[Influence of anterior fracture line on anterior cortical reduction loss after cephalomedullary nail fixation in intertrochanteric fractures].

Objective: To investigate the position of the anterior fracture line in AO/Orthopaedic Trauma Association (AO/OTA) type A2 unstable intertrochanteric fractures and its impact on the incidence of anterior cortical reduction loss after cephalomedullary nail fixation. Methods: A clinical data of 95 patients with intertrochanteric fractures who met the selection criteria between April 2020 and February 2023 was retrospectively analyzed. All patients were treated with cephalomedullary nail fixation, and the intra- and post-operative imaging data were complete. Among them, there were 37 males and 58 females. The age ranged from 61 to 97 years, with an average of 79.6 years. The time from injury to operation ranged from 7 hours to 11 days, with an average of 2.8 days. According to the 2018-AO/OTA classification standard, there were 39 cases of type 31-A2.2 and 56 cases of type 31-A2.3. Intraoperative fluoroscopy was used to record the number of patients with satisfactory fracture alignment. The preoperative CT data were imported into Mimics17.0 software to simulate the fracture reduction and measure the distance between the anterior fracture line and the intertrochanteric line bony ridge. The fractures were classified as transcapsular fractures, extra-capsular fractures, and intra-capsular fractures according to the distance. CT three-dimensional reconstruction was performed within 2 weeks after operation to observe the number of patients with anterior cortical reduction loss. The postoperative anterior cortical reduction loss incidence in patients with satisfactory fracture alignment, and the relationship between postoperative anterior cortical reduction loss and the position of the anterior fracture line were observed. Results: There were 52 cases (54.7%) of transcapsular fractures, 24 cases (25.3%) of extra-capsular fractures, and 19 cases (20.0%) of intra-capsular fractures. Among them, 41 of the 52 transcapsular fractures had satisfactory fracture alignment, and 4 (9.8%) of them experienced anterior cortical reduction loss after operation; 19 of the 24 extra-capsular fractures had satisfactory fracture alignment, and no anterior cortical reduction loss occurred; 16 of the 19 intra-capsular fractures had satisfactory fracture alignment, and 7 (43.8%) of them experienced anterior cortical reduction loss after operation. There was a significant difference in the incidence of anterior cortical reduction loss between groups ( χ 2=8.538， P=0.003). All patients were followed up 3-26 months (mean, 9 months). Among them, 91 cases had fracture healing, and 4 cases had nonunion. Conclusion: In AO/OTA type A2 unstable intertrochanteric fractures, where the anterior fracture line is located within the joint capsule, there is a high risk of anterior cortical reduction loss after operation.

Importance of the Posterior Plate in Three-Column Tibial Plateau Fractures: A Finite Element Analysis and Clinical Validation.

OBJECTIVE: Dual-plate fixation was thought to be the gold standard for treating complicated bicondylar tibial plateau fractures, yet it was found to be hard to accommodate the posterior column in three-column fractures. Currently, column-specific fixation is becoming more and more recognized, but no comprehensive investigation has been performed to back it up. Therefore, the objective of this study was to validate the importance of posterior column fixation in the three-column tibial fractures by a finite element (FE) analysis and clinical study. METHODS: In FE analysis, three models were developed: the longitudinal triple-plate group (LTPG), the oblique triple-plate group (OTPG), and the dual-plate group (DPG). Three loading scenarios were simulated. The distribution of the displacement and the equivalent von Mises stress (VMS) in each structure was calculated. The comparative measurements including the maximum posterior column collapse (MPCC), the maximum total displacement of the model (MTD), the maximum VMS of cortical posterior column (MPC-VMS), and the maximum VMS located on each group of plates and screws (MPS-VMS). The clinical study evaluated the indicators between the groups with or without the posterior plate, including operation time, blood loss volume, full-weight bearing period, Hospital for Special Surgery Knee Scoring system (HSS), Rasmussen score, and common postoperative complications. RESULTS: In the FE analysis, the MPCC, the MPC-VMS, and the MTD were detected in much lower amounts in LTPG and OTPG than in DPG. In comparison with DPG, the LTPG and OTPG had larger MPS-VMS. In the clinical study, 35 cases were included. In the triple-plate (14) and dual-plate (21) groups, the operation took 115.6 min and 100.5 min (p < 0.05), respectively. Blood loss in both groups was 287.0 mL and 206.6 mL (p < 0.05), and the full-weight bearing period was 14.5 weeks and 16.2 weeks (p < 0.05). At the final follow-up, the HSS score was 85.0 in the triple-plate group and 77.5 in the dual-plate (p < 0.05), the Rasmussen score was 24.1 and 21.6 (p < 0.05), there were two cases with reduction loss (9.5%) in the dual-plate group and one case of superficial incision infection found in the triple-plate group. CONCLUSION: The posterior implant was beneficial in optimizing the biomechanical stability and functional outcomes in the three-column tibial plateau fractures.

[Off target of distal interlocking screw in short cephalomedullary nail fixation for intertrochanteric femur fractures].

Objective: To analyze the causes and treatment of off target of the distal interlocking screws when short cephalomeduallry nails were installed through jig-guided targeting device, and to put forward the technical points to prevent off target. Methods: Retrospective analysis of 9 patients with intertrochanteric fractures treated between July 2014 and June 2023 was conducted, in which off target occurred during the insertion of the distal interlocking screw by jig-guided targeting device in short cephalomedullary nailling (<24 cm). There were 1 male and 8 females, with an average age of 82.7 years (range, 73-94 years). There were 3 cases of type A1, 5 cases of type A2, and 1 case of type A3 according to 2018-AO/Orthopaedic Trauma Association (AO/OTA) fracture classification. As for the misaligned distal interlocking screw, six parameters were collected and analyzed, including the time of finding, the position, the type of passing through the cortical bone, the special circumstances during operation (such as the need to remove the intramedullary nail for reaming the diaphysis, hammering, etc.), the treatment, and the patient follow-up results. Results: In the 9 patients, the off target of the distal interlocking screw was found in 7 cases during operation and in 2 cases after operation; the locking screw was located behind the nail in 7 cases and in front of the nail in 2 cases; the off target locking screw was passing tangentially in transcortical patern in 6 cases and in bicortical pattern through the medullary cavity in 3 cases. Three cases were attributed to the mismatch between the nail and the femur, two of which were attributed to the narrow femoral medullary cavity, one of which was attributed to the large anterolateral femoral bowing, and the other 6 cases were attributed to technical errors such as the loosening of the jig-guided targeting device, the tension of the fascia lata, and the blunt of the drill. In the 7 cases found during operation, the misaligned interlocking screw was removed first and the screw hole was left vacant, then in 2 cases, the interlocking screw was not used further; in 1 case, the distal dynamic hole was successfully inserted with a dynamic guide frame, and in 4 cases, the interlocking screw was successfully put after 2-3 attempts, leaving a large hole in the lateral cortex. No special treatment was performed in 2 cases found after operation. One patient was out of bed early after operation, 7 patients were in bed for 1 month, and 1 patient deteriorated to A3 type after operation and was in bed for 3 months. All the 9 patients were followed up 6-12 months, with an average of 8 months. Fracture healing was achieved in 8 patients. One patient with vacant interlocking screw had a secondary spiral fracture of the femoral shaft 3 months later, and was refixed with a long cephalomedullary nail and circlage wiring. Conclusion: Distal interlocking screw off target is rare, but when it occurs, it leaves a large cortical hole in the osteoporotic femoral shaft, reducing bone strength; the use of precision instruments and attention to technical details can reduce this adverse phenomenon.

Spem2, a novel testis-enriched gene, is required for spermiogenesis and fertilization in mice.

Spermiogenesis is considered to be crucial for the production of haploid spermatozoa with normal morphology, structure and function, but the mechanisms underlying this process remain largely unclear. Here, we demonstrate that SPEM family member 2 (Spem2), as a novel testis-enriched gene, is essential for spermiogenesis and male fertility. Spem2 is predominantly expressed in the haploid male germ cells and is highly conserved across mammals. Mice deficient for Spem2 develop male infertility associated with spermiogenesis impairment. Specifically, the insufficient sperm individualization, failure of excess cytoplasm shedding, and defects in acrosome formation are evident in Spem2-null sperm. Sperm counts and motility are also significantly reduced compared to controls. In vivo fertilization assays have shown that Spem2-null sperm are unable to fertilize oocytes, possibly due to their impaired ability to migrate from the uterus into the oviduct. However, the infertility of Spem2-/- males cannot be rescued by in vitro fertilization, suggesting that defective sperm-egg interaction may also be a contributing factor. Furthermore, SPEM2 is detected to interact with ZPBP, PRSS21, PRSS54, PRSS55, ADAM2 and ADAM3 and is also required for their processing and maturation in epididymal sperm. Our findings establish SPEM2 as an essential regulator of spermiogenesis and fertilization in mice, possibly in mammals including humans. Understanding the molecular role of SPEM2 could provide new insights into future therapeutic treatment of human male infertility and development of non-hormonal male contraceptives.

[Research progress on valgus impacted proximal humeral fractures].

Objective: To review the advancement made in the understanding of valgus impacted proximal humeral fracture (PHF). Methods: The domestic and foreign literature about the valgus impacted PHF was extensively reviewed and the definition, classification, pathological features, and treatment of valgus impacted PHFs were summarized. Results: PHF with a neck shaft angle ≥160° is recognized as a valgus impacted PHF characterized by the preservation of the medial epiphyseal region of the humeral head, which contributes to maintenance of the medial periosteum's integrity after fracture and reduces the occurrence of avascular necrosis. Therefore, the valgus impacted PHF has a better prognosis when compared to other complex PHFs. The Neer classification designates it as a three- or four-part fracture, while the AO/Association for the Study of Internal Fixation (AO/ASIF) categorizes it as type C (C1.1). In the management of the valgus impacted PHF, the selection between conservative and surgical approaches is contingent upon the patient's age and the extent of fracture displacement. While conservative treatment offers the advantage of being non-invasive, it is accompanied by limitations such as the inability to achieve anatomical reduction and the potential for multiple complications. Surgical treatment includes open reduction combined with steel wire or locking plate and/or non-absorbable suture, transosseous suture technology, and shoulder replacement. Surgeons must adopt personalized treatment strategies for each patient with a valgus impacted PHF. Minimally invasive surgery helps to preserve blood supply to the humeral head, mitigate the likelihood of avascular necrosis, and reduce postoperative complications of bone and soft tissue. For elderly patients with severe comminuted and displaced fractures, osteoporosis, and unsuitable internal fixation, shoulder joint replacement is the best treatment option. Conclusion: Currently, there has been some advancement in the classification, vascular supply, and management of valgus impacted PHF. Nevertheless, further research is imperative to assess the clinical safety, biomechanical stability, and indication of minimally invasive technology.

The remnant axial cortical length of the proximal femur in pertrochanteric fractures: a three-dimensional computed tomography study and its clinical implications.

BACKGROUND: Cortical buttress are important factors for postoperative stable reconstruction of per/inter-trochanteric fractures. The study aimed to measure the remnant axial cortical length (RACL) of the proximal circumference of the femur, and to determine which part of the RACL can be used reliably to postoperatively sustain the head-neck fragment as a cortical support pattern. METHODS: Eighty patients with trochanteric hip fractures admitted from January 2015 to January 2016 were included in a retrospective study. Their pre-operative computed tomography (CT) images were used to form 3D-CT reconstructions via Mimics software. After simulated rotation and movement for fracture reduction, the RACL, its three component parts-namely, the remnant anterior cortex (RAC), remnant lateral cortex (RLC), and remnant posterior cortex (RPC) -the γ angle between the anterior and posterior cortex, and the Hsu's lateral wall thickness (LWT) were evaluated. RESULTS: Patients with an A1 fracture (21/80) had a longer RACL (88.8 ± 15.8 mm) than those with an A2 fracture (60.0 ± 11.9 mm; P < 0.01). The RAC, RLC, and RPC of the RACL in A1 fractures were also significantly longer than those in A2 fractures (P < 0.001). However, the most significant difference among the three components of the RACL was in the RPC, which was 27.3 ± 7.8 mm in A1 fractures and 9.2 ± 6.6 mm in A2 fractures. In addition, the coefficient of variation of the RAC was only 20.0%, while that of the RPC was 75.5%. The average γ angle in A1 fractures was 16.2 ± 13.1°, which was significantly smaller than that in A2 fractures, which was 40.3 ± 14.5° (P < 0.001). There was a significant statistical difference in the LWT between A1 and A2 fractures (P < 0.001). There were significant differences in the RACL, RAC, RLC, RPC, γ angle, and LWT among the five subtypes (P < 0.001). CONCLUSIONS: The RAC is relatively stable in pertrochanteric fractures. Fracture reduction through a RAC buttress may help to enhance the postoperative stable reconstruction of per/inter-trochanteric fractures and make possible good mechanical support for fracture healing.

Two-Part Intertrochanteric Femur Fractures with Bisection of the Lesser Trochanter: An Irreducible Fracture Pattern.

Objective: To introduce the clinical features of and surgical techniques for a rare type of irreducible pertrochanteric femur fracture pattern with bisection of the lesser trochanter. Methods: From January 2017 to December 2019, 357 patients with per/intertrochanteric femur fractures underwent surgery by closed reduction and internal fixation, of whom 12 patients were identified with rare preoperative imaging features, the lesser trochanter was almost equally bisected. The main fracture pathoanatomy of these cases included: The anterior fracture line passed along the intertrochanteric line to the medial lesser trochanter and bisected it into 2 equal parts from mid-level of the lesser trochanteric protrusion. The proximal part of the lesser trochanter connected to the head-neck fragment and attached by the psoas major tendon, while the distal part of the lesser trochanter connected to the femoral shaft and attached by the tendon of the iliac muscle. These fractures were irreducible by a closed maneuver and were reduced with limited assistance by some devices, and short intramedullary nails were used for fixation of these fractures. Results: All patients were followed up for an average of 14.2 ± 2.1 months. Clinical fracture union occurred at an average of 10.8 ± 1.5 weeks, while radiographic union occurred at an average of 12.7 ± 1.2 weeks. No cut out of the helical blade was visible on radiographs. The average Parker-Palmer score was 6.9 ± 1.3 (range, 5-9) at the last follow up, including 8 cases rated as excellent, 2 as good and 2 as fair. Conclusion: Two-part pertrochanteric femur fractures with bisection of the lesser trochanter have an irreducible fracture pattern with cortical locking and soft tissue incarceration. Soft tissue release and short cephalomedullary nail fixation for this fracture pattern provide stable fixation and allow early exercise. This treatment appears to have excellent outcomes in the short and medium terms.

PRSS37 deficiency leads to impaired energy metabolism in testis and sperm revealed by DIA-based quantitative proteomic analysis.

Our previous studies have reported that a putative trypsin-like serine protease, PRSS37, is exclusively expressed in testicular germ cells during late spermatogenesis and essential for sperm migration from the uterus into the oviduct and sperm-egg recognition via mediating the interaction between PDILT and ADAM3. In the present study, the global proteome profiles of wild-type (wt) and Prss37-/- mice in testis and sperm were compared employing data independent acquisition (DIA) technology. Overall, 2506 and 459 differentially expressed proteins (DEPs) were identified in Prss37-null testis and sperm, respectively, when compared to control groups. Bioinformatic analyses revealed that most of DEPs were related to energy metabolism. Of note, the DEPs associated with pathways for the catabolism such as glucose via glycolysis, fatty acids via ß-oxidation, and amino acids via oxidative deamination were significantly down-regulated. Meanwhile, the DEPs involved in the tricarboxylic acid cycle (TCA cycle) and oxidative phosphorylation (OXPHOS) were remarkably decreased. The DIA data were further confirmed by a markedly reduction of intermediate metabolites (citrate and fumarate) in TCA cycle and terminal metabolite (ATP) in OXPHOS system after disruption of PRSS37. These outcomes not only provide a more comprehensive understanding of the male fertility of energy metabolism modulated by PRSS37 but also furnish a dynamic proteomic resource for further reproductive biology studies.

Increased Anxiety-like Behaviors in Adgra1-/- Male But Not Female Mice are Attributable to Elevated Neuron Dendrite Density, Upregulated PSD95 Expression, and Abnormal Activation of the PI3K/AKT/GSK-3ß and MEK/ERK Pathways.

Adhesion G protein-coupled receptor A1 (ADGRA1) belongs to the G protein-coupled receptor (GPCR) family, and its physiological function remains largely unknown. We found that Adgra1 is highly and exclusively expressed in the brain, suggesting that Adgra1 may be involved in the regulation of neurological behaviors including anxiety, depression, learning and memory. To this end, we comprehensively analyzed the potential role of ADGRA1 in the neurobehaviors of mice by comparing Adgra1-/- and their wild-type (wt) littermates. We found that Adgra1-/- male but not female mice exhibited elevated anxiety levels in the open field, elevated plus maze, and light-dark box tests, with normal depression levels in the tail-suspension and forced-swim tests, and comparable learning and memory abilities in the Morris water maze, Y maze, fear condition, and step-down avoidance tests. Further studies showed that ADGRA1 deficiency resulted in higher dendritic branching complexity and spine density as evidenced by elevated expression levels of SYN and PSD95 in amygdalae of male mice. Finally, we found that PI3K/AKT/GSK-3ß and MEK/ERK in amygdalae of Adgra1-deficient male mice were aberrantly activated when compared to wt male mice. Together, our findings reveal an important suppressive role of ADGRA1 in anxiety control and synaptic function by regulating the PI3K/AKT/GSK-3ß and MEK/ERK pathways in amygdalae of male mice, implicating a potential, therapeutic application in novel anti-anxiety drug development.

Choline acetyltransferase and vesicular acetylcholine transporter are required for metamorphosis, reproduction, and insecticide susceptibility in Tribolium castaneum.

Choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) are essential enzymes for synthesizing and transporting acetylcholine (ACh). But their functions in metamorphosis, reproduction, and the insecticide susceptibility were poorly understood in the insects. To address these issues, we identified the orthologues of chat and vacht in Tribolium castaneum. Spatiotemporal expression profiling showed Chat has the highest expression at the early adult stage, while vacht shows peak expression at the early larval stage. Both of them were highly expressed at the head of late adult. RNA interference (RNAi) of chat and vacht both led to a decrease in ACh content at the late larval stage. It is observed that chat knockdown severely affected larval development and pupal eclosion, but vacht RNAi only disrupted pupal eclosion. Further, parental RNAi of chat or vacht led to 35 % or 30 % reduction in fecundity, respectively, and knockdown of them completely inhibited egg hatchability. Further analysis has confirmed that both the reduction in fecundity and hatchability caused through the maternal specificity in T. castaneum. Moreover, the transcript levels of chat and vacht were elevated after carbofuran or dichlorvos treatment. Reduction of chat or vacht decreased the resistance to carbofuran and dichlorvos. This study provides the evidence for chat and vacht not only involved in development and reproduction of insects but also could as the potential targets of insecticides.

[Three-dimensional finite element analysis of exo-cortical placement of humeral calcar screw for reconstruction of medial column stability].

Objective: To explore the biomechanical stability of the medial column reconstructed with the exo-cortical placement of humeral calcar screw by three-dimensional finite element analysis. Methods: A 70-year-old female volunteer was selected for CT scan of the proximal humerus, and a wedge osteotomy was performed 5 mm medially inferior to the humeral head to form a three-dimensional finite element model of a 5 mm defect in the medial cortex. Then, the proximal humeral locking plate (PHILOS) was placed. According to distribution of 2 calcar screws, the study were divided into 3 groups: group A, in which 2 calcar screws were inserted into the lower quadrant of the humeral head in the normal direction for supporting the humeral head; group B, in which 1 calcar screw was inserted outside the cortex below the humeral head, and the other was inserted into the humeral head in the normal direction; group C, in which 2 calcar screws were inserted outside the cortex below the humeral head. The models were loaded with axial, shear, and rotational loadings, and the biomechanical stability of the 3 groups was compared by evaluating the peak von mises stress (PVMS) of the proximal humerus and the internal fixator, proximal humeral displacement, neck-shaft angle changes, and the rotational stability of the proximal humerus. Seven cases of proximal humeral fractures with comminuted medial cortex were retrospectively analyzed between January 2017 and December 2020. Locking proximal humeral plate surgery was performed, and one (5 cases) or two (2 cases) calcar screws were inserted into the inferior cortex of the humeral head during the operation, and the effectiveness was observed. Results: Under axial and shear force, the PVMS of the proximal humerus in group B and group C was greater than that in group A, the PVMS of the internal fixator in group B and group C was less than that in group A, while the PVMS of the proximal humerus and internal fixator between group B and group C were similar. The displacement of the proximal humerus and the neck-shaft angle change among the 3 groups were similar under axial and shear force, respectively. Under the rotational torque, compared with group A, the rotation angle of humerus in group B and group C increased slightly, and the rotation stability decreased slightly. All the 7 patients were followed up 6-12 months. All the fractures healed, and the healing time was 8-14 weeks, with an average of 10.9 weeks; the neck-shaft angle changes (the difference between the last follow-up and the immediate postoperative neck-shaft angle) was (1.30±0.42)°, and the Constant score of shoulder joint function was 87.4±4.2; there was no complication such as humeral head varus collapse and screw penetrating the articular surface. Conclusion: For proximal humeral fractures with comminuted medial cortex, exo-cortical placement of 1 or 2 humeral calcar screw of the locking plate outside the inferior cortex of the humeral head can also effectively reconstruct medial column stability, providing an alternative approach for clinical practice.

Testis-specific serine protease PRSS54 regulates acrosomal granule localization and sperm head morphogenesis in mice†.

Serine proteases (PRSS) constitute nearly one-third of all proteases, and many of them have been identified to be testis-specific and play significant roles during sperm development and male reproduction. PRSS54 is one of the testis-specific PRSS in mouse and human but its physiological function remains largely unclear. In the present study, we demonstrate in detail that PRSS54 exists not only in testis but also in mature sperm, exhibiting a change in protein size from 50 kDa in testis to 42 kDa in sperm. Loss of PRSS54 in mice results in male subfertility, acrosome deformation, defective sperm-zona penetration, and phenotypes of male subfertility and acrosome deformation can be rescued by Prss54 transgene. Ultrastructure analyses by transmission electronic microscopy further reveal various morphological abnormalities of Prss54-/- spermatids during spermiogenesis, including unfused vacuoles in acrosome, detachment and eccentrical localization of the acrosomal granules, and asymmetrical elongation of the nucleus. Subcellular localization of PRSS54 display that it appears in the acrosomal granule at the early phase of acrosome biogenesis, then extends along the inner acrosomal membrane, and ultimately presents in the acrosome region of the mature sperm. PRSS54 interacts with acrosomal proteins ZPBP1, ZPBP2, ACRBP, and ZP3R, and loss of PRSS54 affects the distribution of these proteins in testis and sperm, although their protein levels are largely unaffected. Moreover, Prss54-/- sperm are more sensitive to acrosome reaction inducers.

Surgical exposure to posterolateral quadrant tibial plateau fractures: an anatomic comparison of posterolateral and posteromedial approaches.

BACKGROUND: Management of posterolateral tibial plateau quadrant fractures can be challenging, and two posterior approaches were frequently used for exposure, reduction, and fixation: posterolateral approach and posteromedial approach. The purpose of this study was to compare their deep anatomical structure and analyze their limits and the risk of injury to important structures during surgical dissection of two approaches. METHOD: Five lower limb specimens were used in this study. After dissection of the skin and superficial fascia of each specimen, deep structures were dissected via posteromedial and posterolateral approach, and several parameters including perpendicular distance from the anterior tibial artery coursing through the interosseous membrane fissure to the lateral joint line and apex of fibular head and so on were measured and analyzed. RESULT: The perpendicular distance from the ATA coursing through the interosseous membrane fissure to the lateral joint line was 49.3 ± 5.6 mm (range 41.3-56.7 mm), while the distance to the apex of fibular head was 37.7 ± 7.2 mm (range 29.0-48.0 mm). The transverse distance of the anterior tibial vascular bundle is around 10 mm. The perpendicular distance from the top accompanying vein of the ATA bundle to lateral joint line and apex of fibular head was 44.1 ± 6.3 mm and 32.5 ± 7.6 mm, respectively. The maximum proportion of posterolateral tibial plateau shielded by the fibular head from the posterior view was 61.7 ± 4.9% (range 55.6-64.1%). The average length of popliteus muscle outside the joint was 83.1 ± 6.0 mm (range 76.5-92.2 mm), and the width in the middle was 28.1 ± 4.3 mm (range 26.6-29.1 mm). CONCLUSION: Although posterolateral approach seems more direct for exposure of posterolateral quadrant tibial plateau fracture, it has three major disadvantages in deep dissection. Posteromedial approach through the medial board of medial head of gastrocnemius-soleus may be safer, but it was hard for direct visualization of articular surface which limits it usage for only a few cases.

Calcar fracture gapping: a reliable predictor of anteromedial cortical support failure after cephalomedullary nailing for pertrochanteric femur fractures.

BACKGROUND: Maintaining anteromedial cortical support is essential for controlling sliding and decreasing postoperative implant-related complications. However, adequate fracture reduction with cortical support in immediate postoperative fluoroscopy is not invariable in postoperative follow-ups. This study was conducted to investigate the risk factors leading to anteromedial cortical support failure in follow up for pertrochanteric femur fractures treated with cephalomedullary nails. METHODS: This retrospective study enrolled 159 patients with pertrochanteric fractures (AO/OTA- 31A1 and 31A2) that fixed with cephalomedullary nails. All patients were evaluated as adequate fracture reduction in immediate postoperative fluoroscopy before leaving the operation theater. The patients were separated into two groups based on the condition of the anteromedial cortex in the postoperative 3D CT with full-range observation: those with calcar support maintained in Group 1 and those with calcar support lost in Group 2. Demographic information, fracture classification, TAD (tip-apex distance), Cal-TAD, Parker ratio, NSA (neck-shaft angle), reduction quality score, and calcar fracture gapping were collected and compared. Logistic regression analysis was conducted to explore the risk factors leading to anteromedial cortex change. RESULTS: Anteromedial cortical support failure was noted in 46 cases (29%). There was no significant difference between the two groups concerning age, sex, side injury, TAD, Cal-TAD, Parker ratio, or NSA. There was a significant difference in the AO/OTA fracture classification in univariate analysis but no difference in the multivariable analysis. The reduction quality score, calcar fracture gapping in the AP (anteroposterior), and lateral views were significantly associated with anteromedial cortical support failure in follow-up after cephalomedullary nailing in the multivariable analysis. The threshold value of calcar fracture gapping for the risk of loss was 4.2 mm in the AP and 3.8 mm in the lateral fluoroscopies. Mechanical complications (lateral sliding and varus) were frequently observed in the negative anteromedial cortical support group. CONCLUSIONS: Good reduction quality was a protective factor, and larger calcar fracture gapping in the AP and lateral views were risk factors leading to the postoperative loss of anteromedial cortical support. Therefore, we should pay close attention to fracture reduction and minimize the calcar fracture gap during surgery.

Sub-Classification of AO/OTA-2018 Pertrochanteric Fractures Is Associated With Clinical Outcomes After Fixation of Intramedullary Nails.

BACKGROUND: The new edited AO/OTA-2018 classification of pertrochanteric fractures was revised and no longer based on the status of lesser trochanter. This paper aimed to explore the clinical and technical outcomes among the subgroups (31A1 and 31A2) of the new classification treated with cephalomedullary nails. METHODS: A retrospective research of 154 patients diagnosed with pertrochanteric fractures (AO/OTA-2018 31A1.2/3 and 31A2.1/2/3) treated with intramedullary nails was conducted. The baseline data and outcomes were compared among the subgroups. The outcomes included tip-apex distance (TAD), Cal-TAD, Parker ratio, neck shaft angle (NSA), blood loss, varus displacement, and over lateral sliding rate of the blade. RESULTS: There were 154 cases involving 48 males and 106 females. The average age was higher in the sub-classifications of A2.2 and A2.3 than A1.2. Furthermore, the subgroups of A2.2 and A2.3 presented inferior outcomes with regard to blood loss and reduction quality score than A1.2 and A1.3. The subgroup of A2.3 was further poor with respect to calcar fracture gapping in the anteroposterior view and excessive lateral migration occurrence rate than A1.2. CONCLUSIONS: Complex pertrochanteric fractures indicated inferior outcomes compared to simple sub-classifications, which might lead by the incompetent of lateral wall and instability of the fracture. The newly proposed AO/OTA-2018 classification was conductive to forecast the prognosis.

The molecular mechanisms underlying acrosome biogenesis elucidated by gene-manipulated mice†.

Sexual reproduction requires the fusion of two gametes in a multistep and multifactorial process termed fertilization. One of the main steps that ensures successful fertilization is acrosome reaction. The acrosome, a special kind of organelle with a cap-like structure that covers the anterior portion of sperm head, plays a key role in the process. Acrosome biogenesis begins with the initial stage of spermatid development, and it is typically divided into four successive phases: the Golgi phase, cap phase, acrosome phase, and maturation phase. The run smoothly of above processes needs an active and specific coordination between the all kinds of organelles (endoplasmic reticulum, trans-Golgi network, and nucleus) and cytoplasmic structures (acroplaxome and manchette). During the past two decades, an increasing number of genes have been discovered to be involved in modulating acrosome formation. Most of these proteins interact with each other and show a complicated molecular regulatory mechanism to facilitate the occurrence of this event. This review focuses on the progresses of studying acrosome biogenesis using gene-manipulated mice and highlights an emerging molecular basis of mammalian acrosome formation.

Analysis of risk factors for thrombosis of the left atrium/left atrial appendage in patients with non-valvular atrial fibrillation.

OBJECTIVES: Left atrial appendage (LAA) morphology is a powerful predictor of thrombogenesis of the left atrium (LA) in patients with non-valvular atrial fibrillation (NVAF). However, it remains unknown whether LAA morphology is useful for stroke risk stratification in patients with NVAF. METHODS: A total of 555 atrial fibrillation patients were divided into thrombus and non-thrombus groups according to transoesophageal echocardiography. We analysed the correlation between LAA morphology and the CHADS2 score. We determined the L2CHADS2 score and compared the ability to predict LA/LAA thrombosis of the CHADS2, L2CHADS2 and CHA2DS2-VASc scores from the area under the curve (AUC). RESULTS: The odds ratio of non-chicken wing LAA morphology was 11.48. Non-chicken wing LAA morphology was significantly correlated with LA/LAA thrombosis. We incorporated LAA morphology into the CHADS2 score and named it the L2CHADS2 score. The AUC of the L2CHADS2 score (0.767) in predicting LA/LAA thrombosis was significantly higher than that of the CHADS2 (0.558) or CHA2DS2-VASc scores (0.557). The positive and negative predictive values of the L2CHADS2 score (13.1 and 98.7%) were higher than those of the CHADS2 (8.7 and 94.2%) and CHA2DS2-VASc scores (6.9 and 6.9%). CONCLUSIONS: Non-chicken wing LAA morphology was a powerful predictor of LA/LAA thrombosis in NVAF patients. The AUC, sensitivity and specificity of the L2 CHADS2 score were higher than those of the CHADS2 and CHA2 DS2 -VASc scores.

Dissecting the PRSS37 interactome and potential mechanisms leading to ADAM3 loss in PRSS37-null sperm.

A disintegrin and metalloproteinase 3 (ADAM3) is a sperm membrane protein critical for sperm migration from the uterus into the oviduct and sperm-egg binding in mice. Disruption of PRSS37 results in male infertility concurrent with the absence of mature ADAM3 from cauda epididymal sperm. However, how PRSS37 modulates ADAM3 maturation remains largely unclear. Here, we determine the PRSS37 interactome by GFP immunoprecipitation coupled with mass spectrometry in PRSS37-EGFP knock-in mice. Three molecular chaperones (CLGN, CALR3 and PDILT) and three ADAM proteins (ADAM2, ADAM6B and ADAM4) were identified to be interacting with PRSS37. Coincidently, five of them (except ADAM4) have been reported to interact with ADAM3 precursor and regulate its maturation. We further demonstrated that PRSS37 also interacts directly with ADAM3 precursor and its deficiency impedes the association between PDILT and ADAM3. This could contribute to improper translocation of ADAM3 to the germ cell surface, leading to ADAM3 loss in PRSS37-null mature sperm. The understanding of the maturation mechanisms of pivotal sperm plasma membrane proteins will pave the way toward novel strategies for contraception and the treatment of unexplained male infertility.

[Research progress on intra-articular screw penetration in proximal humeral fracture treated with locking plate].

OBJECTIVE: To review the research progress on intra-articular screw penetration in proximal humeral fracture treated with locking plate. METHODS: The domestic and foreign literature about the proximal humeral fracture treated with locking plate was extensively reviewed. The incidence of screw penetration and risk factors were summarized from both primary and secondary screw penetrations, and the reasons of the intra-articular screw penetration and the technical solutions to avoid the penetration were analyzed. RESULTS: The incidence of intra-articular screw penetration is about 11%-30%, which includes primary and secondary screw penetrations. The primary screw penetration is related to improper operation, inaccurate measurement, and "Steinmetz solid" effect, which results in inadequate fluoroscopy and blind zone. The secondary screw penetration is related to the loss of reduction and varus, collapse, and necrosis of the humeral head. The risk factors for intra-articular screw penetration include the bone mass density, the fracture type, the quality of fracture reduction, the applied location, number, and length of the plate and screws, and whether medial column buttress is restored. Improved fracture reduction, understanding the geometric distribution of screws, good intraoperative fluoroscopy, and reconstruction of medial column buttress stability are the key points for success. CONCLUSION: The risk of the intra-articular screw penetration in the proximal humeral fractures treated with locking plates is still high. Follow-up studies need to further clarify the cause and mechanism of screw penetration, and the risk factors that lead to screw penetration, in order to effectively prevent the occurrence of this complication.

ADGRA1 negatively regulates energy expenditure and thermogenesis through both sympathetic nervous system and hypothalamus-pituitary-thyroid axis in male mice.

Adhesion G protein-coupled receptor A1 (ADGRA1, also known as GPR123) belongs to the G protein-coupled receptors (GPCRs) family and is well conserved in the vertebrate lineage. However, the structure of ADGRA1 is unique and its physiological function remains unknown. Previous studies have shown that Adgra1 is predominantly expressed in the central nervous system (CNS), indicating its important role in the transduction of neural signals. The aim of this study is to investigate the central function of Adgra1 in vivo and clarify its physiological significance by establishing an Adgra1-deficient mouse (Adgra1-/-) model. The results show that Adgra1-/- male mice exhibit decreased body weight with normal food intake and locomotion, shrinkage of body mass, increased lipolysis, and hypermetabolic activity. Meanwhile, mutant male mice present elevated core temperature coupled with resistance to hypothermia upon cold stimulus. Further studies show that tyrosine hydroxylase (TH) and ß3-adrenergic receptor (ß3-AR), indicators of sympathetic nerve excitability, are activated as well as their downstream molecules including uncoupling protein 1 (UCP1), coactivator 1 alpha (PGC1-α) in brown adipose tissue (BAT), and hormone-sensitive lipase (HSL) in white adipose tissue (WAT). In addition, mutant male mice have higher levels of serum T3, T4, accompanied by increased mRNAs of hypothalamus-pituitary-thyroid axis. Finally, Adgra1-/- male mice present abnormal activation of PI3K/AKT/GSK3ß and MEK/ERK pathways in hypothalamus. Overexpression of ADGRA1 in Neuro2A cell line appears to suppress these two signaling pathways. In contrast, Adgra1-/- female mice show comparable body weight along with normal metabolic process to their sex-matched controls. Collectively, ADGRA1 is a negative regulator of sympathetic nervous system (SNS) and hypothalamus-pituitary-thyroid axis by regulating PI3K/AKT/GSK3ß and MEK/ERK pathways in hypothalamus of male mice, suggesting an important role of ADGRA1 in maintaining metabolic homeostasis including energy expenditure and thermogenic balance.