Clusterin attenuates blood-brain barrier damage and cognitive impairment by inhibiting astrocyte aging in mice with sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE) is a severe complication of sepsis, however, its exact mechanism remains unknown. This study aimed to evaluate whether clusterin is essential to the development of SAE during the aging process of astrocytes. In the study, septic mice were established with cecal ligation and puncture (CLP) and lipopolysaccharides were applied to astrocytes in vitro. Evan's blue dye was used in vivo to show blood-brain barrier (BBB) permeability. A morris water maze test was conducted to assess cognitive functions of the mice. Clusterin-knockout mice were used to examine the effect of clusterin on sepsis. The astrocytes were transfected with lentivirus expressing clusterin cDNA for clusterin overexpression or pYr-LV-clusterin small hairpin RNA for clusterin knockdown in vitro. The expression of clusterin, p-p53, p21, GDNF, and iNOS was detected. he CLP mice exhibited a higher clusterin expression in hippocampus tissue, aging astrocytes, lower GDNF expression and higher iNOS expression, accompanied with BBB damage and cognitive deficiency. Following clusterin knockout, this pathological process was further enhanced. In vitro, following lipopolysaccharides treatment, astrocytes exhibited increased clusterin, p-p53, p21, iNOS and decreased GDNF. Following clusterin knockdown, the cells exhibited a further increase in p-p53, p21, and iNOS and decrease in GDNF. Clusterin overexpression, however, helped inhibit astrocytes aging and neuroinflammation evidenced by decreased p-p53, p21, iNOS and increased GDNF. The present study has revealed that clusterin may exert its neuroprotective effect by preventing aging in astrocytes, suppressing the secretion of iNOS and promoting GNDF release.

A Cable-Stayed Honeycomb Superstructure to Improve the Stability of Li-Rich Materials via Inhibiting Interlaminar Lattice Strain.

In layered Li-rich materials, over stoichiometric Li forms an ordered occupation of LiTM6 in transition metal (TM) layer, showing a honeycomb superstructure along [001] direction. At the atomic scale, the instability of the superstructure at high voltage is the root cause of problems such as capacity/voltage decay of Li-rich materials. Here a Li-rich material with a high Li/Ni disorder is reported, these interlayer Ni atoms locate above the honeycomb superstructure and share adjacent O coordination with honeycomb TM. These Ni─O bonds act as cable-stayed bridge to the honeycomb plane, and improve the high-voltage stability. The cable-stayed honeycomb superstructure is confirmed by in situ X-ray diffraction to have a unique cell evolution mechanism that it can alleviate interlaminar lattice strain by promoting in-plane expansion along a-axis and inhibiting c-axis stretching. Electrochemical tests also demonstrate significantly improved long cycle performance after 500 cycles (86% for Li-rich/Li half cell and 82% for Li-rich/Si-C full cell) and reduced irreversible oxygen release. This work proves the feasibility of achieving outstanding stability of lithium-rich materials through superstructure regulation and provides new insights for the development of the next-generation high-energy-density cathodes.

Clinical and DCE-CT signs in predicting microvascular invasion in cHCC-ICC.

BACKGROUND: To predict the microvascular invasion (MVI) in patients with cHCC-ICC. METHODS: A retrospective analysis was conducted on 119 patients who underwent CT enhancement scanning (from September 2006 to August 2022). They were divided into MVI-positive and MVI-negative groups. RESULTS: The proportion of patients with CEA elevation was higher in the MVI-positive group than in the MVI-negative group, with a statistically significant difference (P = 0.02). The MVI-positive group had a higher rate of peritumoral enhancement in the arterial phase (P = 0.01) whereas the MVI-negative group had more oval and lobulated masses (P = 0.04). According to the multivariate analysis, the increase in CEA (OR = 10.15, 95% CI: 1.11, 92.48, p = 0.04), hepatic capsular withdrawal (OR = 4.55, 95% CI: 1.44, 14.34, p = 0.01) and peritumoral enhancement (OR = 6.34, 95% CI: 2.18, 18.40, p < 0.01) are independent risk factors for predicting MVI. When these three imaging signs are combined, the specificity of MVI prediction was 70.59% (series connection), and the sensitivity was 100% (parallel connection). CONCLUSIONS: Our multivariate analysis found that CEA elevation, liver capsule depression, and arterial phase peritumoral enhancement were independent risk factors for predicting MVI in cHCC-ICC.

Nucleus Pulposus-Targeting Nanocarriers Facilitate Mirna-Based Therapeutics for Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is a common cause of low back pain. Understanding its molecular mechanisms is the basis for developing specific treatment. To demonstrate that miR-22-3p is critical in the regulation of IDD, miRNA microarray analyses are conducted in conjunction with in vivo and in vitro experiments. The miR-22-3p knockout (KO) mice show a marked decrease in the histological scores. Bioinformatic analysis reveals that miR-22-3p plays a mechanistic role in the development of IDD by targeting SIRT1, which in turn activates the JAK1/STAT3 signaling pathway. This is confirmed by a luciferase reporter assay and western blot analysis. Therapeutically, the delivery of miR-22-3p inhibitors and mimics through the synthesized nanoparticles in the IDD model alleviates and aggravates IDD, respectively. The nanocarriers enhance transportation of miR-22-3p to nucleus pulposus cells, thus enabling the in vivo inhibition of miR-22-3p for therapeutic purposes and consequently promoting the development of miRNA-specific drugs for IDD.

Static mechanical analysis of the vertebral body after modified anterior cervical discectomy and fusion (partial vertebral osteotomy): a finite element model.

BACKGROUND: Modified anterior cervical discectomy and fusion (Mod ACDF) can effectively address ossification of the posterior longitudinal ligament (OPLL), which is difficult to remove directly from the posterior edge of the vertebral body, with considerably lesser damage as compared to anterior cervical corpectomy and fusion (ACCF). We compared the static mechanics of different anterior approaches by using an ideal finite element model. METHODS: A complete finite element model was established and classified into the following three surgical models according to different model cutting operations: ACDF, ACCF, and Mod ACDF. Three different bone volume situations (normal bone mineral density, osteopenia, and osteoporosis) were simulated. After fixing the lower surface of C5 or C6, a load was applied to the upper surface of C4, and the stress distribution and displacement of the upper surface of C5 or C6 were observed and the related values were recorded. RESULTS: The average Von Mises Stress and displacement levels of Mod ACDF were between those of ACDF and ACCF; with the peak Von Mises Stress occurring on the posterior side of the vertebral body (Points 1-4). The change in Von Mises Stress of the vertebral body is not significant during bone loss. However, the degree of displacement of the vertebral body surface and risk of vertebral collapse are increased (100 N: 13.91 vs. 19.47 vs. 21.62 µm; 150 N: 19.60 vs. 29.30 vs. 31.64 µm; 200 N: 28.53 vs. 38.65 vs. 44.83 µm). CONCLUSIONS: The static biomechanical effects caused by Mod ACDF are intermediate between ACDF and ACCF, and the risk of vertebral body collapse is lower than that by ACCF. Therefore, Mod ACDF may be an effective solution when targeting OPLL with poorly positioned posterior vertebral body edges.

Administration of modified Gegen Qinlian decoction for hemorrhagic chronic radiation proctitis: A case report and review of literature.

BACKGROUND: Hemorrhagic chronic radiation proctitis (CRP) is a common late complication of irradiation of the pelvis and seriously impairs life quality. There is no standard treatment for hemorrhagic CRP. Medical treatment, interventional treatment, and surgery are available, but they are limited in their applications due to nondefinite efficacy or side effects. Chinese herbal medicine (CHM), as a complementary or alternative therapy, may provide another option for hemorrhagic CRP treatment. CASE SUMMARY: A 51-year-old woman with cervical cancer received intensity-modulated radiation therapy and brachytherapy with a total dose of 93 Gy fifteen days after hysterectomy and bilateral adnexectomy. She received six additional cycles of chemotherapy with carboplatin and paclitaxel. Nine months after radiotherapy treatment, she mainly complained of 5-6 times diarrhea daily and bloody purulent stools for over 10 d. After colonoscopy examinations, she was diagnosed with hemorrhagic CRP with a giant ulcer. After assessment, she received CHM treatment. The specific regimen was 150 mL of modified Gegen Qinlian decoction (GQD) used as a retention enema for 1 mo, followed by replacement with oral administration of 150 mL of modified GQD three times per day for 5 mo. After the whole treatment, her diarrhea reduced to 1-2 times a day. Her rectal tenesmus and mild pain in lower abdomen disappeared. Both colonoscopy and magnetic resonance imaging confirmed its significant improvement. During treatment, there were no side effects, such as liver and renal function damage. CONCLUSION: Modified GQD may be another effective and safe option for hemorrhagic CRP patients with giant ulcers.

Modified ACDF Technique for the Treatment of Centrum Focal Ossification of the Posterior Longitudinal Ligament: A Case Report.

BACKGROUND: Anterior cervical discectomy fusion (ACDF) is a surgical procedure used to treat cervical spondylosis with anterior spinal cord compression. However, there are limitations to traditional ACDF and posterior indirect decompression when the anterior source lesion is in the center of the cervical vertebra. CASE PRESENTATION: On June 8, 2022, our department treated a patient with cervical spondylotic myelopathy-whose high posterior longitudinal ligament (OPLL) occupied the central position of the vertebral body-with modified ACDF. The preoperative surgical plan was designed based on the relevant imaging data and assay index. Also, the visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) scores, and imaging parameters of neck pain were recorded and compared. Postoperative imaging data showed that cervical curvature was recovered and spinal canal compression was relieved. The VAS score for neck pain decreased from 7 preoperatively to 1.5 at the last follow-up, while the JOA score increased from 10 preoperatively to 29 at the last follow-up. The volume of the spinal canal was restored. Simultaneously, the patient's extremity muscle strength improved and muscle tension decreased. CONCLUSIONS: Modified ACDF may be an effective surgical method for resolving spinal cord compression in a specific location when bone mineral density is good. We can effectively avoid iatrogenic nerve injury and symptom recurrence by removing the vertebral body and the lesion directly.

Organizing Pneumonia in A Patient Double-Positive for ANCA and Anti-GBM Antibodies: A Case Report.

Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.

Circular RNA hsa_circ_0004689 (circSWT1) promotes NSCLC progression via the miR-370-3p/SNAIL axis by inducing cell epithelial-mesenchymal transition (EMT).

BACKGROUND: Previous studies have reported the role of circular RNAs (circRNAs) in the progression of non-small-cell lung cancer (NSCLC). SWT1-derived circRNAs were confirmed to affect the apoptosis of cardiomyocytes; however, the biological functions of SWT1-derived circRNAs in cancers are still unknown. Here, we investigated the potential role of SWT1-derived circRNAs in NSCLC. METHODS: We used quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression of circSWT1 in NSCLC tissues and paired normal tissues. The potential functions of circSWT1 in tumor progression were assessed by CCK-8, colony formation, wound healing, and matrigel transwell assays in vitro and by xenograft tumor models in vivo. Next, epithelial-mesenchymal transition (EMT) was evaluated by western blotting, immunofluorescence, and immunohistochemistry (IHC). Moreover, circRIP, RNA pulldown assays, luciferase reporter gene assays, and FISH were conducted to illuminate the molecular mechanisms of circSWT1 via the miR-370-3p/SNAIL signal pathway. Then, we knocked out SNAIL in A549 and H1299 cells to identify the roles of circSWT1 in the progression and EMT of NSCLC through SNAIL. Finally, circSWT1 functions were confirmed in vivo using xenograft tumor models. RESULTS: CircSWT1 expression was significantly upregulated in NSCLC tissues, and high expression of circSWT1 predicted poor prognosis in NSCLC via survival analysis. In addition, overexpression of circSWT1 promoted the invasion and migration of NSCLC cells. Subsequently, we found that overexpression of circSWT1 induced EMT and that knockdown of circSWT1 inhibited EMT in NSCLC cells. Mechanistically, circSWT1 relieved the inhibition of downstream SNAIL by sponging miR-370-3p. Moreover, we found that these effects could be reversed by knocking out SNAIL. Finally, we verified that circSWT1 promoted NSCLC progression and EMT in xenograft tumor models. CONCLUSION: CircSWT1 promoted the invasion, migration, and EMT of NSCLC. CircSWT1 could serve as a potential biomarker and a potential therapeutic target for NSCLC.

TTI1 promotes non-small-cell lung cancer progression by regulating the mTOR signaling pathway.

The role of TELO2-interacting protein 1 (TTI1) in the progression of several types of cancer has been reported recently. The aim of this study was to estimate the expression and potential value of TTI1 in non-small-cell lung cancer (NSCLC) patients. The expression of TTI1 and its prognostic value in NSCLC from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were analyzed. To verify the bioinformatics findings, a tissue microarray containing 160 NSCLC and paired peritumoral tissues from NSCLC patients was analyzed by immunohistochemistry for TTI1. Subsequently, the roles of TTI1 in NSCLC cells were investigated in vivo by establishing xenograft models in nude mice and in vitro by transwell, CCK-8, wound healing, and colony formation assays. In addition, quantitative real-time polymerase chain reaction and western blot were applied to explore the underlying mechanism by which TTI1 promotes tumor progression. Finally, the relationship between TTI1 and Ki67 expression level in NSCLC was probed, and Kaplan-Meier and Cox analyses were performed to assess the prognostic merit of TTI1 and Ki67 in NSCLC patients. We found that the expression of TTI1 was significantly upregulated in NSCLC tissues compared to paired peritumoral tissues, which coincides with the bioinformatics findings from the TCGA and GEO databases. TTI1 was highly expressed in NSCLC patients with large tumors, advanced tumor stage, and lymphatic metastasis. In addition, the prognostic analysis identified TTI1 as an independent indication for poor prognosis of NSCLC patients. In vitro, upregulation of TTI1 in NSCLC cells could facilitate cell invasion, metastasis, viability, and proliferation. Mechanistically, our study verified that TTI1 could regulate mTOR activity, which has a pivotal role in human cancer. Consistently, the expressions of TTI1 and Ki67 had a positive relationship in NSCLC cells and tissues. Notably, patients with overexpression of TTI1 or Ki67 had a shorter overall survival rate and a higher disease-free survival rate compared to patients with low expression of TTI1 or Ki67, and the combination of TTI1 and Ki67 was an independent parameter predicting the prognosis and recurrence of NSCLC patients. We conclude that TTI1 promotes NSCLC cell proliferation, metastasis, and invasion by regulating mTOR activity, and the combination of TTI1 and Ki67 is a valuable molecular biomarker for the survival and recurrence of NSCLC patients.

Finite element analysis of dynamic changes in spinal mechanics of osteoporotic lumbar fracture.

AIM: This study aims to explore the effects of finite element biomechanical properties of different methods in the treatment of osteoporotic thoracolumbar fractures. METHODS: Based on the ultra-thin computed tomography scan data of a volunteer's thoracolumbar spine, the finite element method was used to simulate the treatment of osteoporotic thoracolumbar fracture. Spiral computed tomography scanning was used to obtain images of the thoracolumbar region, which was then imported into Mimics software to obtain the three-dimensional geometric model. The finite element model of normal T11 - L2 segment was established by finite element software Abaqus and the validity of the model loading was verified. The finite element model of T11 vertebral compression fracture was established based on normal raw data. The clinical overextension reduction manipulation was simulated by different treatment methods and the changes in stress and displacement in different parts of injured vertebrae were analyzed. RESULTS: An effective finite element model of T11-L2 segment was established. The maximum stress, axial compression strength, axial compression stiffness, and transverse shear stiffness were significantly better in the percutaneous kyphoplasty and percutaneous vertebroplasty treatment group than in the conservative treatment group and open treatment group (P < 0.05). Additionally, there was no significant difference between the open treatment group and conservative treatment group, or between the PKP and PVP treatment group. CONCLUSION: Percutaneous vertebroplasty and percutaneous kyphoplasty not only met the requirements of normal functional kinematics of thoracolumbar spine, but also restored the stability of thoracolumbar spine. They had good biomechanical properties and remarkable application effects. The application of finite element analysis can help select a scientific, reasonable, and effective treatment scheme for the clinical diagnosis and treatment of osteoporotic thoracolumbar fractures.

[KLF15/mTOR related proteins involved in effect of aerobic interval training on improving skeletal muscle lesions in rats with type 2 diabetes].

Objective: To investigate the effects of aerobic intermittent exercise on the expressions of KLF15/mTOR related proteins to improve skeletal muscle lesions in type 2 diabetes rats. Methods: The experimental model of type 2 diabetes rats was established by feeding high-fat diet for 4 weeks and intraperitoneal injection of streptozotocin (STZ). After modeling, rats were randomly divided into two groups: diabetes model group (DM), diabetes+exercise group (DE), and normal rats were set as control group (C), 10 rats in each group. Group DE was given 8-week aerobic intermittent treadmill exercise intervention, while group C was not given any intervention. At the end of the experiment, the expressions of KLF15, mTOR, p-mTOR, and cleared caspase-3 in gastrocnemius muscle were detected by Western blot. The histopathologic changes of gastrocnemius were observed under microscope; skeletal muscle cells apoptosis rates and muscle mass were examined respectively using HE staining and TUNEL fluorescence staining. At the same time, changes of blood glucose and serum insulin, and weight were examined in the end of the experiment. Results: ①Compared with group C, the wet weight of gastrocnemius muscle and body weight, ratio of wet gastrocnemius muscle and body weight in group DM were decreased(P＜0.05 or P＜0.01); compared with group DM, the wet weight of gastrocnemius muscle, ratio of wet gastrocnemius muscle and body weight in the group DE were increased significantly (P＜0.05). ②Compared with group C, the fasting blood glucose level of group DM was increased significantly (P＜0.01), while serum insulin level of the group DM was decreased significantly(P＜0.01);compared with group DM, the above indexes were opposite in the group DE with intervention(P＜0.05). ③Compared with group C, the morphology of skeletal muscle cells in group DM was abnormal, the number of muscle nuclei was increased, the transverse lines were blurred and disappeared, the sarcomere was broken, and some muscle fibers were dissolved. Compared with group DM, the abnormal cell morphology, segmental injury of sarcomere and dissolution of muscle fibers in group DE were improved. The sarcolemma was more complete and the arrangement of muscle nuclei was more orderly. ④Compared with group C, the expressions of KLF15 and cleaved caspase-3, cells apoptosis rates in group DM were increased significantly(P＜0.01), while p-mTOR/mTOR level was decreased(P＜0.01) ; compared with group DM, the above indexes were opposite in the group with intervention(P＜0.05 or P＜0.01). Conclusion: Aerobic intermittent exercise is beneficial to improve the skeletal muscle pathological changes in type 2 diabetes rats, which may be due to the effective regulation of KLF15/mTOR related protein expression and the reduction of apoptosis damage.

Divergent stem hydraulic strategies of Caragana korshinskii resprouts following a disturbance.

Resprouting plants are distributed in many vegetation communities worldwide. With increasing resprout age post-severe-disturbance, new stems grow rapidly at their early age, and decrease in their growth with gradually decreasing water status thereafter. However, there is little knowledge about how stem hydraulic strategies and anatomical traits vary post-disturbance. In this study, the stem water potential (Ψstem), maximum stem hydraulic conductivity (Kstem-max), water potential at 50% loss of hydraulic conductivity (Kstem  P50) and anatomical traits of Caragana korshinkii resprouts were measured during a 1- to 13-year post-disturbance period. We found that the Kstem-max decreased with resprout age from 1-year-old resprouts (84.2 mol m-1 s-1 MPa-1) to 13-year-old resprouts (54.2 mol m-1 s-1 MPa-1) as a result of decreases in the aperture fraction (Fap) and the sum of aperture area on per unit intervessel wall area (Aap). The Kstem  P50 of the resprouts decreased from 1-year-old resprouts (-1.8 MPa) to 13-year-old resprouts (-2.9 MPa) as a result of increases in vessel implosion resistance (t/b)2, wood density (WD), vessel grouping index (GI) and decreases in Fap and Aap. These shifts in hydraulic structure and function resulted in an age-based divergence in hydraulic strategies i.e., a change from an acquisitive strategy to a conservative strategy, with increasing resprout age post-disturbance.

Percutaneous Endoscopic Posterior Decompression for Therapy of Spinal Cord Compression Due to Ossification of the Ligamentum Flavum: A Long-Term Follow-up.

BACKGROUND: Thoracic ossification of the ligamentum flavum (OLF) is a pathologic condition that affects ligamentation of the OLF and causes slowly progressive myeloradiculopathy. There is a trend toward performing minimally invasive surgery. In this study, we assess the long-term efficacy of percutaneous endoscopic surgical management of thoracic OLF. METHODS: Twenty patients with thoracic myelopathy due to thoracic OLF underwent percutaneous endoscopic surgical management. We investigated clinical outcomes and neurologic improvements. Magnetic resonance imaging was performed on all patients preoperatively and postoperatively, and intramedullary signal changes were evaluated. RESULTS: The operation time averaged at 170.4 minutes (range 110-320 minutes). The mean intraoperative blood loss was 29.6 mL (range 5-100 mL). Cerebrospinal fluid leakage occurred in 1 patient and healed well. The follow-up period ranged from 60 to 72 months. The mean score on the Japanese Orthopedic Association scale improved from (6.0 ± 1.41) preoperatively to (7.83 ± 1.40) at 1 month postoperatively to (9.67 ± 1.30) at the final follow-up (P < 0.05). At the final follow-up stage, 11 patients had excellent outcomes, 6 good, 2 fair, and 1 unchanged, according to the Hirabayashi recovery rate. No patient had postoperative deterioration in neurologic status. CONCLUSIONS: Percutaneous endoscopic surgical management of thoracic OLF has proven to be both safe and effective for the resection of the OLF in the thoracic spine.

A clear trade-off between leaf hydraulic efficiency and safety in an aridland shrub during regrowth.

It has been suggested that a trade-off between hydraulic efficiency and safety is related to drought adaptation across species. However, whether leaf hydraulic efficiency is sacrificed for safety during woody resprout regrowth after crown removal is not well understood. We measured leaf water potential (ψleaf ) at predawn (ψpd ) and midday (ψmid ), leaf maximum hydraulic conductance (Kleaf-max ), ψleaf at induction 50% loss of Kleaf-max (Kleaf P50 ), leaf area-specific whole-plant hydraulic conductance (LSC), leaf vein structure and turgor loss point (πtlp ) in 1- to 13-year-old resprouts of the aridland shrub (Caragana korshinskii). ψpd was similar, ψmid and Kleaf P50 became more negative, and Kleaf-max decreased in resprouts with the increasing age; thus, leaf hydraulic efficiency clearly traded off against safety. The difference between ψmid and Kleaf P50 , leaf hydraulic safety margin, increased gradually with increasing resprout age. More negative ψmid and Kleaf P50 were closely related to decreasing LSC and more negative πtlp , respectively, and the decreasing Kleaf-max arose from the lower minor vein density and the narrower midrib xylem vessels. Our results showed that a clear trade-off between leaf hydraulic efficiency and safety helps C. korshinskii resprouts adapt to increasing water stress as they approach final size.

Severe Pulmonary Embolism, Thrombosis of Lower Extremity, Unexpected Mild Renal Disorder in MPO-ANCA Associated Vasculitis: A Case Report.

Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis is an autoimmune disease usually with severe multiple dysfunction syndrome, especially prominent acute renal failure. A 65-year-old woman was admitted with progressive dyspnoea for six months and fever, sputum with blood, pain of the lower extremities and intermittent claudication for two days, indicating multiple organ involvement (respiratory system, blood vessels). The renal involvement was relatively mild, presenting with microscopic haematuria. The chest computed tomography demonstrated multiple pulmonary embolisms. Ultrasound and computed tomography angiography for the lower extremity vessels showed venous and arterial thrombosis. Exclusion of other diseases that can cause multiple organ damage and thrombosis, the positive perinuclear ANCA and MPO-ANCA strongly support the diagnosis of MPO-ANAC-associated vasculitis. The patient's physical condition has been greatly improved by treatment with corticosteroids and anticoagulation.

Risk Prediction for Locoregional Recurrence in Epidermal Growth Factor Receptor-Mutant Stage III-pN2 Lung Adenocarcinoma after Complete Resection: A Multi-center Retrospective Study.

Background: This study aimed to develop a predictive model based on the risk of locoregional recurrence (LRR) in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma after complete resection. Methods: A total of 11,020 patients with lung surgery were screened to determine completely resected EGFR-mutant stage III-pN2 lung adenocarcinoma. Patients were excluded if they received preoperative therapy or postoperative radiation therapy (PORT). The time from surgery to LRR was recorded. Clinicopathological variables with statistical significance predicting LRR in the multivariate Cox regression were incorporated into the competing risk nomogram. Patients were then sub-grouped based on different recurrence risk as a result of the nomogram. Results: Two hundred and eighty-eight patients were enrolled, including 191 (66.3%) with unforeseen N2 (IIIA1-2), 75 (26.0%) with minimal/single station N2 (IIIA3), and 22 (7.6%) with bulky and/or multilevel N2 (IIIA4). The 2-year overall cumulative incidence of LRR was 27.2% (confidence interval [CI], 16.3%-38.0%). IIIA4 disease (hazard ratio, 2.65; CI, 1.15-6.07; P=0.022) and extranodal extension (hazard ratio, 3.33; CI, 1.76-6.30; P<0.001) were independent risk factors for LRR and were incorporated into the nomogram. Based on the nomogram, patients who did not have any risk factor (low-risk) had a significantly lower predicted 2-year incidence of LRR than those with any of the risk factors (high-risk; 4.6% vs 21.9%, P<0.001). Conclusions: Pre-treatment bulky/multilevel N2 and pathological extranodal extension are risk factors for locoregional recurrence in EGFR-mutant stage III-pN2 lung adenocarcinoma. Intensive adjuvant therapies and active follow-up should be considered in patients with any of the risk factors.

A clinical study regarding the outcomes of symptomatic spinal epidural haematoma after adult spinal deformity surgery.

Symptomatic spinal epidural haematoma (SSEH) is a rare but serious postoperative complication. This study aimed to assess the prevalence, causes and treatment of SSEH after adult spinal deformity (ASD) surgery. The patients admitted from August 2012 till August 2016 were retrospectively reviewed using case notes. During these four years, 102 patients were admitted with adult spinal deformity, out of which 3 (2.9%) developed post-operative SSEH. The duration between surgery to onset of SSEH was 10-13 hours (average 11.7 hours) post-operatively. Three patients were treated by haematoma evacuation at 8.5-14 hour (average 11.4 hours) after the symptoms appeared. One patient had improved by 2 Frankel grades, and two patients had improved by1 Frankel grade at the last followup. The results concluded that post-operative SSEH occurred in 2.9% of ASD patients who underwent corrective spinal procedures. Improvement in neurological deficits can be achieved by early haematoma evacuation.

The Effects of CYP3A5 Genetic Polymorphisms on Serum Tacrolimus Dose-Adjusted Concentrations and Long-Term Prognosis in Chinese Heart Transplantation Recipients.

BACKGROUND AND OBJECTIVES: Effective management of immunosuppressants is extemely important to improve prognosis of heart transplant recipients. We aim to investigate the effects of cytochrome P450 (CYP) 3A5 (rs776746) single nucleotide polymorphisms (SNPs) on serum tacrolimus concentrations/doses (C/Ds, ng/mL per mg/kg) and long-term prognosis in Chinese heart transplant recipients. METHODS: We detected the CYP3A5 SNPs of 203 consecutive Chinese heart transplant recipients between August 2005 and July 2012, and 55 of them who received tacrolimus-based immunosuppressive therapy were enrolled in this study. The tacrolimus C/Ds at 1, 3, 6, 12, 24 and 36 months after transplantation were routinely calculated. X-ray-guided endomyocardial biopsies (EMBs) were performed at 1, 3 and 6 months after heart transplantion to evaluate acute rejection degrees. All participants were then followed up annually until May 2018. The designed primary endpoint was all-cause mortality. RESULTS: In 55 heart transplant recipients (43 males and 12 females), CYP3A5 non-expressors (CYP3A5*3/*3, n = 40) had significantly higher tacrolimus C/Ds than expressors (CYP3A5*1/*3, n = 15) at all time points (P < 0.001). Chi-squared test showed no significant differences in EMB-proven acute rejections between the two groups within 6 months after heart transplantion. The median follow-up period was 94.7 months, and eight patients died. Kaplan-Meier analysis showed CYP3A5 expressors tend to have higher mortality than non-expressors (20% vs 12.5%, log-rank: P = 0.314). CONCLUSIONS: CYP3A5 SNPs affect tacrolimus pharmacokinetics in Chinese heart transplant recipients, and non-expressors have higher tacrolimus C/Ds. In addition, expressors tend to have a worse long-term prognosis than non-expressors.