Objective:To summarize the clinical phenotype and genetic characteristics of children with neurodegeneration caused by UBTF gene mutations in childhood. Methods:The clinical and genetic data of 3 children with neurodegeneration in childhood diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University from February 2020 to January 2023 were retrospectively analyzed. All the 3 probands were found having UBTF gene mutations through the whole exome gene sequencing, and the first generation Sanger sequencing method was used to verify the UBTF gene in their family members. The variation characteristics of the UBTF gene were analyzed, and the treatment and follow-up results of the 3 children were summarized. Results:Among the 3 children with childhood onset neurodegeneration, 2 were male and 1 female, aged 9 months, 4 years and 6 months after birth, respectively. The clinical phenotypes mainly included motor retardation, speech and mental retardation, and dystonia. Among them, case 1 and case 2 had seizures, case 1 had dysphagia, feeding problems, no weight gain and ataxia. Brain MRI plain scan showed that case 1 and case 2 had different degrees of cerebral atrophy, case 1 had hypoplasia of corpus callosum, ventricle expansion and softening focus, and case 3 showed non-specific widening of the subarachnoid space. There were no abnormalities in the chromosome copy number variation and mitochondrial ring gene testing in the 3 children; the whole exon gene testing suggested the de novo missense variant in the UBTF gene [NM_014233.4: c.1414(exon14) G>A (p.Gly472Ser), c.1392(exon14)G>T(p.Lys464Asn)] and the maternal nonsense variant [NM_014233.4:c.520C>T(p.Arg174 *)], which were unreported site variants. In terms of treatment, the 3 children received comprehensive rehabilitation function training, and achieved a certain degree of language and intelligence improvement. Seizure control was effectively managed in case 1 with a single antiepileptic drug. Epileptic seizures were effectively treated and controlled in case 2 using more than 4 types of antiepileptic drugs. Conclusions:Neurodegenerative changes caused by UBTF gene mutations in childhood are relatively rare, and some cases may be accompanied with brain atrophy. De novo missense variation and maternal nonsense variation of the UBTF gene are the genetic etiology of the 3 probands.

Objective:To design and evaluate a novel arcuate multi-channel rectal endoluminal applicator to enhance dose coverage of tumors in the upper and middle rectum and reduce pressure on the rectal wall.Methods:Pelvic MRI images of 200 Chinese cases without rectal lesions in the Peking University Third Hospital from July 2022 to August 2022 were retrospectively analyzed. Based on the image data, a rectal model with general characteristics of the population and two novel hard and soft rectal endoluminal applicators were designed and fabricated. The following properties of the conventional applicators and two new applicators were compared: deformation to the model rectal wall, maximum pressure, stable pressure, D 90%, D 100%, V 100%, V 150% and V 200% of the GTV, and D 2 cm3, D 1 cm3, and D 0.1 cm3 of the organs at risk (OAR). ANOVA or Kruskal-Wallis H-test was used to compare the differences among three applicators, and Dunnett's multiple comparison test was used for pairwise comparisons. Results:The novel hard and soft rectal endoluminal applicators caused less deformation of the model rectal wall. The maximum pressure on the rectal wall was (0.606 ± 0.182) kPa and (0.481 ± 0.229) kPa for the hard arcuate applicator and soft arcuate applicator, respectively, and the stable pressure was (0.207 ± 0.137) kPa and (0.055 ± 0.097) kPa, respectively, which were significantly smaller than those of the conventional applicator ( P <0.001, <0.001; P =0.024, <0.001), and the degree of reduction was at or near 50%. Under the premise of ensuring target dose, the D 2 cm3, D 1 cm3, and D 0.1 cm3 of OAR in the treatment plan designed with the novel applicator were significantly reduced compared to the cylindrical applicator (all P<0.001). Conclusion:The novel arcuate multi-channel rectal endoluminal applicator can significantly reduce rectal wall pressure and deformation, while also reducing the dose to OAR without compromising target dose coverage, offering certain therapeutic advantages.

Objective: miR-663a has been reported to be downregulated by X-ray irradiation and participates in radiation-induced bystander effect via TGF-β1. The goal of this study was to explore the role of miR-663a during radiation-induced Epithelium-to-mesenchymal transition (EMT). Methods: TGF-β1 or IR was used to induce EMT. After miR-663a transfection, cell migration and cell morphological changes were detected and the expression levels of miR-663a, TGF-β1, and EMT-related factors were quantified. Results: Enhancement of cell migration and promotion of mesenchymal changes induced by either TGF-β1 or radiation were suppressed by miR-663a. Furthermore, both X-ray and carbon ion irradiation resulted in the upregulation of TGF-β1 and downregulation of miR-663a, while the silencing of TGF-β1 by miR-663a reversed the EMT process after radiation. Conclusion Our findings demonstrate an EMT-suppressing effect by miR-663a via TGF-β1 in radiation-induced EMT.
Down-Regulation ; Epithelial-Mesenchymal Transition ; Epithelium/metabolism* ; MicroRNAs/metabolism* ; Transforming Growth Factor beta1/pharmacology*

Objective:To investigate the accuracy and feasibility of 3D-printing individualized template-guided and CT-guided 192Ir interstitial brachytherapy in the central recurrent gynecologic tumors by comparing pre-plan and intraoperative physical dosimetric parameters. Methods:This study involved 38 patients with central recurrent gynecologic tumors who underwent 3D printing individual template (3D-PIT)-assisted and CT-guided 192Ir interstitial brachytherapy in the Department of Radiation Oncology of the Peking University Third Hospital from Jan 2018 to Dec 2019.The prescription doses for the target tumor areas were 10-36 Gy to be delivered at 5-6 Gy/fraction for 2-6 fractions.The pre-plan and intraoperative dosimetric parameters were compared, including the minimum prescription doses delivered to 90% and 100% of target volume( D90, D100)and the mean percentage of volume receiving 100% of the prescription doses ( V100). Meanwhile, the doses delivered to 2 cm 3 ( D2 cm 3) of organs at risk (bladders, rectums, and colons) were analyzed.The quality parameters of the brachytherapy were studied, including conformity index (CI), homogeneity index (HI), and external index (EI) of the target volume.Perioperative complications were also observed. Results:A total of 194 treatments were included.During the treatment, 5-13 (median 6) needles were inserted, with a prescription dose of 5-6 Gy per fraction.There were no statistical differences between pre-plan and intraoperative D90, D100, V100, CI, HI, and EI as well as the D2 cm 3 of bladders and colons at risk ( P>0.05). In contrast, for the D2 cm 3 of rectums, the intraoperative dose was slightly higher than the pre-plan dose, showing a statistical difference ( t=-0.335, P=0.027). Conclusions:The 3D-PIT-assisted and CT-guided 192Ir interstitial brachytherapy at a high dose rate is accurate and feasible in the treatment of recurrent gynecologic tumors, meeting the pre-plan dose requirement.

Objective:To design a knowledge-based cervical cancer planning model and apply it to cases of endometrial cancer and rectal cancer in order to explore the generalization of the model.Methods:A total of 179 cases of pelvic regions with different prescribed doses of dual-arc volumetric modulated arc therapy clinical plans were collected, of which 99 cases of cervical cancer clinical plans with a prescribed dose of 50.4 Gy were used as the training set to establish the RapidPlan model, and the remaining clinical plans were divided into 4 validation groups with 20 cases in each group. The clinical plans for cervical cancer and endometrial cancer with a prescription dose of 50.4 Gy were named groups A and B, while the clinical plan for endometrial cancer and rectal cancer with a prescription dose of 45 Gy were named groups C and D. The model was used to redesign the clinical plans in the 4 groups and the automatic plans were obtained. The planning target volume (PTV) and organ at risk (OAR) dosimetry parameters were compared between automatic plans and clinical plans.Results:The conformity index (CI) of the automatic plans in the A, B, C, and D groups were equivalent to that of the clinical plans ( P>0.05). The homogeneity index (HI) and D2% of the automatic plans in groups A, B, and C were all lower than those in clinical plans(HI, Z=-3.248, -3.360, -2.329, P<0.05; D2%, Z=-2.987, -3.397, -2.442, P<0.05). The HI and D2% of the automatic plans in group D were similar those in the clinical plans ( P>0.05). While ensuring the PTV coverage, the average value of OAR dosimetry parameters in all automatic plans groups were lower than that of the clinical plans. Conclusions:The RapidPlan model established by the cervical cancer clinical plans can complete the automatic plan design for endometrial cancer and rectal cancer under different prescription doses, which preliminarily proves the possibility of the generalization of the RapidPlan model.

The main treatment options for cervical cancer include surgery and/or radiotherapy combined with chemotherapy. Radiotherapy consists of external beam radiotherapy and brachytherapy (BT). BT contains high-dose-rate (HDR-BT) and low-dose-rate brachytherapy (LDR-BT). The prognosis of cervical cancer is relatively good. However, some patients experience substantial treatment failures, such as intra-pelvic and/or extra-pelvic recurrences. Recurrent cervical cancer (RCC) has poor prognosis due to lack of effective and safe approach. In 2002, Professor Wang Junjie introduced CT-guidance into the field of LDR-BT, and fully applied 3D printing technology in BT in 2015, which met the requirement of preoperative LDR-BT planning, and significantly improving the precision, quality and efficiency of BT. In 2018, Professor Wang Junjie proposed the concept of stereotactic ablation brachytherapy (SABT). Chinese experts have attempted to treat RCC with BT for nearly two decades and accumulated certain clinical experience. Based on the 3D-printing template (3D-PT) assisted CT-guidance, the standard and consensus of BT for RCC were established, including the indications, dosimetric requirements, technological procedures and radiation protection, etc. At present, there is still a lack of phage Ⅲ clinical and evidence-based medicine for the treatment of RCC with 3D-PT guidance, which requires prospective multi-center, randomized studies to improve the evidence-based level of BT.

OBJECTIVE: To investigate the efficacy of image-guided radioactive 125I seed (IGRIS) implantation for pelvic recurrent cervical cancer (PRCC) after external beam radiotherapy (EBRT), and analyze the influence of clinical and dosimetric factors on efficacy. METHODS: From July 2005 to October 2015, 36 patients with PRCC received IGRIS. We evaluated local progression-free survival (LPFS) and overall survival (OS). RESULTS: The median follow up was 11.5 months. The 1- and 2-year LPFS rate was 34.9% and 20%, respectively. The multivariate analysis indicated recurrence site (central or pelvic wall) (hazard ratio [HR]=0.294; 95% confidence interval [CI]=0.121–0.718), lesion volume (HR=2.898; 95% CI=1.139–7.372), D 90 (HR=0.332; 95% CI=0.130–0.850) were the independent factors affecting LPFS. The 1- and 2-year OS rate was 52.0% and 19.6%, respectively. The multivariate analysis suggested pathological type (HR=9.713; 95% CI=2.136–44.176) and recurrence site (HR=0.358; 95% CI=0.136–0.940) were the independent factors affecting OS. The dosimetric parameters of 33 patients mainly included D 90 (128.5±47.4 Gy), D 100 (50.4±23.7 Gy) and V 100 (86.7%±12.9%). When D 90 ≥105 Gy or D 100 ≥55 Gy or V 100 ≥91%, LPFS was extended significantly, but no significant difference for OS. The 79.2% of 24 patients with local pain were suffering from pain downgraded after radioactive 125I seed implantation. CONCLUSION: IGRIS implantation could be a safe and effective salvage treatment for PRCC after EBRT, which could markedly release the pain. Recurrence site, tumor volume and dose were the main factors affected efficacy. Compared with central recurrence, it was more suitable for patients with pelvic wall recurrent cervical cancer after EBRT.
Brachytherapy ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Radiometry ; Radiotherapy* ; Radiotherapy, Image-Guided ; Recurrence ; Salvage Therapy* ; Tumor Burden ; Uterine Cervical Neoplasms*

Objective To investigate the feasibility of 3D-printing coplanar coordinate template (3D-PCT) for guiding 125I radioactive seed implantation in the treatment of pelvic wall recurrence of cervical cancer on ensuring the accuracy of dose.Methods From Oct 2016 to Dec 2017 in Peking University Third Hospital,totally 10 patients with pelvic wall recurrent cervical cancer after radiotherapy were treated with 125I radioactive seed implantation assisted by 3D-PCT.The median age was 53.5 years old (37-71 years old).KPS score of the cohort were more than 70.All patients had received pelvic radiation therapy previously.The median volume of the lesion was 31.9 cm3 (3.5-58.0 cm3).The prescription dose was 120-180 Gy.The activity of seeds was 0.55-0.67 mCi(1 Ci =3.7 × 1010Bq),while the number of seeds was 12-81 (median 50) on preoperative plan.Radioactive seeds implantation was performed under 3D-PCT guidance according to the preoperative plan.The actual number of implanted seeds was 53 (10-82).Dosimetry parameters of preoperative plan and postoperative plan including D90,D100,V100,V150,V200,external index (EI),conformal index (CI),heterogeneity index (HI),and organat-risk doses of D2 cm3,D1 cm3 and D0.1 cm3 were compared using the nonparametric test.Results The seed number of postoperative plan was more than that of preoperative plan (Z =-2.255,P ＜ 0.05),but all of the dosimetric parameters showed no significant difference (P ＞ 0.05).D2 cm3 and D1 cm3 of rectum for postoperative plan were lower than that of preoperative plan (Z =-2.100,-2.240,P ＜ 0.05),while other dose parameters of normal tisssues showed no statistically significant difference (P ＞ 0.05).Conclusions Assisted by 3D-PCT for 125I radioactive seed implantation in pelvic wall recurrence of cervical cancer,the actual postoperative dose could meet the requirement of the preoperatie plan through the intraoperative optimization of dose.3D-PCT could ensure the precise of delivered dose of 125I radioactive seed implantation.

Objective To evaluate the efficacy and adverse effects of 125I seeds implantation for pelvic recurrence of cervical cancer (PRCC) after radiotherapy.Methods From July 2005 to October 2015,36 PRCC patients (median 44 years) after radiotherapy in Peking University Third Hospital were enrolled in this retrospective study.All patients underwent 125I seeds implantation under ultrasound or CT guidance.Treatment planning was performed before implantation to estimate the number and activity of 125I seeds.The seed numbers ranged from 10-140 (median:62.5),and the activity ranged from 18.5-29.6 (median:25.9) MBq.Postoperatively,the median dose delivered to 90％ gross tumor volume (D90) was 127.3 Gy.Kaplan-Meier method was used to calculate local progress free survival (LPFS) rate and overall survival (OS) rate,and log rank test and Cox regression were used for univariate and multivariate analyses.Results The median follow-up time was 11.5 months.The local control rate was 88.89％(32/36).The 1-year LPFS rate was 34.9％ and the 1-year OS rate was 52.0％.Thirty-one patients died,of which 22 (70.97％,22/31) died from cancer.Univariate analysis showed that the location of recurrence (x2=5.195),volume of lesion (hazard ratio (HR)=1.012) and D90(HR=0.988) were significantly correlated with LPFS (all P＜0.05).Multivariate analysis showed that the location of the recurrence was significantly related with LPFS (HR =0.215,P＜0.05).The 1-year LPFS rates of pelvic wall recurrence and central recurrence were 41.6％ and 26.7％ (x2 =5.195,P＜0.05),and 1-year OS rates were 54.7％ and 49.5％ (x2 =2.535,P＞0.05),respectively.Vaginal fistula,which may be caused by the treatment,occurred in 1 case.No other sever adverse effects were observed.Conclusions 125I seeds implantation is a safe and effective treatment for PRCC after radiotherapy.With the treatment of 125I seeds implantation,patients with pelvic wall recurrence may achieve better therapeutic effects than those with central recurrence.