Objective Our purpose was to investigate the pathogenic gene mutation of a Han Chinese family with vitreous amyloidosis.Methods The 9 individuals(proband,1 affected member and 7 unaffected members) of the family were selected and their DNA was extracted from peripheral blood.The 4 exons of transthyretin(TTR) gene were amplified by polymerase chain reaction(PCR) technique.The amplified products of TTR gene were sequencing by Sanger technique.We also selected 100 unrelated healthy individual as the control group.Results By DNA sequencing,a heterozygous mutation was found in 4 of the 9 subjects from the family.The transition of adenine to cytosine(AAG ＞ ACG) was detectable in exon 2 of TTR,which changed the amino acid composition at codon 35 (Lys35Thr).This mutation did not presented in control group.Conclusion The heterozygosis mutation of TTR gene Lys35Thr should be a pathogenic mutation for the family with vitreous amyloidosis.

Objective:To evaluate the efficacy of infra-acetabular screw placement assisted by orthopedic navigation robot in the treatment of acetabular fractures.Methods:The data of 34 patients who were treated and followed up from September 2021 to September 2022 were retrospectively analyzed. According to the fixation method, the patients were divided into the robot group (robot assisted placement of infra-acetabular screws) and the control group (placement of the pubis-ischium plate manually). There were 16 patients in the robot group, 7 males and 9 females, aged 57.00±6.00 years (range, 51-70 years). According to Letournel classification, there were 8 cases of both-column fractures, 4 cases of anterior column and posterior hemitransverse fractures, and 4 cases of T-shaped fractures. There were 18 cases in the control group, 8 males and 10 females, aged 54.22±8.95 years (range, 38-69 years). According to Letournel classification, there were 10 cases of both-column fractures, 6 cases of anterior column and posterior hemitransverse fractures, and 2 cases of T-shaped fractures. The intraoperative fluoroscopy times, total operation time, exposure time and screw placement (plate) time, blood loss, Matta evaluation, Majeed score, and screw placement accuracy rate (the degree of screw cutting-out was evaluated according to Lonstein criteria) were compared between the two groups.Results:All patients were followed up for 12.21±3.62 months (range, 6-17 months). In the robot group, the fluoroscopy frequency was 9.69±0.95 times (range, 8-11 times), the screw placement time was 34.32±5.28 min (range, 21-45 min), and the blood loss was 461.88±228.71 ml (range, 200-800 ml). The control group was 10.11±1.41 times (range, 7-13 times), 42.89±4.38 min (range, 36-55 min), 674.44±220.65 ml (range, 420-1,100 ml), respectively. There were significant differences in screw (plate) placement time ( t=5.18, P<0.001) and blood loss ( t=2.76, P<0.001). The accuracy of robot screw placement was 100%. According to Lonstein evaluation, there were 14 cases of grade 0 (87.5%, 14/16) and 2 cases of grade I (12.5%, 2/16). At 30 days of follow-up, all patients had good fracture ends and no internal fixation failure occurred. One week after surgery, the results of Matta evaluation in robot group were excellent in 11 cases, good in 3 cases, and poor in 2 cases, with an excellent and good rate of 87.5%. In the control group, 11 cases were excellent, 4 cases were good, and 3 cases were poor, with an excellent and good rate of 83.3%. There was no significant difference in the excellent and good rate of Matta evaluation between the two groups (χ 2=0.23, P=0.892). At last follow-up, the Majeed score of robot group was 87.81±8.82 (range, 71-98), including excellent in 10 cases, good in 5 cases, and fair in 1 case. The score of the control group was 86.22±6.85 (range, 70-95), including 12 cases of excellent, 4 of good, and 2 of fair. There was no significant difference in Majeed score between the two groups ( t=0.59, P=0.551). No complications related to the use of robot-assisted navigation or plate fixation were observed in both groups. Conclusion:Through the navigation planning and assistance of the robot, the infra-acetabular screws can be accurately and safely placed, which avoids the shortcomings of excessive exposure and bleeding during the application of the pubis-ischium plate, the outcome was similar to that of plate treatment.

Objective:To investigate the efficacy and safety of the "frame and buttress" fixation in the treatment of acetabular quadrilateral fractures.Methods:A total of 26 patients with acetabular quadrilateral fractures treated with the "Frame and buttress" fixation strategy (reconstructing frame and providing buttress for quadrilateral surface) from January 2017 to January 2021 were retrospectively analyzed in the Department of Orthopaedics, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, including 17 males and 9 females, aged 47.7±16.5 years, (range, 25-71 years). There were 13 cases from car accidents, 8 cases from falls, and 5 cases from heavy objects. Quadrilateral fractures were classified according to whether the anterior column (A) and posterior column (P) of the acetabulum were fractured and whether the quadrilateral plate (Q) was partially (1) or completely (2) separated from the two columns. Among these cases, there were 5 cases of type AQ1, 1 case of type AQ2, 1 case of type PQ2, 14 cases of type APQ1 and 5 cases of type APQ2. The "frame and buttress" fixation strategy was used to perform open reduction and internal fixation. The Matta scale was used to assess the quality of resurfacing based on pelvic radiographs, and the Matta modified Merle d'Aubigne and Postel scores were referenced to evaluate hip function.Results:All the 26 patients successfully completed the operation, the operation time was 88.1±57.8 min (range, 90-320 min), the intraoperative bleeding was 753.8±309.5 ml (range, 400-1 400 ml). There were 14 cases of anatomical reduction, 8 cases of satisfactory reduction and 4 cases of unsatisfactory reduction with an excellent rate of 85% (22/26), the excellence rate was 85% (22/26). All patients were followed up for 16.3±4.3 months (range, 12-24 months). The hip function score after operation was higher than that before operation, and the difference was statistically significant ( F=19.80, P<0.001). The hip function score was 13.1±2.2 at 3 months postoperatively, increased to 15.9±2.3 at 6 months postoperatively, and increased to 16.6±1.9 at the last follow-up, with a statistically significant difference ( P<0.001). After operation, 5 patients showed symptoms of lateral femoral cutaneous nerve injury such as hypoesthesia and numbness in the anterolateral thigh. During the follow-up, there was no ectopic ossification, traumatic arthritis, necrosis of the femoral head and central dislocation of the femoral head. Conclusion:The "frame and buttress" fixation strategy based on quadrilateral fracture typing for acetabular quadrilateral fracture open reduction internal fixation provides strong fixation, satisfactory reduction quality, and facilitates joint function recovery after operation.

Objective:To compare the efficacy of acetabular magic hook plates versus quadrilateral area combined plates in treating complicated acetabular fractures.Methods:A retrospective analysis was conducted on 44 cases of complicated acetabular fractures treated at the Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, from June 2017 to August 2022. Among these cases, 21 were treated with magic hook plate internal fixation (hook plate group) and 23 with quadrilateral area combined plate internal fixation (combined plate group). In the hook plate group, there were 15 males and 6 females, with an average age of 43.1±11.8 years. According to the Letournel-Judet classification, there were 13 double-column fractures, 5 anterior column with posterior semi-transverse fractures, and 3 T-type fractures. Additionally, 8 cases were classified as B2.2 type, 5 as C1 type, 4 as C2 type, and 4 as C3 type; 15 cases were APQ1 type and 6 were APQ2 type. In the combined plate group, there were 16 males and 7 females, with an average age of 41.7±12.8 years. This group included 15 double-column fractures, 6 anterior column with posterior semi-transverse fractures, and 2 T-type fractures. Additionally, there were 8 cases of B2.2 type, 6 cases of C1 type, 4 cases of C2 type, and 5 cases of C3 type; 15 cases were APQ1 type and 8 were APQ2 type. Comparative analyses included operative time, intraoperative blood loss, fracture healing time, Matta standard assessment, modified Merle d'Aubign-Postel scores, and postoperative complications.Results:All 44 patients were followed up for 10 to 24 months, with an average follow-up of 14 months. The acetabular fractures healed in all cases. The healing time was 3.6±0.9 months for the hook plate group and 3.7±0.9 months for the combined plate group, with no significant difference between the groups ( t=0.549, P=0.586). The hook plate group had an operative time of 138.3±30.7 minutes and intraoperative blood loss of 735.7±159.8 ml, compared to 163.9±48.7 minutes and 843.5±181.1 ml, respectively, in the combined plate group, both of which were statistically significant ( P<0.05). The reduction quality was excellent in 13 cases, good in 5 cases, and poor in 3 cases in the hook plate group, with an excellent and good rate of 86% (18/21). In the combined plate group, the reduction quality was excellent in 13 cases, good in 6 cases, and poor in 4 cases, with an excellent and good rate of 83% (19/23), showing no significant difference between the groups (χ 2=0.143, P=0.931). The modified Merle d'Aubign Postel scores of the hook plate group were 13.8±2.2 points, 15.3±2.5 points and 16.7±1.8 points at 3 months, 6 months and the last follow-up, respectively, and the combined plate group were 13.1±1.9 points, 14.6±2.1 points and 16.4±2.0 points, respectively ( P>0.05). However, both groups showed statistically significant improvements in hip function over time ( F=9.658, P<0.001; F=16.195, P<0.001). Wound fat liquefaction and lateral femoral cutaneous nerve injury occurred in one case each in both groups. In the combined plate group, there were 3 cases of incision fat liquefaction, 2 cases of lateral femoral cutaneous nerve injury, and 1 case of traumatic hip arthritis. No other complications such as incision infection, iliac vascular injury, or loss of internal fixation were observed in either group. Conclusion:Both magic hook plate fixation and quadrilateral area combined plate fixation are safe and effective for treating complex acetabular fractures. However, magic hook plate fixation offers advantages in reducing operative time and intraoperative blood loss, thereby simplifying and enhancing the safety of the procedure.

As an important protein acylation modification, lysine succinylation (Ksucc) is involved in diverse biological processes, and participates in human tumorigenesis. Here, we collected 26,243 non-redundant known Ksucc sites from 13 species as the benchmark data set, combined 10 types of informative features, and implemented a hybrid-learning architecture by integrating deep-learning and conventional machine-learning algorithms into a single framework. We constructed a new tool named HybridSucc, which achieved area under curve (AUC) values of 0.885 and 0.952 for general and human-specific prediction of Ksucc sites, respectively. In comparison, the accuracy of Hybrid-Succ was 17.84％–50.62％better than that of other existing tools. Using HybridSucc, we conducted a proteome-wide prediction and prioritized 370 cancer mutations that change Ksucc states of 218 important proteins, including PKM2, SHMT2, and IDH2. We not only developed a high-profile tool for predicting Ksucc sites, but also generated useful candidates for further experimental con-sideration. The online service of HybridSucc can be freely accessed for academic research at http://hybridsucc.biocuckoo.org/.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).