StereoPhan (SP) phantoms and SRS MapCHECK (SMC) semiconductor matrices in the dose verification of HyperArc (HA) plans for patients with brain metastases (BM).Methods:A total of 16 BM patients who received HA radiotherapy in the Peking Union Medical College Hospital were enrolled in this study. The ion chamber and the SMC semiconductor matrix were inserted into SP phantoms, respectively. The point and planar doses in HA verification plans were measured and compared with the calculated data of the treatment planning system (TPS). The criteria for planar dose γ analysis were set at 2 mm/3%, 2 mm/2%, 1 mm/3%, and 1 mm/2%.Results:The mean deviation of point doses in 16 patients was 1.33%±0.84%. Based on the above criteria, the γ pass rates of planar doses were 99.72%±0.46%, 98.93%±1.32%, 98.85%±1.79%, and 97.13%±3.19%, respectively.Conclusions:SP phantoms and SMC semiconductor matrices are applicable to the dose verification of HA plans for BM patients. The analytical criteria of 3% and 1 mm/2% can be used for verifying point and planar doses, respectively.

Application of artificial intelligence in brachytherapy for cervical cancer / 中华放射肿瘤学杂志

Brachytherapy (BT) provides the opportunity to deliver highly potent radiation doses to the tumor, while more effectively sparing the surrounding organs at risk (OAR) due to the proximity of radiation sources to the tumor target and rapid fall-off of the source dose profile. As an important part of radiotherapy for cervical cancer, BT plays an irreplaceable role. The BT process is complex and can be divided into a series of steps. Long time waiting for patients in the state of implantation of the applicator may cause changes in the position of the applicator relative to the tumor and the movement of the OAR. In recent years, artificial intelligence (AI) has made great progress in the medical field. Machine learning and neural network have been widely applied in all aspects of BT, such as implantation of the applicator, image acquisition, segmentation of target area and OAR, reconstruction of the applicator, plan optimization, and treatment delivery, etc. In addition, BT significantly reduces the overall time, improves the homogeneity of operation, and enhances the accuracy of treatment. In this article, the application, development prospects, and challenges of AI in the BT of cervical cancer in recent years were reviewed, aiming to provide novel ideas for the application of AI in BT.

Three-Dimensional Resistive Metamaterial Absorber Loaded with Metallic Resonators for the Enhancement of Lower-Frequency Absorption.

Resistive patch array incorporating with metallic backplane provided an effective way to achieve broadband metamaterial absorbers (MAs) in microwave frequency, and the outstanding construction contributed more flexible and diversified broadband absorption. In this paper, we attempted to load metallic resonators (MRs) to three-dimensional resistive MA to further enhance the lower-frequency absorption performance. Simulation showed that the partial absorption peak was separated to the lower frequency, while the rest of broadband absorption was unaffected. Meanwhile, after combining multi-unit of the proposed MAs, the stair-stepping broadband absorption was also achieved. Finally, three samples were fabricated. The agreements between simulations and experimental results demonstrated that resistive MA loaded with MRs provided an effective way for further enhancement of lower-frequency absorption with almost no change of the absorbing structure and lightweight characteristic. Thus, it was worthy to expect a wide range of applications to emerge inspired from the proposed attempt.