Search

Objective: To clarify the intervention guidance of return to sports WeChat applet and evaluate the rehabilitation effectiveness after anterior cruciate ligament (ACL) reconstruction., Methods: Between September 2020 and September 2022, 80 patients who met the selection criteria and underwent ACL anatomical single bundle reconstruction were selected as the research objects. According to the double-blind random method, they were divided into the applet group and the regular group, with 40 cases in each group. Patients in the applet group were rehabilitated under the guidance of the return to sports WeChat applet, and the patients were asked to perform the test once a month after operation, including patients' subjective scores [Tegner score, knee injury and osteoarthritis outcome score (KOOS), International Knee Documentation Committee (IKDC) score, American Hospital for Special Surgery (HSS) score], psychological assessment [ACL recovery sports injury scale (ACL-RSI) score], jumping test, balance test, bending angle test. Patients in the regular group were followed up by doctors and nurses regularly by telephone every month. All the patients were reexamined at 3, 6, 9, and 12 months after operation, and the range of motion of the knee joint with 6 degrees of freedom (flexion and extension angle, varus and valgus angle, internal and external rotation angle, anteroposterior displacement, superior and inferior displacement, and internal and external displacement) recorded by Opti&#95;Knee three-dimensional knee joint motion measurement gait analysis system was observed. The anterior tibial translation difference (ATTD) was measured by Ligs knee measuring instrument when a forward thrust of 120 N was applied to the posterior part of the proximal tibia. Tegner score, IKDC score, KOOS score (including KOOS-Pain score, KOOS-Symptoms score, KOOS-Activities of daily living score, KOOS-Sport score, and KOOS-Quality of life score), HSS score, ACL-RSI score, jumping ability, balance ability, patients' satisfaction with the rehabilitation process, and ACL healing grading according to ACL continuity and signal intensity shown by MRI., Results: There were significant differences in various indicators between different time points after operation in the two groups ( P <0.05). At 3 months after operation, except that the ACL-RSI score of the applet group was significantly higher than that of the regular group ( P <0.05), there was no significant difference in the other indicators between the two groups ( P >0.05). At 6 months after operation, the ACL-RSI score, IKDC score, Tegner score, KOOS scores of different items, HSS score, balance and jumping ability of the applet group were significantly higher than those of the regular group ( P <0.05), and there was no significant difference in the other indicators between the two groups ( P >0.05). At 9 months after operation, there was no significant difference in all indicators between the two groups ( P >0.05). At 12 months after operation, 27 cases (67.5%) in the applet group and 21 cases (52.5%) in the regular group returned to sport, with a significant difference of the return to sports incidence between the two groups [ RR (95% CI )=1.50 (1.00, 2.25), P =0.049]. In the applet group, 27 cases were very satisfied with the rehabilitation process, 10 cases were satisfied, 2 cases were basically satisfied, and 1 case was not satisfied, while 19, 13, 5, and 3 cases in the regular group, respectively. The satisfaction degree of the applet group was significantly better than that of the regular group ( P =0.049). MRI examination of the two groups showed that the ACL was continuous without secondary rupture or necrosis. The ACL healing grade of the applet group was 31 cases of grade 1 and 9 cases of grade 2, and that of the regular group was 28 cases of grade 1 and 12 cases of grade 2, there was no significant difference in ACL healing grade between the two groups ( P =0.449)., Conclusion: The application of return to sports WeChat applet in the rehabilitation of patients after ACL reconstruction can significantly reduce the fear of return to sports and improve the rate of return to sports. The return to sports WeChat applet is convenient to operate, with high utilization rate and high patient compliance, which significantly improves the satisfaction.

Background: Despite multiple attempts have been made to develop risk stratification within high-risk neuroblastoma (NB) patients (age of diagnosis ≥ 18 month-old with metastatic NB), the definition of "ultra high-risk NB" is still lack of consensus, and indicators for identifying this subgroup are still unclear. This study aimed to develop a nomogram based on easy-to-obtain blood-derived biofactors for identifying ultra high-risk NB patients with highest risk of death within 3 or 5 years., Methods: One hundred sixty-seven NB patients who treated at Sun Yat-sen University Cancer Center between 2015 and 2023 were recruited and clustered randomly into training and validation cohorts (116 and 51 cases, respectively). Univariate and multivariate Cox analysis were performed in training set to screen independent prognostic indicators for constructing nomogram model of predicting 1-, 3- and 5-year overall survival (OS). The discrimination power of the nomogram in training and validation sets were assessed by concordance index (C-index) and calibration plot. Based on the risk score obtained from nomogram model, the prognostic accuracy of 1-, 3- and 5-year OS rates in training and validation cohorts were further evaluated using the area under receiver operating characteristic (ROC) curves (AUC)., Results: Through univariate and multivariate Cox analysis, independent prognostic indicators, including serum lactate dehydrogenase (LDH) and albumin (ALB), were identified in training set, and used to establish a nomogram model. The model showed good discrimination power with C-index in training cohort being 0.706 (95%CI: 0.633-0.788). According to the cut-point calculated based on the established nomogram, patients with a nomogram score > 34 points could be stratified to ultra high-risk NB subgroup, and this subgroup had poorer OS than those in non-ultra one (p < 0.001). AUC values of ROC curves for 3- and 5-year OS rates in the training set were 0.758 and 0.756, respectively. Moreover, based on the cut-point score (34 points) developed in training set, The model also showed good discrimination power with C-index of 0.773 (95%CI: 0.664-0.897) and powerful prognostic accuracy of AUC for 3- and 5-year OS rates being 0.825 and 0.826, respectively, in validation cohort., Conclusions: We developed a simple-to-use nomogram based on common laboratory indicators to identify the subgroup of ultra high-risk NB before treatment, providing these children even from developing countries or regions access to intensified multimodal treatments earlier and thus improving their long-term outcome., (© 2023. BioMed Central Ltd., part of Springer Nature.)

To investigate the effects of heating time and induction methods on the physicochemical properties and in vitro digestion behavior of emulsion gels, rice bran protein aggregates (RBPAs) were formed by acid-heat induction (90 °C, pH 2.0) and the emulsion gels were further prepared by adding GDL or/and laccase for single/double cross-linked induction. Heating time affected the aggregation and oil/water interfacial adsorption behavior of RBPAs. Suitable heating (1-6 h) was conducive to faster and more adsorption of aggregates at the oil/water interface. While excessive heating (7-10 h) resulted in protein precipitation, which inhibited the adsorption at the oil/water interface. The heating time at 2, 4, 5 and 6 h was thus chosen to prepare the subsequent emulsion gels. Compared with the single cross-linked emulsion gels, the double-cross-linked emulsion gels showed higher water holding capacity (WHC). After simulated gastrointestinal digestion, the single/double cross-linked emulsion gels all exhibited slow-release effect on free fatty acid (FFA). Moreover, the WHC and final FFA release rate of emulsion gels were closely related to the surface hydrophobicity, molecular flexibility, sulfhydryl, disulfide bond and interface behavior of RBPAs. Generally, these findings proved the potential of emulsion gels in designing fat alternatives, which could provide a novel technique for the fabrication of low-fat food., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Long noncoding RNAs (lncRNAs) are involved in tumor formation and development. KCNQ1OT1 regulates the malignant proliferation of retinoblastoma (RB), but the specific mechanism remains to be further investigated., Methods: The KCNQ1OT1, miR-339-3p and KIF23 expression levels in RB were detected by qRT-PCR and western blotting. The cell viability, proliferation, migration ability and caspase-3 activity of RB cells were evaluated by CCK-8, BrdU, transwell and caspase-3 activity analysis. Western blot was used to detect the Bax and Bcl-2 protein expression in RB cells. The binding relationship between KCNQ1OT1, miR-339-3p and KIF23 was detected by luciferase, RIP and RNA pull-down assay., Results: KCNQ1OT1 and KIF23 were up-regulated frequently in RB, and miR-339-3p was down-regulated. Functional studies showed that downregulation of KCNQ1OT1 or KIF23 inhibited the survival and migration of RB cells, and facilitated apoptosis. Interference with miR-339-3p showed the opposite effect. Mechanisms suggested that KCNQ1OT1 exited its oncogenic activity by positively regulating the expression of KIF23 and sponging miR-339-3p., Conclusion: KCNQ1OT1/miR-339-3p/KIF23 may be a new biomarker for the diagnosis and treatment of RB., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To summarize the evaluation methods of return to sports (RTS) after anterior cruciate ligament reconstruction (ACLR) in recent years, in order to provide reference for clinical practice., Methods: The literature related to the RTS after ACLR was searched from CNKI, Wanfang, PubMed, and Foreign Medical Information Resources Retrieval Platform (FMRS) databases. The retrieval range was from 2010 to 2023, and 66 papers were finally included for review. The relevant literature was summarized and analyzed from the aspects of RTS time, objective evaluation indicators, and psychological evaluation., Results: RTS is the common desire of patients with ACL injury and doctors, as well as the initial intention of selecting surgery. A reasonable and perfect evaluation method of RTS can not only help patients recover to preoperative exercise level, but also protect patients from re-injury. At present, the main criterion for clinical judgement of RTS is time. It is basically agreed that RTS after 9 months can reduce the re-injury. In addition to time, it is also necessary to test the lower limb muscle strength, jumping, balance, and other aspects of the patient, comprehensively assess the degree of functional recovery and determine the different time of RTS according to the type of exercise. Psychological assessment plays an important role in RTS and has a good clinical predictive effect., Conclusion: RTS is one of the research hotspots after ACLR. At present, there are many related evaluation methods, which need to be further optimized by more research to build a comprehensive and standardized evaluation system.

Background: Nonerythrocytic spectrin beta 1 (SPTBN1) is an important cytoskeletal protein that involves in normal cell growth and development via regulating TGFβ/Smad signaling pathway, and is aberrantly expressed in various cancer types. But, the exact role of SPTBN1 in pan-cancer is still unclear. This report aimed to display expression patterns and prognostic landscapes of SPTBN1 in human cancers, and further assess its prognostic/therapeutic value and immunological role in kidney renal carcinoma (KIRC) and uveal melanoma (UVM)., Methods: We firstly analyzed expression patterns and prognostic landscapes of SPTBN1 in human cancers using various databases and web-based tools. The relationships between SPTBN1 expression and survival/tumor immunity in KIRC and UVM were further investigated via R packages and TIMER 2.0 platform. The therapeutic roles of SPTBN1 in KIRC and UVM were also explored via R software. Following this, the prognostic value and cancer immunological role of SPTBN1 in KIRC and UVM were validated in our cancer patients and GEO database., Results: Overall, cancer tissue had a lower expression level of SPTBN1 frequently in pan-cancer, compared with those in adjacent nontumor one. SPTBN1 expression often showed a different effect on survival in pan-cancer; upregulation of SPTBN1 was protective to the survival of KIRC individuals, which was contrary from what was found in UVM patients. In KIRC, there were significant negative associations between SPTBN1 expression and pro-tumor immune cell infiltration, including Treg cell, Th2 cell, monocyte and M2-macrophage, and expression of immune modulator genes, such as tumor necrosis factor superfamily member 9 (TNFSF9); while, in UVM, these correlations exhibited opposite patterns. The following survival and expression correlation analysis in our cancer cohorts and GEO database confirmed these previous findings. Moreover, we also found that SPTBN1 was potentially involved in the resistance of immunotherapy in KIRC, and the enhance of anti-cancer targeted treatment in UVM., Conclusions: The current study presented compelling evidence that SPTBN1 might be a novel prognostic and therapy-related biomarker in KIRC and UVM, shedding new light on anti-cancer strategy., (© 2023. The Author(s).)

Objective: To explore the genetic basis for a child with congenital disorder of glycosylation type 1y (CDG-1y) in conjunct with congenital dysplasia of external auditory canal., Methods: Trio-whole exome sequencing (trio-WES) was carried out for the family. Candidate variant was verified by Sanger sequencing. Pathogenicity of the variant was predicted with a variety of bioinformatic tools., Results: The proband, a 10-years-old boy, presented with mental retardation, microcephaly and dysplasia of external auditory canal. Trio-WES revealed that he has harbored a de novo frameshift variant c.302dupC (p.Y102Lfs*2) in exon 4 of SSR4 gene, which was unreported previously (PS2). The variant was absent in major allele frequency databases (PM2) and was predicted to be pathogenic by multiple bioinformatic tools (PP3). UCSF chimera software suggested that the c.302dupC (p.Y102Lfs*2) variant can induce significant alteration to the structure of SSR4 protein, resulting loss of function (PVS1+PM1). Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was classified as pathogenic (PVS1+PS2+PM1+PM2+PP3)., Conclusion: The de novo frameshift variant c.302dupC (p.Y102Lfs*2) of the SSR4 gene probably underlay the child's condition. Above finding has enriched the spectrum of SSR4 mutations and the phenotypic spectrum of CDG-1y.

Objective: To analyze pathogenic variant s of KMT2A gene in a child with Wiedemann-Steiner syndrome (WDSTS) and provide reliable evidences for clinical diagnosis of WDSTS., Methods: Whole-DNAs were extracted from an 9 years-old boy and his parents. Trio-whole exome sequencing (trio-WES) was performed to identify candidate pathogenic variants that can explain the boy's condition and sanger sequencing was conducted to prove it. The impact of detected variants were predicted and validated by bioinformatics tools., Results: A de novo frameshift variant c.10488dupG (p.Leu3498Thrfs*41) in exon 27 of KMT2A gene was detected and this de novo variant (PS2) had not been reported in the world previously. This frameshift variant was absent in major allele frequency databases (PM2) and had been predicted to be pathogenic based on MutationTaster. Through HomoloGene and CD-search system, the 3498 locus (Leu) in KMT2A protein, which was an important histone modifying enzyme that regulated gene expression in early embryonic development and encoded by the KMT2A gene, was predicted as a high conserved locus (PP3), and that replacement of Lue3498 may result in frame-shifts with premature termination in 3539 locus by introducing stop codon, causing deletion of multiple functional domains which all played important roles on histone modifications and recognition (PVS1+PM1). According to the American College of Medical Genetics and Genomics variant classification guideline, the variant c.10488dupG (p.Leu3498Thrfs*41) in KMT2A was classified as pathogenic variant (PVS1+PS2+PM1+PM2+PP3)., Conclusion: The patient's condition may be attributed to the de novo frameshift variant c.10488dupG (p.Leu3498Thrfs*41) in KMT2A gene. This study reported a pathogenic KMT2A variant that had not been reported previously in WDSTS, it expanded the genotypic spectrums of KMT2A variants.

To realize the co-encapsulation of multiple nutraceuticals with different solubilities, Pickering emulsions stabilized by freshly-prepared liposome suspension stabilized emulsion (Fre-Lip-Sus-E) and hydrated lyophilized liposome stabilized emulsion (Hyd-Lyo-Lip-E) were prepared, in comparison with the phospholipid stabilized emulsion (Pho-E). The particle size, zeta-potential, emulsification activity (EAI), emulsion stability (ESI), morphology, environmental stability and rheological properties of the three emulsions were compared. In addition, the in vitro digestive stability and bioaccessibility of three emulsions loaded with vitamin B 2 , vitamin E and β-carotene were assessed. The results showed that the Fre-Lip-Sus-E and Hyd-Lyo-Lip-E were characterized by smaller particles and higher environmental stability than the Pho-E. The slight difference between the Hyd-Lyo-Lip-E and Fre-Lip-Sus-E might be due to the partial destruction of the phospholipid bilayer during the lyophilization of lyophilized liposomes. Rheological analysis demonstrated that all emulsions had high interfacial viscosity and significant shear thinning characteristics of pseudoplastic fluids. Compared with the Pho-E, the liposome-stabilized emulsions demonstrated good environmental stability and antioxidant properties, and the Fre-Lip-Sus-E and Hyd-Lyo-Lip-E exhibited comparable stabilising effects. Higher bioaccessibility of vitamin B 2 and vitamin E in the Fre-Lip-Sus-E and Hyd-Lyo-Lip-E was observed, while β-carotene had higher bioaccessibility in Pho-E. These results provide valuable insight into the potential for designing emulsion co-encapsulation delivery systems using liposomes as stabilizers.

Objective: To report on a patient with congenital muscular dystrophy (CMD) due to a missense variant of LMNA gene and explore its pathogenicity., Methods: The 1-year-and-1-month-old boy has presented with motor development delay and elevation of muscle enzymes for more than half a year. Congenital myopathy was suspected. Following muscle biopsy, HE staining, immunostaining and electron microscopy were conducted to clarify the clinical diagnosis. Meanwhile, DNA was extracted from the child and his parents' peripheral venous blood samples. Trio-whole exome sequencing (trio-WES) was carried out to detect pathogenic variant in the child. Candidate variant was verified by Sanger sequencing and bioinformatic analysis., Results: Both light and electron microscopy showed a large area of necrotic muscle tissues with infiltration of inflammatory cells. Immunohistochemistry revealed a large amount of muscle cells to be diffusely positive for Dysferlin. The patient's motor delays, elevations of muscle enzymes and histopathological results suggested a clinical diagnosis of CMD. A de novo missense c.1072G>A (p.E358K) variant was detected in the LMNA gene by trio-WES. The variant was unreported previously (PS2) and was absent from major allele frequency databases (PM2). It was a loss of function variant and was considered as hotspot variant in the LMNA gene (PM1) as the amino acid (E), located in position 358, was highly conserved, and change of this amino acid was found to cause destruction of the filament domain (AA: 30-386), which may result in serious damage to the intermediate filament protein. Furthermore, c.1072G>A (p. E358K) in LMNA gene was also predicted to be pathogenic based on MutationTaster, PROVEAN and PolyPhen-2 (PP3) analysis. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was classified to be likely pathogenic (PS2+PM1+PM2+PP3)., Conclusion: The child's condition may be attributed to the de novo missense c.1072 G>A (p.E358K) variant of the LMNA gene. Above discovery has expanded the variant spectrum of the LMNA gene.

Objective: To analyze a pathogenic variant of MEFV gene in a family with autosomal dominant-familial Mediterranean fever (AD-FMF)., Methods: A 5-year-old boy presented with recurrent aseptic meningitis and his major symptoms included recurrent fever with headache and vomiting. His family members including his mother, sister and brother also had recurrent fever. A genetic disease was considered. DNAs were extracted from patient and all his family members' blood samples. Whole exome sequencing was performed to identify putative pathogenic variants that can explain this family's condition and Sanger sequencing was conducted. The impact of detected variants were predicted and validated by bioinformatics., Results: A missense variant c.2229C>G (p.Phe743Leu) in MEFV gene was identified in the proband and his family members including his mother, sister and brother. This variant had not been reported in China previously, but the locus of it had already been reported in Arabic patient with AD-FMF (PS1). This variant was absent in major allele frequency databases (PM2) and had been predicted to be pathogenic based on Mutationtaster, PROVEAN and PolyPhen-2. In addition, the change of amino acid, locating in 743 locus of pyrin protein, encoding by MEFV gene, was found to cause SPRY&#95;PRY&#95;TRIM20 and SPRY&#95;superfamily domain destroyed and finally influenced the fuction of pyrin protein. On the other hand, using UCSF chimera software, we find the variant c.2229C>G (p.Phe743Leu) can induce serious influence to the spatial structure of pyrin protein and loss of protein fuction (PP3). According to the ACMG variant classification guideline, the variant c.2229C>G (p.Phe743Leu) in MEFV gene was classified as likely pathogenic (PS1+PM2+PP3)., Conclusion: The condition of this AD-FMF family may be attributed to the missense variant c.2229C>G (p.Phe743Leu) in MEFV gene. The recurrent aseptic meningitis was a very rare manifestation in AD-FMF patients and had not been reported in China previously. The clinical and genetic findings of the present study are helpful for the further understanding of AD-FMF.

Objective: To explore the genetic basis for a child suspected for Say-Barber-Biesecker-Young-Simpson syndrome., Methods: Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing was carried out for the proband. Suspected variants were validated by Sanger sequencing. The impact of the variants was predicted by bioinformatic analysis., Results: The child was found to harbor a de novo missense variant c.2623C>T (p.Asp875Tyr) in exon 13 of the KAT6B gene. The variant was previously unreported, and was not recorded in the major allele frequency database and predicted to be pathogenic based on PolyPhen-2, MutationTaster and PROVEAN analysis. As predicted by UCSF chimera and CASTp software, the variant can severely impact the substrate-binding pocket of histone acetyltransferase, resulting in loss of its enzymatic activity. Based on standards and guidelines by the American College of Medical Genetics and Genomics, the variant was classified to be likely pathogenic (PS2+PM2+PP3)., Conclusion: The child's condition may be attributed to the de novo missense c.2623C>T (p.Asp875Tyr) variant of the KAT6B gene.

This study aimed to improve the nutritional quality of Harbin dry sausages using natural plant-based Jerusalem artichoke powder (JAP) and olive oil as animal fat replacers. Low-fat Harbin dry sausages were manufactured with 2 different formulations containing JAP and olive oil as pork fat replacers. The texture, rheological properties, microstructure, water holding capacity, muscle protein structure, physicochemical indices, microbiological characteristics, and sensory evaluation of the sausages were analyzed. The result showed that Harbin dry sausages with JAP and olive oil were healthier than control sausages based on the lower fat content and improved fatty acid composition. Scanning electron microscopy showed gel network formation in sausages with a high JAP content. Low-field nuclear magnetic resonance illustrated that the water-holding capacity of the modified sausages was improved, suggesting that the replacers enhanced protein gel formation by changes in C-H stretching and bending vibrations, a reduction in α-helixes, and increases in β-sheets and random coils accompanying the exposure of reactive groups and microenvironment of the tertiary structure. Dynamic rheological and texture tests indicated that the replacers improved the elasticity of sausages. The reduction of fat and addition of replacers significantly enhanced lipid oxidative resistance. Overall, JAP and olive oil improved the fatty acid composition, gel structure, lipid oxidative resistance, and sensory quality of the sausages. These results may contribute to the development of healthy meat products to further reduce animal fat., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To explore the molecular basis for a child featuring with Floating-Harbor syndrome., Methods: The 2-year-and-8-month-old child presented with retarded growth and language development. Genomic DNA was extracted from peripheral blood samples from the child and his parents with informed consent and subjected to whole exome sequencing. Suspected variants were verified by Sanger sequencing. Pathogenecity of the variants were predicted by using bioinformatic tools., Results: The child was found to carry a de novo frameshift variant c.7273dupA (p. Thr2425Asnfs*18) in the SRCAP gene. The variant was unreported previously and predicted to be pathogenic by MutationTaster. Analysis using HomoloGene system and MEGA software indicated position 2425 of the SRCAP protein to be highly conserved. Substitution of amino acid (Thr) at this position may cause destruction of three AT-hook domains (Amino acid 2857-2869, 2936-2948 and 3004-3016) and serious damage to the function of SRCAP protein., Conclusion: The patient's condition may be attributed to the de novo frameshift variant c.7273dupA (p. Thr2425Asnfs*18) of the SRCAP gene. Above finding can facilitate diagnosis of Floating-Harbor syndrome among Chinese population.

The possibility of combining the health benefits of kafirin and polyphenols and improving the bioavailability of resveratrol using hollow kafirin nanoparticles via gallic acid crosslinking was investigated. The size, morphology, charge state, loading efficiency, physicochemical stability, and redispersity after lyophilization of hollow resveratrol-loaded kafirin nanoparticles formed via gallic acid crosslinking were characterized and compared with their solid counterparts and those without crosslinking. The nanoparticles formed were anionic spheres with an average diameter of <100 nm when loading amounts of resveratrol were less than 20%. The hollow nanoparticles were homogenous and still achieved stable colloidal dispersion after lyophilization. The hollow nanoparticles crosslinked with gallic acid displayed stability against pancreatin and delayed release in stimulated digestion. The results suggested that hollow kafirin nanoparticles could be a favorable colloidal delivery system for incorporating resveratrol., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To explore the genetic basis for a child featuring X-linked intellectual disability., Methods: The 1-year-and-6-month-old child presented with growth retardation, intellectual disability and bilateral alternating squint. With DNA extracted from the child and his parents' peripheral venous blood samples, whole exome sequencing was carried out to identify potential variants that can explain his condition. Suspected variants were validated by Sanger sequencing. The impact of variants was predicted by bioinformatic tools., Results: The child was found to harbor a de novo nonsense c.3163C>T (p.Arg1055*) variant of the IQSEC2 gene. The variant, unreported previously, was predicted to be pathogenic based on MutationTaster, PROVEAN and SIFT. Analysis using a HomoloGene system suggested Arg1055 in IQSEC2 residues to be highly conserved evolutionarily, and that replacement of Arg1055 may cause destroy of the PH domain (AA 951-1085) and serious damage to the function of IQSEC2 protein. Analysis with UCSF chimera software suggested that the c.3163C>T (p.Arg1055*) variant can induce serious damages to the secondary structures of IQSEC2 protein, causing loss of its function., Conclusion: The patient's condition may be attributed to the de novo nonsense variant c.3163C>T (p.Arg1055*) of the IQSEC2 gene.

Objective: To analyze pathogenic variant of CSNK2A1 gene in a boy with Okur-Chung neurodevelopmental syndrome (OCNS)., Methods: The 8-year-old boy presented with growth retardation, intellectual disability and spells of breath holding. With genomic DNA extracted from peripheral blood samples of the patient and his parents, whole exome sequencing was carried out. Putative pathogenic variants were verified with Sanger sequencing. The nature and impact of detected variants were predicted through bioinformatic analysis., Results: A novel de novo missense variant c.149A>G (p.Tyr50Cys) of the CSNK2A1 gene was identified, which was unreported previously. The variant was predicted to be pathogenic by PolyPhen-2, Mutation Taster and SIFT software. Based on a HomoloGene system, 50 loci within the CK2alpha protein are highly conserved. The change of amino acid (Cys) at position 50 has destroyed the ATP binding loop domain, causing serious damage to its function. As predicted by a Swiss PDB viewer, the variant can significantly alter the spatial structure of CK2alpha, resulting in loss of protein function., Conclusion: The patient's condition may be attributed to the novel de novo missense variant c.149A>G (p.Tyr50Cys) of the CSNK2A1 gene.

Objective: To detect pathogenic variant in a juvenile with severe type Cornelia de Lange syndrome (CdLS)., Methods: A 12-year-old female presented with comprehensive developmental retardation and deformity of lower limbs. Genomic DNA was extracted from peripheral blood sample of the patient. Whole exome sequencing was performed to identify pathogenic variants. Putative variant was verified by Sanger sequencing. The impact of variants was predicted and validated by bioinformatic analysis., Results: A de novo missense variant, c.1507A>G (p. Lys503Glu), was found in the NIPBL gene of the proband. The variant was unreported previously and predicted to be pathogenic by PolyPhen-2, MutationTaster and SIFT. Using HomoloGene system, the 503 loci in the NIPBL protein are highly conserved. The change of amino acid (Glu), locating in 503 locus, was found to cause the Neuromodulin&#95;N superfamily domain destroyed, resulting in severe damage to the function of NIPBL protein., Conclusion: The de novo missense variant c.1507A>G (p. Lys503Glu) of the NIPBL gene probably underlies the disease in this patient.

Objective: To detect pathogenic variant of ARSA gene in an infant with late infantile metachromatic leukodystrophy (MLD)., Methods: The male proband had an onset of walking dysfunction and seizure at 28 months. Arylsulfatase A activity of his peripheral blood leucocytes was 26.9 nmol/mg.17h, and cranial MRI showed wild symmetrical demyelination. With genomic DNA extracted from his peripheral blood sample, all coding exons and splicing sites of the ARSA gene were subjected to Sanger sequencing. PubMed Protein BLAST system was employed to analyze cross-species conservation of the mutant amino acid. Ucsf chimera software was used to analyze the impact of candidate variants on the secondary structure of the protein product. Impact of potential variants was also analyzed with software including PolyPhen-2, Mutation Taster, SIFT and PROVEAN. Whole-exome sequencing was carried out to identify additional variants which may explain the patient's condition., Results: The proband was found to harbor compound heterozygous variants of the ARSA gene [c.467G>A (p.Gly156Asp) and c.960G>A (p.Trp320*)], neither of which was reported previously. As predicted by Ucsf chimera software, the c.960G>A (p.Trp320*) variant may demolish important secondary structures including α-helix, β-strand and coil of the ARSA protein, causing serious damage to its structure and loss of function. The c.467G>A (p.Gly156Asp) variant was predicted to be "probably damaging" by PolyPhen-2, Mutation Taster and SIFT software., Conclusion: The patient's condition may be attributed to the compound heterozygous c.467G>A (p.Gly156Asp) and c.960G>A (p.Trp320*) variants of the ARSA gene. Above results have facilitated genetic counseling and prenatal diagnosis for this family.

Objective: To detect potential mutations of HEXB gene in an infant with Sandhoff disease (SD)., Methods: Genomic DNA was extracted from peripheral blood sample of the infant. All coding exons (exons 1 to 14) and splicing sites of the HEXB gene were subjected to PCR amplification and direct sequencing.PubMed Protein BLAST system was employed to analyze cross-species conservation of the mutant amino acid. PubMed BLAST CD-search was performed to identify functional domains destroyed by thecandidate mutations. Impact of the mutations was analyzed with software including PolyPhen-2, Mutation Taster and SIFT. Whole-exome sequencing was carried out to identify additional mutations., Results: The infant was found to carry compound heterozygous mutations c.1652G>A(p.Cys551Tyr) and c.1389C>G (p.Tyr463*) of the HEXB gene. The c.1389C>G (p.Tyr463*) mutation may lead to destruction of two functional domains in β subunit of the Hex protein. The c.1652G>A(p.Cys551Tyr) mutation, unreported previously,was predicted to be probably damaging by Bioinformatic analysis., Conclusion: Compound heterozygous mutations c.1652G>A(p.Cys551Tyr) and c.1389C>G (p.Tyr463*) in the HEXB gene probably underlie the disease in this patient.

EBV-associated myoid tumor (EBVMT) comprises a specific group of soft tissue tumors with divergent histologic appearances, which typically occur in immunocompromised patients. To the best of our knowledge, there have been no previous reported of EBVMT in patients with normal immunity. EBVMT with lipoblast-like cells (EBVMT-LIC) is an extremely rare variant of EBVMT. Here, a male patient with normal immunity and EBVMT-LIC is presented. Comprehensive EBV latency expression pattern and tumorigenesis molecular analyses are performed to detail the pathologic features of this disease. Our patient was a 14-year-old who suffered from Burkitt's lymphoma 6 years ago and got complete remission for 5 years. At his last visit, he presented with pain and weakness in arms and legs. Subsequent MRI revealed an extramedullary mass at the cervical areas. CT-guided resection was then performed and comprehensive histopathologic examination was conducted. We found a haemangiopericytoma-like pattern with EBER-positive lipoblasts exist in this neoplasm and these features were in accordance with the diagnosis of EBVMT-LIC. Also, the EBV type I latency pattern was observed and the activation of Akt/mTOR pathway and Bcl-2 overexpression were found to be involved in the tumorigenesis of EBVMT-LIC. In conclusion, the results of this study suggest that EBVMT can occur in patients with normal immunity. EBV could achieve a latency type I pattern and may promote the development of EBVMT by activation of Akt/mTOR pathway and Bcl-2 overexpression. The role of chronic latent EBV infection in the development of EBVMT may be more important than previously thought., Competing Interests: None., (IJCEP Copyright © 2019.)

Objective: To study the effects of decabrominated biphenyl ether (BDE-209) exposure on differentiation capacity of human embryonic stem cells., Methods: Human embryonic stem cell line FY-hES-10 cells were exposed to the concentrations of 0 (solvent control), 1, 10 to 100 nmol/L BDE-209 for 96 h and then were differentiated into embryoid bodies (EBs) in vitro. The RNA of EBs derived from FY-hES-10 cells at Day 10 was collected. OCT4,three-layer differentiation-related genes (AFP,SMA and PAX6) and oxidative stress-related genes (HIF1a, HIF2a and SOD1) expression was detected by Q-PCR. The contents of SOD was measured by using kit., Results: Compared with the solvent control group, the expression levels of OCT4, SMA, HIF1a and HIF2a in BDE-209 exposure groups were increased, the expression levels of AFP, PAX6 and SOD1 were decreased, with statistically significant differences (P < 0.05). With the increase of the BDE-209 dose, the expression levels of OCT4 showed an increasing trend while the expression levels of SOD1 and the activity of the SOD showed a decreasing trend., Conclusion: BDE-209 may interfere with differentiation capacity of human embryonic stem cells resulting in developmental toxicity.

Objective: To analyze the correlation between environmental factors and the lipophilic and hydrophilic constituents of Polygalae Radix., Method: The contents of lipophilic constituent were determined by GC-MS and hydrophilic constituents by HPLC. Geographical factors were collected by on-site inspection and climate factors by the local meteorological data. The relationship between the content of the lipophilic and hydrophilic constituents and the factors were analyzed by SPSS 18.0., Result: There was linear relationship between the content of lipophilic constituent and climate factors such as average temperature of July, average temperature of January. There was also linear relationship between hydrophilic constituents and climate factors such as annual average temperature, latitude, annual average rainfall., Conclusion: The main climate factors that affect liposoluble constituent content were average temperature of July, average temperature of January, and the main climate factors that affect hydrophilic constituent content were annual average temperature, latitude, annual average rainfall. The study would contribute to the quality evaluation and suitability of origin of Polygalae Radix.