[Analysis of the efficacy of left subclavian artery laser in situ fenestration combined with hybrid arch debranching surgery for aortic arch reconstruction in patients with Stanford type A aortic dissection].

Objective: To observe the short-and mid-term efficacy of left subclavian artery(LSA) laser in situ fenestration combined with arch debranching surgery for aortic arch reconstruction in patients with Stanford type A aortic dissection aged 60 years and above. Methods: This is a retrospective cohort study. A total of 41 Stanford type A aortic dissection patients aged 60 years and above who received combined surgery in Department of Endovascular Surgery, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were retrospectively analyzed. There were 25 males and 16 females, aged (67.3±5.9)years(range: 60 to 75 years). Among them, 19 patients underwent LSA laser in situ fenestration combined with arch debranching surgery(combined surgery group) and 22 patients underwent hybrid aortic arch debranching surgery(non-combined surgery group). Independent sample t test, χ2 test and Fisher exact probability method were used to compare the clinical characteristics of the two groups. Kaplan-Meier method was used for survival analysis, and the 5-year survival rate of the two groups was compared by Log-rank test. Results: Body mass index in the combined operation group was significantly higher than that in the non-combined operation group ((27.1±1.6)kg/m2 vs.(26.9±1.9)kg/m2; t=2.766,P=0.006), and the difference was statistically significant. There was no statistical significance in the comparison of other general data (all P>0.05). The operation time ((320.9±21.7) minutes vs. (326.7±22.5)minutes; t=14.838, P<0.01)) and LSA reconstruction time ((32.6±3.2)minutes vs. (44.7±6.0)minutes; t=46.913, P<0.01) in the combined operation group were significantly shortened, and the difference was statistically significant. The rate of LSA reconstruction in the combined operation group (100% vs. 72.7%; P=0.023) was significantly higher than that in the non-combined operation group, and the difference was statistically significant. There were no significant differences in the incidence of pulmonary infection, unplanned second operation, continuous renal replacement therapy, neurological complications and the in-hospital mortality between the two groups. Compared with the non-combined surgery group, the total complication rate related to LSA reconstruction was significantly lower in the combined surgery group (0 vs. 27.3%; P=0.023). Kaplan-Meier survival analysis showed that there was no difference in 5-year survival rate between the combined operation group and the non-combined operation group (84.2% vs 77.3%; χ2=0.310, P=0.578). Conclusion: Laser in situ fenestration of the LSA combined with arch debranching surgery to reconstruct the aortic arch can significantly shorten the operation and LSA reconstruction time in patients with Stanford type A aortic dissection, improve the success rate of LSA reconstruction, and reduce the occurrence rate of LSA reconstruction complications.

[Mid- and long-term results of surgical treatment of brachiocephalic Takayasu arteritis].

Objective: To examine the mid - and long-term outcomes of surgical treatment of brachiocephalic Takayasu arteritis. Methods: This is a retrospective case series study. The clinical data of 39 patients,which had been diagnosed as brachiocephalic Takayasu arteritis (244 cases),who underwent surgical treatment,were analyzed between July 2012 to November 2022 at Department of Endoluminal Vascular Surgery, the First Affiliated Hospital of Zhengzhou University. There were 5 males and 34 females, aged (37.9±14.0)years (range:13 to 71 years). Despite medical treatment, the patients suffered severe ischemic symptoms continually and then underwent surgical interventions. Among them, 20 patients underwent endovascular procedures, 11 underwent open surgical procedures, and 8 underwent hybrid procedures. Patients were followed up through outpatient visits at 1, 3, 6 months after surgery and once every year later. Follow-up was conducted until November 2022. Operation status, postoperative complications and re-intervention of patients were recorded and the Kaplan-Meier survival curves were used to analyze postoperative vascular patency rates. Results: All 39 surgeries were successful, with no intraoperative death or serious complications. The follow-up period was (48.8±38.2) months(range:1 to 123 months). Thirty-three patients experienced symptom relief after surgery, and 6 patients required secondary surgical interventions. The patency rates for the endovascular treatment group at 1-, 3-, 5-, and 10-year were 95.0%, 75.2%, 60.2%, and 60.2%, respectively, while the patency rates for open surgery were all 90.9%. In the hybrid surgery group, the patency rates at 1-, 3-, 5-, and 8-year were all 87.5%. Conclusion: For patients with brachiocephalic Takayasu arteritis, choice of an appropriate blood flow revascularization intervention should be based on the patient's condition,and the mid-and long-term outcomes are satisfactory.

[Clinical characteristics and efficacy analysis of various treatments for spontaneous carotid artery dissection].

Objective: To investigate the clinical features of spontaneous carotid artery dissection (SCAD) and the efficacy of different treatment methods. Methods: The clinical data of 164 patients with SCAD who were treated at the First Affiliated Hospital of Zhengzhou University from June 2018 to January 2023 were retrospectively analyzed. There were 127 males and 37 females, with a mean age of (49.5±11.1) years. They were divided into conservative treatment group (n=100) and surgical treatment group (n=64) according to whether they received surgical treatment. Patients were followed at 3, 6, and 12 months after discharge and annually thereafter through outpatient or inpatient visits. The incidence of cerebral ischemic events, cerebral hemorrhage events, and mortality rates during hospitalization and follow-up periods were analyzed in the two patient groups. To examine correlates of revascularization in SCAD, multifactorial logistic regression analysis was used. Results: Of the 164 patients, 18 patients had bilateral SCAD and a total of 182 carotid arteries were included in the study. Ischemic stroke (85 cases, 51.8%) and transient ischemic attack (31 cases, 18.9%) were the main clinical manifestations in SCAD patients. Hypertension (81 cases, 49.4%) and hyperlipidemia (39 cases, 23.8%) were the main comorbidities in SCAD patients. During hospitalization, 100 patients in the conservative treatment group received medication in 113 carotid arteries, no new cerebral ischemic events or symptomatic intracranial hemorrhage events occurred, and no death occurred. A total of 69 carotid arteries were surgically treated in 64 patients in the surgical treatment group. The success rate was 97.1% (67/69). In the surgical treatment group, the proportion of carotid stenosis degree≥90% was 47.8% (33/69), the proportion of type Ⅱ SCAD was 60.9% (42/69), and the proportion discharged from the hospital to receive antiplatelet therapy was 92.8% (64/69), which were higher than those in the conservative treatment group, which were 25.7% (29/113), 45.1% (51/113), and 73.5% (83/113), respectively (all P<0.05). The follow-up time [M(Q1, Q3)] in the conservative treatment group was 24 (13, 34) months, with an 8% (9/113) rate of ischemic events and a 7.1% (8/113) rate of readmission; in the surgical treatment group, the follow-up time was 24 (11, 38) months, and there were no new ischemic events or deaths. The results of multifactorial logistic regression analysis showed that the degree of true luminal stenosis<90% (OR=2.738, 95%CI: 1.067-7.026, P=0.036) and type Ⅰ dissections (OR=2.656, 95%CI: 1.189-5.935, P=0.017) were the correlates of complete revascularization. Conclusions: Ischemic stroke and transient ischemic attack are the main clinical manifestations in patients with SCAD. Pharmacological antithrombotic therapy remains the method of choice, and endovascular treatment after failure of conservative therapy reduces the risk of recurrent long-term cerebral ischemic events and the re-admission rate of patients.

[Novel frameshift mutations in SALL4 in two Chinese families with Okihiro syndrome].

In the present study, clinical manifestations of two Chinese Okihiro syndrome families were analyzed, and genetic detections were performed on the two probands by exome sequencing and verified by Sanger sequencing for family members to determine the biological pathogenesis. Prenatal diagnoses were provided for three high-risk fetuses. The affected members exhibited a wildly spectrum of phenotypes, including ultrasound abnormalities of skeletal system (radius deformity and abnormal posture), and cardiac system (persistent common arterial trunk and ventricular septal defect) in the prenatal period of family 1, the severe phenotypes (grossly shortened and deformed forearm, Duane's anomaly and hearing loss), and the mild ones (usually only thenar dysplasia, or short radius styloid process). Two SALL4 variants, c.844delC p.(Q282Kfs*8) and c.2210delG p.(G737Vfs*23), have been identified respectively in two probands, and c.2210delG of SALL4 gene was unreported previously. The two variants were verified in all affected individuals, not in normal family members. Genotyping results of three fetuses indicated that one fetus was normal, and the two fetuses with heterozygous variation were affected. The two variants of SALL4 gene, c.844delC p.(Q282Kfs*8) and c.2210delG p.(G737Vfs*23), were the molecular pathological cause of Okihiro syndrome in the present study and enriched the spectrum of SALL4 variants. Our study provides accurate prenatal genetic diagnosis for the two families to avoid the birth of affected children.

Trends in clinical validation and usage of US Food and Drug Administration-cleared artificial intelligence algorithms for medical imaging.

AIM: To examine the current landscape of US Food and Drug Administration (FDA)-approved artificial intelligence (AI) medical imaging devices and identify trends in clinical validation strategy. MATERIALS AND METHODS: A retrospective study was conducted that analysed data extracted from the American College of Radiology (ACR) Data Science Institute AI Central database as of November 2021 to identify trends in FDA clearance of AI products related to medical imaging. Product and clinical validation information of each device was gathered from their respective public 510(k) summary or de novo request submission, depending on their type of authorisation. RESULTS: Overall, the database included a total of 151 AI algorithms that were cleared by the FDA between 2008 and November 2021. Out of the 151 FDA summaries reviewed, 97 (64.2%) reported the use of clinical data to validate their device, with six (4%) revealing study participant demographics, and eight (5.3%) reporting the specifications of the machines used. A total of 51 (33.8%) AI devices characterised their clinical data as multicentre, three (2%) as single-centre, and the remaining 97 (64.2%) did not specify. The ground truth used for clinical validation was specified in 78 (51.6%) FDA summaries. CONCLUSION: A wide breadth of AI algorithms has been developed for medical imaging. Most of the FDA summaries of the devices mention their use of clinical data and patient cases for device validation; however, few devices revealed the patient demographics or machine specifications used in their clinical studies, which may lead some consumers to question their external validation.

[Analysis of the factors influencing positive predictive value of noninvasive prenatal testing for chromosome aneuploidies].

Objective: To investigate the influence of Z-score and different risk factors on positive predictive value (PPV) of noninvasive prenatal testing (NIPT) for chromosome aneuploidies. Methods: A total of 81 838 NIPT samples from January 1, 2016 to May 31, 2021 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Invasive prenatal diagnosis was applied to verify the diagnosis of NIPT-positive results and the corresponding PPV was calculated. The PPV of the samples with different Z-score were compared. The women were divided into high-risk group and non-high-risk group: high-risk group (n=39 114) included those with ultrasound soft index abnormalities, advanced maternal age or high risk for maternal serum screening, while non-high-risk group (n=42 724) included those with intermediate risk for maternal serum screening or no indications. The differences of the PPV between these two groups were compared. Finally, the comprehensive influence of Z-score and different risk factors on PPV were analyzed. Results: A total of 471 high-risk cases were detected by NIPT results, including 362 cases of trisomy 21, 77 cases of trisomy 18 and 32 cases of trisomy 13. For trisomy 21, trisomy 18 and trisomy 13, there were 226 cases, 46 cases and 6 cases which were confirmed via invasive prenatal diagnosis respectively. The corresponding PPV were 79.3% (226/285), 82.1% (46/56) and 27.3% (6/22), respectively. PPV of trisomy 21 and trisomy 18 were positively correlated with the corresponding Z-score (r=0.92, 0.62, all P<0.05), while trisomy 13 could not be analyzed due to the small sample size. The PPV of high-risk group was 85.2% (207/243), which was higher than that of the non-high-risk group with PPV of 59.2%(71/120, χ2=30.30, P<0.01). When the Z-score was between 3-<4 and 4-<5, the PPV of the high-risk group were 46.2%(12/26)and 62.5%(15/24) respectively, which were higher than those of the non-high-risk group [16.0%(4/25) and 14.3%(3/21), χ2=4.10, 8.90, all P<0.05]. With the increase of Z-score, there was no significant difference in PPV between the two groups (all P>0.05). Conclusions: The PPV of trisomy 21 and trisomy 18 are positively correlated with Z-score. The PPV of high-risk group is higher than that of non-high-risk group. The combination of Z-score and other risk factors may provide more accurate genetic counseling for those with NIPT positive results.

Utility of trio-based prenatal exome sequencing incorporating splice-site and mitochondrial genome assessment in pregnancies with fetal ultrasound anomalies: prospective cohort study.

OBJECTIVE: To evaluate the utility of trio-based prenatal exome sequencing (pES), incorporating splice-site and mitochondrial genome assessment, in the prenatal diagnosis of fetuses with ultrasound anomalies and normal copy-number variant sequencing (CNV-seq) results. METHODS: This was a prospective study of 90 ongoing pregnancies with ultrasound anomalies that underwent trio-based pES after receiving normal CNV-seq results, from September 2020 to November 2021, in a single center in China. By using pES with a panel encompassing exome coding and splicing regions as well as mitochondrial genome for fetuses and parents, we identified the underlying genetic causes of fetal anomalies, incidental fetal findings and parental carrier status. Information on pregnancy outcome and the impact of pES findings on parental decision-making was collected. RESULTS: Of the 90 pregnancies included, 28 (31.1%) received a diagnostic result that could explain the fetal ultrasound anomalies. The highest diagnostic yield was noted for brain abnormalities (3/6 (50.0%)), followed by hydrops (4/9 (44.4%)) and skeletal abnormalities (13/34 (38.2%)). Collectively, 34 variants of 20 genes were detected in the 28 diagnosed cases, with 55.9% (19/34) occurring de novo. Variants of uncertain significance (VUS) associated with fetal phenotypes were detected in six (6.7%) fetuses. Interestingly, fetal (n = 4) and parental (n = 3) incidental findings (IFs) were detected in seven (7.8%) cases. These included two fetuses carrying a de-novo likely pathogenic (LP) variant of the CIC and FBXO11 genes, respectively, associated with neurodevelopmental disorders, and one fetus with a LP variant in a mitochondrial gene. The remaining fetus presented with unilateral renal dysplasia and was incidentally found to carry a pathogenic PKD1 gene variant resulting in adult-onset polycystic kidney, which was later confirmed to be inherited from the mother. In addition, parental heterozygous variants associated with autosomal recessive diseases were detected in three families, including one with additional fetal diagnostic findings. Diagnostic results or fetal IFs contributed to parental decision-making about termination of the pregnancy in 26 families (26/72 (36.1%)), while negative pES results or identification of VUS encouraged 40 families (40/72 (55.6%)) to continue their pregnancy, which ended in a live birth in all cases. CONCLUSION: Trio-based pES can provide additional genetic information for pregnancies with fetal ultrasound anomalies without a CNV-seq diagnosis. The incidental findings and parental carrier status reported by trio-based pES with splice-site and mitochondrial genome analysis extend its clinical application, but careful genetic counseling is warranted. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

High-entropy induced a glass-to-glass transition in a metallic glass.

Glass-to-glass transitions are useful for us to understand the glass nature, but it remains difficult to tune the metallic glass into significantly different glass states. Here, we have demonstrated that the high-entropy can enhance the degree of disorder in an equiatomic high-entropy metallic glass NbNiZrTiCo and elevate it to a high-energy glass state. An unusual glass-to-glass phase transition is discovered during heating with an enormous heat release even larger than that of the following crystallization at higher temperatures. Dramatic atomic rearrangement with a short- and medium-range ordering is revealed by in-situ synchrotron X-ray diffraction analyses. This glass-to-glass transition leads to a significant improvement in the modulus, hardness, and thermal stability, all of which could promote their applications. Based on the proposed high-entropy effect, two high-entropy metallic glasses are developed and they show similar glass-to-glass transitions. These findings uncover a high-entropy effect in metallic glasses and create a pathway for tuning the glass states and properties.

Accuracy of digital templates for guidance of custom-made total temporomandibular joint replacement.

This study evaluated the application of digital templates to guide custom-made total temporomandibular joint (TMJ) replacement. Patients treated with a custom-made total TMJ prosthesis for TMJ osteoarthrosis, ankylosis, or tumours were included prospectively. Before surgery, two types of digital template (articular eminence and condyle neck templates) were designed to guide the bone osteotomy and prosthesis positioning. The reconstructive outcomes were assessed through clinical examinations and accuracy analysis by superimposing the postoperative three-dimensional craniomaxillofacial model onto the preoperative virtual plan. Thirty-seven patients (45 joints) underwent successful TMJ reconstruction with the custom-made TMJ prosthesis guided by the digital templates, without intermaxillary fixation. For all patients, the occlusal relationship was stable in reference to the preoperative state. There were significant improvements in pain and maximum inter-incisal opening. Through merging of the pre- and postoperative craniomaxillofacial models, the maximum implanted error was 1.17 ± 0.23 mm in linear measurement and 1.19 ± 0.14 mm in surface deviation. There was more deviation in the anteromedial part of the fossa and inferior part of the mandibular handle. The digital templates were able to assist in the accurate placement of the TMJ prosthesis without the need for intermaxillary fixation.

Performance Verification of SeqType® P52 Human Ancestry Identification SNP Detection Kit.

ABSTRACT: Objective To evaluate the discrimination efficiency of the SeqType® P52 Human Ancestry Identification SNP Detection Kit based on a high-throughput sequencing platform in five Chinese ethnic groups. Methods Using the SeqType® P52 Human Ancestry Identification SNP Detection Kit based on a high-throughput sequencing platform, a total of 350 samples from Han, Tibetan, Mongolian, Uygur, and Yi populations in China were detected and population cluster analysis was performed. Results The effective sequencing depth of a single site in a single sample was ≥720×, and the average report rate was 96%. The mean values of allele frequency differences between the Tibetan, Mongolian, Uygur, Yi and Han population were 0.20, 0.05, 0.24 and 0.11, respectively. Using Structure 2.3.4 software under K=5 mode, independent ancestral component in Han, Tibetan and Uygur could be detected, which was consistent with the result observed from the principal component analysis （PCA）. For the Yi population, two thirds of them had relatively independent ancestral component close to the Tibetan population and one third were similar to the Uygur population. The Mongolian population had similar ancestral origin component with Han population. Conclusion The composite detection system with 52 screened ancestry-informative SNP sites has been established in this study, which can effectively analyze the composition and individual genetic components of populations from Han, Tibetan and Uygur. The ability to discriminate among Han, Mongolian and Yi needs to be further improved. The SeqType® P52 Human Ancestry Identification SNP Detection Kit can be used to infer the origin of an individual's ancestors in some forensic DNA cases.

[Development and clinical application of custom-made temporomandibular joint-skull base combined prosthesis].

Objective: To introduce the design, manufacture and clinical application of the custom-made temporomandibular joint (TMJ)-skull base combined prosthesis and evaluate its safety, effectiveness and accuracy. Methods: The patients diagnosed with the TMJ-skull base lesion in Department of Oral Surgery, Shanghai Ninth People's Hospital from October 2016 to November 2020 were recruited in this study. The maxillofacial CT data for all the patients were obtained and transformed into the Mimics 18.0 software preoperatively. The custom-made TMJ-skull base combined prosthesis, included four components, was designed based on the anatomy, stress distribution and movement of the TMJ and skull base, and fabricated by three-dimensional printing and 5-axis milling technologies. The TMJ-skull base lesion was excised completely with the help of digital templates from modified preauricular and/or post and submandibular incisions. The combined prosthesis were implanted and fixed after the lesion resection. The examinations including general situation, cranio-maxillofacial structure and function were taken during and after surgery to assess its using effect. Results: Ten patients [6 females and 4 males, (43.2±13.6) years old] were included and all prostheses were positioned accurately and fixed excellently. After (29.4±17.3) months follow-up, the occlusion relationship was stable and no adverse symptoms such as dizziness, headache, meningeal irritation and permanent facial nerve injury occurred. The pain, diet, mandibular movement function, lateral movement to diseased side and mouth opening had significant improvements. The forward movement and lateral movement to normal side were not improved significantly. There were no prosthesis displacement, loosening and fracture in X-ray and CT postoperatively. With the pre and postoperative craniomaxillofacial model merging, the maximal implanted error was (0.52±0.17) mm for fossa and condyle and (1.62±0.26) mm for skull base and mandibular handle in surface deviation analysis. Conclusions: The custom-made TMJ-skull base combined prosthesis with customized design and 3D printing fabrication is safe, effective and precise in clinical application.

[Variation analysis of genes associated with Usher syndrome type 1 in 136 Chinese deafness families].

Objective: To investigate the variation of genes associated with Usher syndrome type 1(USH1)in 136 Chinese deafness families from Henan province. Methods: The data of 136 deafness families tested by next-generation sequencing(NGS) which identified in the center of genetics and prenatal diagnosis of the First Affiliated Hospital of Zhengzhou University from November 2016 to December 2019 were analysized and the variation frequency of six genes related to Usher syndrome type 1(MYO7A, USH1C, CDH23, PCDH15, USH1G, CIB2) were summarized. Results: Five deafness families were detected nine pathogenic or likely pathogenic variations in two genes, accounting for 3.7% of all families. Among them, four families were caused by MYO7A variations and one family was caused by CDH23 variation. Meanwhile, seven variations of two genes were reported for the first time. They were c.313delG, c.5257dupA, c.5435A>T, c.5636G>C, c.5722T>G of MYO7A, and c.155_166del, c.4802delA of CDH23. The patients' vision of family 2 and family 3 had no obvious abnormality at present, but according to genetic diagnosis and walking dealy, they were considered to be USH1. Conclusions: MYO7A is the most common caustive gene associated with USH1 in Henan deafness patients, the application of next-generation sequencing technology can make USH1 patients diagnosed earlier before the visual symptoms appear.

Atmospheric pressure plasma treatment induces abscisic acid production, reduces stomatal aperture and improves seedling growth in Arabidopsis thaliana.

Cold atmospheric pressure plasmas (CAPPs) have been widely used for pre-sowing treatment in agriculture to accelerate seed germination; however, information on their application to pre-transplant seedlings is scarce. The roles of the phytohormone abscisic acid (ABA) on guard cell aperture that control air exchange with the environment were investigated after CAPPs treatment. In this study, Arabidopsis thaliana seedling growth was evaluated under CAPPs treatment at different doses. Besides, the optimal growth stimulation dose was selected to further evaluate changes in ABA, ROS, Ca2+ and stomatal aperture during growth .The expression of most ABA signalling genes were aslo examined to investigate the mechanism. CAPPs treatment for 1 min significantly promoted Arabidopsis seedling growth; the ABA concentration in seedlings increased and peaked 48 h after treatment but was lower than in the control after 96 h. Transcript levels of most ABA signalling genes were markedly enhanced at 48 h, although their transcripts were significantly downregulated after 96 h. CAPPs treatment also reduced stomatal aperture after 24 h and accelerated ROS accumulation in guard cells. The Ca2+ concentration in the treatment group was markedly higher than in the control at 24 and 96 h. The results suggest that CAPPs treatment accelerates ABA accumulation in Arabidopsis at early growth stages and ABA regulates ROS and Ca2+ concentrations to affect stomatal aperture, and both ABA and stoma size are affected in CAPPs stimulation of Arabidopsis seedling growth.

[Analysis of MYO15A variation in children with DFNB3].

Objective: To analyze the genetic and clinical characteristics of MYO15A variants associated non-syndromic autosomal recessive deafness3 (DFNB3). Methods: The hearing test and high-throughput sequencing data of 108 families with non-syndromic hearing loss, who visited the Center of Genetics and Prenatal Diagnosis in the First Affiliated Hospital of Zhengzhou University from November 2016 to February 2019, were retrospectively analyzed to investigate the characteristics of MYO15A variation. Results: Compound heterozygous MYO15A variations were detected in nine patients from eight families, accounting for 7.4% of all 108 families. The variants were c.5910+1G>A/c.9417_9418insTA, c.4234T>G/c.8324G>T, c.3926A>T/c.5002delC, c.9690+1G>A/c.10257_10259delCTT, c.8324G>T/c.10419_10423delCAGCT, c.4519C>T/c.6454G>C, c.6177+1G>T/c.10257_10259delCTT and c.5692C>T/c.7396-1G>A. All patients had severe to profound hearing loss. Among the 14 variations, 12 variations were located in the main structural domains, including 5 in motor domain, 3 in FERM domain, 3 in MyTH4 domain and 1 in IQ motif. The c.3926A>T, c.4234T>G, c.4519C>T, c.5002delC, c.6454G>C, c.8324G>T, c.9417_9418insTA and c.10419_10423delCAGCT had not been reported in the Human Gene Mutation Database up to February 2020. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), 6 reported variants and the first reported c.4519C>T, c.5002delC, c.9417_9418insTA and c.10419_10423delCAGCT were identified as pathogenic variants, while c.8324G>T was likely pathogenic variant, and c.3926A>T, c.4234T>G and c.6454G>C were variants of uncertain significance. Conclusions: The variations of MYO15A in patients with DFNB3 are mainly complex heterozygous. The clinical phenotypes are mostly severe to profound hearing loss, and the mutation loci are mainly in the motor, FERM and MyTH4 domains.

Lamin B1 deficiency promotes malignancy and predicts poor prognosis in gastric cancer.

Gastric cancer (GC) is a kind of global malignancy. However, the expression pattern and clinical relevance of lamin B1 in GC remain to be elucidated. We endeavored to investigate how GC is influenced by lamin B1 and the related mechanisms. The lamin B1 expression in GC tissues from 71 patients was assessed by using immunohistochemistry (IHC). The expression of lamin B1 was connected with the clinical stage, depth of invasion, and poorer overall survival. Colony formation assays and methyl thiazolyl tetrazolium (MTT) were used to assess cell viability. The migration ability of GC cells was determined by cell scratch assay and Transwell invasion assay. Moreover, we used two cell lines of GC to explore the underlying mechanism of lamin B1 in boosting the GC cells proliferation and invasion in vitro by assessing the effects on related signal transduction pathways. Our data demonstrated that the expression level of lamin B1 was downregulated in GC tissues, and low expression level of lamin B1 was significantly correlated with higher clinical stage, depth of invasion, nodal stage, and poor prognosis. Moreover, in vitro experiments demonstrated that lamin B1 knockdown promoted, whereas lamin B1 overexpression inhibited, gastric cancer cell proliferation and migration. We also observed that lamin B1 knockdown could promote the activity of the PI3K/PTEN/Akt and MAPK/ERK pathway with a decrease in the p53/p21WAF1/CIP1 expression, whereas lamin B1 overexpression contributed to the opposite results. In conclusion, our studies indicate that lamin B1 deficiency is crucial in GC progression. Furthermore, the results elucidating the biological mechanisms of lamin B1 may potentially contribute to current GC treatment modalities.

Ultrahigh-strength and ductile superlattice alloys with nanoscale disordered interfaces.

Alloys that have high strengths at high temperatures are crucial for a variety of important industries including aerospace. Alloys with ordered superlattice structures are attractive for this purpose but generally suffer from poor ductility and rapid grain coarsening. We discovered that nanoscale disordered interfaces can effectively overcome these problems. Interfacial disordering is driven by multielement cosegregation that creates a distinctive nanolayer between adjacent micrometer-scale superlattice grains. This nanolayer acts as a sustainable ductilizing source, which prevents brittle intergranular fractures by enhancing dislocation mobilities. Our superlattice materials have ultrahigh strengths of 1.6 gigapascals with tensile ductilities of 25% at ambient temperature. Simultaneously, we achieved negligible grain coarsening with exceptional softening resistance at elevated temperatures. Designing similar nanolayers may open a pathway for further optimization of alloy properties.

Investigation on saturable absorbers based on nonlinear Kerr beam cleanup effect.

We experimentally investigate characteristics of saturable absorbers (SAs) based on nonlinear Kerr beam cleanup effect (NL-KBC). The SAs are formed by a long graded-index multimode fiber (GRIN MMF) with a short single-mode fiber served as a diaphragm. We studied the evolution of output spectrum and beam profiles from the GRIN MMF in order to investigate the mechanism of these SAs. We further performed saturable absorption measurements to evaluate their modulation depths and saturation intensities. We experimentally observed and first theoretically analyzed the "relaxation oscillation" behavior of the optical transmittance with increasing input intensity. We also studied their nonlinear polarization dynamics and observed the repolarized effect in NL-KBC regime. Our results confirm the optical properties of the SAs based on NL-KBC, and these SAs can find applications in Q-switched and mode-locked lasers.

[Analysis of genetic variation in patients with Waardenburg syndrome type â ¡ by next generation sequencing].

Objective: To detect gene mutation sassociated with deafness in four Waardenburg syndrome (WS) type Ⅱ patients, and to explore the possible mechanism of molecular genetics. Methods: All patients with WS were identified at the genetic and prenatal diagnosis center of the First Affiliated Hospital of Zhengzhou University from August 2015 to December 2018.Clinical materials and peripheral blood were collected from patients and family members. The genes associated with deafness of the patients were tested by next generation sequencing(NGS). And suspected mutations were verified by Sanger sequencing. Results: All patients carried heterozygous mutations in SOX10, they were c.355_356insTCAGGCAGCGC, c.1106_1107insTGGGGCCCCCCACACTA, c.511T>C (p.Y171H), c.91_100del. According to the guidelines for genetic variation of the Amercian College of Medical Genetics and Genomics (ACMG), three frameshift mutations were pathogenic mutations, one missense mutation was likely pathogenic mutation. Conclusion: Application of next generation sequencing technologies make gene diagnosis of Waardenburg syndrome efficiently and accurately.

Amorphophallus konjac anthracnose caused by Colletotrichum siamense in China.

AIMS: Amorphophallus konjac is an important commercial crop grown in China because it is the only plant species which is rich in glucomannan concentration. Recently, an outbreak of anthracnose (incidence ranging from 10-15%) was observed in a field survey conducted from June to August 2018. This study aims to identify the causal agent of A. konjac anthracnose. METHODS AND RESULTS: The pathogen was isolated on potato dextrose agar (PDA) medium. The fungal colony on PDA was greyish to dark grey. Conidia were falcate, one-celled and hyaline. Based on the micro-morphological and cultural characteristics, the pathogen was identified as Colletotrichum sp. blast search and phylogenetic analysis of the ITS, GAPDH, CHS1, ACT, CAL and TUB2 genes revealed the pathogen as Colletotrichum siamense. Koch's postulates were conducted on 2-month konjac leaves with conidial suspension. Development of typical anthracnose disease was recorded 5 days after inoculation and the pathogen's identity was confirmed by re-isolation and molecular identification. CONCLUSIONS: Amorphophallus konjac anthracnose was caused by C. siamense in China. SIGNIFICANCE AND IMPACT OF THE STUDY: Identification of causal agent of A. konjac anthracnose will be helpful in designing effective disease control strategies.

Wnt pathway regulates IL-34 level in lupus nephritis.

OBJECTIVE: The aim of this study was to investigate the role of the Wnt pathway in regulating the IL-34 level of lupus nephritis (LN) patients, and to explore the underlying mechanism. MATERIALS AND METHODS: Human mesangial cells (HMCs) of LN patients were selected. The expression level of IL-34 was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. Subsequently, HMCs were treated with the Wnt pathway antagonist, DDK1. Meanwhile, the IL-34 level in DDK1 transfected HMCs was then detected. In addition, the viability of HMCs treated with DDK1 was detected by cell counting kit-8 (CCK-8) and colony formation assay, respectively. RESULTS: Both the mRNA and protein levels of IL-34 were significantly upregulated in HMCs of LN patients. Higher expression of ß-catenin was observed in HMCs of LN patients than those of controls, which was reduced after DDK1 treatment. Meanwhile, IL-34 level in HMCs of LN patients was significantly downregulated after DDK1 treatment. In addition, DDK1 treatment remarkably increased the proliferative ability and colony formation ability of HMCs in LN patients. CONCLUSIONS: IL-34 is highly expressed in HMCs of LN patients and is negatively regulated by the Wnt pathway. Furthermore, HMCs viability is remarkably enhanced after blocking the Wnt pathway.