Tofacitinib Promotes Functional Recovery after Spinal Cord Injury by Regulating Microglial Polarization via JAK/STAT Signaling Pathway.

Background: The JAK/STAT signaling pathway is the main inflammatory signal transduction pathway, whether JAK/STAT contributes the pathology of SCI and targeting the pathway will alleviate SCI needs to be addressed. Here, we explored the therapeutic effect of pan-JAK inhibitor tofacitinib (TOF) on secondary injury after SCI and explained the underlying mechanisms. Methods: SCI model in rat was established to evaluate the therapeutic effects of TOF treatment in vivo. Histological and behavioral analyses were performed at different time points after SCI. In vitro, the effects of TOF on pro-inflammatory activation of primary microglia and BV2 cells were analyzed by western blot analysis, fluorescent staining, qPCR and flow cytometry. The neuroprotection of TOF was detected using a co-culture system with primary neurons and microglia. Results: TOF can effectively improve motor dysfunction caused by spinal cord injury in rats. TOF administration in the early stage of inflammation can effectively inhibit neuronal apoptosis and scar tissue formation, and promote the repair of axons and nerve fibers. Further studies have demonstrated that TOF suppresses inflammation caused by spinal cord injury by inhibiting the activation of microglia to pro-inflammatory phenotype in vivo and in vitro. Additionally, an interesting phenomenon is revealed in our results that TOF exhibits superior neuronal protection during inflammation in vitro. Conclusions: Our study showed that TOF could regulate microglial activation via JAK / STAT pathway and promote the recovery of motor function after SCI, which is of great significance for the immunotherapy of SCI.

Increasing Chemotherapeutic Efficacy Using pH-Modulating and Doxorubicin-Releasing Injectable Chitosan-Poly(ethylene glycol) Hydrogels.

Modulation of pH is crucial to maintaining the chemical homeostasis of biological environments. The irregular metabolic pathways exhibited by cancer cells result in the production of acidic byproducts that are excreted and accumulate in the extracellular tumor microenvironment, reducing the pH. As a consequence of the lower pH in tumors, cancer cells increase the expression of metastatic phenotypes and chemotherapeutic resistance. A significant limitation in current cancer therapies is the inability to locally deliver chemotherapeutics, leading to significant damage to healthy cells in systemic administration. To overcome these challenges, we present an injectable chitosan-poly(ethylene glycol) hydrogel that is dual-loaded with doxorubicin and sodium bicarbonate providing alkaline buffering of extracellular acidity and simultaneous chemotherapeutic delivery to increase chemotherapeutic efficacy. We conducted in vitro studies of weak base chemotherapeutic and alkaline buffer release from the hydrogel. The release of doxorubicin from hydrogels increased in a low-pH environment and was dependent on the encapsulated sodium bicarbonate concentration. We investigated the influence of pH on the doxorubicin efficacy and viability of MCF-7 and MDA-MB-231 breast cancer cell lines. The results show a 2- to 3-fold increase in IC50 values from neutral pH to low pH, showing decreased cancer cell viability at neutral pH as compared to acidic pH. The IC50 results were shown to correlate with a decrease in intracellular uptake of doxorubicin at low pH. The proposed hydrogels were confirmed to be nontoxic to healthy MCF-10A mammary epithelial cells. Rheological studies were performed to verify that the dual-loaded hydrogels were injectable. The mechanical and release properties of the hydrogels were maintained after extended storage. The chemotherapeutic activity of doxorubicin was evaluated in the presence of the proposed pH-regulating hydrogels. The findings suggest a promising nontoxic, biodegradable hydrogel buffer delivery system that can achieve two simultaneous important goals of local acidosis neutralization and chemotherapeutic release.

Comparative study of halo-vest reduction and skull traction reduction in the treatment of cervical fracture dislocation in patients with ankylosing spondylitis.

Background: This study aimed to investigate the safety and efficacy of the halo-vest in the treatment of cervical fracture in patients with ankylosing spondylitis (AS) and kyphosis. Methods: From May 2017 to May 2021, 36 patients with cervical fractures with AS and thoracic kyphosis were included in this study. The patients with cervical spine fractures with AS underwent preoperative reduction by halo-vest or skull tractions. Instrumentation internal fixation and fusion surgery were then performed. The level of cervical fractures, the operative duration, blood loss, and treatment outcomes were investigated preoperatively and postoperatively. Results: A total of 25 cases were included in the halo-vest group and 11 cases were included in the skull tractions group. The intraoperative blood loss and the surgery duration were significantly less in the halo-vest group than in the skull traction group. A comparison of American Spinal Injury Association scores at admission and final follow-up showed that the neurological function of patients improved in both groups. All patients had reached solid bony fusion during the follow-up. Conclusion: This study presented a unique approach to use halo-vest treatment fixation of unstable cervical fracture in patients with AS. The patient should also have early surgical stabilization with a halo-vest to correct spinal deformity and avoid worsening of neurological status.

Fabrication of Pulsatile Polymeric Microparticles Encapsulating Rabies Antigen.

The current guidelines for rabies post-exposure prophylaxis require multiple injections administered over several weeks. This can be disproportionately burdensome to those living in low- and middle-income countries (LMICs), where the majority of deadly exposures to rabies occur. Different drug delivery strategies have been explored to condense vaccine regimens to a single injection by encapsulating antigens into polymeric particles. However, harsh stressors during the encapsulation process can cause denaturation of the encapsulated antigen. This article describes a method for encapsulating the rabies virus (RABV) antigen into polymeric microparticles that exhibit tunable pulsatile release. This method, termed Particles Uniformly Liquified and Sealed to Encapsulate Drugs (PULSED), generates microparticles using soft lithography to create inverse polydimethylsiloxane (PDMS) molds from a multi-photon, 3D-printed master mold. Poly(lactic-co-glycolic acid) (PLGA) films are then compression-molded into the PDMS molds to generate open-faced cylinders that are filled with concentrated RABV using a piezoelectric dispensing robot. These microstructures are then sealed by heating the top of the particles, allowing the material to flow and form a continuous, nonporous polymeric barrier. Post-fabrication, an enzyme-linked immunosorbent assay (ELISA) specific to the detection of intact trimeric rabies virus glycoprotein is used to confirm the high recovery of immunogenic antigen from the microparticles.

The influence of the ultrasonic treatment of working fluids on electrospun amorphous solid dispersions.

Based on a working fluid consisting of a poorly water-soluble drug and a pharmaceutical polymer in an organic solvent, electrospinning has been widely exploited to create a variety of amorphous solid dispersions However, there have been very few reports about how to prepare the working fluid in a reasonable manner. In this study, an investigation was conducted to determine the influences of ultrasonic fluid pretreatment on the quality of resultant ASDs fabricated from the working fluids. SEM results demonstrated that nanofiber-based amorphous solid dispersions from the treated fluids treated amorphous solid dispersions exhibited better quality than the traditional nanofibers from untreated fluids in the following aspects: 1) a straighter linear morphology; 2) a smooth surface; and 3) a more evener diameter distribution. The fabrication mechanism associated with the influences of ultrasonic treatments of working fluids on the resultant nanofibers' quality is suggested. Although XRD and ATR-FTIR experiments clearly verified that the drug ketoprofen was homogeneously distributed all over the TASDs and the traditional nanofibers in an amorphous state regardless of the ultrasonic treatments, the in vitro dissolution tests clearly demonstrated that the TASDs had a better sustained drug release performance than the traditional nanofibers in terms of the initial release rate and the sustained release time periods.

The association of rod curvature with postoperative outcomes in patients undergoing posterior lumbar interbody fusion for spinal stenosis: a retrospective case-control study.

BACKGROUND: Restoration of sagittal balance is a crucial consideration in posterior lumbar interbody fusion (PLIF) surgery and adverse postoperative outcomes are associated with inadequate restoration of sagittal alignment. However, there remains a shortage of substantial evidence regarding the effect of rod curvature on both sagittal spinopelvic radiographic parameters and clinical outcomes. METHOD: A retrospective case-control study was conducted in this study. Patient demographics (age, gender, height, weight and BMI), surgical characteristics (number of fused levels, surgical time, blood loss and hospital stay) and radiographic parameters (lumbar lordosis [LL], sacral slope [SS], pelvic incidence [PI], pelvic tilt [PT], PI-LL, Cobb angle of fused segments [Cobb], rod curvature [RC], Posterior tangent angle of fused segments [PTA] and RC-PTA) were analyzed. RESULTS: Patients in the abnormal group had older mean age and suffered more blood loss than those in the normal group. In addition, RC and RC-PTA were significantly lower in the abnormal group compared to the normal group. Multivariate regression analysis revealed that lower age (OR = 0.94; 95% CI: 0.89-0.99; P = 0.0187), lower PTA (OR = 0.91; 95% CI: 0.85-0.96; P = 0.0015) and higher RC (OR = 1.35; 95% CI: 1.20-1.51; P < 0.0001) were related to higher odds of better surgical outcomes. The receiver operating characteristic curve analysis showed that the ROC curve (AUC) for predicting outcomes of surgery by RC classifier was 0.851 (0.769-0.932). CONCLUSIONS: In patients who underwent PLIF surgery for lumbar spinal stenosis, those who had a satisfactory postoperative outcome tended to be younger, had lower blood loss, and higher values of RC and RC-PTA compared to those who had poor recovery and required revision surgery. Additionally, RC was found to be a reliable predictor of postoperative outcomes.

The Relationship Between Cervical Sagittal Balance and Type of Atlantoaxial Dislocation Secondary to Os Odontoideum.

OBJECTIVE: To analyze the effect of cervical sagittal balance on the direction and type of atlantoaxial dislocation. METHODS: Data of 55 patients seen at our hospital for atlantoaxial instability/dislocation caused by os odontoideum were reviewed. Radiographic variables, including T1 slope (T1S), C1-C2 angle, C2-C7 angle, C1-C2 sagittal vertical axis (SVA), C2-C7 SVA, and atlanto-dens interval (ADI), were measured preoperatively. Patients were divided into three groups according to ADI: anterior atlantoaxial dislocation, atlantoaxial instability, and posterior atlantoaxial dislocation. Differences within and between groups in radiographic variables and relationships between the investigated variables were analyzed. RESULTS: ADI was strongly negatively associated with C1-C2 angle (r = -0.805, P < 0.05); whereas ADI had a medium-strength positive relationship with C2-C7 angle (r = 0.425, P < 0.05) and a medium-strength negative relationship with C2-C7 SVA (r = -0.411, P < 0.05). However, ADI was not significantly correlated with T1 slope (r = -0.092, P > 0.05). CONCLUSIONS: The type and direction of atlantoaxial dislocation is closely associated with cervical sagittal balance. C2-C7 SVA is an important factor in assessing the direction of atlantoaxial subluxation secondary to os odontoideum. ADI decreases with increasing C2-C7 SVA. The larger the C2-C7 SVA, the more likely the atlantoaxial dislocation is to be posterior.

Biomechanical Evaluation of the Cross-link Usage and Position in the Single and Multiple Segment Posterior Lumbar Interbody Fusion.

OBJECTIVE: Previous studies have neither explored the usage of cross-links nor investigated the optimal position of the cross-links in posterior lumbar interbody fusion (PLIF). This study evaluates biomechanical properties of cross-links in terms of different fixation segments and optimal position in single- and multi-segment posterior lumbar interbody fusion. METHODS: Two finite element (FE) models of instrumented lumbosacral spine with single-(L4/5) and multi-segment (L3-S1) PLIF surgery were simulated. On the basis of the two models, the benefits of the usage of cross-links were assessed and compared with the status of no application of cross-links. Moreover, the effects of position of cross-links on multi-segment PLIF surgery were studied in Upper, Middle, and Lower positions. RESULTS: No significant difference was found in the range of motion (ROM), intersegmental rotational angle (IRA) of adjacent segments, and intradiscal pressure (IDP) regardless of the usage of cross-links in the single-segment PLIF surgery, while the cross-link increased the maximum von Mises stress in the fixation (MSF) under the axial rotation (53.65 MPa vs 41.42 MPa). In the multi-segment PLIF surgery, the usage of cross-links showed anti-rotational advantages indicated by ROM (Without Cross-link 2.35o , Upper, 2.24o ; Middle, 2.26o ; Lower, 2.30o ) and IRA (Without Cross-link 1.19o , Upper, 1.08o ; Middle, 1.09o ; Lower, 1.13o ). The greatest values of MSF were found in without cross-link case under the flexion, lateral bending, and axial rotation (37.48, 62.61, and 86.73 MPa). The application of cross-links at the Middle and Lower positions had lower values of MSF (48.79 and 69.62 MPa) under the lateral bending and axial rotation, respectively. CONCLUSION: The application of cross-links was not beneficial for the single-segment PLIF, while it was found highly advantageous for the multi-segment PLIF. Moreover, the usage of cross-links at the Middle or Lower positions resulted in a better biomechanical stability.

Inhibition of IL1R1 or CASP4 attenuates spinal cord injury through ameliorating NLRP3 inflammasome-induced pyroptosis.

Spinal cord injury (SCI) is a devastating trauma characterized by serious neuroinflammation and permanent neurological dysfunction. However, the molecular mechanism of SCI remains unclear, and few effective medical therapies are available at present. In this study, multiple bioinformatics methods were used to screen out novel targets for SCI, and the mechanism of these candidates during the progression of neuroinflammation as well as the therapeutic effects were both verified in a rat model of traumatic SCI. As a result, CASP4, IGSF6 and IL1R1 were identified as the potential diagnostic and therapeutic targets for SCI by computational analysis, which were enriched in NF-κB and IL6-JAK-STATA3 signaling pathways. In the injured spinal cord, these three signatures were up-regulated and closely correlated with NLRP3 inflammasome formation and gasdermin D (GSDMD) -induced pyroptosis. Intrathecal injection of inhibitors of IL1R1 or CASP4 improved the functional recovery of SCI rats and decreased the expression of these targets and inflammasome component proteins, such as NLRP3 and GSDMD. This treatment also inhibited the pp65 activation into the nucleus and apoptosis progression. In conclusion, our findings of the three targets shed new light on the pathogenesis of SCI, and the use of immunosuppressive agents targeting these proteins exerted anti-inflammatory effects against spinal cord inflammation by inhibiting NF-kB and NLRP3 inflammasome activation, thus blocking GSDMD -induced pyroptosis and immune activation.

Cervical Myelopathy Due to Idiopathic Retro-odontoid Pseudotumor.

OBJECTIVE: A retro-odontoid pseudotumor (ROP) is commonly associated with atlantoaxial instability or rheumatoid arthritis. However, ROP in the absence of atlantoaxial instability or rheumatoid arthritis, which is termed idiopathic ROP (IROP), is a rare condition. The pathomechanisms and optimal treatment strategies for IROP remain controversial. The aim of the present study was to evaluate the radiographic and clinical characteristics of IROP patients and to assess the efficiency of atlantoaxial/occipitocervical fusion on IROP regression. METHODS: Data from 5 patients diagnosed with IROP were retrospectively reviewed. Posterior atlantoaxial or occipitocervical fixation and fusion were performed in 4 patients and C1 posterior arch resection alone in 1 patient. The patients' features, surgical procedures, and complications were recorded. The retro-odontoid soft tissue thickness was measured on preoperative and postoperative magnetic resonance imaging to evaluate IROP regression. RESULTS: The mean follow-up time was 37 months. ROP regression was achieved in patients who received atlantoaxial/occipitocervical fusion, but not for the patient with C1 posterior resection alone. There were no observed neurovascular complications associated with surgery. CONCLUSIONS: IROP was related to a restricted range of motion of the subaxial spine. Upper cervical fixation is an optional treatment that produces IROP regression over time. By contrast, direct removal of the IROP is unnecessary.

Anterior Canal Reconstruction and Fusion for Myelopathy Caused by Degenerative Cervical Kyphosis and Stenosis With or Without Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: This was a retrospective study. OBJECTIVE: To introduce an anterior surgical technique for myelopathy caused by degenerative cervical kyphosis and stenosis (DCKS) with or without ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: The optimal approach in the treatment of DCKS remains a controversy because each anterior or posterior route surgery has advantages and disadvantages. MATERIALS AND METHODS: In the period from June 2017 through June 2019, a consecutive cohort of adults diagnosed with DCKS underwent anterior canal reconstruction and fusion (ACRF). All patients underwent x-ray, computed tomography, and magnetic resonance imaging of the cervical spine. Radiologic assessment included kyphosis, canal area, canal reconstruction, OPLL, and spinal cord curvature and morphology. The Japanese Orthopaedic Association (JOA) scoring system was used to evaluate the neurological status. Surgery-related and implant-related complications were all recorded. Follow-up was carried out at 3, 6, 12, 24, and 36 months postoperation. RESULTS: Fourty-one patients were included in the study, of which 19 presented with OPLL. Postoperatively, the canal area were significantly greater at last follow-up compared with preoperation (208.4 vs. 123.2 mm2; P=0.001). There was significant kyphosis correction (-17.6 vs. 8.5 degrees, P=0.001) at last follow-up. Ninety-six segmental canal reconstruction were performed, 89 (92.7%) reached bone fusion at both grooves with a mean time of 7.9 months. On sagittal magnetic resonance imaging, 33 (80.5%) patients presented with lordosis in the spinal cord curvature, 8 (19.5%) with straight. The mean JOA score at last follow-up was significantly better than preoperation (15.0 vs. 9.3 points; P<0.01). One patient presented with cerebrospinal fluid leakage, 1 with screw displacement and 2 with dysphagia. CONCLUSION: ACRF, receiving good correction of kyphosis, amplified canal area, solid instrumented fusion and circumferential decompression, is an effective and safe surgical technique for cervical myelopathy caused by DCKS with or without OPLL. LEVEL OF EVIDENCE: Level III-a retrospective analysis.

Cervical spine fracture-dislocation in patients with ankylosing spondylitis and severe thoracic kyphosis: Application of halo vest before and during surgical management.

Cervical spine fracture-dislocation in patients with ankylosing spondylitis (AS) and severe thoracic kyphosis is extremely unstable. This study was performed to investigate the efficacy and safety of halo vest application before and during surgery for these patients. We retrospectively analyzed the case histories, operations, neurologic outcomes, follow-up data, and imaging records of 25 patients with AS and severe thoracic kyphosis who underwent surgical treatment of cervical fracture-dislocation in our department from 2008 to 2019. A halo vest was used to reduce and immobilize the fractured spinal column ends before and during surgery. The neurologic injury was evaluated using the American Spinal Injury Association (ASIA) impairment scale score, visual analog scale (VAS) score, and Japanese Orthopaedic Association (JOA) score before and after the operation. Twenty-two patients achieved closed anatomical reduction; two achieved successful reduction and one underwent failed reduction after halo vest application. No fracture site displacement occurred after movement into the prone position. No patients developed secondary neurological deterioration. The mean Cobb angle of thoracic kyphosis was 69.0° ± 12.3°. All patients underwent posterior or combined anterior-posterior surgery. The ASIA grade improved significantly (P < 0.01). The mean VAS and JOA scores also increased significantly after the operation (14.6 ± 3.0 vs. 10.4 ± 4.3 and 0.5 ± 0.6 vs. 4.6 ± 1.9, respectively; P < 0.01). One patient died 3 weeks after the operation. No other severe complications occurred. All patients had reached solid bony fusion by the 12-month follow-up. Use of a halo vest before and during the operation is safe and effective in patients with AS and severe thoracic kyphosis who develop cervical fracture-dislocation. This technique makes positioning, awake nasoendotracheal intubation, nursing, and the operation more convenient. It can also provide satisfactory reduction and rigid immobilization and prevent secondary neurologic deterioration.

Exclusion of Ossified Ligaments Behind C2 Vertebra Combined with Anterior Controllable Antedisplacement and Fusion for Cervical Ossification of the Posterior Longitudinal Ligament Extending to C2 Segment.

OBJECTIVE: We sought to introduce an anterior surgical technique for cervical ossification of posterior longitudinal ligament (OPLL) extending to C2. METHODS: A total of 29 patients with multilevel OPLL extending to C2 underwent surgery from January 2016 to January 2019. The rationale of our surgical technique is to transect the ossified ligament at the level of C2/3, dividing OPLL into 2 parts. OPLL behind the C2 vertebra is reserved as "focus exclusion," and OPLL below C2 is performed anterior controllable antedisplacement and fusion. Neurologic condition was evaluated using the Japanese Orthopaedic Association scoring system and its improvement ratio. Radiologic assessment included type and extent of OPLL, occupying rate, thickness and length of ossified mass, and curvature of spinal cord. Surgery- and implant-related complications were recorded. RESULTS: The mean Japanese Orthopaedic Association score increased from 9.4 to 15.8 points at last follow-up, with a significant improvement (P < 0.01). The mean preoperative length of the ossified mass behind C2 was 15.4 mm, and its thickness was 2.2 mm, with no significant progression at last follow-up (15.3 mm and 2.2 mm, P > 0.05). There was also no statistical difference in OPLL thickness at the largest occupying rate level between preoperation and last follow-up (7.4 mm vs. 7.3 mm, P > 0.05). Four patients presented with cerebrospinal fluid leakage, 1 with screw displacement, and 1 with dysphagia. CONCLUSIONS: For patients with cervical OPLL extending to C2, exclusion of ossified ligaments behind C2 combined with anterior controllable antedisplacement and fusion below C2 is an effective and alternative technique.

Consensus statement on diagnosis and treatment of cervical ossification of posterior longitudinal ligament from Asia Pacific Spine Society (APSS) 2020.

PURPOSE: The study aimed to develop an evidence-based expert consensus statement on diagnosis and treatment of cervical ossification posterior longitudinal ligament (OPLL). METHOD: Delphi method was used to perform such survey, and the panel members from Asia Pacific Spine Society (APSS) 2020 were invited to answer the open-ended questions in rounds 1 and 2. Then the results were summarized and developed into a Likert-style questionnaire for voting in round 3, and the level of agreement was defined as 80%. In the whole process, we conducted a systematic literature search on evidence for each statement. RESULTS: Cervical OPLL can cause various degrees of neurological symptoms, an it's thought to be more common in Asia population. CT reconstruction is an important imaging examination to assist diagnosis and guide surgical choice. Segmental, continuous, mixed, and focal type is the most widely used classification system. The non-surgical treatment is recommended for patients with no or mild clinical symptoms, or irreversible neurological damage, or failed surgical decompression, or condition cannot tolerant surgery, or refusing surgery. As OPLL may continue to develop gradually, surgical treatment would be considered in their course inevitably. The surgical choice should depend on various conditions, such as involved levels, thickness, and type of OPLL, skill-experiences of surgeons, which are listed and discussed in the article. CONCLUSION: In this statement, we describe the clinical features, classifications, and diagnostic criteria of cervical OPLL, and review various surgical methods (such as their indications, complications), and provide a guideline on their choice strategy.

Efficacy of Neoadjuvant Chemotherapy with Epirubicin and Cyclophosphamide and Weekly Paclitaxel and Trastuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Carcinoma: A Real-World Study.

BACKGROUND: Trastuzumab has been introduced a decade ago and demonstrated improvement in the prognosis in patients with human epidermal growth factor receptor 2- (HER2-) positive (+) breast carcinoma (BC). This study is aimed at evaluating the efficacy of epirubicin/cyclophosphamide with weekly paclitaxel-trastuzumab as neoadjuvant chemotherapies in HER2+ BC patients. METHODS: A total of 234 HER2+ BC patients were given neoadjuvant chemotherapy (NAC) between 2010 and 2016. The primary endpoints were pathologic complete response (pCR) and disease-free survival (DFS). Univariate and multivariate analyses of clinical and pathological factors associated with pCR and DFS were conducted. RESULTS: The pCR (30.4% vs. 14.8%; P = 0.004) and DFS (P = 0.036) showed significant differences between patients administered with neoadjuvant trastuzumab therapy and those who did not. Multivariate logistic regression analysis showed that neoadjuvant trastuzumab treatment was regarded as an independent predictor of pCR. Patients with pCR had prolonged DFS (P = 0.025). In patients who did not achieve pCR (non-pCR), those who received trastuzumab had more prolonged DFS (P = 0.046). The luminal B/HER2+ subtypes had prolonged DFS when compared with nonluminal B/HER2+ subtypes (P = 0.010). The luminal B/HER2+ subgroup also showed improved DFS in non-pCR patients (P = 0.010). In the subgroup of non-pCR, the luminal B/HER2+ subgroup administered with trastuzumab showed no superior DFS (P = 0.168). However, a positive result was observed in patients without trastuzumab (P = 0.039). Multivariate analysis showed cT stage (P = 0.006) and tumor grade (P = 0.041), considering them as significant prognostic factors of DFS. CONCLUSIONS: HER2+ BC patients showed improvement in pCR and DFS after neoadjuvant trastuzumab treatment. Patients without pCR had prolonged DFS after trastuzumab maintenance. Although the prognosis of luminal B/HER2+ BC showed favorable outcomes in the non-pCR subgroup, those receiving trastuzumab showed no survival advantage.

Comparison of Anterior Controllable Antedisplacement and Fusion With Posterior Laminoplasty in the Treatment of Multilevel Cervical Ossification of the Posterior Longitudinal Ligament: A Prospective, Randomized, and Control Study With at Least 1-Year Follow Up.

STUDY DESIGN: A prospective, randomized, controlled study. OBJECTIVE: To compare anterior controllable antidisplacement and fusion (ACAF) with laminoplasty in the treatment of multilevel ossification of the posterior longitudinal ligament (OPLL), and evaluate the efficacy and safety of this procedure. SUMMARY OF BACKGROUND DATA: The optimal approach for the treatment of OPLL still remains controversial. Both anterior and posterior approaches have their advantages and disadvantages. METHODS: Between September 2016 and April 2018, a total of 80 patients with multilevel OPLL were randomized in a 1:1 ratio to ACAF group and laminoplasty group. All patients were followed up at least 1 year. Clinical and radiological results were compared between ACAF group and laminoplasty group. RESULTS: ACAF took a longer operation time. C5 palsy and axial pain occurred more commonly in laminoplasty group, whereas dysphagia and hoarseness appeared easily in ACAF group. At 1-year follow-up, the final Japanese Orthopedic Association (JOA) score and recovery rate were significant higher in ACAF group than those in laminoplasty group, when occupying rate (OR) was not less than 60%, or K-line was negative. ACAF was also good at preservation of cervical lordosis and sagittal balance, but range of movement of cervical spine in both groups decreased significantly. CONCLUSION: Generally speaking, ACAF is a safe and effective alternative for multilevel OPLL. Compared with laminoplasty, ACAF is more effective in the cases when OR is not less than 60%, or K-line is negative. LEVEL OF EVIDENCE: 2.

Long Non-coding RNA XIST May Influence Cervical Ossification of the Posterior Longitudinal Ligament Through Regulation of miR-17-5P/AHNAK/BMP2 Signaling Pathway.

Long non-coding RNAs (lncRNAs) play an important role in the development of bone-related diseases. This study was conducted to investigate the role and mechanism of lncRNA X inactive specific transcript (XIST) in the occurrence of cervical ossification of the posterior longitudinal ligament (OPLL). Here, primary human ligament fibroblasts cells (LFCs) were isolated from 30 cases of OPLL and 30 normal cervical posterior longitudinal ligament (non-OPLL) tissues to perform the qPCR and Western blot assay. We found that the mRNA level of lncRNA XIST was significantly increased in OPLL LFCs compared to non-OPLL LFCs. By bioinformatics analysis, we found that lncRNA XIST has four binding sites for miR-17-5p and found that the mRNA level of miR-17-5p was also significantly decreased in OPLL LFCs compared to non-OPLL LFCs. Since AHNAK is the target gene of miR-17-5p, we further found that the expression of AHNAK was significantly reduced in non-OPLL LFCs after being transfected with miR-17-5p mimic. The qPCR results showed that the mRNA expressions of BMP2 and Runx2 were significantly decreased. After being transfected with lncRNA XIST siRNA in the non-OPLL LFCs, the mRNA levels of lncRNA XIST, AHNAK, BMP2, and Runx2 were significantly decreased and the phosphorylated protein of Smad1/5/8 was reduced. After being cultured by mechanical vibration, the mRNA levels of lncRNA XIST, AHNAK, BMP2, Runx2, COL1, OC, OPN, and Phospho1 were significantly increased, but the mRNA expression of miR-17-5p was significantly decreased. The expression of phosphorylated Smad1/5/8 protein was also significantly increased. Together, this study was the first to determine that XIST gene inhibition plays an important role in the occurrence of cervical OPLL, through the mechanism of regulation of miR-17-5P/AHNAK/BMP2 signaling pathway. Thus, XIST may be a potential target that could be modulated for the treatment of cervical OPLL.

How to Avoid Postoperative Remaining Ossification Mass in Anterior Controllable Antedisplacement and Fusion Surgery.

OBJECTIVES: To retrospectively review the cases with ossification of the posterior longitudinal ligament (OPLL) treated with anterior controllable antedisplacement and fusion (ACAF). Patients with postoperative remaining ossification mass (PROM) are analyzed to figure out the causes and preventions of this problem. METHODS: A total of 115 patients were included. PROM was identified as remaining OPLL existed in the spinal canal other than included in the vertebral-OPLL complex on postoperative computed tomography. The Japanese Orthopaedic Association scoring system was used to evaluate the neurologic status. Surgery-related complications such as cerebrospinal fluid (CSF) leakage and spinal cord or nerve injury were all recorded. The patients with the PROM group and those without the PROM group were compared. RESULTS: There were 14 patients with wide-base OPLL (12.2%) and 10 patients (8.7%) with PROM among the 115 patients with OPLL. The 10 patients with PROM were all with wide-base OPLL. The average improvement rate of Japanese Orthopaedic Association score in patients without PROM was significantly larger than that in patients with PROM (69.5 ± 22.6% vs. 36.7 ± 22.0, P < 0.01). Incidence rate of postoperative CSF leakage and neural deterioration were significantly higher in patients with PROM than that in patients without PROM (CSF leakage, 40.0% vs. 5.9%; neural deterioration, 50.0% vs. 3.0%). No other complications were observed. CONCLUSIONS: The occurrence of PROM might cause complications and poor neural function recovery in patients treated with ACAF. Surgical techniques should be noted to avoid PROM in ACAF surgery.

Profiling and bioinformatics analysis of differentially expressed circular RNAs in human intervertebral disc degeneration.

The functional changes of nucleus pulposus (NP) cells are considered to be the initiating factors of intervertebral disc degeneration (IDD), and the differentially expressed circRNAs in NP cells may play an important role in the process of IDD. To identify circular RNAs (circRNAs) associated with human IDD, we isolated the NP cells from human degenerated and non-degenerated intervertebral disc and identified NP cells by microscopy and cell proliferation. CircRNA microarray expression profiles were obtained from NP cells of degenerated and non-degenerated intervertebral disc and further validated by quantitative reverse transcription PCR (qRT-PCR). The expression data were analyzed by bioinformatics. Microarray analysis identified 7294 circRNAs differentially expressed in degenerated human IDD NP cells. Among them, 3724 circRNAs were up-regulated and 3570 circRNAs were down-regulated by more than 2 folds. After validating by qRT-PCR, we predicted the possible miRNAs of the top dysregulated circRNAs using TargetScan, and miRanda. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most modulated circRNAs regulate the viability, degradation, apoptosis and oxidative stress in NP cells, and the possible mechanism underlying IDD was discussed. These results revealed that circRNAs may play a role in IDD and might be a promising candidate molecular target for gene therapy.