Objective:To summarize and analyze the clinical characteristics, treatment and prognosis of glycogen storage disease type Ⅱ(GSD Ⅱ) patients admitted to pediatric intensive care units(PICU), and to improve the pediatricians' understanding of children with severe GSD Ⅱ.Methods:Children with GSD Ⅱ admitted to PICU at Beijing Children's Hospital of Capital Medical University between January 2010 and December 2021 were included. Patient's data were collected through the electronic medical record system.After the patient was discharged,telephone follow-ups were conducted regularly for over a year.Results:A total of eight patients with a median age of 30.5 months were included. There were four patients with infantile GSD Ⅱ, whose median age of onset was 5.5 months. There were four patients with late-onset GSD Ⅱ, whose median age of onset was 36.0 months. Eight patients required continuous noninvasive/invasive respiratory support. Three patients with infantile GSD Ⅱ required respiratory support within one month of onset, and three patients with late onset GSD Ⅱ required respiratory support within one year of onset. A total of six patients had cardiac arrest during the course of the disease. One patient was regularly treated with enzyme replacement therapy during hospitalization but his condition did not improve significantly. Three patients were discharged following medical advice,including one patient continuing noninvasive respiratory support after discharge, and two patients requiring onging invasive respiratory support.A total of four children died,including one being an in-hospital death,and three occuring within one year after hospital discharge. A total of 14 genotypes were detected in eight patients, of which three were newly discovered gene mutations.Conclusion:The children with GSD Ⅱ admitted to PICU have severe respiratory dysfunction and need continuous respiratory support during the early stage of the disease. The incidence of cardiopulmonary arrest caused by infection and respiratory muscle weakness is high. It is recommended to closely monitor the lung function and cardiac function of such children, and actively give the prevention and treatment of infectious diseases. Whether enzyme replacement therapy can benefit patients with severe GSD Ⅱ and whether the newly identified mutations correlate with disease severity needs to be further evaluated.

Objective To explore the effects of Atractylenolide-Ⅲ(AT-Ⅲ)on the intestinal immune barrier and kidney of rats with immunoglobulin A nephropathy(IgAN),and develop AT-Ⅲ nanoparticles to optimize its protective efficacy.Methods In this study,the zeolitic imidazolate framework(ZIF-8)loaded with AT-Ⅲ was used to prepare ZIF-8@AT-Ⅲnanoparticles.Morphological and structural characterization of the prepared samples was conducted using transmission electron microscopy and X-ray powder diffraction.48 rats were randomly divided into the normal control group,IgAN group,IgAN+AT-Ⅲ group,and IgAN+ZIF-8@AT-Ⅲ group.IgAN rats were treated with AT-Ⅲ and ZIF-8@AT-Ⅲ,and the detections of hepatic and renal function,glomerular IgA deposition,and intestinal immune barrier function were performed.Results The synthesis of ZIF-8@AT-Ⅲ nanoparticles with elevated drug loading,stability,and pH responsiveness had been successfully accomplished.The average particle size of ZIF-8@AT-Ⅲ nanoparticles was(70.62±1.07)nm,the Zeta potential was(-26.46±1.22)mV,the drug loading capacity was(19.2±1.3％),and the encapsulation efficiency was(64.0％±0.6％).Furthermore,rapid release was observed in a pH 5.5 environment,which was significantly higher than that in the pH 7.4 environment.Both AT-Ⅲ and ZIF-8@AT-Ⅲcould alleviate the destruction of intestinal wall structure and the infiltration of inflammatory cells,significantly downregulate the levels of(DAO)and(D-LA)in the serum.Moreover,there is a noteworthy upregulation in the expression of(ZO-1)and Claudin-5 in intestinal mucosal tissue,thereby substantially improving the immune barrier function and intestinal permeability in IgAN rats.This intervention also inhibited the deposition of IgA in renal glomeruli and alleviated kidney damage,and ZIF-8@AT-Ⅲ was more effective than AT-Ⅲ.Conclusion AT-Ⅲ alleviates IgAN in rats by improving intestinal immune barrier function and permeability.ZIF-8-loaded AT-Ⅲ serves as an excellent drug delivery system,enhancing the therapeutic efficacy of AT-Ⅲ in IgAN treatment.

Tooth number abnormality is one of the most common dental developmental diseases, which includes both tooth agenesis and supernumerary teeth. Tooth development is regulated by numerous developmental signals, such as the well-known Wnt, BMP, FGF, Shh and Eda pathways, which mediate the ongoing complex interactions between epithelium and mesenchyme. Abnormal expression of these crutial signalling during this process may eventually lead to the development of anomalies in tooth number; however, the underlying mechanisms remain elusive. In this review, we summarized the major process of tooth development, the latest progress of mechanism studies and newly reported clinical investigations of tooth number abnormality. In addition, potential treatment approaches for tooth number abnormality based on developmental biology are also discussed. This review not only provides a reference for the diagnosis and treatment of tooth number abnormality in clinical practice but also facilitates the translation of basic research to the clinical application.
Gene Expression Regulation, Developmental ; Odontogenesis ; Signal Transduction ; Tooth/metabolism* ; Humans

In growing children, growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest. Interestingly, one type of fracture injuries within the growth plate achieve amazing self-healing, however, the mechanism is unclear. Using this type of fracture mouse model, we discovered the activation of Hedgehog (Hh) signaling in the injured growth plate, which could activate chondrocytes in growth plate and promote cartilage repair. Primary cilia are the central transduction mediator of Hh signaling. Notably, ciliary Hh-Smo-Gli signaling pathways were enriched in the growth plate during development. Moreover, chondrocytes in resting and proliferating zone were dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the ciliary core gene Ift140 in cartilage disrupted cilia-mediated Hh signaling in growth plate. More importantly, activating ciliary Hh signaling by Smoothened agonist (SAG) significantly accelerated growth plate repair after injury. In sum, primary cilia mediate Hh signaling induced the activation of stem/progenitor chondrocytes and growth plate repair after fracture injury.
Mice ; Animals ; Hedgehog Proteins/genetics* ; Receptors, G-Protein-Coupled/metabolism* ; Cilia/metabolism* ; Cartilage/metabolism* ; Regeneration

With the dramatically development of artificial intelligence (AI), especially the advent of deep learning, now it can be applied to medicine reliably and efficiently. In the field of colorectal surgery, the application of AI has resulted in profound affect. The detection of colon polyp and assessment of invasiveness depth of colorectal cancer were improved by AI-assisted colonoscopy. Based on the routine data from medical imaging, demographic and clinicopathological parameters, AI may provide more accurate predictions about prognosis, surgical complication and outcome, so to help decision making and perioperative management. And the advent of real intelligent operative robot will make automatic operation possible in the future. The application of AI will improve the development of colorectal surgery significantly and make it more precise, effective and intelligent.

Objective: : To explore the clinical efficacy and safety of microvascular decompression (MVD) combined with internal neurolysis (IN) in the treatment of recurrent trigeminal neuralgia (TN) after MVD. Methods: : Sixty-four patients with recurrent TN admitted to the hospital from January 2014 to December 2017 were divided into two groups according to the surgical method. Twenty-nine patients, admitted from January 2014 to December 2015, were treated with MVD alone, whereas 35 admitted from January 2016 to December 2017 were treated with MVD+IN. The postoperative efficacy, complications, and pain recurrence rate of the two groups were analyzed. Results: : The efficacy of the MVD+IN and MVD groups were 88.6% and 86.2%, and the cure rates were 77.1% and 65.5% respectively. There was no statistically significant difference between the two groups (p>0.05). The cure rate (83.3%) of patients in the MVD+IN group, who were only found thickened arachnoid adhesions during the operation that could not be fully released, was significantly higher than that of the MVD group (30.0%) (p<0.05), while the efficacy (91.7% vs. 70%) of the two groups was not statistically different (p>0.05). For patients whose arachnoid adhesions were completely released, there had no significant difference (p>0.05) in the efficacy (87% vs. 94.7%) and recurrence rate (5.0% vs. 11.1%). The incidence of postoperative facial numbness (88.6%) in the MVD+IN group was higher than that in the MVD group (10.3%) (p<0.01). The long-term incidence of facial numbness was not statistically significant (p>0.05). In the 18–36 months follow-up, the recurrence rate of patients in the MVD+IN group (9.7%) and in the MVD group (16%) were not statistically different (p>0.05). Conclusion : A retrospective comparison of patients with recurrent TN showed that both MVD and MVD combined with IN can effectively treat recurrent TN. Compared with MVD alone, MVD combined with IN can effectively improve the pain cure rate of patients with recurrent TN who have only severe arachnoid adhesions. The combination does not increase the incidence of long-term facial numbness and other complications.

Objective: To investigate the efficacy and safety of rapamycin in children with tuberous sclerosis complex (TSC) associated renal disease. Methods: A prospective self-control study was conducted. The clinical data of 92 children diagnosed with tuberous sclerosis complex associated kidney disease at the People′s Liberation Army General Hospital from January 2011 to January 2019 were collected. The long-term rapamycin treatment for all patients initiated at 1 mg/(m²·d), which was gradually adjusted to reach a blood concentration of 5-10 μg/L. The changes of the maximum diameter of renal lesions in children after rapamycin treatment were observed and analyzed with Wilcoxon test. Results: Ninety-two children, including 52 males and 40 females, who met the criteria were analyzed. Sixty patients had only renal angiomyolipoma(RAML), while 24 patients had only multiple renal cysts(MRC), and 8 patients had both lesions. The age of TSC diagnosis was 16.0 (7.0, 42.0) months, and the age of initial treatment with rapamycin was 63.5 (21.0, 103.0) months. The follow-up lasted for 12.0 (4.0, 23.0) months. Sequencing of TSC1 and TSC2 genes was performed in 54 children with TSC, including 3 patients (6%) with mutations in TSC1 gene and 51 patients (94%) with mutations in TSC2 gene. The maximum RAML diameter before treatment was 7.0 (4.0, 9.0) mm. The best effect reached at 3 months of treatment, with the diameter of 4.0 (0,7.0) mm. The maximum diameters at 6 months, 1 year and 1-2 years were 5.0 (0,9.8) mm, 5.0 (1.5, 8.5) mm, 5.5 (3.0, 9.0) mm, respectively, and were significantly different from the baseline (Z=-2.404,-2.350,-2.750,P=0.016,0.019,0.006, respectively). The maximum diameter after 2-3 years, and ≥3 years were 5.0 (3.9,7.0) mm and 6.0 (1.0, 11.0) mm, without significant difference from the baseline (Z=-0.856,-0.102,P=0.393,0.919, respectively).The maximum diameters of MRC after 3 months, 6 months, 1 year,1-2 years, 2-3 years, and ≥3 years were 11.0 (5.0, 14.0) mm,3.0 (0.0,11.0) mm,5.0 (0,21.0) mm,0 (0,14.0) mm,0 (0,10.0) mm, and 0 (0,18.3) mm, respectively, but were not significantly different rom the baseline (7.0 (5.0, 15.7) mm)(Z=-0.944,-1.214,-1.035,-1.896,-1.603,-1.214,P=0.345,0.225,0.301,0.058,0.109,0.225, respectively).Twenty-nine patients (32%) had oral ulcers during the entire treatment period, and no serious adverse reactions were observed. Conclusions Rapamycin could decrease the diameter of TSC-related RAML, but could not inhibit the growth of cysts. It is well tolerated in the treatment of renal diseases associated with tuberous sclerosis complex.

To investigate the efficacy and safety of rapamycin in children with tuberous sclerosis complex (TSC) associated renal disease. Methods A prospective self?control study was conducted. The clinical data of 92 children diagnosed with tuberous sclerosis complex associated kidney disease at the People's Liberation Army General Hospital from January 2011 to January 2019 were collected. The long?term rapamycin treatment for all patients initiated at 1 mg/(m2·d), which was gradually adjusted to reach a blood concentration of 5-10 μg/L. The changes of the maximum diameter of renal lesions in children after rapamycin treatment were observed and analyzed with Wilcoxon test. Results Ninety?two children, including 52 males and 40 females, who met the criteria were analyzed. Sixty patients had only renal angiomyolipoma(RAML), while 24 patients had only multiple renal cysts(MRC), and 8 patients had both lesions. The age of TSC diagnosis was 16.0 (7.0, 42.0) months, and the age of initial treatment with rapamycin was 63.5 (21.0, 103.0) months. The follow?up lasted for 12.0 (4.0, 23.0) months. Sequencing of TSC1 and TSC2 genes was performed in 54 children with TSC, including 3 patients (6%) with mutations in TSC1 gene and 51 patients (94%) with mutations in TSC2 gene. The maximum RAML diameter before treatment was 7.0 (4.0, 9.0) mm. The best effect reached at 3 months of treatment, with the diameter of 4.0 (0, 7.0) mm. The maximum diameters at 6 months, 1 year and 1-2 years were 5.0 (0,9.8) mm, 5.0 (1.5, 8.5) mm, 5.5 (3.0, 9.0) mm, respectively, and were significantly different from the baseline (Z=-2.404,-2.350,-2.750, P=0.016,0.019,0.006, respectively). The maximum diameter after 2-3 years, and≥3 years were 5.0 (3.9,7.0) mm and 6.0 (1.0, 11.0) mm, without significant difference from the baseline (Z=-0.856,-0.102, P=0.393, 0.919, respectively).The maximum diameters of MRC after 3 months, 6 months, 1 year,1-2 years, 2-3 years, and≥3 years were 11.0 (5.0, 14.0) mm,3.0 (0.0,11.0) mm,5.0 (0,21.0) mm,0 (0,14.0) mm,0 (0,10.0) mm, and 0 (0, 18.3) mm, respectively, but were not significantly different rom the baseline (7.0 (5.0, 15.7) mm) (Z=-0.944,-1.214,-1.035,-1.896,-1.603,-1.214, P=0.345, 0.225, 0.301, 0.058, 0.109, 0.225, respectively). Twenty?nine patients (32%) had oral ulcers during the entire treatment period, and no serious adverse reactions were observed. Conclusions Rapamycin could decrease the diameter of TSC?related RAML, but could not inhibit the growth of cysts. It is well tolerated in the treatment of renal diseases associated with tuberous sclerosis complex.

Objective To investigate the effect of cinacalcet combined with low －dose calcitriol in the treatment of patients with secondary hyperparathyroidism of end －stage renal disease.Methods A prospective analysis was conducted in 129 patients with end－stage renal disease and secondary hyperparathyroidism from April 2015 to August 2017 in the Department of Nephrology of Integrative Medicine Hospital of Wenzhou City,Zhejiang Province.The patients were randomly divided into 3 groups:group A received cinacalcet,group B received calcitriol, group C received cinacalcet and low－dose calcitriol for 3 months,respectively.Before and after treatment,the levels of serum phosphorus and serum calcium in the three groups were measured.The levels of parathyroid hormone and the parathyroid hormone clearance rate were measured to find out the therapeutic effect.Results The levels of serum calcium,phosphorus and total parathyroid hormone in group A were significantly lower than those before treatment(t＝3.269,2.263,4.233,all P＜0.05).PTH was significantly decreased,blood calcium and phosphorus significantly in-creased compared with those before treatment,the differences were statistically significant(t＝2.827,2.386,3.342, all P＜0.05).The phosphorus,total parathyroid hormone levels of group C were significantly decreased(t＝3.085, 5.142,all P＜0.05),and no significant change in serum calcium level(t＝0.258,P＞0.05).The total parathyroid hormone level:group B＞group A ＞group C,the whole parathyroid hormone clearance rate:group C ＞group A ＞group B,the differences were statistically significant(t ＝3.642,3.263,all P＜0.05).After treatment,the serum calcium level among the three groups had statistically significant difference,group B＞group C＞group A,the serum phosphorus level among the three groups after treatment had statistically significant difference,group B＞group A ＞group C (t＝3.265,3.332,all P＜0.05).Conclusion The combined use of cinacalcet and low－dose calcitriol in the treatment of secondary hyperparathyroidism in patients with end－stage renal disease can significantly reduce the level of parathyroid hormone and serum phosphorus,and without affecting serum calcium concentration.