Citrin deficiency due to SLC25A13 exon deletion in a Chinese infant: A case report.

INTRODUCTION: Citrin is a calcium-bound aspartate-glutamate carrier protein encoded by the gene SLC25A13, mutations of which can cause citrin deficiency, an autosomal recessive disorder. The manifestations of citrin deficiency include neonatal intrahepatic choledeposits caused by citrin deficiency (NICCD: OMIM#605814), intermediate growth disorders and dyslipidemia caused by citrin deficiency, and citrullinemia type II (OMIM#603471) in adults. NICCD is a classical metabolic disorder that causes cholestasis in newborns. PATIENT CONCERN AND CLINICAL FINDINGS: Here, we present the case of a 2-month-old male patient treated in our hospital on March 20, 2023, due to "postnatal skin xanthochromia and transaminases higher than normal values". Since birth, the child's skin had yellowed all over the body, and his condition did not improve after multiple medical treatments. DIAGNOSIS/INTERVENTION/OUTCOMES: The child underwent full exome gene testing at the age of 2 months and 13 days, and the results indicated heterozygous deletion of exon 3 of the SLC25A13 gene, while genetic testing of the parents revealed no gene mutations. The variant was preliminarily judged as being pathogenic according to the ACMG guidelines, and the patient was diagnosed with "citrin deficiency". Skin yellowing eventually subsided, and liver function returned to normal without special treatment. CONCLUSIONS: Here, we report a rare case of citrin deficiency caused by a heterozygous deletion of the SLC25A13 gene. This case increases the clinical phenotypic profile of NICCD, suggesting that clinicians must be vigilant regarding such genetic metabolic diseases in the clinic for early diagnosis and treatment. NICCD should always be considered in the differential diagnosis of neonatal cholestasis.

Multifunctional Phase-Transition Nanoparticles for Effective Targeted Sonodynamic-Gene Therapy Against Thyroid Papillary Carcinoma.

Introduction: In order to diagnose and treat papillary thyroid carcinoma (PTC) accurately, phase-transition nanoparticles, P@IP-miRNA (PFP@IR780/PLGA-bPEI-miRNA338-3p), was engineered. The nanoparticles (NPs) can target the tumor cells, realize the multimodal imaging, and provide sonodynamic-gene therapy for PTC. Methods: P@IP-miRNA NPs were synthesized through double emulsification method, and miRNA338-3p was attached to the surface of the NPs by electrostatic adsorption. The characterization of NPs was detected to screen out qualified nanoparticles. In vitro, laser confocal microscopy and flow cytometry were used to detect the targeting and subcellular localization of NPs. Western blot, qRT-PCR, and immunofluorescence were used to detect the ability to transfect miRNA. CCK8 kit, laser confocal microscopy and flow cytometry were used to detect the inhibition on TPC-1 cells. In vivo experiments were performed based on tumor-bearing nude mice. The efficacy of combined treatment by NPs was comprehensively evaluated, and the multimodal imaging ability of NPs in vivo and in vitro was detected. Results: P@IP-miRNA NPs were successfully synthesized which have spherical shape, uniform size, good dispersion and positive potential. The encapsulation rate of IR780 was (82.58±3.92) %, the drug loading rate was (6.60±0.32) %, and the adsorption capacity of miRNA338-3p was 41.78 µg/mg. NPs have excellent tumor targeting ability, miRNA transfection ability, ROS production ability and multimodal imaging ability in vivo and in vitro. The antitumor effect of combined treatment group was the best, and the efficacy was better than that of single factor treatment group, and the difference was statistically significant. Conclusion: P@IP-miRNA NPs can realize multimodal imaging and sonodynamic-gene therapy, providing a new idea for accurate diagnosis and treatment of PTC.

Two novel mutations in the VPS33B gene in a Chinese patient with arthrogryposis, renal dysfunction and cholestasis syndrome 1: A case report.

BACKGROUND: The VPS33B (OMIM: 608552) gene is located on chromosome 15q26.1. We found a female infant with autosomal recessive arthrogryposis, renal dysfunction and cholestasis syndrome 1 (ARCS1) caused by mutation in VPS33B. The child was diagnosed with ARCS1 (OMIM: 208085) after the whole exome sequencing revealed two heterozygous mutations (c.96+1G>C, c.242delT) in the VPS33B gene. CASE SUMMARY: We report a Chinese female infant with neonatal cholestasis disorder, who was eventually diagnosed with ARCS1 by genetic analysis. Genetic testing revealed two new mutations (c.96+1G>C and c.242delT) in VPS33B, which is the causal gene. The patient was compound heterozygous, and her parents were both heterozygous. CONCLUSION: This study extends the mutational spectrum of the VPS33B gene to provide a molecular basis for the etiological diagnosis of ARCS1 and for genetic counseling of the family.

A photothermal-hypoxia sequentially activatable phase-change nanoagent for mitochondria-targeting tumor synergistic therapy.

To enhance the specificity and efficiency of anti-tumor therapies, we have designed a multifunctional nanoparticle platform for photochemotherapy using fluorescence (FL) and photoacoustic (PA) imaging guidance. Nanoparticles (NPs) composed of a eutectic mixture of natural fatty acids that undergo a solid-liquid phase transition at 39 °C were used to encapsulate materials for the rapid and uniform release of the hypoxia-activated prodrug tirapazamine (TPZ) and the photosensitizer IR780, which targets the mitochondria of tumor cells and can be used to induce hypoxic cell death via photodynamic therapy and photothermal therapy. In vitro, the NPs containing TPZ and IR7890 exhibited appreciable cell uptake and triggered drug release when irradiated with a NIR laser. In vivo, photochemotherapy of the NPs achieved the best anti-tumor efficacy under PA and FL imaging guidance and monitoring. By combining IR780 mitochondria-targeting phototherapy with TPZ, we observed improved anti-tumor effectiveness and this has the potential to reduce the side effects of traditional chemotherapy. Herein, we demonstrate a new intracellular photochemotherapy nanosystem that co-encapsulates photosensitizers and hypoxia-activated drugs to enhance the overall anti-tumor effect precisely and efficiently.

Comparison of ultrasound-guided thermal ablation and conventional thyroidectomy for benign thyroid nodules: a systematic review and meta-analysis.

Objective: To compare the safety and efficacy of ultrasound-guided thermal ablation and conventional thyroidectomy for benign thyroid nodules (TNs) by performing a systematic review and meta-analysis.Methods: We searched PubMed, Embase, Web of Science and Cochrane Library databases for clinical trials from the date of their inception to 1 April 2019. Two investigators independently examined the trials to select qualified studies, extracted relevant information and assessed the risk of bias according to the Cochrane Collaboration checklist (Oxford, UK). The primary study outcomes were safety (hoarseness, hypothyroidism and postoperative pain) and efficacy (symptom improvement, postoperative cosmetic effects and hospitalization time). This study is registered with PROSPERO (CRD42019125643).Results: Seven studies involving 1289 patients were included. The results demonstrated that the incidences of hoarseness [odds ratio (OR) 0.33, 95% confidence interval (95% CI) (0.14, 0.79)], hypothyroidism [risk difference (RD) -0.31, 95% CI (-0.34, -0.28)] and postoperative pain [OR 0.35, 95% CI (0.25, 0.49)] were lower, and the hospitalization time was shorter [standard mean difference (SMD) -4.01, 95% CI (-4.22, -3.81)], in the thermal ablation group than in the conventional thyroidectomy group, and postoperative cosmetic effects were better [relative risk (RR) ratio 1.12, 95% CI (1.01, 1.24)] (p < 0.05). For symptom improvement, the difference was not statistically significant.Conclusions: This study shows that for benign TNs, ultrasound-guided thermal ablation may have potential advantages in terms of safety, cosmetic effects and shorter hospitalization time compared with conventional thyroidectomy, while symptom improvement is the same.

A sequential targeting nanoplatform for anaplastic thyroid carcinoma theranostics.

Effective accumulation of nanoparticles (NPs) in tumor regions is one of the major motivations in nanotechnology research and that the establishment of an efficient targeting nanoplatform for the treatment of malignant tumors is urgently needed for theranostic applications. In this study, we engineered multifunctional sequential targeting NPs for achieving synergistic antiangiogenic photothermal therapy (PTT) and multimodal imaging-guided diagnosis for anaplastic thyroid carcinoma (ATC) theranostics. Antibody bevacizumab with an affinity towards vascular endothelial growth factor (VEGF) on the tumor cell surface was conjugated onto the surface of polymer NPs for VEGF targeting and antiangiogenic therapy. Encapsulated IR825 was employed as a photothermal agent (PTA) with a mitochondrial targeting capability, which further cascades NPs into mitochondria to enhance hyperthermic efficiency in the ablation of tumor cells. Importantly, the combination of bevacizumab and IR825 in a single nanosystem achieved desirable accumulations of NPs and that sequential targeted PTT combined with antiangiogenesis significantly promoted the therapeutic efficiency in eradicating tumors by near-infrared (NIR) laser irradiation. Furthermore, these NPs are extraordinary contrast agents for photoacoustic, ultrasound and fluorescence imaging applications, providing multimodal imaging capabilities for therapeutic monitoring and a precise diagnosis. Therefore, this multifunctional nanoplatform provides a promising theranostic strategy for extremely malignant ATC. STATEMENT OF SIGNIFICANCE: Anaplastic thyroid carcinoma (ATC), with extremely aggressive behavior, lacks a satisfactory therapeutic method and a comprehensive early diagnostic strategy. Herein, we successfully synthesized a sequential targeting nanoplatform (IR825@Bev-PLGA-PFP NPs) with theranostic function, which specifically binds to VEGF on the tumor cell surface and further cascades into mitochondria to achieve effective accumulation of NPs in the tumor regions. As a result, it solves the urgent demand for ATC detection and therapy. By breaking the limitation of traditional target, such as low efficacy and frequent recurrence as the results of low accumulation, sequential targeting combined with synergistic antiangiogenic PTT completely eradicates tumors without any residual tissue and side effect. Therefore, this strategy paves a solid way for further investigation in the theranostic progressing of ATC.

Three-dimensional anatomic analysis of retrosigmoid approach with thin-section computed tomographic image.

OBJECTIVE: This study aimed to locate and measure the distances between important structures of the retrosigmoid approach using both three-dimensional reconstruction technique and volume-rendering technique. METHODS: We scanned skulls of 120 volunteers to get the final result with thin-section computed tomographic image. RESULTS: The distance of AC was measured as 39.46 (4.22) mm (range, 15.80-50.80 mm; 95% confidence interval (CI), 38.69-40.22 mm). The diameter of internal auditory pore was measured as 5.39 (0.77) mm (range, 3.40-8.20 mm; 95% CI, 5.25-5.53 mm). The distance of AB was measured as 41.10 (4.22) mm (range, 34.90-51.30 mm; 95% CI, 39.43-42.77 mm). The distance of BC was measured as 5.93 (1.31) mm (range, 4.10-7.50 mm; 95% CI, 5.70-6.17 mm). The vertical distance was measured as 2.33 (0.26) mm (range, 1.87-2.80 mm; 95% CI, 2.23-2.42 mm). CONCLUSIONS: These abovementioned results can help to locate these structures to help in minimizing surgical trauma to the nerve and blood vessels.