Original Designed Uniportal-Bichannel Spinal Endoscopic System (UBiSES) for Foraminoplasty in Percutaneous Endoscopic Transforaminal Discectomy.

OBJECTIVE: The study introduced uniportal-bichannel spinal endoscopic system (UBiSES) and explored the feasibility of applying UBiSES to conduct lumbar foraminoplasty in percutaneous endoscopic transforaminal discectomy (PETD). METHODS: This is a cohort study. 36 patients confirmed as L5/S1 lumbar disc herniation (LDH) in our hospital from March, 2019 to November, 2019 were enrolled. 36 patients were divided into two groups named the UBiSES group (n = 18, male: female = 8:10) and the TESSYS group (n = 18, male: female = 10:8). The average age of the UBiSES group and the TESSYS group were 40.94 ± 12.39 years old and 39.78 ± 13.02 years old respectively. PETD via uniportal-bichannel foraminoplasty assisted by UBiSES was adopted on the UBiSES group while PETD via conventional foraminoplasty was performed on the TESSYS group. One experienced surgeon with more than 4000 cases of lumbar surgery performed PETD on all patients. The demographic data, the duration of working cannula placement (minutes), decompression time (minutes), radiation exposure time (seconds), complications, Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) scores and modified MacNab criteria were recorded and analyzed. The magnetic resonance imaging (MRI) and computed tomography (CT) were conducted to evaluate the radiographic improvement. RESULTS: PETD via lumbar foraminoplasty was successfully performed in all cases. The follow-up points were 3 months, 6 months, and 12 months. The average follow-up period of all patients was 15.78 ± 2.29 months. There was no statistic difference in age (P = 0.81), sex (P = 0.51) and follow-up (P = 0.14) between two groups. The duration of working cannula placement was 19.08 ± 2.30 min in the UBiSES group and 24.90 ± 4.71 min in the TESSYS group and there was significant difference between two groups (P < 0.05). There was no statistic difference in decompression time between the UBiSES group (44.18 ± 5.70 min) and the TESSYS group (47.46 ± 5.96 min) (P = 1.70). The radiation exposure time was 28.00 ± 4.70 s in the UBiSES group and 40.50 ± 5.73 s in the TESSYS group respectively, and has significant difference between two groups (P < 0.05). Furthermore, there was significant different in the duration of working cannula placement and radiation exposure time in male or female between the UBiSES group and the TESSYS group (P < 0.05). For male or female, no difference observed in decompression time and follow-up period between two groups. Postoperative VAS of low back and leg at every follow-up point (1 day, 3 months, 6 months, 12 months) was improved significantly in both groups compared with their preoperative VAS (P < 0.05). The postoperative ODI (3 months, 6 months, 12 months) has decreased significantly in both the UBiSES group and the TESSYS group compared with their preoperative ODI (P < 0.05). 94.44% patients received an excellent or good recovery in the UBiSES group and 88.89% for the TESSYS group. There was no poor result reported in both groups. The radiographic images showed satisfactory foraminoplasty and sufficient decompression of nerve in both groups. No postoperative complications were observed during follow-ups in the UBiSES group. Two patients in the TESSYS group experienced postoperative dysesthesia and the symptom was disappeared in 5 days and 7 days respectively with dexamethasone and neurotrophic drugs treatment. CONCLUSIONS: The original designed UBiSES could effectively and safely enlarge the foramen with an extensive surgical view and space under full-time and real-time visualization and get satisfactory efficacy.

Dexamethasone-loaded thermo-sensitive hydrogel attenuates osteoarthritis by protecting cartilage and providing effective pain relief.

BACKGROUND: We utilized the destabilization of medial meniscus (DMM)-induced mice to illustrate the osteoarthritis (OA) suppressing and pain-relieving effects of a novel prolonged-release intra-articular (IA)-dexamethasone-loaded thermo-sensitive hydrogel (DLTH). METHODS: The effects of temperature and pH on DLTH formation and in vitro DLTH release profile were assessed. C57BL/6J mice were randomly divided into three groups: Ctrl group, Model group and DLTH group. The DLTH group received joint injections of 10 µL DLTH (1 mg/kg) into the right knee once a week from week 2 to week 11. We performed micro-computed tomography (Micro-CT) and histological analyses of safranin O-fast green, hematoxylin and eosin, and tartrate-resistant acid phosphatase in knee joints. We also carried out immunohistochemical (IHC) staining for matrix metalloproteinase-9 (MMP-9), MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) in cartilage and Ki-67 in synovia. Pain behavioral testing was carried out in all mice. The serum content of prostaglandin E2 (PGE2) and real-time polymerase chain reaction (PCR) of inflammatory cytokines and pain-related factors in dorsal root ganglia (DRGs) were evaluated. RESULTS: It took 20 minutes to form DLTH at pH 7.0 and 37 °C. The cumulative release profiles of dexamethasone (Dex) from DLTH at 37 °C revealed a rapid release in the first 24 h and a sustained slow release for 7 days. In vivo study illustrated that DLTH attenuated OA bone destruction and ameliorated synovitis and progression of OA in DMM-induced mice. The chondroprotective effects of DLTH were mediated by decreased expressions of MMP-9, MMP-13, and ADAMTS-5. The results showed that IA-DLTH exerted pain-relieving effects in OA mice. Upregulation of nociceptive response time (NRT) and downregulations of serum PGE2, inflammatory factors, and pain-related mediators in DRGs of mice in the DLTH group were recorded. CONCLUSIONS: Data presented in this study elucidated that DLTH exhibited a long and lasting Dex release and it is a potential sustainable drug delivery system (DDS) to treat OA locally. IA-DLTH injection exerted chondroprotective and pain-relieving effects in DMM-induced arthritis. The involvement of MMP-9, MMP-13, ADAMTS-5, and inflammatory and pain-related factors, may account for the suppression of OA progression and pain.

Upper Lumbar Intradural Disc Herniation: A Rare Case Report and Etiologic Analysis.

BACKGROUND: Intradural disc herniation (IDH) is a rare type of disc degeneration that infrequently affects the upper lumbar spine. Pre- and intraoperative diagnosis and surgical management of IDH are challenging. The present case study provides insight into these aspects of upper lumbar IDH and discusses possible mechanisms. CASE DESCRIPTION: A 63-year-old female with a history of chronic lower back and leg pain presented with an acute lumbar sprain that had occurred 1 month prior. The pain progressed and spread to the front of the left thigh, which affected her ability to lift her leg when ascending/descending stairs. Sagittal gadolinium-enhanced magnetic resonance imaging (MRI) revealed a disc protruding into the ventral dural sac showing a hawk-beak sign, and the posterior edge of the disc annulus and local posterior longitudinal ligament was broken. Total L2 laminectomy was performed, and the dorsal side of the dural sac was exposed and incised to enable exploration of the ventral side of the dura. We found two free fragments protruding into the inner wall of the dura through the left ventral dura mater defect. After carefully and completely removing the mass, we repaired the defect and performed internal fixation. Postoperative pathologic analysis confirmed that the mass was nucleus pulposus tissue from the degenerated disc. The patient's pain significantly improved after surgery, and she was able to walk normally at the 1-month follow-up. CONCLUSION: Upper lumbar IDH is an extremely rare type of disc degeneration. An enhanced MRI scan can provide diagnostic evidence, but the final diagnosis requires surgical exploration of the path of herniation and pathologic examination of the mass lesion.

Percutaneous Endoscopic Lumbar Discectomy via Transforaminal Approach Combined with Interlaminar Approach for L4/5 and L5/S1 Two-Level Disc Herniation.

OBJECTIVE: The purpose of the present study was to discuss a new surgical strategy that combines percutaneous endoscopic transforaminal discectomy (PETD) with percutaneous endoscopic interlaminar discectomy (PEID) for L4/5 and L5/S1 two-level disc herniation. METHODS: This was a retrospective study. A total of 19 patients with L4/5 and L5/S1 two-level lumbar disc herniation (LDH) who underwent percutaneous endoscopic lumbar discectomy (PELD) in our hospital from January 2015 to June 2016 were retrospectively examined. The average age of these 19 patients was 42.21 ± 14.88 years old, including 12 men and 7 women. One experienced surgeon who had carried out more than 3000 lumbar surgeries performed PELD for these patients. During the PELD surgery, the transforaminal approach was adopted for L4/5 level disc herniation and the interlaminar approach was adopted for L5/S1 level disc herniation. The demographic data, operation time (min), fluoroscopy times, hospital stay (days), and complications were recorded and analyzed. The visual analogue scale (VAS), Oswestry disability index (ODI) scores, and the modified MacNab criteria were used to evaluate the surgical outcomes. MRI was conducted to evaluate the radiographic improvement. RESULTS: All patients underwent PELD via the transforaminal approach combined with the interlaminar approach successfully and achieved satisfactory efficacy. The follow-up points were 3, 12, and 18 months. The average hospital stay (days) and the average follow up (months) were 3.32 ± 0.98 and 18.63 ± 3.84, respectively. The operation time and fluoroscopy times were 85.79 ± 12.90 min and 39.05 ± 4.59 times, respectively. The fluoroscopy times (frequency) for L4/5 and L5/S1 were 26.95 ± 6.41 and 12.11 ± 3.49 (t = 7.00, P < 0.05). Furthermore, there was no significant difference for fluoroscopy times between male and female patients (t = 0.89, P = 0.99). The preoperative back pain (VAS-Back) and the last follow-up VAS-Back were 5.58 ± 2.01 and 2.37 ± 1.01, respectively (t = 7.14, P < 0.05). The preoperative leg pain (VAS-Leg) and the last follow-up VAS-Leg were 7.00 ± 1.56 and 1.63 ± 1.01, respectively (t = 20.97, P < 0.05). There were significant differences between preoperative VAS-Back and the last follow-up VAS-Back in men (t = 4.61, P < 0.05) and women (t = 6.57, P < 0.05). In addition, there was significant differences between preoperative VAS-Leg and the last follow-up VAS-Leg in men (t = 13.48, P < 0.05) and women (t = 26.87, P < 0.05). There were significant differences between preoperative ODI scores (44.84 ± 10.82%) and the last follow-up ODI scores (11.12 ± 5.80%) (t = 10.92, P < 0.05). Preoperative ODI scores and the last follow-up ODI scores were significantly different for men (t = 8.80, P < 0.05) and women (t = 6.63, P < 0.05). All patients received significant pain relief and functional improvement after the surgery. Except for two cases of postoperative dysesthesia and one dural tear, no severe complications occurred. The dysesthesia symptoms of these two patients disappeared within 1 week with the application of dexamethasone and neurotrophic drugs and the dural tear case also recovered well as the dural laceration was small. No poor results were reported and 89.47% of patients achieved excellent or good recovery. CONCLUSION: Percutaneous endoscopic lumbar discectomy via the transforaminal approach combined with the interlaminar approach under epidural anesthesia can treat L4/5 and L5/S1 two-level disc herniation safely and effectively.

Interactions in DNA Condensation: An Important Factor for Improving the Efficacy of Gene Transfection.

The rapid developments of gene therapy are benefit from the construction of efficient gene vectors, which help therapy genes efficiently overcome the barriers in the transport and transfection. Condensing DNA into nanoparticles is a crucial role in gene transfection, and the electrostatic interactions of synthetic cationic liposomes and cationic polymers with DNA are generally used for condensing DNA. Recent research has shown that the introduction of the hydrophobic interaction, hydrogen bonding, and coordinative interactions to the gene delivery vectors is also very important for DNA condensation, delivery, and transfection. This review focuses on the four types of interactions in condensed DNA nanoparticles, which could provide a new perspective for improving gene transfection efficacy.

Co-self-assembled nanoaggregates of BODIPY amphiphiles for dual colour imaging of live cells.

Co-self-assembled vesicular nanoparticles of two structurally comparable amphiphilic boron-dipyrromethene (BODIPY) dyes with dequenchable dual colour fluorescence were prepared for ratiometric imaging of live cells.

Molecular structural transformation regulated dynamic disordering of supramolecular vesicles as pH-responsive drug release systems.

The spontaneous release of drug payloads in the whole body always results in the compromised drug bioavailability and ultimate therapeutic efficacy. To achieve enhanced therapeutic efficacy and reduced side effects, pH-responsive targeted drug delivery systems have been studied due to their enhanced tumor accumulation and controllable maximum drug release feature. The present study described a co-assembly constructed by a pH responsive molecule (i.e., malachite green carbinol base (MG)) and liposome for highly efficient doxorubicin (DOX) release in tumor cells (MG-DOX⊂L). The structural transformation of MG effectively regulates the drug release profile in acidic environment. The pH-responsive sensitivity of co-assembly can be fine-tuned by altering the mixing ratios of building blocks with pH responders (i.e., MG molecules). MG-DOX⊂L was beneficial for the DOX release at pH5.0 and showed a higher cytotoxicity in KB cells owing to the pH-responsive drug release in acidic organelles following endocytosis pathway. In vivo tumor targetability and growth inhibition were evaluated in KB cell-xenografted nude mice. We have demonstrated that effective tumor growth inhibition in vivo is attributed to the synergistic contributions from highly efficient cellular entry and responsive intracellular release of DOX from MG-DOX⊂L.

Host-guest supramolecular nanosystems for cancer diagnostics and therapeutics.

Extensive efforts have been devoted to the construction of functional supramolecular nanosystems for applications in catalysis, energy conversion, sensing and biomedicine. The applications of supramolecular nanosystems such as liposomes, micelles, inorganic nanoparticles, carbon materials for cancer diagnostics and therapeutics have been reviewed by other groups. Here, we will focus on the recent momentous advances in the implementation of typical supramolecular hosts (i.e., cyclodextrins, calixarenes, cucurbiturils and metallo-hosts) and their nanosystems in cancer diagnostics and therapeutics. We discuss the evolutive process of supramolecular nanosystems from the structural control and characterization to their diagnostic and therapeutic function exploitation and even the future potentials for clinical translation.

Anti-bacterial and in vivo tumor treatment by reactive oxygen species generated by magnetic nanoparticles.

Photodynamic therapy is widely used in clinics and for anti-bacterial applications. The major challenge is the limited depth of tissue penetration of light and poor targetability. In this study, magnetite nanoparticles were used as a highly sensitive T2-weighted MR imaging contrast agents to target the tumor and mimic horseradish peroxidase (HRP), which could catalyze the decomposition of hydrogen peroxide to generate reactive oxygen species (ROS) to inhibit the tumor in vivo. In these experiments, MNPs were demonstrated to possess the enzyme-mimicking activity in different pH values, and the activity was dependent on the size of the MNPs: the smaller the size, the higher the activity. We demonstrated that MNPs showed highly efficient anti-bacterial (E. coli) activity in presence of H2O2. The E. coli inhibition ratio reached nearly 100% at optimal concentration. The anti-tumor activity was evaluated through HeLa cell viability under treatment with MNPs and H2O2. Consequently, the cell viability was significantly decreased and more than 80% of HeLa cells were dead after treatment with MNPs and H2O2 under different pH values. MR imaging was used to demonstrate the tumor targetability of 13 nm MNPs in vitro and in vivo. Consequently, the relaxivity of the 13 nm MNPs was determined to be r2 = 104 s-1 mM-1. The MR signal was much more negative and the intensity was significantly diminished with the increase of the concentration of 13 nm MNPs in vitro. The tumor signal was clearly visualized and a 3-fold decrease of the MR signal intensity of the tumor site of the mice was observed after 24 h-post treatment with the 13 nm MNPs. Finally, the tumor inhibition in vivo was investigated using 6 nm MNPs in BALB/c nude female mice bearing subcutaneously implanted HeLa cells on the right flank. The results show statistically significant efficacy in delaying tumor growth from day 6, and an approximately 99% tumor inhibition ratio was shown by the combination of MNPs and H2O2 after treatment for 17 days. By leveraging the passive targeting and MR imaging properties, we expect that the enzyme-mimicking MNPs could be used for cancer theranostics and may open up a new avenue for the treatment of epidermal infections.