Genetic analysis of developmental and epileptic encephalopathy caused by novel biallelic SZT2 gene mutations in three Chinese Han infants: a case series and literature review.

BACKGROUND: Developmental and epileptic encephalopathy (DEE) exhibits phenotypic and genetic heterogeneity. Biallelic variants of the SZT2 gene can lead to DEE18, of which few cases have been reported. This study aimed to analyze the potential pathogenic factors in three cases of DEE18. METHODS: Trio-whole exome sequencing and crystal structure simulation analysis were performed, along with a literature review of DEE18 cases. RESULTS: All three patients had compound heterozygous variants in the SZT2 gene (patient 1, c.2887A > G/c.7970G > A; patient 2, c.3508A > G/c.7936C > T; and patient 3, c.2489G > T/c.8640_8641insC). The variants were predicted to have structural effects on the protein. Particularly, c.3508A > G/p.Ser1170Gly may lead to impaired binding of SZT2 to GATOR1, potentially resulting in the overactivation of the mTORC1 signaling pathway, causing seizures. Through the literature review, we observed that 27 patients with DEE had different degrees of intellectual and developmental disorders (DDs), and the variants leading to protein truncation cause severe DD and refractory epilepsy. Therefore, the phenotypic severity of patients may be related to the residual activity of variant SZT2 protein. CONCLUSION: We provide recently developed knowledge on the DEE18 genotype-phenotype spectrum and suggest that gene detection is of great value for the accurate diagnosis of patients with early-onset epilepsy. Further research is required for the development of individualized interventions for patients with DEE.

GJA1-20k attenuates Ang II-induced pathological cardiac hypertrophy by regulating gap junction formation and mitochondrial function.

Cardiac hypertrophy (CH) is characterized by an increase in cardiomyocyte size, and is the most common cause of cardiac-related sudden death. A decrease in gap junction (GJ) coupling and mitochondrial dysfunction are important features of CH, but the mechanisms of decreased coupling and energy impairment are poorly understood. It has been reported that GJA1-20k has a strong tropism for mitochondria and is required for the trafficking of connexin 43 (Cx43) to cell-cell borders. In this study, we investigated the effects of GJA1-20k on Cx43 GJ coupling and mitochondrial function in the pathogenesis of CH. We performed hematoxylin-eosin (HE) and Masson staining, and observed significant CH in 18-week-old male spontaneously hypertensive rats (SHRs) compared to age-matched normotensive Wistar-Kyoto (WKY) rats. In cardiomyocytes from SHRs, the levels of Cx43 at the intercalated disc (ID) and the expression of GJA1-20k were significantly reduced, whereas JAK-STAT signaling was activated. Furthermore, the SHR rats displayed suppressed mitochondrial GJA1-20k and mitochondrial biogenesis. Administration of valsartan (10 mg· [Formula: see text] d-1, i.g., for 8 weeks) prevented all of these changes. In neonatal rat cardiomyocytes (NRCMs), overexpression of GJA1-20k attenuated Ang II-induced cardiomyocyte hypertrophy and caused elevated levels of GJ coupling at the cell-cell borders. Pretreatment of NRCMs with the Jak2 inhibitor AG490 (10 µM) blocked Ang II-induced reduction in GJA1-20k expression and Cx43 gap junction formation; knockdown of Jak2 in NRCMs significantly lessened Ang II-induced cardiomyocyte hypertrophy and normalized GJA1-20k expression and Cx43 gap junction formation. Overexpression of GJA1-20k improved mitochondrial membrane potential and respiration and lowered ROS production in Ang II-induced cardiomyocyte hypertrophy. These results demonstrate the importance of GJA1-20k in regulating gap junction formation and mitochondrial function in Ang II-induced cardiomyocyte hypertrophy, thus providing a novel therapeutic strategy for patients with cardiomyocyte hypertrophy.

The Preparation and Properties Study of High CRI White LED Based on Remote Phosphor Technology.

Focusing on the defects in the lighting color of LED lamps and the chip heat exists in the traditional LED package which caused phosphor performance degradation, color temperature drift and the uneven light, the remote phosphor package which is emerging in recent years is used in this paper. With yellow-green YGG phosphor and nitrogen red phosphors mixing with silica gel, the remote phosphor is made and then encapsulated as the LED lamps. A lot of experiments were made to determine the best ratio of yellow green phosphor, red phosphor and silica gel, LED lamps with different color temperature was prepared. The lamps were also tested and analyzed with some parameters such as e color coordinates, luminous efficiency, color rendering index (CRI), R9, color quality scale (CQS), color temperature, and the gamut area index (GAI), which provide a more objective and comprehensive evaluation to the high quality LED lighting. Experimental results show that the optimum ratio of red and yellow-green phosphor is 1∶7.6, and total phosphor with silica gel is 1∶5，at this time the white LED lighting color temperature is 4 113 K, the color coordinate (x, y) is (0.375 4, 0.373 1), luminous efficiency is 52.33 lm·w-1, color gamut is 0.981, color rendering index is up to 96, R9 is 97, color quality scale Qa is up to 93, and the gamut area index is 79. Compared with the traditional packaging，the surface temperature ofthe remote phosphor encapsulated fluorescent plate is much lower than that of adhesive dispensing encapsulation, which can effectively avoid the harmful effect caused by high temperature on the LED.

Failure analysis and design improvement of retrieved plates from revision surgery.

Background: The fracture of bone plate can cause considerable pain for the patient and increase the burden on the public finances. This study aims to explore the failure mechanism of 49 plates retrieved from revision surgery and introduce pure magnesium (Mg) block to improve the biomechanical performance of the plate via decreasing the stiffness and to stimulate the biological response of the plate potentially by the degradation of Mg block. Methods: The morphological analysis and component analysis of the plates were conducted to determine the fracture reason of the plates combining the clinical data. According to the structural feature, the 49 retrieved plates were divided into: traditional plate (TP), asymmetrical plate (AP), reconstructive plate (RP) and central enhancement plate (CEP), and their structure features are normalized in a commercial plate, respectively. The biomechanical performance of the plates was evaluated using a validated femoral finite element model. A block of pure Mg with a thickness of 1 mm, 1.5 mm and 2 mm was also incorporated into the CEP to be assessed. Results: The results indicated that the retrieved plates mainly failed due to fatigue fracture induced by delayed union or nonunion (44/49), and using pure titanium plates in weight-bearing areas increased the risk of fracture compared with Ti alloy plates when the delayed union or nonunion occurred. The TP demonstrated the highest compression resistance and bending resistance, while CEP had the highest rotational resistance. As the thickness of the Mg block was increased, the stress on the plate in compression decreased, but the stress in rotation increased. The plate with a 1.5 mm Mg block demonstrated excellent compression resistance, bending resistance and rotational resistance. Conclusion: Fatigue fracture resulting from the delayed union or nonunion is the primary failure reason of plates in clinic. The incorporation of Mg block into plate improves the biomechanical performance and has the potential to promote bone healing. The plate with a 1.5 mm Mg block may be suitable for use in orthopaedics. The translational potential of this article: This study assessed the failure mechanism of retrieved bone plates and used this data to develop a novel plate incorporating a 1.5 mm block of pure Mg block at the position corresponding to the fracture line. The novel plate exhibited excellent compression resistance, bending resistance and rotational resistance due to the alleviation of stress concentrations. The Mg block has the potential to degrade over time to promote fracture healing and prevents fatigue fracture of plates.

Failure analysis of a locking compression plate with asymmetric holes and polyaxial screws.

Locking compression plates (LCP) with asymmetrical holes and polyaxial screws are effective for treating mid-femoral fractures, but are prone to failure in cases of bone nonunion. To understand the failure mechanism of the LCP, this study assessed the material composition, microhardness, metallography, fractography and biomechanical performance of a retrieved LCP used for treating a bone fracture of AO type 32-A1. For the biomechanical assessment, a finite element surgical model implanted with the intact fixation-plate system was constructed to understand the stresses and structural stiffness on the construct. Also, to avoid positioning screws around the bone fracture, different working lengths of the plate (the distance between the two innermost screws) and screw inclinations (±5°, ±10° and ±15°) were investigated. The fracture site of the retrieved LCP was divided into a narrow side and broad side due to the asymmetrical distribution of holes on the plate. The results indicated that the chemical composition and microhardness of the LCP complied with ASTM standards. The fatigue failure was found to originate on the narrow side of the hole, while the broad side showed overloading characteristics of crack growth. When the screws were inserted away from the region of the bone fracture by increasing the working length, the stress of the fixation-plate system decreased. Regardless of the screw insertion angle, the maximum stress on the LCP always appeared on the narrow side, and there was little change in the structural stiffness. However, angling the screws at -10° resulted in the most even stress distribution on the fixation-plate system. In conclusion, the LCP assessed in this study failed by fatigue fracture due to bone nonunion and stress concentration. The narrow side of the LCP was vulnerable to failure and needs to be strengthened. When treating an AO type 32-A1 fracture using an LCP with asymmetrical holes and polyaxial screws, inserting the screws at -10° may reduce the risk of implant failure and positing screws around the fractured area of the bone should be avoided.

Biomechanical evaluation of a novel intervertebral disc repair technique for large box-shaped ruptures.

Objective: The purpose of this study was to analyze the feasibility of repairing a ruptured intervertebral disc using a patch secured to the inner surface of the annulus fibrosus (AF). Different material properties and geometries for the patch were evaluated. Methods: Using finite element analysis, this study created a large box-shaped rupture in the posterior-lateral region of the AF and then repaired it with a circular and square inner patch. The elastic modulus of the patches ranged from 1 to 50 MPa to determine the effect on the nucleus pulposus (NP) pressure, vertical displacement, disc bulge, AF stress, segmental range of motion (ROM), patch stress, and suture stress. The results were compared against the intact spine to determine the most suitable shape and properties for the repair patch. Results: The intervertebral height and ROM of the repaired lumbar spine was similar to the intact spine and was independent of the patch material properties and geometry. The patches with a modulus of 2-3 MPa resulted in an NP pressure and AF stresses closest to the healthy disc, and produced minimal contact pressure on the cleft surfaces and minimal stress on the suture and patch of all models. Circular patches caused lower NP pressure, AF stress and patch stress than the square patch, but also caused greater stress on the suture. Conclusion: A circular patch with an elastic modulus of 2-3 MPa secured to the inner region of the ruptured annulus fibrosus was able to immediately close the rupture and maintain an NP pressure and AF stress similar to the intact intervertebral disc. This patch had the lowest risk of complications and produced the greatest restorative effect of all patches simulated in this study.

[Epileptiform discharges and sleep structure in children with nocturnal epilepsy].

OBJECTIVE: To study the epileptiform discharges and sleep structure in children with nocturnal epilepsy. METHODS: A total of 54 children with nocturnal epilepsy (NE group) between December 2009 and June 2011 were enrolled in this study using a cluster sampling method. Their epileptiform discharges and sleep structure were monitored using nocturnal 12 h-video-echoencephalography (EEG) and polysomnography. Meanwhile, 40 age- and gender-matched normal children were enrolled as the control group. RESULTS: All the 54 children in the NE group suffered from epileptiform discharges and a varied number of clinical seizures, especially at S1 and S2 states. Compared with the control group, S1 and S2 states had significantly higher proportions in the NE group, and S3 and S4 states and REM state had significantly lower proportions (P<0.01). CONCLUSIONS: Epileptiform discharges and clinical seizures are more common in children with nocturnal epilepsy, especially during the non-rapid eye movement sleep. Meanwhile, remarkably disordered sleep structure also exists.

Effects of intracavitary administration of elemene combined with nedaplatin on malignant pleural effusion.

AIM: To investigate the therapeutic effect of Elemene combined with Nedaplatin (ECN) on malignant pleural effusion (MPE) and its adverse reactions. METHOD: A retrospective study was conducted, three hundred and fifty-two patients with MPE were divided into two groups according to different treatment methods. One hundred and eighty-nine patients were given intrathoracic injection of ECN and classified in ECN group; one hundred and sixty-three cases in the Nedaplatin group were given intrathoracic injection of nedaplatin. Routine treatments were used to prevent adverse reactions. RESULT: The effective rate of the ECN group was 57.05%, and that of the Nedaplatin group was 23.08%. The comparison results of adverse reactions between the two groups showed that there was no significant difference in leukopenia, thrombopenia, anemia, vomitting and diarrhea, fever, hepatic damage and renal damage. The level of thoracalgia in the ECN group was higher than that in the Nedaplatin group. There was no significant change in the number of CD8+ T cells between the two groups after treatment. The number of CD4+T cells in the ECN group increased after treatment was higher than the Nedaplatin group after treatment. CONCLUSION: ECN treatment can improve clinical control of MPE with no serious adverse reaction, can effectively reduce the immunosuppressive effect of nedaplatin and enhance the immune function of MPE patients which is worthy of clinical application.

Biomechanical changes at the adjacent segments induced by a lordotic porous interbody fusion cage.

Biomechanical changes at the adjacent segments after interbody fusion are common instigators of adjacent segment degeneration (ASD). This study aims to investigate how the presence of a lordotic porous cage affects the biomechanical performance of the adjacent segments. A finite element model (FEM) of a lumbar spine implanted with a lordotic cage at L3-L4 was validated by in-vitro testing. The stress distribution on the cage and range of motion (ROM) of L3-L4 were used to assess the stability of the implant. Three angles of cage (0° = non-restoration, 7° = normal restoration and 11° = over-restoration) were modelled with different porosities (0%, 30% and 60%) and evaluated in the motions of flexion, extension, lateral bending and rotation. The ROM, intervertebral disc pressure (IDP) and facet joint force (FJF) were used to evaluate biomechanical changes at the adjacent segments in each model. The results indicated that porous cages produced more uniform stress distribution, but cage porosity did not influence the ROM, IDP and FJF at L2-L3 and L4-L5. Increasing the cage lordotic angle acted to decrease the ROM and IDP, and increase the FJF of L4-L5, but did not alter the ROM of L2-L3. In conclusion, changes in ROM, IDP and FJF at the adjacent segments were mainly influenced by the lordotic angle of the cage and not by the porosity. A larger angle of lordotic cage was shown to reduce the ROM and IDP, and increase the FJF of the lower segment (L4-L5), but had little effect on the ROM of the upper segment (L2-L3).

Biomechanical evaluation of a short-rod technique for lumbar fixation surgery.

Objective: The purpose of this study was to analyze the stability and instrument-related complications associated with fixation of the lumbar spine using the Short-Rod (SR) technique. Methods: Using finite element analysis, this study assessed the stability of a bilateral lumbar fixation system when inserting the pedicle screws at angles of 10°, 15°, and 20° to the endplate in the sagittal plane. Using the most stable construct with a screw angle, the model was then assessed with different rod lengths of 25, 30, 35, and 45 mm. The optimal screw inclination angle and rod length were incorporated into the SR model and compared against traditional parallel screw insertion (pedicle screws in parallel to the endplate, PPS) in terms of the stability and risk of instrument-related complications. The following parameters were evaluated using the validated L4-L5 lumbar finite element model: axial stiffness, range of motion (ROM), stress on the endplate and facet joint, von-Mises stress on the contact surface between the screw and rod (CSSR), and screw displacement. Results: The results showed that the SR model with a 15° screw inclination angle and 35 mm rod length was superior in terms of construct stability and risk of complications. Compared to the PPS model, the SR model had lower stiffness, lower ROM, less screw displacement, and lower stress on the facet cartilage, the CSSR, and screws. However, the SR model also suffered more stress on the endplate in flexion and lateral bending. Conclusion: The SR technique with a 15° screw inclination and 35 mm rod length offers good lumbar stability with a low risk of instrument-related complications.

In Vitro Analysis of Wearing of Hip Joint Prostheses Composed of Different Contact Materials.

Cobalt-chromium-molybdenum alloy (CoCrMo) and ceramic are the two most common materials for the femoral head in hip joint prostheses, and the acetabular liner is typically made from ultra-high molecular weight polyethylene (UHMWPE), highly cross-linked polyethylene (XLPE), or highly cross-linked polyethylene blended with Vitamin E (VEXLPE). The selection of suitable materials should consider both wear performance and cost-effectiveness. This study compared the wear rate between different friction pairs using a hip joint simulator and then recommended a suitable prosthesis based on the corresponding processing technology and cost. All wear simulations were performed in accordance with ISO 14242, using the same hip joint simulator and same test conditions. This study found that when using the same material for the femoral head, the XLPE and VEXLPE liners had a lower wear rate than the UHMWPE liners, and the wear rate of the XLPE liners increased after blending with Vitamin E (VEXLPE). There was no significant difference in the wear rate of XLPE when using a CoCrMo or ceramic head. Considering the wear rate and cost-effectiveness, a CoCrMo femoral head with an accompanying XLPE liner is recommended as the more suitable combination for hip prostheses.

Simultaneous determination of 16 alkaloids in blood by ultrahigh-performance liquid chromatography-tandem mass spectrometry coupled with supported liquid extraction.

Alkaloids are widely present in food and medicine. However, many alkaloids have poisoning effect. Thus, a sensitive and rapid method for determination of alkaloids is highly desired. In this study, a convenient, reliable and accurate method is developed for the simultaneous determination of 16 poisonous alkaloids in human blood by ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) coupled with supported liquid extraction (SLE). The 16 alkaloids include colchicine, anisodamine, scopolamine, atropine, sinomenine, dicaine, thebaine, papaverine, strychnine, brucine, aconitine, hypaconitine, yunaconitine, deoxyaconitine, bullatine A and bullatine B. Low limits of detection (LODs) were obtained ranging in 0.002-0.03 µg L-1. The linear ranges are 0.005-200 µg L-1 for colchicine, papaverine, brucine, aconitine, hypaconitine, yunaconitine and deoxyaconitine, 0.01-200 µg L-1 for anisodamine and scopolamine, 0.05-200 µg L-1 for atropine, strychnine, bullatine A and bullatine B, 0. 1-200 µg L-1 for other target analytes, all with correlation coefficients (R2) higher than 0.995. The recoveries range from 79.2% to 95.8%. The relative standard deviation (RSD) values are lower than 15% and the values of matrix effect (ME) range in 86.3%-118.2%. This method of UPLC-MS/MS coupled with SLE has high potential for analyzing multiple alkaloids in blood samples.

Challenges of pre-clinical testing in orthopedic implant development.

The market for orthopedic implants is growing rapidly with the increasing prevalence of orthopedic diseases in an aging society. Different designs and materials have been developed over the years and have, in general, shown excellent results in pre-clinical testing. However, there have been incidences of serious complications when novel implants or materials are put into clinical use, with some well-known cases being metallosis in patients implanted with metal-on-metal hip replacements and osteolysis from polyethylene wear debris generated in hip and knee joint replacements. Unforeseen factors related to new designs, materials and surgical techniques can lead to different outcomes for pre-clinical testing and clinical use. While often an excellent indicator of a device's performance in clinical settings, pre-clinical testing does sometime fail to predict critical flaws in implant development. This article aims to explore the gaps in the current approach to testing. The ISO international standard of pre-clinical testing should be modified to more adequately capture actual clinical use of the implant and simulate daily activities. This article will also introduce modern methods for implant development, such as FEM, 3D printing and computer-aided orthopedic surgery, which can be widely applied to improve pre-clinical testing procedures and reduce the incidence of surgical malalignment by analyzing biomechanical performance, planning surgical procedure and providing surgical guide.

[3-dimensional visualization study of angle nerve of facial nerve].

OBJECTIVE: To validate the previous anatomic study result about angle nerve of facial nerve through 3-dimensional (3-D) visualization technique, so as to provide theory basis for clinic treatment of nerve loss. METHOD: The full-thickness soft tissue at internal side of inner canthus was harvested from adult cadaveric head. The skin was 3 cm in length and 1 cm in width, with 2 parallel cut lines as location markers. The specimen was sliced continuously into 120 slices, with 10 microm in thickness for every slice, 0.25 mm apart. The slices underwent HE staining and 2-D digital image was gained by high resolution scanner. Then 3-D reconstruction was performed. RESULTS: (1) It showed the 3-D structures and routes of angle nerve, as well as the relationship between angle nerve and angle arteriovenous. All the reconstructed structures can be displayed together or separately, also from any angles. (2) It confirmed the accuracy of microscopic anatomy study about angle nerve. (3) The 3-D reconstruction of angle nerve, as well as the surrounding structure could be very useful for clinical application. CONCLUSION: Based on the histologic study and computer technology, the 3-D reconstruction of angle nerve could provide accurate basis for the feasibility of clinic treatment of angle nerve loss.

[Anatomic study of malar fat pad and aging analysis].

OBJECTIVE: To discuss the midface aging mechanism through anatomic study of malar fat pad. METHODS: 10 fresh adult cadaveric heads (20 sides) fixed by vascular perfusion of formalin were used for anatomic study with microsurgery technique under microscope. The midfacial ligament and connective tissue between skin and subcutaneous fat were observed carefully in different parts of midface. The location, shape and extent of malar fat pad was also recorded and photographed. RESULTS: The malar fat pad has a triangle shape. The bottom is a curve along the orbicularis retaining ligament at the lower eyelid. The fat pad is extended internally to the nasolabial fold and labiomandibular fold, externally from the major zygomatic muscle end point at the malar surface to the angulus oris and submandibular edge. (2) The malar fat pad is composed of meshed fibrous tissue, with big fat particles in it. It becomes tight when being stretched in horizontal direction along nasolabial fold and loosen when being stretched in vertical direction. (3) There is tight connection between skin and fat pad, which is divided into four areas as I, II, III, IV. The areas I, II, III are strip-shaped parelled to the nasolabial fold. The area IV is a irregular quadrilateral. (4) There are six fixation ligaments between malar fat pad and deep tissue: orbicularis retaining ligament upper layer of lower eyelid, orbicularis retaining ligament substratum of lower eyelid, zygomaticus ligament, zygomatic cutaneous ligament, zygomatic cutaneous ligament substratum, platysma There are four closely connected areas cutaneous forward ligament, cheek maxilla ligament. CONCLUSIONS: between the facial skin and malar fat pad which makes malar fat pad and skin keep relatively consistent. The malar fat pad moving down mainly resulted from slack of ligaments support which is one of the reasons for aging face.

[Angular nerve of facial nerve: anatomic research].

OBJECTIVE: To study the anatomy of angular nerve (AN), so as to provide safe approach for the denervation surgery of corrugator supercilii, depressor supercilii and procerus. METHODS: 10 fresh cadaver (20 sides)were perfused and fixed with formalin. Dissection was performed in the 10 x operating microscope. The plexus of the zygomatic branch and the buccal branch were detected to confirm the AN. The relationship of AN with the surrounding blood vessels was observed. We tracked AN until it entered corrugator supercilii, depressor supercilii and procerus. RESULTS: (1) AN was classified into I, II, III type according to its formation pattern. Type I (20%, 4/20 sides) AN is single, which is mainly from the plexus of buccal branch plus the zygomatic branch from the orbicularis oculi muscle. In type II (20%, 4/20 sides), the single AN was formed by buccal branch plexus and zygomatic branch plexus in the "Four Muscle Gap". In type III (60%, 12/20 sides), the AN had two branches in the "Four Muscle Gap". (2) The three types AN passed inferior to the support ligament at the suborbital part, and then transversed medial to the support ligament at the medial canthus, along the vessels of medial canthus. (3) The branch of AN enters the depressor supercilii or procerus 2.19 to 4.28 mm above the medial canthus ligament. The backward branch enters the levator labii superioris alaeque nasi 6.89 to 9.38 mm below the medial canthus ligament. CONCLUSIONS: The approach of denervation surgery for AN should be performed medial to the support ligation, between 2.19 mm above the medial canthus and 6.89 mm below the medial canthus.