Non-muscle myosin heavy chain 9-related disease (MYH9-RD) is an autosomal dominant disease caused by the mutations of the MYH9 gene encoding the non-muscle mysoin heavy chain ⅡA and leads to abnormal accumulation of myosin in cells. These further causes functional disorders of the blood, eye, ear, kidney, and liver systems. MYH9-RD displays heterogeneous kidney involvement and outcomes, but doctors still lack understandings of the mechanism and treatment strategies, owing to difficulty of conducting renal biopsies. Here, we report a case of MYH9-RD with tail fragments heterozygous mutation, which renal pathology is presented as glomerular minor lesion. Moreover, we reviewed related relevant to strengthen clinical diagnosis and understanding of MYH9-RD.

Objective This study aims to elucidate the structure-activity domain of LBP1C-2 targeting Kvβ.2 through an exploration of the structure-activity relationship.This study may also provide the scientific basis for the development of drug candidate with anti-early-onset dementia activity.Methods After partial acid hydrolysis,various structural fragments were obtained and subjected to monosaccharide composition and molecular weight analysis.Potential target proteins were selected using a protein chip,followed by validation of the targeting specificity of each structural fragment using surface plasmon resonance(SPR)technology.Results Through high-throughput screening using the HuProtTM human protein array,potential target protein Kvβ.2 was identified for LBP1C-2.SPR experiments revealed a strong binding affinity between LBP1C-2 and Kvβ.2 protein,with a binding constant(KD)of 1.9×10-7 M.The various structural fragments of LBP1C-2 exhibited different binding strengths with the target protein Kvβ.2.Among them,the segment LBP1C-2-1I(18.1 k Da)with a molar ratio of rhamose to galecturonic acid of 1:1 showed a binding strength to Kvβ.2 similar to that of the polysaccharide LBP1C-2,with a KD of approximately 3.3×10-7 M.Structural analysis indicates that the structure of LBP1C-2-1I contains 1,2-linked Rha and 1,4-linked GalA which are alternatively linked.The acid-hydrolyzed extracellular portion corresponding to this segment,LBP1C-2-1O may also bind to Kvβ.2.However,compared to other segments,it demonstrated a higher tendency to dissociate from the protein.Knockdown of the KCNAB2 gene(Kvβ.2)in BV2 cells inhibited the uptake of Aβ in BV2 cells,suggesting that protein Kvβ.2 may be a functional protein in the development of Alzheimer's disease.Conclusion LBP1C-2-1I has been identified as the primary active domain through which LBP1C-2 targets Kvβ.2.This suggests that the active domain of LBP1C-2 predominantly resides on the main chain rather than the side chain.This study provides crucial insights for a deeper understanding of the anti-early-onset dementia activity of LBP1C-2 and lays an experimental foundation for the design and development of targeted drugs for anti-early-onset dementia based on Lycium barbarum polysaccharides.

To date, there is no report on the genetic diversity of ticks in these regions. A total of 370 representative ticks from the south and east regions of Kazakhstan (SERK) and Xinjiang Uygur Autonomous Region (XUAR) were selected for molecular comparison. A fragment of the mitochondrial cytochrome c oxidase subunit I (cox1) gene, ranging from 631 bp to 889 bp, was used to analyze genetic diversity among these ticks. Phylogenetic analyses indicated 7 tick species including Hyalomma asiaticum, Hyalomma detritum, Hyalomma anatolicum, Dermacentor marginatus, Rhipicephalus sanguineus, Rhipicephalus turanicus and Haemaphysalis erinacei from the SERK clustered together with conspecific ticks from the XUAR. The network diagram of haplotypes showed that i) Hy. asiaticum from Almaty and Kyzylorda Oblasts together with that from Yuli County of XUAR constituted haplogroup H-2, and the lineage from Chimkent City of South Kazakhstan was newly evolved; and ii) the R. turanicus ticks sampled in Israel, Almaty, South Kazakhstan, Usu City, Ulugqat and Baicheng Counties of XUAR were derivated from an old lineage in Alataw City of XUAR. These findings indicate that: i) Hy. asiaticum, R. turanicus and Ha. erinacei shared genetic similarities between the SERK and XUAR; and ii) Hy. marginatum and D. reticulatus show differences in their evolution.

FLASH radiotherapy (FLASH-RT) is a treatment modality that delivers ultra-high dose rate and ultra-fast radiation for cancer treatment. Compared to conventional dose rate radiotherapy, FLASH-RT can yield similar efficacy for tumors and achieve normal tissue protection, translating to an increased therapeutic window. Due to this unique feature, FLASH-RT is attracting increasing attention from the radiotherapy community, both academia and industry. Due to its unique Bragg peak as well as intrinsic high dose rate, application of FLASH has more value and profound significance in proton therapy while achieving highly conformal dose deposition simultaneously. This article reviews research progress on FLASH-RT, relevant cell and animal studies, experimental conditions and results. Moreover, this article also investigates the potential biological mechanisms, technical challenges for implementation and potential clinical applications of FLASH-RT.

Objective:To explore the relationship between semi-quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and long-term prognosis of locally advanced nasopharyngeal carcinoma, and to find prognostic indicators from non-invasive images of locally advanced nasopharyngeal carcinoma.Methods:Data were collected from January 2011 to January 2012 via a prospective clinical trial with locally advanced nasopharyngeal carcinoma. Clinical information was from 71 patients who completed the treatment plan with long-term follow-ups and UICC 2010 stage Ⅲ, Ⅳ A, Ⅳ B. The patients received three cycles of Taxotere-Platinol-Fluorouracil (TPF) regimen chrono-chemotherapy, followed by two cycles of concurrent paclitaxel chemotherapy with intensity-modulated radiotherapy (IMRT). DCE-MRI examination was performed before induction chemotherapy to obtain DCE-MRI related semi-quantitative parameters. Correlation analysis was conducted between DCE-MRI related semi-quantitative parameters and short-term efficacy of nasopharyngeal lesions after concurrent radiotherapy and chemotherapy. Results:Of all 77 patients, 71 completed treatment and were followed up from 9 to 86 months, with a median follow-up of 77 months, with 80.2% and 67.6% in 3- and 5-year OS, 73.2% and 60.5% in 3- and 5-year PFS, respectively. Evaluation of short-term efficacy of nasopharyngeal lesions after concurrent chemoradiotherapy: the difference in tissue arrival time of contrast agent between complete response (CR) group and partial response (PR) group was statistically significant ( t=0.537, P<0.05). Univariate survival analysis found that OS ( χ2=3.982, P<0.05) and PFS ( χ2=4.019, P<0.05) in the group with short contrast arrival time were significantly higher than those in the group with long contrast arrival time. OS ( χ2=7.593, P<0.05) and PFS ( χ2=5.624, P<0.05) of patients aged over 45 years were significantly lower than those aged less than 45 years. Cox multivariate regression model showed that advanced clinical stage (stage Ⅳ A, Ⅳ B) ( P=0.048) and age≥45 years ( P=0.031) were independent prognostic factors of OS in patients with nasopharyngeal carcinoma. Long arrival time of contrast agent ( P=0.018), age≥45 years ( P=0.004), advanced N(2-3) stage ( P=0.032) and enhancement peak<3 000 ( P=0.005) were independent prognostic factors of PFS in patients with nasopharyngeal carcinoma. Conclusions:The arrival time of the contrast agent in DCE-MRI may be a reliable prognostic factor for locally advanced nasopharyngeal carcinoma.

Objective:To understand the clinical phenotype and spectrum of ATP7B gene mutation in children with Wilson’s disease (WD). Methods:A total of 55 cases diagnosed with WD at the Children's Hospital Affiliated to Nanjing Medical University from June 2012 to June 2018 were taken as the research subject. ATP7B gene point mutation was detected by direct sequencing after PCR amplification. Heterozygous mutation in children was discovered by sequencing. Furthermore, the long segment mutation of exon was analyzed by multiplex ligation-dependent probe amplification (MLPA). Results:All 55 WD children had varying degree of liver damage symptoms. Among them, 2 cases had combined neurological symptoms. The positive rates of K-F ring (21%), 24-hour urine copper (97.7%), and ceruloplasmin were all abnormal. The results of ATP7B gene had identified 8 homozygous, 41 compound heterozygous and 6 heterozygous in 55 cases. Direct sequencing method had detected ten cases of ATP7B heterozygotes. In addition, MLPA analysis showed that other allele in four cases had a deletion of the ATP7B gene exon. In all cases, 35 different ATP7B gene mutations were detected, including 23 missense mutations, 3 frameshift mutations, 4 nonsense mutations, 3 exon deletions and 2 splicing changes. The most common allele mutation was c.2333G > T/p.R778L in exon 8, with an allele frequency of 36.54%, followed by c.2975C > T/p.P992L in exon 13, with an allele frequency of 14.42%. Conclusion:ATP7B gene c.2333G > T/p.R778L and c.2975C > T/p.P992L mutations are the most common mutations in children with WD in China. WD patients report shows that there are three long deletion mutations in the exon of the ATP7B gene. For WD children whose DNA sequencing is heterozygous ATP7B gene, it is suggested to further use MLPA method to detect deletion mutations of exons.

Objective To summarize the prenatal diagnosis and genetic counseling of Turner syndrome fetuses with 46,X,i(X)(q10).Methods Two gravidas admitted to the Obstetrics and Gynecology Hospital of Dalian were enrolled in this study.One gravida,who was admitted in October 2016,was classified as high risk of Down syndrome based on prenatal serologic screening and systematic ultrasonography,which found remarkably shorter humeri and femora than fetus of the same gestations.The other was suggested to be monosomy X after non-invasive prenatal testing and admitted in November 2017.Fluorescence in situ hybridization (FISH) and karyotyping were performed for prenatal diagnosis.Peripheral blood karyotyping was also offered to the two women and their partners.Results FISH test for amniotic fluid did not find numerical abnormality in 13,18,21,and sex chromosomes in these two fetuses.Karyotype analysis showed that the two fetuses were both 46,X,i(X) (q10),while their parents were normal.Both cases were terminated after genetic counseling.Conclusions Prenatal serological screening,systematic ultrasonography and non-invasive prenatal testing may help to identify Turner syndrome fetus of 46,X,i(X) (q10).Timely and accurate prenatal diagnosis may prevent the affected fetus from being born.

Objective To investigate the clinical manifestations and gene mutation of a pedigree with retinal lattice degeneration and granular corneal dystrophy (GCD) type 2.Methods Ten members in 3 generations of a pedigree with retinal lattice degeneration and GCD2 were included in the study, including 6 patients (3 males and 3 females) and 4 healthy family members. All members underwent visual acuity, slit lamp microscope, three-mirror lens, fundus color photography, optical coherence tomography, and corneal endothelial cells counting. Genomic DNA was extracted from peripheral venous blood (2 ml) from all the subjects and their spouses, who had no related inherited diseases. The next generation sequencing method was used to detect the mutation sites of transforming growth factor β (TGFBI), and all results underwent Sanger verification.Results Among the 12 eyes of 6 patients, the visual acuity was FC/20 cm-1.0. In the superficial central corneal stroma, snowflake-like deposits were observed in three cases (6 eyes), and a small amount of granular deposits were observed in three cases (6 eyes). Corneal endothelial cell counts were normal. Retinal lattice degeneration were observed in 3 cases, 6 eyes (including 3 cases of rhegmatogenous retinal detachment in 4 eyes); retinal thinning without obvious lattice degeneration in 4 eyes of 2 patients. Nystagmus in 1 patient and fundus examination showed no significant abnormalities. DNA sequencing results showed that the proband and 4 patients had missense mutation of TGFBI gene in exon 4 c.371G> A, the mutation site corresponding to the amino acid change encoded by TGFBI gene No. 124 Amino acids, from arginine to histidine (p.R124H). Patients with this mutation have varying degrees of clinical phenotype.Conclusions The mutation of c.701G> A (p.R124H) in TGFBI gene is the causative gene of GCD in this pedigree. The patients with this mutation have different clinical phenotypes.

Objective To observe the surgical outcome of the modified transconjunctival technique for minimal segmental buckling on rhegmatogenous retinal detachment (RRD).Methods This is a retrospective case series.Seventy-six patients (78 eyes) with uncomplicated RRD who underwent the modified transconjunctival technique for minimal segmental buckling were enrolled in this study.There were 41 male (42 eyes) and 35 female (36 eyes).The average age was (33.9± 15.6) years.Best corrected vision acuity (BCVA),fundus examination with three-mirrors lens,ocular B ultrasound,optical coherence tomography (OCT) were performed in all patients.BCVA was examined through Standard logarithmic visual acuity chart and transferred to logMAR vision for statistical analysis.The logMAR BCVA was 0.88± 0.88.The technique was successfully performed in all 78 eyes.After transconjunctival location of the retinal break was made,a 5 to 6 mm radial conjunctival incision was performed corresponding to the retinal break without cutting the limbal conjunctiva-Tenon's capsule.After cryopexy,a minimal explant was fixed with one to two sutures through the conjunctival opening,expanded by a pediatric speculum.BCVA,intraocular pressure,tear film stability,conjunctival recovery and retinal reattachment were collected 1 week,1 month,3 months,6 months after surgery.Results One week after surgery,retinal reattachments were achieved in 77 of 78 (98.7％) eyes and 1 eye (1.3％) received vitrectomy.Compared before surgery,the logMAR BCVA improved to 0.44± 0.41,with significant difference (t=3.092,P＜0.01).Conjunctival incision tear occurred in 1 eye.Subretinal hemorrhage occurred in 5 eyes during subretinal fluid drainage procedure.Subretinal hemorrhage occurred in 5 eyes during subretinal fluid drainage procedure.Hemorrhage was absorbed in 2 of the 5 eyes at 3 months after surgery and absorbed in all 5 eyes at 6 months after surgery.Subretinal fluid occurred in 10 eyes at 1 week after surgery and be absorbed completely at 6 months after surgery.Tear film stability improved to preoperative lever at 1 week after surgery.Less change in corneal and conjunctival sensitivity was observed in all eyes.No other surgical complications were observed within the follow-up period,such as scleral perforation,explant extrusion,diplopia or infection.Conclusions The modified transconjunctival technique for minimal segmental buckling minimizes the damage to conjunctiva without reducing the retinal reattachment rate.It can effectively treat uncomplicated RRD with preserving an intact limbal conjunctiva and rapid tear film stability recovery.

Objective: To investigate the association between the internal exposure levels of phthalic acid esters (PAEs) and executive function (EF) of preschool children. Methods: Between October 2008 and October 2010, pregnant women who accepted pregnancy health care services in four municipal medical and health institutions in Ma'anshan city, Anhui Province, were recruited as study objects. A total of 5 084 pregnant women and 4 669 singleton live births were enrolled in this cohort. The follow-up study was conducted from April 2014 to April 2015. A total of 3 725 data-completed preschool children aged 3 to 6 years older entered in this study. The method of analysis seven metabolites of phthalates in urine was high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and divided objects into low (P₀-P₂₄), medium (P₂₅-P₇₄) and high (P₇₅-P₁₀₀) groups according to their exposure concentrations. To investigate the executive function of preschool children, we used the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Univariate and multivariate statistical method was used to analyze the etiology association between the phthalate metabolites levels and preschool children's executive function. Results: In this study, 53.6% (1 997/3 725) of preschoolers were boys, children's age was (51.5±5.6) months. The detection rates of seven phthalate esters were: mono-n-methyl phthalate (MMP) was 99.89% (3 721/3 725); mono-ethyl phthalate (MEP) was 99.97% (3 724/3 725); mono-benzyl phthalate (MBzP) was 69.10% (2 574/3 725); mono-butyl phthalate (MBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono- (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were 100.00% and mono-ethylhexyl phthalate (MEHP) was 99.95% (3 723/3 725). The median concentrations of the seven phthalate metabolites were: 17.71, 15.36, 0.07, 155.24, 10.73, 14.67, 3.59 µg/L, respectively. The median concentrations corrected by urinary creatinine were 29.65, 26.65, 0.12, 257.73, 17.94, 24.80, 6.27 µg/g Cr, respectively. The P₂₅ and P₇5 concentration of the total PAEs metabolites corrected by urinary creatinine were 1.20 µmol/g Cr and 3.04 µmol/g Cr. After adjusted the relevant demographic information: children sex, children age in month, maternal age, parental education levels, household exposure to secondhand smoke and whether the child is the only child as confounds, multivariate logistic regression model showed that the risk of inhibitory self-control index (ISCI) dysplasia in MEHHP high concentration group and MEOHP high concentration group were 1.71 and 1.54 times (OR=1.71, 95% CI: 1.11-2.62; OR=1.54, 95% CI: 1.01-2.34) than in low concentration group. The risk of ISCI dysplasia in total PAEs metabolites high concentration group was 1.55 times (OR=1.55, 95% CI: 1.00-2.38) than in low concentration group. Conclusion Phthalates exposure may damage the executive function of preschool children.