Application and prospect of gene therapy for fundus vascular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Fundus vascular diseases, including neovascular age-related macular degeneration(nAMD)and diabetic retinopathy(DR), are the leading causes of visual impairment worldwide. With the accelerated aging and increased incidence of diabetes, the prevalence of these two fundus diseases will continue to rise. Currently, intraocular injection of anti-vascular endothelial growth factor(anti-VEGF)remains the first-line treatment for fundus vascular diseases, but disadvantages exist, such as frequent intraocular injections, high cost and poor compliance, thus more durable and effective therapeutic strategies need to be explored. The successful application of gene therapy in inherited retinal diseases(IRDs)provides a new idea for the treatment of fundus vascular diseases. With the ongoing of several clinical trials, gene therapy for fundus vascular diseases is expected to be employed in the clinical setting. But there still remain some concerns, including the optimal therapeutic targets selection, administration route and safety issues. This review focuses on the application and prospect of gene augmentation and gene editing-mediated anti-VEGF therapy for the treatment of nAMD and DR.

Roles and perspectives of inflammatory factors in diabetic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy is the leading cause of blindness in the working-age population, in which diabetic macular edema(DME)is the most common reason resulting in the vision impairment. Studies showed that inflammation factors play an important role in the pathogenesis and development of DME. Chronic hyperglycemia activates several biochemical pathways, leading to retinal hypoxia, oxidative stress and chronic inflammation. Intraretinal inflammation-related cells, such as microglia, monocytes/macrophages, Müller cells and retinal pigment epithelial cells, become activated and release a large number of inflammation-related factors and mediators, including the complement system, vascular endothelial growth factor(VEGF), placental growth factor(PlGF), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-6 and IL-8, etc., resulting in the breakdown of the blood-retinal barrier and neuronal degeneration. In addition, up-regulatethe expression of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)by retinal vascular endothelial cells increased the adhesion of leukocyte and leukostasis, further aggravating retinal hypoxia and breakdown of the blood-retinal barrier, leading to the increased retinal vascular leakage and macular edema. Therefore, early treatment with anti-VEGF and anti-inflammatory are pivotal for the treatment of DME. In this review, we will discuss the role of inflammation factors in the pathogenesis of DME and the research status of the targeted drugs targeting inflammation, so as to provide reference for the treatment of DME.

A scenario on the stepwise evolution of the genetic code / 基因组蛋白质组与生物信息学报·英文版

It is believed that in the RNA world the operational (ribozymes) and the informational (riboscripts) RNA molecules were created with only three (adenosine, uridine, and guanosine) and two (adenosine and uridine) nucleosides, respectively, so that the genetic code started uncomplicated. Ribozymes subsequently evolved to be able to cut and paste themselves and riboscripts were acceptive to rigorous editing (adenosine to inosine); the intensive diversification of RNA molecules shaped novel cellular machineries that are capable of polymerizing amino acids-a new type of cellular building materials for life. Initially, the genetic code, encoding seven amino acids, was created only to distinguish purine and pyrimidine; it was later expanded in a stepwise way to encode 12, 15, and 20 amino acids through the relief of guanine from its roles as operational signals and through the recruitment of cytosine. Therefore, the maturation of the genetic code also coincided with (1) the departure of aminoacyl-tRNA synthetases (AARSs) from the primordial translation machinery, (2) the replacement of informational RNA by DNA, and (3) the co-evolution of AARSs and their cognate tRNAs. This model predicts gradual replacements of RNA-made molecular mechanisms, cellular processes by proteins, and informational exploitation by DNA.

The anatomical study of transoral atlantoaxial reduction plate internal fixation / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To study relevant anatomical features of the structures involved in transoral atlanto-axial reduction plate (TARP) internal fixation through transoral approach for treating irreducible atlanto-axial dislocation and providing anatomical basis for the clinical application of TARP.</p><p><b>METHODS</b>Ten fresh craniocervical specimens were microsurgically dissected layer by layer through transoral approach. The stratification of the posterior pharyngeal wall, the course of the vertebral artery, anatomical relationships of the adjacent structures of the atlas and axis, and the closely relevant anatomical parameters for TARP internal fixation were measured.</p><p><b>RESULTS</b>The posterior pharyngeal wall consisted of two layers and two interspaces: the mucosa, prevertebral fascia, retropharyngeal space, and prevertebral space. The range from the anterior edge of the foramen magnum to C(3) could be exposed by this approach. The thickness of the posterior pharyngeal wall was (3.6+/-0.3) mm (ranging 2.9-4.3 mm) at the anterior tubercle of C1, (6.1+/-0.4) mm (ranging 5.2-7.1 mm) at the lateral mass of C(1) and (5.5+/-0.4) mm (ranging 4.3-6.5 mm) at the central part of C(2), respectively. The distance from the incisor tooth to the anterior tubercle of C(1), C(1) screw entry point, and C(2)screw entry point was (82.5+/-7.8) mm (ranging 71.4-96.2 mm), (90.1+/-3.8) mm (ranging 82.2-96.3 mm), and (89.0+/-4.1) mm (ranging 81.3-95.3 mm), respectively. The distance between the vertebral artery at the atlas and the midline was (25.2+/- 2.3) mm (ranging 20.4-29.7 mm) and that between the vertebral artery at the axis and the midline was (18.4+/- 2.6) mm (ranging 13.1-23.0 mm). The allowed width of the atlas and axis for exposure was (39.4+/-2.2) mm (ranging 36.2-42.7 mm) and (39.0+/-2.1) mm (ranging 35.8-42.3 mm), respectively. The distance (a) between the two atlas screw insertion points (center of anterior aspect of C(1) lateral mass) was (31.4+/-3.3) mm (ranging 25.4-36.6 mm). The vertical distance (b) between the line connecting the two C(1) screw entry points and that connecting the two C(2) screw entry points (at the central part of the vertebrae, namely 3-4 mm lateral to the midline of C(2) vertebrae) was (21.3+/-2.7) mm (ranging 19.4-24.3 mm), with an a/b ratio of 1.3-1.5. The screws of TARP had a lateral tilt of 12.2 degrees+/-0.4 degrees(ranging 10.2 degrees-14.6 degrees) at C(1) and a medial tilt of 7.3 degrees+/-0.3 degrees (ranging 5.1 degrees-9.4 degrees) at C(2) relative to the coronal plane.</p><p><b>CONCLUSIONS</b>An atlanto-axial surgery through transoral approach is safe and feasible. This approach is suitable for an anterior TARP internal fixation, and the design of the internal fixation system should be based on the above anatomical data.</p>

Transoral atlantoaxial reduction plate fixation for irreducible atlantoaxial dislocation / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To design a clinically applicable transoralpharyngeal atlantoaxial reduction plate (TARP), introduce the operation procedure, and evaluate its preliminary clinical effects.</p><p><b>METHODS</b>A novel TARP system, including butterfly titanium alloy plate, self-locking screws, atlantoaxial reductor and other operational instruments was developed. This system was applied clinically on five patients with irreducible atlantoaxial dislocation of congenital or traumatic origin. During operation, the reduction was completed by the combined action of the plate and the atlantoaxial reductor after transoral joint release and cord decompression. Bone graft granules were implanted between the bilateral atlantoaxial joints and TARP was used to immobilize subsequently the atlas and axis.</p><p><b>RESULTS</b>Clinical application demonstrated that TARP could induce instant reduction and that the method was operationally feasible and its postoperational effect was satisfactory.</p><p><b>CONCLUSIONS</b>The design of TARP is novel. The operational procedure is simple and easy to use. Furthermore, instant reduction can be completed during the operation and the fixation is relatively stable. TARP is an ideal alternative for irreducible atlantoaxial dislocation and may have excellent prospects for further clinical applications.</p>

Anatomic evaluation the entry point of C2 pedicle screw / 中华外科杂志

<p><b>OBJECTIVE</b>To study the relevant position of C(2) pedicle to C(2) inferior articular process, set up a technique of C(2) pedicle screw placement with the inferior articular process of axis as an anatomic landmark.</p><p><b>METHODS</b>Fifty C(2) bone specimens were used to measure the distance from the sagittal midline to the medial border, the midpoint and the lateral border of C(2) inferior articular process or C(2) pedicle; the width and the height of the C(2) pedicle were also evaluated. The anatomic relation between the measurements data of C(2) pedicle and that of C(2) inferior articular process were analyzed, and the technique of C(2) pedicle screw fixation was established.</p><p><b>RESULTS</b>The medial border of C(2) inferior articular process was averaged (3.67 +/- 0.41) mm lateral to that of C(2) pedicle, and the midpoint C(2) inferior articular process was averaged (1.15 +/- 0.44) mm lateral to the lateral border of C(2) pedicle, respectively. Using the C(2) inferior articular process as landmark, two techniques was established for C(2) pedicle screw placement. The entry point of method A was located in 2 mm medial and superior to the central point of C(2) inferior articular process; the entry point of method B was at the crossing point of the medial border C(2) inferior articular process with the superior quarter of C(2) inferior articular process.</p><p><b>CONCLUSIONS</b>There is a steady anatomic relation between C(2) pedicle and C(2) inferior articular process, the C(2) inferior articular process could be as a convenient key anatomic landmark to determine the location of C(2) pedicle and the position of C(2) pedicle screw entry point.</p>

Anatomic identification of the location of the pedicle of atlas with the lateral mass of C2 to C4 as the landmark / 中华外科杂志

<p><b>OBJECTIVE</b>To study the relevant position of the pedicle of C1 to the lateral mass of C(2-4), set up an identification technique for the entry point decision of C1 pedicle screw by using the lateral mass of C(2-4) as anatomic landmarks.</p><p><b>METHODS</b>Twenty cadaver specimens were used to measure the distance from the sagittal midline of spine to the medial border, the midpoint and the lateral border of C1 pedicle or the lateral mass of C2, C3 or C4. The anatomic relation between the measurements data of C1 pedicle and that of the lateral masses of the cervical vertebrae were analyzed, and the technique of C1 pedicle screw fixation was established.</p><p><b>RESULTS</b>The average medial border of the lateral mass of C2, C3 and C4 was 0.37 mm, 0.27 mm and 0.24 mm lateral to that of C1 pedicle, the average midpoint of the lateral mass of C2, C3 and C4 was 1.18 mm, 1.41 mm and 1.74 mm lateral to that of C1 pedicle, and the average lateral border of the lateral mass of C2, C3 and C4 was 1.96 mm, 2.54 mm and 3.24 mm lateral to that of C1 pedicle, respectively.</p><p><b>CONCLUSION</b>There is a steady anatomic location relation between C1 pedicle and the lateral mass of C2, C3 or C4. As well as the lateral mass of C2, the lateral mass of C3 or that of C4 could be convenient anatomic landmarks to determine the location of C1 pedicle and the position of C1 pedicle screw entry point.</p>

Design and preliminary clinical application of transoralpharyngeal atlantoaxial reduction plate / 中华外科杂志

<p><b>OBJECTIVE</b>To design transoralpharyngeal atlantoaxial reduction plate (TARP), evaluate its biomechanical performance and observe its preliminary clinical effect.</p><p><b>METHODS</b>A brand-new TARP system was designed, including butterfly titanium alloy plate, self-locking screws, atlantoaxial reductor and other operation instruments. Twelve fresh occipital bone-C(3) specimen were designed for biomechanical test including range of motion (ROM) (n = 6) and screw pull-out strength (n = 12). Preliminary clinical application of TARP was reported.</p><p><b>RESULTS</b>The reduction mechanism of the TARP system was designed cleverly. TARP had equal effect with Magerl + Brooks and it was more stable than the other three clinically widely used atlantoaxial fixators: Magerl, Brooks and anterior transarticular screw fixation through C(2) vertebral body. TARP's C(1) and C(2) screws were strong enough for atlantoaxial arthrodesis and their antipull-out performance was excellent. Clinical application on irreducible atlantoaxial dislocation proved that TARP had the function of instant reduction, the operation was feasible and the operation effect was significant.</p><p><b>CONCLUSION</b>TARP's design is novel and it has excellent biomechanical performance. The operation procedure is simple and reasonable. Furthermore, instant reduction could be completed during the operation and the fixation is strong. Above all, TARP is creative and will have excellent prospect.</p>

Results of 1310 knees of meniscal treatment evaluated by arthroscopy / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate results of 1310 knees of meniscal treatments by arthroscopy and to present good method of meniscal treatment.</p><p><b>METHODS</b>Their age, traumatic mechanism and effects under arthroscopy were analysed in a series of 254 patients with meniscal injuries, there were 880 males and 374 females, the average of the patients was 25.5 years. The meniscal repair in 68 knee, partial meniscectomy in 756 knee, total meniscectomy in 480 knee and conservative treatment in 6 cases.</p><p><b>RESULTS</b>The patients were followed up 1 to 12 years with the average of 4 years and 3 months. The mean Lysholm score was 86.3 points in arthroscopic meniscal repair, 84.0 points in partial meniscectomy and 76.1 points in total meniscectomy. The mean Lysholm 98.7 points in all children patients with conservative treatment. They showed significant difference (P < 0.01) in the results of three treatments.</p><p><b>CONCLUSIONS</b>Meniscal injuries should not cut off as it, should be repaired in 5 mm from meniscus to synovium and or partial meniscectomy. The general adoption is not the surgical operation on meniscal injuries of the child.</p>

The reason and prevention of upper cervical reoperations / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the reasons for the operation performed on 13 patients with upper cervical disease and to explore the management and prevention of upper cervical disease.</p><p><b>METHODS</b>Thirteen patients with upper cervical disease were retrospectively reviewed. The reason for of reoperations on these patients were analyzed. The measures to reduce upper cervical operational complication and bad prognosis were discussed to avoid reoperations.</p><p><b>RESULTS</b>The reasons for reoperations included 9 cases with unstable or re-dislocated atlantoaxial joint, 10 cases with residual spinal cord compression, 1 case with malposition of odontoid screw, 1 case with adjacent cervical spine regression, 1 case with occipital-cervical fusion failure, 1 case with spinal cord injury during operation, 1 case with bone-plant slipped into canales spinalis, and 1 case with demand to take out internal fixation for aggravated symptom.</p><p><b>CONCLUSIONS</b>The common reasons for upper cervical reoperations were due to instability or redislocation of atlantoaxial joint and residual of spinal cord compression. Some measures such as reducing operate miss, using firm internal fixation and decompressing were advisable to decrease the incidence of reoperations.</p>

ANTI-MUTATION ACTIVITES OF TORTOISE SHELL AND TURTLE SHELL / 中国海洋药物

Sister chromatid exchange in myelogenous cell of mice was measured to evaluate the effects of anti- mutation by the Chinese triditional medicine , Turtle shell and tortoise shell. The results showed both of them have significant anti-mutation activites.