Study on the pharmacokinetics, tissue distribution and excretion of Penthorum chinense Pursh in normal and acute alcoholic liver injury rats using validated UPLC-MS/MS method.

Penthorum chinense Pursh (PCP), as a traditional medicine of Miao nationality in China, is often used for the treatment of various liver diseases. At present, information regarding the in vivo process of PCP is lacking. Herein, a sensitive and robust ultra-performance liquid chromatography tandem with mass spectrometry (UPLC-MS/MS) was developed and validated for the quantification of several components to study their pharmacokinetics, tissues distribution and excretion in normal and acute alcoholic liver injury (ALI) rats. Prepared samples were separated on a Thermo C18 column (4.6 mm × 50 mm, 2.4 µm) using water containing 0.1 % formic acid (A) and acetonitrile (B) as the mobile phase for gradient elution. Negative electrospray ionization was performed using multiple reaction monitoring (MRM) mode for each component. The validated UPLC-MS/MS assay gave good linearity, accuracy, precision, recovery rate, matrix effect and stability. This method was successfully applied to the pharmacokinetics, tissue distribution and excretion in normal and acute ALI rats. There were differences in pharmacokinetic process, tissue distribution and excretion characteristics, indicating that ALI had a significant influence on the in vivo process of PCP in rats. The research provided an experimental basis for the study of PCP quality control and further application in the clinic.

A novel MRI-based Cervical-Endplate Bone Quality score independently predicts cage subsidence after Anterior Cervical Discectomy and Fusion.

INTRODUCTION: Postoperative cage subsidence after Anterior Cervical Discectomy and Fusion (ACDF) often has adverse clinical consequences and is closely related to Bone Mineral Density (BMD). Previous studies have shown that cage subsidence can be better predicted by measuring site-specific bone density. MRI-based Endplate Bone Quality (EBQ) scoring effectively predicts cage subsidence after lumbar interbody fusion. However, there is still a lack of studies on the practical application of EBQ scoring in the cervical spine. PURPOSE: To create a similar MRI-based scoring system for Cervical-EBQ (C-EBQ) and to assess the correlation of the C-EBQ with endplate Computed Tomography (CT)-Hounsfield Units (HU) and the ability of this scoring system to independently predict cage subsidence after ACDF, comparing the predictive ability of the C-EBQ with the Cervical-Vertebral Bone Quality (C-VBQ) score. METHODS: A total of 161 patients who underwent single-level ACDF for degenerative cervical spondylosis at our institution from 2012 to 2022 were included. Demographics, procedure-related data, and radiological data were collected, and Pearson correlation test was used to determine the correlation between C-EBQ and endplate HU values. Cage subsidence was defined as fusion segment height loss of ≥ 3 mm. Receiver operating characteristic analysis and area-under-the-curve values were used to assess the predictive ability of C-EBQ and C-VBQ. A multivariate logistic regression model was developed to identify potential risk factors associated with subsidence. RESULTS: Cage subsidence was present in 65 (40.4%) of 161 patients. The mean C-EBQ score was 1.81 ± 0.35 in the group without subsidence and 2.59 ± 0.58 in the group with subsidence (P < 0.001). Multivariate analysis showed that a higher C-EBQ score was significantly associated with subsidence (OR = 5.700; 95%CI = 3.435-8.193; P < 0.001), was the only independent predictor of cage subsidence after ACDF, had a predictive accuracy of 93.7%, which was superior to the C-VBQ score (89.2%), and was significantly negatively correlated with the endplate HU value (r = -0.58, P < 0.001). CONCLUSIONS: Higher C-EBQ scores were significantly associated with postoperative cage subsidence after ACDF. There was a significant negative correlation between C-EBQ and endplate HU values. The C-EBQ score may be a promising tool for assessing preoperative bone quality and postoperative cage subsidence and is superior to the C-VBQ.

Long-term Outcome of Isobar TTL System for the Treatment of Lumbar Degenerative Disc Diseases.

OBJECTIVE: The Isobar TTL dynamic fixation system has demonstrated favorable outcomes in the short-term treatment of lumbar degenerative disc diseases (LDDs). However, there is a paucity of extensive research on the long-term effects of this system on LDDs. This study aimed to evaluate the long-term clinical and radiological outcomes of patients with LDDs who underwent treatment utilizing the Isobar TTL dynamic fixation system. METHODS: The study analyzed the outcomes of 40 patients with LDDs who underwent posterior lumbar decompression and received single-segment Isobar TTL dynamic internal fixation at our hospital between June 2010 and December 2016. The evaluation of clinical therapeutic effect involved assessing postoperative pain levels using the visual analogue scale (VAS) and Oswestry disability index (ODI), both before surgery, 3 months after, and the final follow-up. To determine the preservation of functional motion in dynamically stable segments, we measured the range of motion (ROM) and disc height of stabilized and adjacent segments preoperatively and during the final follow-up. Additionally, we investigated the occurrence of adjacent segment degeneration (ASD). RESULTS: Forty patients were evaluated, with an average age of 44.65 years and an average follow-up period of 79.37 months. Fourteen patients belonged to the spondylolisthesis group, while the remaining 26 were categorized under the stenosis or herniated disc group. The preoperative ROM of the stabilized segment exhibited a significant reduction from 8.15° ± 2.77° to 5.00° ± 1.82° at the final follow-up (p < 0.001). In contrast, there was a slight elevation in the ROM of the adjacent segment during the final follow-up, increasing from 7.68° ± 2.25° before surgery to 9.36° ± 1.98° (p < 0.001). The intervertebral space height (IH) in the stabilized segment exhibited a significant increase from 10.56 ± 1.99 mm before surgery to 11.39 ± 1.90 mm at the one-week postoperative follow-up (p < 0.001). Conversely, there was a notable decrease in the IH of the adjacent segment from 11.09 ± 1.82 mm preoperatively to 10.86 ± 1.79 mm at the one-week follow-up after surgery (p < 0.001). The incidence of ASD was 15% (6/40) after an average follow-up period of 79.37 months, with a rate of 15.38% (4/26) in the stenosis or herniated disc group and 14.29% (2/14) in the spondylolisthesis group; however, no statistically significant difference was observed in the occurrence of ASD among these groups (p > 0.05). CONCLUSION: The Isobar TTL dynamic fixation system is an effective treatment for LDDs, improving pain relief, quality of life (QoL) and maintaining stabilized segmental motion. It has demonstrated excellent long-term clinical and radiographic results.

The Comparison of Posterior Intervertebral Release Combined with Posterior Column Osteotomy and Posterior Column Osteotomy Alone for the Treatment of Moderate-to-Severe Rigid Scoliosis: A Prospective Controlled Study.

OBJECTIVES: There is no consensus on the treatment of moderate-to-severe rigid scoliosis. Anterior release and three-column osteotomy are excessively traumatic, whereas posterior column osteotomy (PCO) alone results in poor outcomes. An emerging surgical technique, posterior intervertebral release (PR), can release the rigid spine from the posterior approach. This study was performed to compare the multi-segment apical convex PR combined with PCO and PCO alone in patients with moderate-to-severe rigid scoliosis. METHODS: From June 2021 to June 2022, this prospective study of moderate-to-severe (Cobb: 70-90°) rigid scoliosis (flexibility of main curve <25%) involved two groups defined by surgical procedure: the PR group, the patients undergoing PR combined with PCO; and the PCO group, the patients undergoing PCO alone. Follow-up was at least 12 months. Radiographic results mainly included main curve Cobb, correction of per PR/PCO segment, apical vertebra rotation (AVR) and apical vertebra translation (AVT). Demographics, surgical data, complications were also recorded. Student's independent samples t test and Pearson's chi-square test were used to compare the differences between groups. RESULTS: Forty patients with an average age of 16.65 years were included (PR group, n = 20; PCO group, n = 20). The main curves averaged 77.56° ± 5.86° versus 78.02° ± 5.72° preoperatively and 20.07° ± 6.73° versus 33.58° ± 5.76° (p < 0.001) at the last follow-up in the PR and PCO groups, respectively. The mean correction rates were 74.30% and 56.84%, respectively (p < 0.001). The average coronal curve correction was 13.49° per release segment, which was significantly higher than the PCO correction of 6.20° (p < 0.001). The correction of apical vertebra rotation and translation in the main thoracic curve was significantly better in the PR group than in the PCO group (p < 0.05). Several minor complications in the two groups improved after conservative treatment. CONCLUSION: The multi-segment apical convex PR combined with PCO offers more advantages than PCO alone in the treatment of patients with moderate-to-severe rigid scoliosis. Owing to its excellent corrective effect and few complications, this is a high benefit-risk ratio surgical strategy for rigid scoliosis.

Health-related Quality of Life (HRQOL) Outcomes of Selective/Nonselective Thoracic Fusion for Lenke 1C Adolescent Idiopathic Scoliosis (AIS) Patients with a Minimum 4-year Follow-up.

OBJECTIVE: Both the selective thoracic fusion (STF) and nonselective thoracic fusion (NSTF) are treatments for Lenke 1C adolescent idiopathic scoliosis (AIS). To date, the impacts of the two surgical strategies on patients' long-term quality of life remain unclear. Therefore, the purpose of this study was to explore the long-term effects of STF/NSTF on the quality of life in Lenke 1C AIS patients through a 4-10-year follow-up. METHODS: From January 2011 to April 2018, according to the inclusion and exclusion criteria, a retrospective single-center study of 75 surgical patients with Lenke 1C curves was performed (n = 75). They all underwent posterior fusion, and patients were divided into the selective thoracic fusion (STF) group (n = 42) and the nonselective thoracic fusion (NSTF) group (n = 33) based on their surgical approach. All participants received the survey of the visual analogue scale (VAS), SRS30, SF12, and Oswestry disability index (ODI) scales. Patients' gender, age, body mass index (BMI), surgical approach (STF/NSTF), surgical segments (UIV and LIV), follow-up time, complications, preoperative, postoperative, and last follow-up Cobb angles, and health-related quality of life (HRQOL) outcomes were collected, and analyzed through the Shapiro-Wilks test, Wilcoxon rank-sum test, t-test, and χ2 test. RESULTS: The mean follow-up of the entire cohort was 73 ± 5.6 months. The lumbar Cobb angle in the STF group improved from 31.8 ± 6.5° to 11.5 ± 5.1° after the operation and 10.3 ± 6.9° at the last follow-up. The postoperative correction rate of the lumbar curve was 63.8%, which increased to 67.7% at the last follow-up. In the NSTF group, the lumbar Cobb angle improved from 34.3 ± 11.3° to 4.3 ± 3.7° after the operation, and was 5.1 ± 3.1° at the last follow-up. The postoperative correction rate of the lumbar curve was 87.4%, and 85.1% at the last follow-up. At the last follow-up, the STF group had higher overall HRQOL scores than the NSTF group, and there were statistically differences between the different groups (STF/NSTF) in SRS-30-Mental health (p = 0.03), SRS-30-Satisfaction with management (p = 0.02), SRS-30-Pain (p = 0.03), ODI (p = 0.01), SF-12 PCS (p = 0.03), VAS back pain (p = 0.005) and VAS leg pain (p = 0.001). No statistically differences were found in SF12 MCS, SRS-30-Self-image/Appearance and SRS-30 Function/activity. CONCLUSION: After 4-10 years of follow-up, we found that the STF group achieved satisfactory correction results, and compared with the NSTF group, their overall HRQOL scores were higher, especially in terms of pain and satisfaction, where the STF group shows a significant advantage.

A Novel Multiple Screw Distraction Reducer System in the Treatment of Scoliosis with a Severe Rib Hump.

OBJECTIVES: The treatment of scoliosis with a severe rib hump remains a major challenge. Traditional vertebral rotation techniques are not satisfactory, and thoracoplasty has many pulmonary complications that limit its application. A novel surgical device, the multiple screw distraction reducer (MSDR) system, provides longitudinal distraction during the corrective operation while at the same time providing lateral translation and axial derotation, which may facilitate the correction of a rib hump. This study was performed to investigate the effectiveness of the MSDR system for adolescent idiopathic scoliosis (AIS) with a severe rib hump. METHODS: This was a case-matched study of patients with retrospectively collected data from our hospital between January 2017 and December 2021. Sixty-eight patients who underwent one-stage posterior pedicle screw-instrumented spinal fusion were matched by the Cobb angle of the main curve and rib hump. All patients underwent a minimum of 2 years of follow-up. The patients were divided into two groups: the MSDR group (using the MSDR system, n = 34) and the DVR group (using direct vertebral derotation, n = 34). The patients were evaluated for the height of the rib hump, deformity correction, complications, and SRS-30 scores. The unpaired Student's t-test and Pearson's χ2 -test were used to compare the outcome measures between the two groups. Multiple linear regression analysis was used to examine the variables that affected the correction of a rib hump. RESULTS: The rib hump was 30.21 ± 6.21 mm versus 29.35 ± 6.52 mm (p = 0.583) preoperatively and 9.18 ± 4.06 mm versus 13.82 ± 5.54 mm (p < 0.001) at the last follow-up in the MSDR and DVR groups, respectively. The correction rates were 70.83% and 53.56%, respectively (p < 0.001). Preoperatively, the main thoracic curve was 58.43° ± 7.97° and 57.84° ± 6.32° (p = 0.736) and was corrected to 10.92° ± 5.47° and 19.14° ± 5.32° (p < 0.001) at last follow-up in the MSDR and DVR group, respectively. Thoracic kyphosis was restored from 18.24° ± 5.19° and 17.98° ± 5.28° (p = 0.836) in the MSDR and DVR group to 24.59° ± 4.41° and 19.32° ± 4.96° (p < 0.001), respectively. Correction of apical vertebra rotation and translation in the main thoracic curve were significantly better in the MSDR group than in the DVR group (p < 0.05). There was no significant difference in the Lenke type, implant density, estimated blood loss, or follow-up duration between the two groups, whereas the operation time in the DVR group was significantly less than that in the MSDR group. There were only two minor pulmonary complications in the MSDR group. At the last follow-up, the MSDR group scored higher in terms of appearance and satisfaction (p < 0.05). CONCLUSION: The MSDR system, enabling better coronal alignment, thoracic kyphosis, and axial derotation, could be a safe and effective technique for severe rib hump correction in AIS.

The Quality of Life of the Patients with Thoracic Ossification of the Ligamentum Flavum after Surgery Using EQ-5D-5L.

OBJECTIVE: There is a lack of studies on the quality of life (QoL) after posterior laminectomy in patients with thoracic ossification of the ligamentum flavum (TOLF), and risk factors associated with poor prognosis remain controversial. Therefore, the present study was conducted to illustrate the QoL for TOLF patients after surgery and determine its relationship with their demographic, surgery-related, clinical characteristics and imaging data. METHODS: One hundred and eighteen patients diagnosed with thoracic myelopathy because of TOLF were enrolled in this retrospective study. They all underwent posterior decompressive laminectomy from August 2010 to January 2022. The QoL was evaluated based on the EQ-5D-5L. Collecting gender, age, number of operations, compressed segments, Frankel grade, complications, body mass index (BMI), symptoms and duration, modified Japanese Orthopaedic Association (mJOA) score (preoperative), follow-up time and type of ossification, increased signal on Sagittal T2-weighted Images (ISST2I), occupancy rate and analyzing by Mann-Whitney U-test, Kruskal-Wallis test, the χ2 -test, and logistic regression tests. RESULTS: Average follow-up 70.8 months (18-149), the mean age was 59.74 ± 9.81 years and the mean score for the QoL based on the EQ-5D-5 L and visual analogue scale (VAS) score were 0.71 ± 0.28 and 78.88 ± 10.21 at the final follow-up. Moderate and severe problems were found in the pain/discomfort in 22.0% of the patients. These mobility and usual activities numbers were slightly higher (24.6% and 30.4%, respectively). The mean scores for QoL and VAS were significantly higher in patients with mild and moderate neurological impairment, normal BMI, <60 years of age, no dural tears, symptom relief at hospital discharge, unilateral and bilateral ossification on axial CT scan, ≤ 50% spinal canal occupancy on CT and MRI, and none or fuzzy on ISST2I. CONCLUSION: QoL after posterior laminectomy in TOLF patients is generally satisfactory compared to preoperative levels. Preoperative mJOA score, Age, comorbid diabetes, the major symptom is activity limitation, BMI, ISST2I, Intraoperative dural tears and spinal canal occupancy rate correlate significantly with the corresponding dimensions and are predictive. Age, spinal canal occupancy rate, ISST2I, preoperative mJOA score, BMI are significantly associated with and have predictive value for overall postoperative QoL.

Preparation, characterization, and in vitro/vivo evaluation of a multifunctional electrode coating for cochlear implants.

Cochlear implantation (CI) is the primary intervention for patients with sensorineural hearing loss to restore their hearing. However, approximately 90 % of CI recipients experience unexpected fibrosis around the inserted electrode arrays due to acute and chronic inflammation. This fibrosis leads to progressive residual hearing loss. Addressing this complication is crucial for enhancing CI outcomes, yet an effective treatment has not yet been found. In this study, we developed a multifunctional dexamethasone (DXM)-loaded polytrimethylene carbonate (PTMC) electrode coating to mitigate inflammatory reactions and fibrosis after CI. This thin and flexible coating could preserve the mechanical performance of the electrode and reduce the implantation resistance for CI. The in vitro release studies demonstrated the DXM-PTMC coating's efficient drug loading and sustained release capability over 90 days. DXM-PTMC also showed long-term stability, high biocompatibility, and effective anti-inflammatory effects in vitro and in vivo. Compared with the uncoated group, DXM-PTMC coating significantly inhibited the expression of inflammatory factors, such as NO, TNF-α, IL-1ß, and IL-6. DXM-PTMC coating suppressed fibrosis in rat implantation models for 3 weeks by reducing both acute and chronic inflammation. Our findings suggest that DXM-PTMC coating is a novel strategy to improve the outcomes of CI.

Radiation Dose Reduction in Digital Breast Tomosynthesis by MTANN with Multi-scale Kernels.

Digital breast tomosynthesis (DBT) is an advanced three-dimensional screening modality for the early detection of breast cancer. DBT is able to reduce the problem of tissue overlap in standard two-dimensional mammograms, thus improving the sensitivity and specificity of cancer detection. Although DBT can improve diagnostic accuracy, it leads to higher radiation dose to patients compared to two-dimensional mammography. In this paper, we propose a novel radiation dose reduction technique that introduces multi-scale kernels to our original massive-training artificial neural network (MTANN) to reduce radiation dose substantially, while maintaining high image quality in DBT. After training our new MTANN with low-dose (LD) images and the corresponding "teaching" high-dose (HD) images, we can convert new LD images to "virtual" high-dose (VHD) images where noise and artifact in the LD images are significantly reduced. In VHD images, it is critical to preserve subtle structures and tiny patterns such as microcalcifications (MCs) which are essential for breast cancer diagnosis. We developed anatomical MTANN experts including an MC-specific expert with multi-scale kernels, which are combined by gating layers to generate whole VHD images. Our MTANN scheme was able to achieve a 79% dose reduction while preserving details of MCs. Experimental results demonstrated that our method achieved the highest performance among the best-known noise-reduction techniques and state-of-the-art deep-learning techniques.Clinical Relevance- Our method can decrease the dose radiation dose in DBT and maintain the image quality.

Postoperative Sclerotic Modic Changes after Transforaminal Lumbar Interbody Fusion: The Prevalence, Risk Factors, and Impact on Fusion.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: This study aimed to assess postoperative sclerotic Modic changes (MCs) following transforaminal lumbar interbody fusion (TLIF) for lumbar degenerative disc disease (LDD), investigating their prevalence, risk factors and association with clinical outcomes. SUMMARY OF BACKGROUND DATA: Sclerotic MCs may occur in patients with LDD after lumbar interbody fusion. The incidence and characteristics of postoperative sclerotic MCs, as well as their clinical impact, are unknown. METHODS: The study included 467 patients (510 levels) who underwent single or two-level TLIF surgery, divided into a postoperative sclerotic MC group (60 patients, 66 levels) and non-MC group (407 patients, 444 levels). The time of development and location of postoperative sclerotic MCs, fusion rate, cage subsidence, bilateral process decompression, and cross-link usage were recorded. Preoperative, postoperative, and follow-up VAS and ODI scores were collected. Multivaraible logistic regression was used to evaluate factors associated with the development of postoperative sclerotic MCs. RESULTS: The prevalence of postoperative sclerotic MCs was 12.8%. The postoperative sclerotic MC group had higher BMI. The postoperative sclerotic MC group demonstrated a fusion rate of 47%, significantly lower than that of the non-MC group (71%) at 6 months post-operation. At final follow-up, the fusion rate in the postoperative sclerotic MC group was 62%, significantly lower than that of the non-MC group (86%). Post-operative VAS and ODI scores were significantly higher in the group with postoperative sclerotic MCs. BMI and osteoporosis were significantly associated with the development of postoperative sclerotic MCs. CONCLUSION: Postoperative sclerotic MCs generally appear within the first year after surgery, with a prevalence of 12.8%. The presence of postoperative sclerotic MCs can adversely impact post-operative outcomes. To prevent postoperative sclerotic MCs, we postulate extending the immobilization period with external bracing and improving the management of BMI and osteoporosis in the peri-operative time window.

High strength, self-healing sensitive ionogel sensor based on MXene/ionic liquid synergistic conductive network for human-motion detection.

Ionogels with both high strength and high conductivity for wearable strain and pressure dual-mode sensors are needed for human motion and health monitoring. Here, multiple hydrogen bonds are introduced through imidazolidinyl urea (IU) as a chain extender to provide high mechanical and self-healing properties for the water-borne polyurethane (WPU). The MXene/ionic liquids synergistic conductive network provides excellent conductivity and also reduces the relative content of ionic liquids to maintain the mechanical properties of the ionogels. The mechanical strength of this ionogel reached 1.81-2.24 MPa and elongation at break reached 570-624%. It also has excellent conductivity (22.7-37.5 mS m-1), gauge factor (GF) (as a strain sensor, GF = 1.8), sensitivity (S) (as a press sensor, S1 = 29.8 kPa-1, S2 = 1.3 kPa-1), and fast response time (as a strain sensor = 185 ms; as a press sensor = 204 ms). The ionogel also exhibits rapid photothermal self-healing capabilities due to the inherent photothermal behavior of MXene. It can maintain good elasticity and conductivity at low temperatures. In addition, this ionogel is able to stretch for 1200 cycles without significant change in the relative change of resistance. The ionogel can be assembled as a strain sensor for monitoring human motion and as a pressure sensor array for obtaining pressure magnitude and position information.

Comparison between Three-Dimensional Printed Titanium and PEEK Cages for Cervical and Lumbar Interbody Fusion: A Prospective Controlled Trial.

OBJECTIVES: The three-dimensional printing titanium (3DPT) cage with excellent biomechanical properties and osseointegration capabilities has been initially used in spinal fusion, while the polyetheretherketone (PEEK) cage, a bioinert material device, has been a widely used for decades with relatively excellent clinical outcomes. This study was performed to investigate the early radiographic and clinical outcomes of 3DPT cage versus PEEK cage in patients undergoing anterior cervical discectomy and fusion (ACDF) and transforaminal lumbar interbody fusion (TLIF). METHODS: This prospective controlled trial, from December 2019 to June 2022, included patients undergoing ACDF and TLIF with 3DPT cages and compared them to patients using PEEK cages for treating spinal degenerative disorders. The outcome measures included radiographic parameters (intervertebral height [IH], subsidence, fusion status, and bone-cage interface contact) and clinical outcomes (Japanese Orthopaedic Association [JOA], Neck Disability Index [NDI], Oswestry Disability Index [ODI], Short Form 12-Item Survey [SF-12], Visual Analog Scale [VAS], and Odom's criteria). Student's independent samples t test and Pearson's chi-square test were used to compare the outcome measures between the two groups before surgery and at 1 week, 3 and 6 months after surgery. RESULTS: For the patients undergoing ACDF, the 3DPT (18 patients/[26 segments]) and PEEK groups (18 patients/[26 segments]) had similar fusion rates at 3 months and 6 months follow-up (3 months: 96.2% vs. 83.3%, p = 0.182; 6 months: 100% vs. 91.7%, p = 0.225). The subsidence in the 3DPT group was significantly lower than that in the PEEK group (3 months: 0.4 ± 0.2 mm vs. 0.9 ± 0.7 mm p = 0.004; 6 months: 0.7 ± 0.3 mm vs. 1.5 ± 0.8 mm, p < 0.001). 3DPT and PEEK cage all achieved sufficient contact with the cervical endplates. For the patients undergoing TLIF, the 3DPT (20 patients/[26 segments]) and PEEK groups (20 patients/[24 segments]) had no statistical difference in fusion rate (3 months: 84.6% vs. 58.3%, p = 0.059; 6 months: 92.3% vs. 75%, p = 0.132). The subsidence was lower than that in the PEEK group without significantly difference (3 months: 0.9 ± 0.7 mm vs.1.2 ± 0.9 mm p = 0.136; 6 months: 1.6 ± 1.0 mm vs. 2.0 ± 1.0 mm, p = 0.200). At the 3-month follow-up, the bone-cage interface contact of the 3DPT cage was significantly better than that of the PEEK cage (poor contact: 15.4% vs. 75%, p < 0.001). The values of UAR were higher in the 3DPT group than in the PEEK group during the follow-up in cervical and lumbar fusion, there were more statistical differences in lumbar fusion. There were no significant differences in the clinical assessment between 3DPT or PEEK cage in spinal fusion. CONCLUSION: The 3DPT cage and PEEK cage can achieve excellent clinical outcomes in cervical and lumbar fusion. The 3DPT cage has advantage in fusion quality, subsidence severity, and bone-cage interface contact than PEEK cage.

Association of mechanical power during one-lung ventilation and post-operative pulmonary complications among patients undergoing lobectomy: a protocol for a prospective cohort study.

The association of intra-operative mechanical power (MP) with post-operative pulmonary complications (PPCs) has been described before, but it is uncertain whether the potential inherent bias can limit the use of this parameter, particularly in the context of one-lung ventilation. This single-center study aims to investigate the effect of MP during one-lung ventilation (OLV), and the risks of PPCs in patients undergoing thoracoscopic lobectomy. This prospective observational study is being conducted in an academic tertiary hospital in mainland China. Participants diagnosed with lung cancer, and aged 50 to 80 years are eligible. Video-assisted thoracoscopic surgery (VATS) lobectomy is performed for all patients. The primary outcome is the occurrence of PPCs over 5 consecutive days after the surgery, or until discharge from the hospital. Secondary outcomes include the composite conditions of PPCs, in-hospital stay, systematic inflammation tested by blood samples, and changes in aeration compartments in the ventilated lung as assessed by CT scans. We aim to evaluate the association of mean MP and the temporal patterns in the trend of MP during OLV with the occurrence of PPCs. A total of 120 patients will be enrolled in this study. The study protocol has received approval from the Ethics Committee of the affiliated hospital of Southwest Medical University, China (Reference number: KY2022162). The findings will be made available to the funder and researchers via scientific conferences and peer-reviewed publications. This controlled trial was approved by the Ethics Committee of Southwest Medical University(ChiCTR2200062173), and registered in the Chinese Clinical Trial Register website ( http://www.chictr.org.cn/edit.aspx?pid=172533&htm=4 , ChiCTR2200062173). A written consent was obtained from each patient.

Discovery of tetrahydroisoquinolineindole derivatives as first dual PRMT5 inhibitors/hnRNP E1 upregulators: Design, synthesis and biological evaluation.

Protein arginine methyltransferase 5 (PRMT5) is an epigenetics related enzyme that has been validated as an important therapeutic target for treating various types of cancer. Upregulation of tumor suppressor hnRNP E1 has also been considered as an effective antitumor therapy. In this study, a series of tetrahydroisoquinolineindole hybrids were designed and prepared, and compounds 3m and 3s4 were found to be selective inhibitors of PRMT5 and upregulators of hnRNP E1. Molecular docking studies indicated that compounds 3m occupied the substrate site of PRMT5 and formed essential interactions with amino acid residues. Furthermore, compounds 3m and 3s4 exerted antiproliferative effects against A549 cells by inducing apoptosis and inhibiting cell migration. Importantly, silencing of hnRNP E1 eliminated the antitumor effect of 3m and 3s4 on the apoptosis and migration in A549 cells, suggesting a regulatory relationship between PRMT5 and hnRNP E1. Additionally, compound 3m exhibited high metabolic stability on human liver microsomes (T1/2 = 132.4 min). In SD rats, the bioavailability of 3m was 31.4%, and its PK profiles showed satisfactory AUC and Cmax values compared to the positive control. These results suggest that compound 3m is the first class of dual PRMT5 inhibitor and hnRNP E1 upregulator that deserves further investigation as a potential anticancer agent.

Transmission and infection risk of COVID-19 when people coughing in an elevator.

People in cities use elevators daily. With the COVID-19 pandemic, there are more worries about elevator safety, since elevators are often small and crowded. This study used a proven CFD model to see how the virus could spread in elevators. We simulated five people taking in an elevator for 2 min and analyzed the effect of different factors on the amount of virus that could be inhaled, such as the infected person's location, the standing positions of the persons, and the air flow rate. We found that the position of the infected person and the direction they stood greatly impacted virus transmission in the elevator. The use of mechanical ventilation with a flow rate of 30 ACH (air changes per hour) was effective in reducing the risk of infection. In situations where the air flow rate was 3 ACH, we found that the highest number of inhaled virus copies could range from 237 to 1186. However, with a flow rate of 30 ACH, the highest number was reduced to 153 to 509. The study also showed that wearing surgical masks decreased the highest number of inhaled virus copies to 74 to 155.

Additional growth of the spine and changes in spinal alignment after posterior spinal fusion in adolescent idiopathic scoliosis.

OBJECTIVE: Previous studies have evaluated growth in spinal height immediately following surgical posterior correction of idiopathic scoliosis, yet have not reported on further spinal growth following surgery. The aims of this study were to investigate the characteristics of spinal growth after scoliosis surgery and determine whether they affect spinal alignment. METHODS: The study included 91 patients (mean age 13.93 years) who underwent spinal fusion using pedicle screws for the treatment of adolescent idiopathic scoliosis (AIS). The study population included 70 female and 21 male patients. The height of the spine (HOS), length of the spine (LOS), and spinal alignment parameters were measured on anteroposterior and lateral radiographs. A stepwise multiple linear regression analysis was used to examine the variables that affected HOS gain from growth. The patients were divided into two groups, the growth group and the nongrowth group, according to whether the HOS gain from growth exceeded 1 cm, to analyze the effect of spinal growth on its alignment. RESULTS: The mean (± SD) HOS gain from growth was 0.88 ± 0.66 (range -0.46 to 3.21) cm, with 40.66% of patients exhibiting growth ≥ 1 cm. This increase was significantly related to young age, male sex, and a small Risser stage (sex: b = -0.532, p < 0.001, male = 1, female = 2; Risser stage: b = -0.185, p < 0.001; age: b = -0.125, p = 0.011; adjusted R2 = 0.442). The variation in LOS was similar to that of HOS. Thoracic kyphosis and upper instrumented vertebra-lowest instrumented vertebra Cobb angle were reduced in both groups, with a greater reduction observed in the growth group. Patients with an increase in HOS < 1 cm showed a larger lumbar lordosis and a greater tendency for the sagittal vertical axis (SVA) to shift backward and the pelvic tilt to decrease (anteverted pelvis) than in the growth group. CONCLUSIONS: The spine still has growth potential after corrective fusion surgery for AIS, and 40.66% of the patients in this study continued to vertically grow by 1 cm or more. Unfortunately, the height changes cannot be accurately predicted by currently measured parameters. Changes in the sagittal alignment of the spine may affect the vertical growth increment.

Comparative pharmacokinetics of four major compounds after oral administration of Mori Cortex total flavonoid extract in normal and diabetic rats.

Introduction: Mori Cortex has been used in traditional Chinese Medicine as an antidiabetic agent. The aim of this study was to establish a UPLC-MS/MS method for simultaneous determination of morin, morusin, umbelliferone and mulberroside A in rat plasma and investigate the pharmacokinetics differences between normal and diabetic rats following oral administration of Mori Cortex total flavonoid extract. Methods: Samples were pre-treated by protein precipitation and genkwanin was used as internal standard. Chromatographic separation was performed using a Hypersil GOLD C18 column (50 mm × 2.1 mm, 3 µm). The mobile phase consisted of acetonitrile and water (containing 0.1% formic acid) in gradient mode at a flow rate of 0.5 ml/min. The transitions of m/z 300.9→107.1, m/z 419.3→297.1, m/z 160.9→77.0, m/z 567.1→243.2 and m/z 283.1→268.2 were selected for morin, morusin, umbelliferone, mulberroside A and internal standard, respectively. Results: The intra- and inter-day precision for analytes were less than 12.5% and the accuracy ranged from -8.1% to 3.5%. The extraction recovery was >88.5% and no obvious matrix effect was observed. The AUC (0-t) and C max of morin were 501.3 ± 115.5 ng/mL*h and 127.8 ± 56.0 ng/mL in normal rats and 717.3 ± 117.4 ng/ml*h and 218.6 ± 33.5 ng/ml in diabetic rats. Meanwhile, the AUC (0-t) and C max of morusin were 116.4 ± 38.2 ng/ml*h and 16.8 ± 10.1 ng/mL in normal rats and 325.0 ± 87.6 ng/mL*h and 39.2 ± 5.9 ng/ml in diabetic rats. For umbelliferone and mulberroside A, the AUC (0-t) and C max also increased significantly in diabetic rats (p < 0.05). Discussion: The validated method was successfully applied to the pharmacokinetic study in normal and diabetic rats.

A novel nanohydroxyapatite/polyamide-66 cage for reducing the subsidence rate after single-level anterior cervical discectomy and fusion: a comparative study of 7-year follow-up.

BACKGROUND: A novel nanohydroxyapatite/polyamide-66 cage (n-HA/PA66 cage) with a horseshoe shape was designed to lower the subsidence rate of the traditional hollow cylindrical n-HA/PA66 cage. However, no studies have compared the incidence of subsidence in the two cages. The purpose of this study was to compare the long-term clinical and radiological outcomes of the novel n-HA/PA66 cage with the hollow cylindrical n-HA/PA66 cage after anterior cervical discectomy and fusion (ACDF) to treat single-level cervical degenerative disk disease (CDDD). METHODS: Fifty-two patients with novel n-HA/PA66 cages (Group A) and fifty-five patients with hollow cylindrical n-HA/PA66 cages (Group B) were included. The radiological parameters included intervertebral height (IH), C2-7 angle (C2-7a), segmental alignment (SA), subsidence rate, and fusion rate. The clinical outcomes were visual analog scale (VAS) scores, Japanese Orthopedic Association (JOA) scores, and patient satisfaction rates. RESULTS: The pre- and postoperative SA, C2-7a, and fusion rates of the patients in Groups A and B were similar. The preoperative and 6-month postoperative IHs in both groups were comparable. However, the final follow-up IH in Group B was significantly smaller than that in Group A (35.9 mm vs. 36.7 mm). The difference in the subsidence rates at the final follow-up between Group A (5.8%, 3/52) and Group B (18.2%, 10/55) was significant. The VAS score, JOA score, and patient satisfaction rate were not significantly different. CONCLUSIONS: The novel n-HA/PA66 cage had similar favorable SA, C2-7a, fusion rate, and clinical outcomes compared to the hollow cylindrical n-HA/PA66 cage for treating single-level ACDF. Moreover, the novel n-HA/PA66 cage achieved a lower subsidence rate and higher IH than the hollow cylindrical n-HA/PA66 cage at the final follow-up.

PANDEMIC: Occupancy driven predictive ventilation control to minimize energy consumption and infection risk.

During the SARS-CoV-2 (COVID-19) pandemic, governments around the world have formulated policies requiring ventilation systems to operate at a higher outdoor fresh air flow rate for a sufficient time, which has led to a sharp increase in building energy consumption. Therefore, it is necessary to identify an energy-efficient ventilation strategy to reduce the risk of infection. In this study, we developed an occupant-number-based model predictive control (OBMPC) algorithm for building ventilation systems. First, we collected the occupancy and Heating, ventilation, and air conditioning system (HVAC) data from March to July 2021. Then, four different models (Auto regression moving average-based multilayer perceptron (ARMA_MLP), Recurrent neural networks (RNN), Long short-term memory networks (LSTM), and Nonhomogeneous Markov with change points detection (NH_Markov)) were used to predict the number of room occupants from 15 min to 24 h ahead with an interval output. We found that each model could predict the number of occupants with 85 % accuracy using a one-person offset. The accuracy of 15 min of the ahead prediction could reach 95 % with a one-person offset, but none of them could track abrupt changes. The occupancy prediction results were used to calculate the ventilation demand using the Wells-Riley equation, and the upper bound can maintain an infection risk lower than 2 % for 93 % of the day. This OBMPC model could reduce the coil load by 52.44 % and shift the peak load by 3 h up to 5 kW compared with 24 × 7 h full outdoor air (OA) system when people wear masks in the space. The occupancy prediction uncertainty could cause a 9 % to 26 % difference in demand ventilation, a 0.3 °C to 2.4 °C difference in zone temperature, a 28.5 % to 44.5 % difference in outdoor airflow rate, and a 10.7 % to 28.2 % difference in coil load.

A hip disarticulation prostheses test system to simulate gait for prostheses evaluation.

BACKGROUND: The limited number of hip prostheses users makes it less feasible to conduct amputee tests for prosthesis development in the clinic, which restricts the development efficiency of the intelligent prostheses. OBJECTIVE: This study proposes a hip disarticulation prostheses test system (HDPTS) to supplement the amputee tests for hip disarticulation prosthesis (HDP) evaluation, which would potentially facilitate the prosthesis evaluation safety and development efficiency. METHODS: The hip trajectory of an individual with normal gait was acquired and reproduced by calculating the corresponding movement joint angle of a manipulator. Then, an HDP was fit on an amputee and on the HDPTS respectively to obtain the hip and knee joint angles of the HDP during walking. Comparing the root mean square error (RMSE) of the expected and planned trajectory, the joint angles between the amputee test and HDPTS test, to verify the feasibility and accuracy of the HDPTS for prosthesis evaluation. RESULTS: The RMSE between the expected and planned trajectory value was less than 1.20 mm (< 0.19%). The RMSE of the joint angles between the amputee test and HDPTS test were 2.18∘ (1.8%) and 3.13∘ (5.92%) for hip and knee joint respectively. CONCLUSION: The HDPTS was found accurate in hip trajectory reproduction and feasible in gait simulation for the prosthesis evaluation, which could potentially supplement the amputee test for prosthesis design thus improving prosthesis test safety and development efficiency.