Vitamin D3 exacerbates steatosis while calcipotriol inhibits inflammation in non-alcoholic fatty liver disease in Sod1 knockout mice: a comparative study of two forms of vitamin D.

The role of vitamin D (VD) in non-alcoholic fatty liver disease (NAFLD) remains controversial, possibly due to the differential effects of various forms of VD. In our study, Sod1 gene knockout (SKO) mice were utilized as lean NAFLD models, which were administered 15 000 IU VD3 per kg diet, or intraperitoneally injected with the active VD analog calcipotriol for 12 weeks. We found that VD3 exacerbated hepatic steatosis in SKO mice, with an increase in the levels of Cd36, Fatp2, Dgat2, and CEBPA. However, calcipotriol exerted no significant effect on hepatic steatosis. Calcipotriol inhibited the expression of Il-1a, Il-1b, Il-6, Adgre1, and TNF, with a reduction of NFκB phosphorylation in SKO mice. No effect was observed by either VD3 or calcipotriol on hepatocyte injury and hepatic fibrosis. Co-immunofluorescence stains of CD68, a liver macrophage marker, and VDR showed that calcipotriol reduced CD68 positive cells, and increased the colocalization of VDR with CD68. However, VD3 elevated hepatocyte VDR expression, with no substantial effect on the colocalization of VDR with CD68. Finally, we found that VD3 increased the levels of serum 25(OH)D3 and 24,25(OH)2D3, whereas calcipotriol decreased both. Both VD3 and calcipotriol did not disturb serum calcium and phosphate levels. In summary, our study found that VD3 accentuated hepatic steatosis, while calcipotriol diminished inflammation levels in SKO mice, and the difference might stem from their distinct cellular selectivity in activating VDR. This study provides a reference for the application of VD in the treatment of lean NAFLD.

TMEM63B channel is the osmosensor required for thirst drive of interoceptive neurons.

Thirst plays a vital role in the regulation of body fluid homeostasis and if deregulated can be life-threatening. Interoceptive neurons in the subfornical organ (SFO) are intrinsically osmosensitive and their activation by hyperosmolarity is necessary and sufficient for generating thirst. However, the primary molecules sensing systemic osmolarity in these neurons remain elusive. Here we show that the mechanosensitive TMEM63B cation channel is the osmosensor required for the interoceptive neurons to drive thirst. TMEM63B channel is highly expressed in the excitatory SFO thirst neurons. TMEM63B deletion in these neurons impaired hyperosmolarity-induced drinking behavior, while re-expressing TMEM63B in SFO restored water appetite in TMEM63B-deficient mice. Remarkably, hyperosmolarity activates TMEM63B channels, leading to depolarization and increased firing rate of the interoceptive neurons, which drives drinking behavior. Furthermore, TMEM63B deletion did not affect sensitivities of the SFO neurons to angiotensin II or hypoosmolarity, suggesting that TMEM63B plays a specialized role in detecting hyperosmolarity in SFO neurons. Thus, our results reveal a critical osmosensor molecule for the generation of thirst perception.

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.

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.

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.

The role of Vps4 in cancer development.

VPS4 series proteins play a crucial role in the endosomal sorting complexes required for the transport (ESCRT) pathway, which is responsible for sorting and trafficking cellular proteins and is involved in various cellular processes, including cytokinesis, membrane repair, and viral budding. VPS4 proteins are ATPases that mediate the final steps of membrane fission and protein sorting as part of the ESCRT machinery. They disassemble ESCRT-III filaments, which are vital for forming multivesicular bodies (MVBs) and the release of intraluminal vesicles (ILVs), ultimately leading to the sorting and degradation of various cellular proteins, including those involved in cancer development and progression. Recent studies have shown a potential relationship between VPS4 series proteins and cancer. Evidence suggests that these proteins may have crucial roles in cancer development and progression. Several experiments have explored the association between VPS4 and different types of cancer, including gastrointestinal and reproductive system tumors, providing insight into the underlying mechanisms. Understanding the structure and function of VPS4 series proteins is critical in assessing their potential role in cancer. The evidence supporting the involvement of VPS4 series proteins in cancer provides a promising avenue for future research and therapeutic development. However, further researches are necessary to fully understand the mechanisms underlying the relationship between VPS4 series proteins and cancer and to develop effective strategies for targeting these proteins in cancer therapy. This article aims to review the structures and functions of VPS4 series proteins and the previous experiments to analyze the relationship between VPS4 series proteins and cancer.

What makes vertical femoral neck fracture with posterior inferior comminution different? An analysis of biomechanical features and optimal internal fixation strategy.

BACKGROUND AND PURPOSE: Fracture comminution occurs in 83.9%-94% of vertical femoral neck fractures (VFNFs), the majority of which were located in posterior-inferior region, and poses a clinical challenge in fixation stability. We conducted a subject-specific finite element analysis to determine the biomechanical features and optimal fixation selection for treating VFNF with posterior-inferior comminution. PATIENTS AND METHODS: Eighteen models with three fracture types (VFNF without comminution [NCOM], with comminution [COM], with comminution + osteoporosis [COMOP]) and six internal fixation types (alpha [G-ALP], buttress [G-BUT], rhomboid [G-RHO], dynamic hip screw [G-DHS], invert triangle [G-ITR], femoral neck system (G-FNS)) were created based on the computed tomography data. By using the subject-specific finite element analysis method, stiffness, implant stress, yielding rate (YR) were compared. Additionally, in order to elucidate distinct biomechanical characters of different fracture types and fixation strategies, we calculated interfragmentary movement (IFM), detached interfragmentary movement (DIM), shear interfragmentary movement (SIM) of all fracture surface nodes. RESULTS: Generally, in comparison with NCOM, COM showed a 30.6% reduction of stiffness and 1.46-times higher mean interfragmentary movement. Besides, COM had a 4.66-times (p = 0.002) higher DIM at the superior-middle position, but similar SIM across fracture line, which presented as varus deformation. In COM and COMOP, among all six fixation strategies, G-ALP had significantly the lowest IFM (p<0.001) and SIM (p<0.001). Although G-FNS had significantly highest IFM and SIM (p<0.001), it had the highest stiffness and lowest DIM (p<0.001). In COMOP, YR was the lowest in G-FNS (2.67%). CONCLUSIONS: Posterior-inferior comminution primarily increases superior-middle detached interfragmentary movement in VFNF, which results in varus deformation. For comminuted VFNF with or without osteoporosis, alpha fixation has the best interfragmentary stability and anti-shear property among six current mainstream fixation strategies, but a relatively weaker stiffness and anti-varus property compared to fixed-angle devices. FNS is advantageous owing to stiffness, anti-varus property and bone yielding rate in osteoporosis cases, but is insufficient in anti-shear property.

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.

Measurement of the Balance Stability Angle to Predict the Stability Ratio in Patients With Recurrent Anterior Shoulder Dislocation: A Novel Computed Tomography-Based Protocol.

Background: The stability ratio (SR) is an important biomechanical parameter for evaluating glenoid stability in patients with recurrent anterior shoulder dislocation (RASD), and it cannot be practically and conveniently measured in clinical scenarios. Purpose: To investigate a novel computed tomography (CT)-based protocol to estimate the SR efficiently. Study Design: Descriptive laboratory study. Methods: A total of 102 patients with RASD were included. Demographic information, CT scans, and bone defect area (BDA) were collected. The new protocol, based on balance stability angle (BSA) measurements on CT, was conducted to estimate the SR (SRCT) by 2 surgeons independently. Biomechanical testing was then performed on patient-specific 3-dimensional (3D)-printed glenoid models to calculate the SR (SR3Dprint), which was used to (1) analyze the reliability of SRCT and (2) examine if the BDA could predict SR3Dprint. To validate whether the 3D-printed glenoid could reflect the actual biomechanical properties of the shoulder, the SR from 5 cadaveric glenoid specimens (SRcadaver) was also calculated and compared with that from the 3D-printed glenoid (SR3Dprint) under 6 osteotomy conditions. Linear regression and intraclass correlation coefficients (ICCs) were used for statistical analysis. Results: The interrater reliability of SRCT measurements was high (ICC = 0.95). SRCT was highly correlated with SR3Dprint (R 2 = 0.86; ICC = 0.92). The mean BDA was 11.44% ± 6.72% by the linear ratio method, with a weak correlation with SR3Dprint (R 2 = 0.31; ICC = -0.46). The cadaveric validation experiment indicated that SRcadaver was highly correlated with SR3Dprint (R 2 = 0.86; ICC = 0.77). Conclusion: Results indicated that (1) the proposed CT-based protocol of obtaining BSA measurements is promising for the SR estimation in patients with RASD, (2) the BDA was not an effective parameter to predict the biomechanical SR, and (3) the 3D-printed glenoid could reflect the biomechanical properties of cadaveric shoulders regarding the SR estimation. Clinical Relevance: Traditional BDA measurements cannot accurately reflect the biomechanical stability of the glenoid. The newly proposed CT-based protocol is practical for surgeons to estimate the SR.

Biomechanical evaluation of compression buttress screw and medial plate fixation for the treatment of vertical femoral neck fractures.

OBJECTIVE: To compare the biomechanical properties of compression buttress screw (CBS) fixation with three plate fixation methods for the treatment of vertical femoral neck fractures (FNFs). METHODS: A total of forty synthetic femoral models with simulated Pauwels type III fractures (angle of 70°) were equally assigned to one of four fixation groups: CBS fixation, anteromedial plate fixation (AMP), medial buttress plate fixation (MBP) and medial buttress plate fixation without proximal screw (MBPw). Within each group, half of the specimens were randomly assigned to two loading settings, an axial compression loading test and a hip-flexion torsion test. RESULTS: There were no significant differences in axial load to failure, axial stiffness, torsional strength, or torsional stiffness when comparing CBS with MBP (p>0.05). In the axial compression loading test, both CBS and MBP showed higher load to failure and axial stiffness than MBPw (p<0.05). In torsional testing, AMP exhibited superior torsional strength and torsional stiffness than both MBPw and MBP (all p<0.05) and a higher torsional strength than CBS fixation (p<0.05). There were no significant differences in torsional stiffness between the CBS and AMP fixation groups (p>0.05). CONCLUSION: The biomechanical parameters of CBS fixation are comparable to that of AMP and MBP, and demonstrate superior axial stiffness than MBPw fixation. Although the CBS method for surgical fixation of vertical FNF holds promise as a less invasive surgical technique than plate fixation with similar biomechanical assessments, further clinical evaluation is warranted.

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.

Echocardiographic assessment of intimal thickness growth of patent ductus arteriosus in neonates and analysis of influencing factors.

The spontaneous closure rate of patent ductus arteriosus (PDA) is high, and the necessity of early intervention is debated. Quantitative echocardiographic assessment of the intima in PDA has not been reported. This study evaluated intimal thickness growth in neonatal cases of PDA via echocardiography and investigated its correlation with clinical factors. Seventy-three neonates were enrolled, and echocardiography was performed three times: within 24 h post-birth (first echo), 48 h after the first echo (second echo), and before discharge (third echo). According to PDA outcome, the neonates were divided into the PDA-open group (n = 18 cases), PDA-closure at second echo group (n = 32 cases), and non-PDA at first echo group (n = 23 cases). We measured the intimal thickness (IT1 and IT2 at first and second echo, respectively), lumen diameter of ductus arteriosus (D1 and D2 at first and second echo, respectively), IT1/D1 ratio, and intimal thickness growth rate (V). Correlations between echocardiographic indicators, perinatal factors, and clinical treatment were analyzed. On first echo, the PDA-open group showed a significantly lower IT1/D1 than the combined PDA-closure group (P < 0.05). On second echo, the PDA-open group showed a significantly lower IT2 and V than the PDA-closure group as well as a significantly higher D2 (P < 0.05). Smaller gestational age correlated with a larger D2 but smaller IT2 and V (P < 0.05) and a higher level of respiratory support within 72 h post-birth correlated with a larger D2 and smaller IT 2 (P < 0.05). Increasing oxygen demand within 72 h of birth correlated with a larger D1 and D2 (P < 0.05). Echocardiographic assessment of intimal thickness growth in PDA may provide an approach for predicting spontaneous PDA closure, thereby guiding decision-making regarding early intervention.

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.

Clinical outcomes of robot-assisted transforaminal percutaneous endoscopic lumbar discectomy / 中华骨科杂志

Objective:To introduce a new TIANJI robot assisted targeted puncture technique, and discuss the feasibility and clinical effect of transforaminal percutaneous endoscopic lumbar discectomy (tPELD) using this technique.Methods:The first 14 consecutive cases of single level lumbar disc herniation who underwent robot assisted tPELD procedure were retrospectively analyzed. The mean age was 46.3±16.0 years old (ranged from 16-72). After data transferred from C-arm to robot system and automatic registration, surgeons made plans of the trajectory on robot system based on intraoperative 3-dimensional images of lumbar spine. Move robotic arm to planned position, guide an accurate puncture pathway and establish working cannula. 25 consecutive patients who underwent conventional C-arm assisted tPELD surgery during the same period of time were assessed as the controlled group. The mean age was 45.5±13.7 years old (ranged from 16-68). All patients were followed up for 12 months. Clinical effect was assessed by visual analogue scale (VAS), Oswestry disability index (ODI) and Modified Macnab criteria. Intraoperative parameters and surgery-related complications were recorded.Results:The baseline data of age, surgical level, types of herniation, preoperative VAS scores and ODI had no significant difference between two groups ( P>0.05). In robot group, one case was converted to open microdiscectomy during operation due to technical failure. The other thirteen cases had successful robot assisted tPELD surgeries and were assessed accordingly. The new technique had good clinical outcomes. The immediate post-operative VAS score 2.85±1.79 and the last follow-up VAS score 1.50±1.04 were both significantly decreased than that before surgery 7.62±0.92 ( F=69.747, P<0.01); the last follow-up ODI 18.89%±12.16% was significantly reduced from the pre-operative ODI 71.19%±12.12% ( t=15.430, P<0.01). Between two groups, the immediate post-operative VAS score ( t=0.568, P=0.574), the last follow-up VAS score ( t=0.713, P=0.481), and last follow-up ODI had no significant difference ( t=0.171, P=0.865). The excellent or good rate of modified Macnab criteria at the last follow-up was 92.30% in robot group, comparing to 84.0% in controlled group. The fluoroscopic times during surgery of robot group 8.8±5.5 was significantly lowered the in controlled group 21.3±8.3 ( P<0.01). One case in robot group and two cases in controlled group had recurrence during follow-up period (recurrence rate 7.7% vs. 8.3%). However, there was no significant complications such as nerve root injury, dura injury or increased intracranial pressure in both groups. Conclusion:This study confirmed the feasibility of this new technique. Preliminary results indicated that TIANJI robot could help to build an easy, accurate and safe procedure of tPELD surgery.

The high-resolution chest CT findings and clinical features of dermatomyositis with anti-melanoma differentiation-associated gene 5 antibody / 中华风湿病学杂志

Objective:To investigate the high resolution computed tomography (HRCT) findings, laboratory test results and clinical manifestations of anti-melanoma differentiation-associated gene 5 (MDA5) antibody positive dermatomyositis complicated with lung interstitial lesions, and to analyze the correlation between the HRCT findings and clinical course of disease.Methods:Twenty-seven patients with anti-MDA5 antibody positive associated dermatomyositis (DM) were included and divided into two groups: acute/subacute group ( n=15) and chronic group ( n=12). HRCT images of lung were analyzed. Clinical data including gender, age, clinical manifestations and course of disease, anti-Ro52 antibody, creatine kinase (CK), antinuclear antibody (ANA), anti-Jo-1 antibody and erythrocyte sedimentation rate (ESR) were also collected. χ2 test was adopted for statistical analysis. Results:① Interstitial changes were 100%(27/27). The proportion of unilateral localized distribution was the most [48%(13/27)], followed by bilateral localized distribution [30%(8/27)], and bilateral diffuse distribution [22%(6/27)). ② Among the HRCT findings of lung interstitial changes, ground glass shadow was the most common presentations [59%(16/27)], followed by subpleural curve sign [63%(17/27)] and interlobular septal thickening [56%(15/27)], while honeycomb sign [0(0/27)] had the lowest rate of presentation. ③ Compared with the chronic progressive group, the acute/subacute progressive group presented as chest tightness (80% vs 8%, χ2=13.715, P<0.05) and dyspnea (47% vs 0, χ2=7.560, P<0.05). Acute/subacute HRCT showed ground glass opacity (87% vs 25%, χ2=10.501, P<0.05). The prominent HRCT showed interlobular septal thickening in the chronic course group (83% vs 33%, χ2=6.750, P<0.05). ④ The anti-MDA5 antibody (+++) index was significantly different (88% vs 25%, χ2=8.168, P<0.05). There was no significant difference in anti-Ro52 antibody (+), ANA(+), anti-Jo-1 antibody(+), CK elevation and ESR elevation between the two groups ( P>0.05). Conclusion:Most dermatomyositis patients with positive anti-MDA5 antibody are complicated with interstitial lung lesions, the HRCT manifestations of lung are diverse. In order to confirm the diagnosis of this disease, clinical manifestations, laboratory and pathological examinations are required.

The Effect of Vertical and Oblique Inclinations on Fracture Stability and Reoperation Risks in Femoral-Neck Fractures of Nongeriatric Patient.

Background: For nongeriatric patients with femoral neck fractures (FNFs), preoperative evaluation of fracture three-dimensional inclination is essential to identify fracture stability, select appropriate fixation strategies, and improved clinical prognoses. However, there is lack of evaluation system which takes into account both vertical and oblique inclinations. The purpose of this study was to comprehensively investigate the effect of vertical and oblique inclinations on fracture stability and reoperation risks. Methods: We retrospectively reviewed the medical records of 755 FNFs patients with over 2 years follow-up. The 3-D inclination angle in vertical (α) and oblique plane (ß) were measured based on CT images. The optimal threshold for unstable 3-D inclination were identified by seeking the highest Youden Index in predicting reoperation and validated in the biomechanical test. According to the cut-off value proposed in the diagnostic analysis, forty-two bone models were divided into seven groups, and were all fixed with traditional three parallel screws. Interfragmentary motion (IFM) was used for comparison among seven groups. The association between reoperation outcome and 3-D inclination was analysed with a multivariate model. Results and Conclusion: The overall reoperation rate was 13.2%. Unstable 3-D inclination angles with an optimally determined Youden index (0.39) included vertical (α > 70°) and oblique (50°<α < 70° and ß > 20°/ß < -20°) types. Biomechanical validation showed these fractures had significantly greater (p < 0.05) interfragmentary motion (1.374-2.387 mm vs. 0.330-0.681 mm). The reoperation rate in 3-D unstable group (32.7%) is significantly (p < 0.001) higher than that in 3-D stable group (7.9%). Multivariate analysis demonstrated that 3-D inclination angle was significantly (OR = 4.699, p < 0.001) associated with reoperation. FNFs with α > 70°; 50°<α < 70° and ß > 20°/ß < -20° are real unstable types with significantly worse interfragmentary stability and higher reoperation risks. Fracture inclination in vertical and oblique planes is closely related to reoperation outcomes and may be a useful complement to the way FNFs are currently evaluated.

Fixation effects of different types of cannulated screws on vertical femoral neck fracture: A finite element analysis and experimental study.

Femoral neck fractures (FNFs) in young patients usually result from high-energy violence, and the vertical transcervical type is typically challenging for its instability. FNFs are commonly treated with three cannulated screws (CS), but the role of screws type on fixation effects (FE) is unclear. The purpose of this study was to evaluate the FE of ten types of CS with different diameters, lengths, depths, and pitches of thread via finite element analysis which was validated by a biomechanical test. Ten vertical FNF models were grouped, fixed by ten types of CS, respectively, all in a parallel, inverted triangular configuration. Their FE were scored comprehensively from six aspects via an entropy evaluation method, as higher scores showed better results. For partial-thread screws, thread length and thread shape factor (TSF) are determinative factors on stability of FNF only if thread depth is not too thick, and they have less cut-out risk, better compression effects and better detached resistance of fracture than full-thread screws, whereas full-thread screws appear to have better shear and shortening resistance. A combination of two superior partial-thread screws and one inferior full-thread screw for vertical FNF may get optimal biomechanical outcomes. The type of cannulated screw is important to consider when treating vertical FNF.

Biomechanical study of two alternative methods for the treatment of vertical femoral neck fractures - A finite element analysis.

BACKGROUND: No consensus has been reached for the treatment of vertical femoral neck fractures (vFNFs). Recently, two alternative methods were invented to treat vFNFs, one of which is a new plate with a sliding groove, which was designed as a substitution of the medial buttress locking plate to combine with cannulated compression screws (CCS) for reducing the breakage possibility of the proximal locking screw during the bone healing. Another one is the femoral neck system (FNS), which was believed with biomechanical superiority. This study aims to compare the biomechanics of these two new implants with three previous methods via finite element analysis (FEA) to validate whether they are suitable for the treatment of vFNFs. METHODS: Five 70-degree Pauwels type III transcervical FNFs (vFNFs, AO/OTA 31B2.3r) models were built and fixed by CCS augmented with the newly designed sliding groove buttress plate (CCS+BS) and FNS. For comparison, models fixed by three parallel cannulated compression screws (CCS), biplane double-supported screw fixation (BDSF), CCS augmented with a medial buttress locking plate (CCS+BL) were also built. A 2100N load was applied along with the mechanical axis. Parameters of the maximal stress as well as the maximal displacement of the implants and bone, the maximal relative displacement of interfragments, and the stiffness, were analyzed to compare the biomechanical characteristics of the five models. RESULTS: CCS+BS and CCS+BL showed stronger fixation strength with improved stiffness (1012.05N/mm, 1092.04N/mm), reduced maximal displacement of the implants (1.976mm, 1.838mm) and bone (2.075mm, 1.923mm), when compared with CCS (925.11N/mm, 2.158mm and 2.270mm) and BDSF (842.36N/mm, 2.299mm and 2.493mm). While FNS showed the weakest stiffness (593.22N/mm) and largest maximal displacement of the implants (3.234mm) and bone (3.540mm) among the five models. CONCLUSIONS: CCS+BS has a better biomechanical performance than CCS and BDSF, which offers a new choice to deal with vFNFs. The construction stability of FNS is weaker than CCS, BDSF, and CCS+BL, indicating that this method may not as stable as reported in the previous study.

Enhanced interfragmentary stability and improved clinical prognosis with use of the off-axis screw technique to treat vertical femoral neck fractures in nongeriatric patients.

BACKGROUND: The optimal internal fixation strategy for vertical femoral neck fractures (VFNFs) in nongeriatric patients remains uncertain. Therefore, the purpose of this study was to compare the clinical prognoses and underlying mechanical characteristics of a novel off-axis screw technique with dynamic hip screws (DHSs) and three traditional parallel screws. METHODS: This study included a clinical investigation and a patient-specific finite element analysis (FEA). In the clinical investigation, VFNF patients were grouped by fixation type: (1) use of three parallel screws (G-TRI); (2) augmentation with an off-axis screw (G-ALP); and (3) DHS with an anti-rotational screw (G-DHS). Fixation failures (nonunion, femoral neck shortening (FNS), varus deformation, screw cut-out) and avascular necrosis (AVN) consequent to the three types of fixations were compared. In the FEA, twenty-four fixation models with the three fixation types were created based on the data of eight healthy volunteers. Models were assessed under walking conditions. Stiffness, interfragmentary motion (IFM), and implant stress were evaluated. RESULTS: In the clinical investigation, the fixation failure rate was significantly (p < 0.05) lower in G-ALP (18.5%) than in G-DHS (37.5%) and G-TRI (39.3%). No significant difference in AVN was observed among the three fixation groups. In the FEA, stiffness and implant stress in the G-DHS models were significantly (p < 0.05) higher, and the IFM of G-ALP was significantly (p < 0.05) lower among the groups. CONCLUSIONS: Among fixation types for VFNFs, the off-axis screw technique exhibited better interfragmentary stability (lowest IFM) and a lower fixation failure rate (especially FNS). Analyzing interfragmentary stability in biomechanical experiments is more consistent with clinical prognosis than construct stability for VFNFs, suggesting that internal fixations should aim for this outcome.

"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.