A splicing-dependent ER retention signal regulates surface expression of the mechanosensitive TMEM63B cation channel.

TMEM63B is a mechanosensitive cation channel activated by hypoosmotic stress and mechanic stimulation. We recently reported a brain-specific alternative splicing of exon 4 in TMEM63B. The short variant lacking exon 4, which constitutes the major isoform in the brain, exhibits enhanced responses to hypoosmotic stimulation compared to the long isoform containing exon 4. However, the mechanisms affecting this differential response are unclear. Here, we showed that the short isoform exhibited stronger cell surface expression compared to the long variant. Using mutagenesis screening of the coding sequence of exon 4, we identified an RXR-type endoplasmic reticulum (ER) retention signal (RER). We found that this motif was responsible for binding to the COPI retrieval vesicles, such that the longer TMEM63B isoforms were more likely to be retrotranslocated to the ER than the short isoforms. In addition, we demonstrated long TMEM63Bs could form heterodimers with short isoforms and reduce their surface expression. Taken together, our findings revealed an ER retention signal in the alternative splicing domain of TMEM63B that regulates the surface expression of TMEM63B protein and channel function.

ZmPHR1 contributes to drought resistance by modulating phosphate homeostasis in maize.

As an essential macronutrient, phosphorus (P) is often a limiting nutrient because of its low availability and mobility in soils. Drought is a major environmental stress that reduces crop yield. How plants balance and combine P-starvation responses (PSRs) and drought resistance is unclear. In this study, we identified the transcription factor ZmPHR1 as a major regulator of PSRs that modulates phosphate (Pi) signaling and homeostasis. We found that maize zmphr1 mutants had reduced P concentration and were sensitive to Pi starvation, whereas ZmPHR1-OE lines displayed elevated Pi concentration and yields. In addition, 57% of PSR genes and nearly 70% of ZmPHR1-regulated PSR genes in leaves were transcriptionally responsive to drought. Under moderate and early drought conditions, the Pi concentration of maize decreased, and PSR genes were up-regulated before drought-responsive genes. The ZmPHR1-OE lines exhibited drought-resistant phenotypes and reduced stomatal apertures, whereas the opposite was true of the zmphr1 mutants. ZmPT7-OE lines and zmspx3 mutants, which had elevated Pi concentration, also exhibited drought resistance, but zmpt7 mutants were sensitive to drought. Our results suggest that ZmPHR1 plays a central role in integrating Pi and drought signals and that Pi homeostasis improves the ability of maize to combat drought.

Organophosphorus-Catalyzed Direct Dehydroxylative Thioetherification of Alcohols with Hypervalent Organosulfur Compounds.

A metal-free and thiol-free organophosphorus-catalyzed method for forming thioethers was disclosed, driven by PIII/PV═O redox cycling. In this work, one-step dehydroxylative thioetherification of alcohols was fulfilled with various hypervalent organosulfur compounds. This established strategy features an excellent functional group tolerance and broad substrate scope, especially inactivated alcohols. The scale-up reaction and further transformation of the product were also successful. Additionally, this method offers a protecting-group-free and step-efficient approach for synthesizing peroxisome proliferator-activated receptor agonists which exhibited promising potential for treating osteoporosis in mammals.

The recombinant human fibroblast growth factor-18 (sprifermin) improves tendon-to-bone healing by promoting chondrogenesis in a rat rotator cuff repair model.

BACKGROUND: Rotator cuff healing is improved by reconstructing the fibrocartilaginous structure of the tendon-to-bone enthesis. Fibroblast growth factor (FGF)-18 (sprifermin) is a well-known growth factor that improves articular cartilage repair via its anabolic effect. This study aimed to investigate the effect of recombinant human FGF-18 (rhFGF-18) on the chondrogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro and tendon-to-bone healing in a rat model of rotator cuff repair. METHODS: Histological and reverse transcription-quantitative real-time polymerase chain reaction analyses of chondral pellets cultured with different concentrations of rhFGF-18 were performed. Bilateral detachment and repair of the supraspinatus tendon were performed on rats. The rats were administered 0.2 mL of sodium alginate (SA) hydrogel with (rhFGF-18/SA group, n = 12) or without (SA group, n = 12) 20 µg of rhFGF-18 into the repaired side. The simple repair group (n = 12) served as a control. At 4 and 8 weeks after surgery, histological analysis and biomechanical tests were performed. RESULTS: After chondrogenesis induction, compared with the control group, 10 ng/mL of rhFGF-18 increased pellet volume significantly (P = .002), with improved histological staining. It was noted that 10 ng/mL of rhFGF-18 upregulated the mRNA expression (relative ratio to control) of aggrecan (2.59 ± 0.29, P < .001), SRY-box transcription factor 9 (1.88 ± 0.05, P < .001), and type II collagen (1.46 ± 0.18, P = .009). At 4 and 8 weeks after surgery, more fibrocartilage and cartilaginous extracellular matrix was observed in rhFGF-18/SA-treated rats. The semiquantitative data from picrosirius red staining test were 31.1 ± 4.5 vs. 61.2 ± 4.1 at 4 weeks (P < .001) and 61.5 ± 2.8 vs. 80.5 ± 10.5 at 8 weeks (P = .002) (control vs. rhFGF-18/SA). Ultimate failure load (25.42 ± 3.61 N vs. 18.87 ± 2.71 N at 4 weeks and 28.63 ± 5.22 N vs. 22.15 ± 3.11 N at 8 weeks; P = .006 and P = .03, respectively) and stiffness (18.49 ± 1.38 N/mm vs. 14.48 ± 2.01 N/mm at 8 weeks, P = .01) were higher in the rhFGF-18/SA group than in the control group. CONCLUSION: rhFGF-18 promoted chondrogenesis in the hBMSCs in vitro. rhFGF-18/SA improved tendon-to-bone healing in the rats by promoting regeneration of the fibrocartilage enthesis. rhFGF-18 (sprifermin) may be beneficial in improving tendon-to-bone healing after rotator cuff repair.

How can medial support for proximal humeral fractures be achieved when positioning of regular calcar screws is challenging? Slotting and off-axis fixation strategies.

BACKGROUND: Achieving medial support for proximal humeral fractures (PHFs) by regular calcar screw positioning is challenging when the humeral head is small or locking plates are placed distally, as there are unable inserted calcar screws into the humeral head. We aimed to investigate the suitability of the 2 strategies, slotting calcar screw (SCS) and off-axis calcar screw (OCS), to achieve medial support for PHFs. METHODS: Regular calcar screw (RCS), SCS, OCS, and noncalcar screw (NCS) were tested via mechanical experiments and finite element analysis (FEA), using synthetic bones for biomechanical comparisons. All PHFs treated in our hospital from March 2017 to March 2019 were reviewed. The patients were divided into 3 groups based on the calcar screw fixation: RCS, SCS, and OCS. The postoperative varus collapse (neck-shaft angle changed to less than 120°) and Disabilities of the Arm, Shoulder and Hand (DASH) scores were recorded. RESULTS: The properties of RCS, SCS, and OCS against the torsion and varus force were superior to those of NCS, whereas the stiffness of SCS, OCS, and RCS were similar. FEA predicted lower peri-screw strains in the OCS and SCS than in the RCS, indicating a lower risk of cut-out. Patients (n = 125; 75 female, 50 male) aged 55.9 ± 13.0 years were evaluated. Compared with the RCS (5/55), varus collapse incidences were not significantly higher following SCS (0/29, P = .094) or OCS (3/41, P = .756), and neither were DASH scores (P = .867 and .736, respectively). CONCLUSIONS: This study is a preliminary study demonstrating that the SCS and OCS fixation strategies could be useful alternatives when regular calcar fixation is not possible using the plate at hand.

Finite element analysis of biomechanical effects of residual varus/valgus malunion after femoral fracture on knee joint.

OBJECTIVE: Post-operative femoral shaft fractures are often accompanied by a residual varus/valgus deformity, which can result in osteoarthritis in severe cases. The purpose of this study was to investigate the biomechanical effects of residual varus/valgus deformities after middle and lower femoral fracture on the stress distribution and contact area of knee joint. METHODS: Thin-slice CT scanning of lower extremities and MRI imaging of knee joints were obtained from a healthy adult male to establish normal lower limb model (neutral position). Then, the models of 3°, 5°, and 10° of varus/valgus were established respectively by modifying middle and lower femur of normal model. To validate the modifying, a patient-specific model, whose BMI was same to former and had 10° of varus deformity of tibia, was built and simulated under the same boundary conditions. RESULT: The contact area and maximum stress of modified models were similar to those of patient-specific model. The contact area and maximum stress of medial tibial cartilage in normal neutral position were 244.36 mm2 and 0.64 MPa, while those of lateral were 196.25 mm2 and 0.76 MPa. From 10° of valgus neutral position to 10° of varus, the contact area and maximum stress of medial tibial cartilage increased, and the lateral gradually decreased. The contact area and maximum stress of medial meniscus in normal neutral position were 110.91 mm2 and 3.24 MPa, while those of lateral were 135.83 mm2 and 3.45 MPa. The maximum stress of medial tibia subchondral bone in normal neutral position was 1.47 MPa, while that of lateral was 0.65 MPa. The variation trend of medial/lateral meniscus and subchondral bone was consistent with that of tibial plateau cartilage in the contact area and maximum stress. CONCLUSION: This study suggested that varus/valgus deformity of femur had an obvious effect on the contact area and stress distribution of knee joint, providing biomechanical evidence and deepening understanding when performing orthopedic trauma surgery or surgical correction of the already existing varus/valgus deformity.

"Fishing net" suture augmenting tension-band wiring fixation in the treatment of inferior pole fracture of the patella.

INTRODUCTION: Inferior pole fracture of the patella (IPFP) is difficult to repair and stabilize clinically. Although various fixation techniques have been developed, fixation strength and mobility remain daunting challenges to orthopedic surgeons. The goal of this research is to evaluate the biomechanical strength and clinical outcomes of a novel "fishing net" suture fixation procedure. MATERIALS AND METHODS: Four finite element models, modified tension-band wiring fixation, anchor suture fixation, basket plate fixation and "fishing net" suture fixation were built to compare the fixing efficacy of "fishing net" suture fixation with three other fixation methods during IPFP fixation. From January 2018 to February 2019, 17 patients who suffered IPFP and treated by "fishing net" suture (FNS) fixation were compared with 20 patients treated by tension-band wiring (TBW) fixation in database and the two groups were evaluated postoperatively using the modified Cincinnati knee rating system. RESULTS: Biomechanical evaluation showed that the relative displacement values of proximal patella measured by three pairs of points on both sides of the fracture line were the lowest using the "fishing net" suture fixation, while fixation using tension-band wiring and basket plate showed similar levels of stability that were less desirable than the "fishing net" method. As to clinical outcomes, there were 17 (100%) patients exhibited excellent or good results with no internal fixation failures in the FNS group compared to three internal fixation failures in the TBW group. CONCLUSION: The biomechanical and clinical results suggest that the "fishing net" suture fixation is a viable candidate for fixation of IPFP.

Impact of nanoceria shape on degradation of diethyl paraoxon: Synthesis, catalytic mechanism, and water remediation application.

A series of nanomaterials have been demonstrated to be powerful for direct degradation of diethyl paraoxon (EP) to diethyl phosphate and 4-nitrophenol in aqueous solution. However, comparison of catalytic activity of different nanomaterials toward EP is rarely explored. In the present study, four different morphological nanoceria (cubes, rods, polyhedral, and spheres) were synthesized, characterized, and evaluated as a catalyst for the degradation of EP in comparison to other commercially available nanomaterials. Among the tested nanoceria, the cerium dioxide (CeO2) nanopolyhedra possess the best catalytic activity toward the hydrolysis of EP owing to their abundant oxygen vacancy sites, optimal ratio of Ce(III) to Ce(IV), and specific exposed facets. Under the conditions of 0.2 M NH3/NH4Cl buffer and 25 °C, the CeO2 nanopolyhedra catalyzed the reduction of EP to 4-nitrophenol with a >99% conversion at pH 8.0 for 50 h, at pH 10.0 for 12 h, and at pH 12.0 for 2.5 h. The catalytic degradation of nearly 100% EP in NH3/NH4Cl buffer (pH 10.0) at 25 °C is in the decreasing order of CeO2 nanopolyhedra > CeO2 nanorods > ZnO nanospheres (NSs) > CeO2 nanocubes > TiO2 NSs > CeO2 NSs > Fe3O4 NSs ~ Co3O4 NSs ~ control experiment. The mechanism for the degradation of EP was confirmed by monitoring catalytic kinetics of the CeO2 nanopolyhedra in the presence of EP, dimethyl paraoxon, 4-nitrophenyl phosphate, and parathion. The nanocomposites were simply fabricated by electrostatic self-assembly of the CeO2 nanopolyhedra and poly(diallyldimethylammonium chloride)-capped gold nanoparticles (PDDA-AuNPs). The resultant nanocomposites still efficiently catalyzed NaBH4-mediated reduction of 4-nitrophenol to 4-aminophenol with a normalized rate constant of 6.68 ± 0.72 s-1 g-1 and a chemoselectivity of >99%. In confirmation of the robustness and applicability of the as-prepared nanocomposites, they were further used to catalyze the degradation of EP to 4-amionphenol in river water and seawater.

Drug-Induced Liver Injury: Clinical and Etiologic Features at a Large Tertiary Teaching Hospital in China.

BACKGROUND Since the epidemiological profile of drug-induced liver injury (DILI) in China, especially the western of China, it has rarely been studied. The aim of this study was to analyze the characteristics of DILI patients in a large tertiary teaching hospital at Chongqing, a municipality in western China. MATERIAL AND METHODS The medical records of hospitalized patients which diagnosed with DILI between January 2011 and December 2016 were searched retrospectively, and demographic, clinical data, and laboratory data were retrieved for analysis. RESULTS A total of 1811 patients had been diagnosed with DILI, accounting for 0.248% of the total admissions during the same period. Among the 1096 patients included in our analysis, DILI was caused by "medications" in 462 cases (42.15%), "herbs" in 391 cases (35.68%), and combined medications in 189 cases (17.24%). The profiles for each etiology were distinctive for age, sex, clinical features, laboratory features, and types and severity of DILI. CONCLUSIONS Our study provides a systematic etiological profile of DILI in Chinese patients, which can represent references for prevention, diagnosis and treatment, supporting and promoting efforts to ease the burden of this liver disease in China.

Biomechanical changes of degenerated adjacent segment and intact lumbar spine after lumbosacral topping-off surgery: a three-dimensional finite element analysis.

BACKGROUND: Previous studies have revealed positive effect of Topping-off technique on upper adjacent segment after fusion surgery, while for the cases with fusion surgery on L5-S1 segment, owning maximal range of motion, and preexisting degenerated upper adjacent disc, it is necessary to clarify the superiority of Topping-ff technique and the effect exerted on the lumbar spine. METHODS: A young healthy male volunteer was selected for thin-slice CT scanning. Then the image information was imported into the computer to establish the whole lumbar spine model as the health model. The medium degeneration model of intervertebral disc was established by changing the material properties of L4-S1 disc on the basis of the health model, and the fusion model and Topping-off model were respectively established on the basis of the degenerated model. The variation trend of ROM of L2-L5 and the stress changes of L4-L5 intervertebral disc, nucleus pulposus and facet joints were calculated respectively. RESULTS: The L4-L5 ROM of fusion model increased significantly but the ROM of L2-L3 and L3-L4 segments did not change significantly. Compared with the degenerated model, L4-L5 activity of the Topping-off model decreased, and ROM of the L2-L3 and L3-L4 increased to some extent in the flexion and extension positions. The stress on the disc, nucleus pulposus and facet joint of the fusion model L4-L5 increased in four positions of flexion, extension, rotation and bending compared with the degenerated model, while the fiber stress on the Topping-off model decreased significantly in all four positions. CONCLUSION: Topping-off technology can decrease the stress and ROM of the adjacent upper degenerated segment, and increase the ROM of other upper segments, thereby protecting the degenerated upper adjacent segments and compensating the lumbar spine mobility.

Influence of the proximal screws of buttress plates on the stability of vertical femoral neck fractures: a finite element analysis.

BACKGROUND: The treatment of vertical femoral neck fractures (vFNFs) in young patients remains challenging, with a high complication rate by using traditional techniques. The use of cannulated screws (CSs) combined with a buttress plate represents an alternative approach for treating vFNFs. However, the biomechanical influence of the use or non-use of the proximal screws of buttress plates on vFNFs stability remains unclear. This study aims to analyse the biomechanics of buttress plate fixation with or without the use of proximal screws through finite element analysis (FEA) to further understand this approach. METHODS: We built five vFNFs (Pauwels angle 70°) finite element models treated using three cannulated screws (CS group) or three cannulated screws plus a locking buttress plate (buttress group). In the buttress group, use or non-use of proximal screws was carried out on two types of plates (4-hole & 6-hole). The following seven parameters were analysed to compare biomechanical properties of the five models: the stiffness; the maximal stress of the plate system (plate and screws), CSs and bone (MPS, MCS, MBS); the maximal displacement of internal fixations (plate system & CSs) and bone (MIFD, MBD); and the maximal relative displacement of interfragments (MID). RESULTS: Compared with CS model, the buttress models exhibited improved biomechanical properties, with increased stiffness and decreased MCS, MBS, MIFD, MBD and MID. The models fixed using buttress plates combined with a proximal screw showed greater stiffness (+ 3.75% & + 8.31% vs + 0.98% & + 4.57%) and MPS (795.6 & 947.2 MPa vs 294.9 & 556.2 MPa) values, and smaller MCS, MBS, MIFD, MBD and MID (- 3.41% to - 15.35% vs - 0.07% to - 4.32%) values than those using the same length plates without a proximal screw. CONCLUSIONS: Based on the FEA results, buttress plates can improve construct mechanics, help to resist shear force and prevent varus collapse; under the modelling conditions, the use of a proximal screw on buttress plate may be a key technical feature in improving anti-shearing ability; additionally, this screw may be essential to reduce stress and prevent re-displacement of cannulated screws and fracture fragments.

ALPL regulates the aggressive potential of high grade serous ovarian cancer cells via a non-canonical WNT pathway.

The ALPL gene is linked to hypophosphatasia, a rare genetic disease. Owing to the inverse relationships between ALPL expression and both the International Federation of Gynecology and Obstetrics (FIGO) stages and histological grades assigned to patients with serous ovarian cancer (SOC), this study was designed to explore the role and possible mechanisms of ALPL in cell motility of high grade SOC (HGSOC). The effects of ALPL overexpression on migration and invasion were detected in HGSOC cell lines SKOV3 and HEY. Gene ontology analysis for differential genes with ALPL overexpression identified several biological processes, including EMT, correlated with cell motility. Genes potentially implicated in EMT and associated with ALPL were screened using The Cancer Genome Atlas (TCGA) database. The WNT receptor Frizzled2 (FZD2) was identified and its role in HGSOC cell motility and survival was investigated. It was found that forced expression of ALPL could inhibit migration, invasion, and EMT in HGSOC cells. It also reduced the expression of FZD2 and its ligand WNT5A, accompanied by suppressed expression of their downstream target phosphorylated-STAT3 (pSTAT3). These effects were initiated via the FZD2 knockdown using siRNA and reversed by recombinant WNT5A protein. The relationship between FZD2 expression and poor HGSOC patient survival was also investigated. This data supports that ALPL might restrict the function of WNT5A-FZD2-STAT3 axis, a non-canonical WNT pathway for promoting EMT progression, which results in attenuated migration and invasion in HGSOC cells and improves survival in patients with SOC.

Biomechanical Comparison of Locking Plate and Cancellous Screw Techniques in Medial Malleolar Fractures: A Finite Element Analysis.

As the commonly used fixation strategy of medial malleolar fractures, cancellous screws (CS) have been challenged for instability, bone destruction, and metal prominence. It is still unclear whether a locking compression plate (LCP) is a better choice in such fractures. Our purpose is to compare the mechanical efficacy of LCP with traditional 4.0-mm CS for transverse, oblique, and vertical medial malleolar fractures by using finite element analysis. In this study, 3-dimensional models of the distal tibia were reconstructed from a computed tomography scan of a young healthy male adult. Conditions included 3 fracture lines at 30°, 60°, and 90°; 2 groups of fixation (LCP and CS); and 3 adduction loads of 300, 500, and 700 N applied to the medial malleolar joint surface. The proximal part of the tibia was fixed for all degrees of freedom. The fracture displacements of the LCP were smaller than those of CS (p < .05). The stiffness of the LCP constructs was much higher than that of the CS constructs, especially in the 90° fractures (490.3 versus 163.6 N/mm). The mean stress around the CS was higher than that in LCP for 60° and 90° fractures, but there was no difference for 30°. Maximal bone stress increased (19.84 to 50.86 MPa) and concentrated on cortical bone in LCP, whereas it concentrated on cancellous bone in CS. The results showed that LCP could improve stability, preventing bone destruction in oblique and vertical medial malleolar fractures. However, in transverse fractures, CS provides sufficient stability, with no need to use LCP.

Synthesis and Positive Inotropic Activity of [1,2,4]Triazolo[4,3-a] Quinoxaline Derivatives Bearing Substituted Benzylpiperazine and Benzoylpiperazine Moieties.

In an attempt to search for more potent positive inotropic agents, two series of [1,2,4]triazolo[4,3-a] quinoxaline derivatives bearing substituted benzylpiperazine and benzoylpiperazine moieties were synthesized and their positive inotropic activities evaluated by measuring left atrial stroke volume in isolated rabbit heart preparations. Several compounds showed favorable activities compared with the standard drug, milrinone. Compound 6c was the most potent agent, with an increased stroke volume of 12.53% ± 0.30% (milrinone: 2.46% ± 0.07%) at 3 × 10-5 M. The chronotropic effects of compounds having considerable inotropic effects were also evaluated.

Tetraspanin 8-rictor-integrin α3 complex is required for glioma cell migration.

The malignant glioma remains one of the most aggressive human malignancies with extremely poor prognosis. Glioma cell invasion and migration are the main causes of death. In the current study, we studied the expression and the potential functions of tetraspanin 8 (Tspan8) in malignant gliomas. We found that Tspan8 expression level is high in both malignant glioma tissues and in several human glioma cell lines, where it formed a complex integrin α3 and rictor, the latter is a key component of mammalian target of rapamycin (mTOR) complex 2 (mTORC2). Disruption of this complex, through siRNA-mediated knockdown of anyone of these three proteins, inhibited U251MG glioma cell migration in vitro. We further showed that Tspan8-rictor association appeared required for mTORC2 activation. Knockdown of Tspan8 by the targeted siRNAs prevented mTOR-rictor (mTORC2) assembly as well as phosphorylation of AKT (Ser-473) and protein kinase C α (PKCα) in U251MG cells. Together, these results demonstrate that over-expressed Tspan8 in malignant glioma forms a complex with rictor and integrin α3 to mediate mTORC2 activation and glioma cell migration. Therefore, targeting Tspan8-rictor-integrin α3 complex may provide a potential therapeutic intervention for malignant glioma.

Necrolytic migratory erythema caused by pancreatic hyperglycemia with emphasis on therapeutic and prognosis: A case report.

BACKGROUND: With the incidence of pancreatic diseases increasing year by year, pancreatic hyperglycemia, as one of the common complications, is gradually gaining attention for its impact on the skin health of patients. CASE SUMMARY: This was the case of an elderly female with clinical manifestations of necrolytic migratory erythema, "three more and one less," diabetes mellitus, hypertension, anemia, hypoproteinemia, and other syndromes, which had been misdiagnosed as eczema. Abdominal computed tomography showed a pancreatic caudal space-occupying lesion, and the magnetic resonance scanning of the epigastric region with dynamic enhancement and diffusion-weighted imaging suggested a tumor of the pancreatic tail, which was considered to be a neuroendocrine tumor or cystadenoma. The patient was referred to a more equipped hospital for laparoscopic pancreatic tail resection. Post-surgery diagnosis revealed a neuroendocrine tumor in the tail of the pancreas. To date, the patient's general condition is good, and she is still under close follow-up. CONCLUSION: Necrolytic migratory erythema can be induced by endocrine system tumors or endocrine metabolic abnormalities, with complex clinical manifestations, difficult diagnosis, and easy misdiagnosis by dermatologists. The initial treatment principles in dermatology include symptomatic supportive therapy and effective drugs to relieve skin lesions. After clarifying the etiology of glucagonoma, comprehensive treatment in collaboration with endocrinologists, general surgeons, and oncologists can help provide individualized treatment for patients and improve their prognosis.

Mechanical impact of regional structural deterioration and tissue-level compensation on proximal femur trabecular bone.

Introduction: Osteoporosis-induced changes in bone structure and composition significantly reduce bone strength, particularly in the human proximal femur. This study examines how these changes affect the mechanical performance of trabecular bone to enhance diagnosis, prevention, and treatment strategies. Methods: A proximal femur sample was scanned using micro-CT at 40 µm resolution. Five regions of interest were selected within the femoral head, femoral neck, and greater trochanter. Structural models simulating various stages of osteoporosis were created using image processing software. Micro-finite element analysis evaluated the mechanical properties of trabecular bone under different conditions of structural deterioration and tissue-level elastic modulus variations. The combined effects of structural deterioration and tissue-level mechanical properties on trabecular bone mechanical performance were further analyzed. Results: The mechanical performance of trabecular bone generally follows a power-law relationship with its microstructural characteristics. However, in any specific region, the apparent mechanical properties linearly decrease with structural deterioration. The femoral neck and greater trochanter are more sensitive to structural deterioration than the femoral head. A 5% bone mass loss in the femoral head led to a 7% reduction in mechanical performance, while the femoral neck experienced a 12% loss. Increasing tissue-level elastic modulus improved mechanical performance, partially offsetting bone mass reduction effects. Conclusion: Trabecular bone in low bone mass regions is more affected by bone mass loss. Structural deterioration primarily reduces bone strength, but improvements in tissue-level properties can mitigate this effect, especially in early osteoporosis. Targeted assessments and interventions are crucial for effective management. Future research should explore heterogeneous deterioration models to better understand osteoporosis progression.

Single-plane osteotomy model is inaccurate for evaluating the optimal strategy in treating vertical femoral neck fractures: A finite element analysis.

BACKGROUND AND OBJECTIVES: The conventional method for simulating vertical femoral neck fractures (vFNFs) is via a vertical single-plane osteotomy (SPO) across the entire femur. However, the accuracy of SPO for evaluating the optimal internal fixation strategy (IFS) and the appropriate assessment parameters is not clear. This study thus aimed to examine the accuracy of SPO in evaluating IFSs and to identify appropriate evaluation parameters using finite element analysis. METHODS: Eighty patient-specific finite element models were developed based on CT images from eight vFNF patients. The natural fracture model was built using structural features of the affected side, while the SPO was simulated on the healthy side. Five different IFSs were applied to both the natural fracture and SPO groups. Thirteen parameters, including stress, displacement, and stiffness, were subjected to a two-way repeated measures ANOVA to determine the effect of IFSs and fracture morphology on stability. A Pearson correlation analysis was performed on varied parameters with various IFSs to identify independent parameters. Based on these independent parameters, the entropy evaluation method (EEM) score was used to rank the performance of IFSs for each patient. RESULTS: Eight of the thirteen parameters were significantly influenced by IFSs (p < 0.05), two by fracture morphology (p < 0.01), and none by the interaction between IFS and fracture morphology. In the natural fracture group, parameters including screw stress and displacement, bone cut rate (BCR), and compression effects varied independently with distinct IFSs. In the SPO group, trunk displacement, BCR, cut-out risk, and compression effects parameters changed independently. The BCR of the Alpha strategy was significantly higher than that of the Inverted strategy in the natural fracture group (p = 0.002), whereas the opposite was observed in the SPO group (p = 0.016). Regarding compression effects, two IFS pairings in the natural fracture group and seven IFS pairings in the SPO group exhibited significant differences. None of the five IFSs achieved the optimal EEM score for each patient. CONCLUSIONS: The single-plane osteotomy model may have limitations in assessing IFSs, particularly when the bone cut rate and compression effects are the main influencing factors. Parameters of the screw stress and displacement, BCR, and compression effects appear to be relevant in evaluating IFSs for natural fracture models. It indicates that individualized natural fracture models could provide more comprehensive insights for determining the optimal IFS in treating vFNFs.

Altered immune pathways in patients of temporal lobe epilepsy with and without hippocampal sclerosis.

Over the past decades, the immune responses have been suspected of participating in the mechanisms for epilepsy. To assess the immune related pathway in temporal lobe epilepsy (TLE), we explored the altered immune pathways in TLE patients with and without hippocampal sclerosis (HS). We analyzed RNA-seq data from 3 TLE-HS and 3 TLE-nonHS patients, including identification of differentially expressed RNA, function pathway enrichment, the protein-protein interaction network and construction of ceRNA regulatory network. We illustrated the immune related landscape of molecules and pathways on human TLE-HS. Also, we identified several differential immune related genes like HSP90AA1 and SOD1 in TLE-HS patients. Further ceRNA regulatory network analysis found SOX2-OT connected to miR-671-5p and upregulated the target gene SPP1 in TLE-HS patients. Also, we identified both SOX2-OT and SPP1 were significantly upregulated in five different databases including TLE-HS patients and animal models. Our findings established the first immune related genes and possible regulatory pathways in TLE-HS patients and animal models, which provided a novel insight into disease pathogenesis in both patients and animal models. The immune related SOX2-OT/miR-671-5p/SPP1 axis may be the potential therapeutic target for TLE-HS.

Pedicle screw path planning for multi-level vertebral fixation.

BACKGROUND: For the spinal internal fixation procedures, connecting rods to the pedicle screws are commonly used in all spinal segments from the cervical to sacral spine. So far, we have only seen single vertebral screw trajectory planning methods in literatures. Joint screw placements in multi-level vertebrae with the constraint of an ipsilateral connecting rod are not considered. PURPOSE: In this paper, a screw trajectory planning method that considers screw-rod joint system with both multi-level vertebral constraints and individual vertebral safety tolerance are proposed. METHODS: The proposed method addresses three challenging constraints jointly for multi-level vertebral fixation with pedicle screws. First, a cylindrical screw safe passage model is suggested instead of a unique mathematical optimal trajectory for a single pedicle. Second, the flexible screw cap accessibility model is also included. Third, the connecting rod is modeled to accommodate the spine contour and support the needed gripping capacity. The retrospective clinical data of relative normal shape spines from Beijing Jishuitan hospital were used in the testing. The screw trajectories from the existing methods based on single vertebra and the proposed method based on multi-level vertebrae optimization are calculated and compared. RESULTS: The results showed that the calculated screw placements by the proposed method can achieve 88% success rate without breaking the pedicle cortex and 100% in clinical class A quality (allow less than 2 mm out of the pedicle cortex) compared to 86.1% and 99.1%, respectively, with the existing methods. Expert evaluation showed that the screw path trajectories and the connecting rod calculated by the new method satisfied the clinical implantation requirements. CONCLUSIONS: The new screw planning approach that seeks an overall optimization for multi-level vertebral fixation is feasible and more advantageous for clinical use than the single vertebral approaches.