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1.
Adv Sci (Weinh) ; : e2308337, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38572504

RESUMO

Physical unclonable functions (PUFs) have emerged as a promising encryption technology, utilizing intrinsic physical identifiers that offer enhanced security and tamper resistance. Multi-level PUFs boost system complexity, thereby improving system reliability and fault tolerance. However, crosstalk-free multi-level PUFs remain a persistent challenge. In this study, a hierarchical PUF system that harnesses the spontaneous phase separation of silk fibroin /PVA blend and the random distribution of silicon-vacancy diamonds within the blend is presented. The thermodynamic instability of phase separation and inherent unpredictability of diamond dispersion gives rise to intricate random patterns at two distinct scales, enabling time-efficient hierarchical authentication for cryptographic keys. These patterns are complementary yet independent, inherently resistant to replication and damage thus affording robust security and reliability to the proposed system. Furthermore, customized authentication algorithms are constructed: visual PUFs authentication utilizes neural network combined structural similarity index measure, while spectral PUFs authentication employs Hamming distance and cross-correlation bit operation. This hierarchical PUF system attains a high recognition rate without interscale crosstalk. Additionally, the coding capacity is exponentially enhanced using M-ary encoding to reinforce multi-level encryption. Hierarchical PUFs hold significant potential for immediate application, offering unprecedented data protection and cryptographic key authentication capabilities.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38651571

RESUMO

PURPOSE: To investigate the validity of using tibial capsular reflection and septum in the posterior compartment as landmark during posterior cruciate ligament (PCL) reconstruction (PCLR). METHODS: Anatomic measurements were obtained for 12 fresh human cadaveric knee specimens to observe the spatial position of the tibial insertion of the PCL in relation to the posterior septum and the capsular reflection in the posterior compartment. Sixty patients who underwent reconstruction of the PCL between 2020 and 2023 were also retrospectively investigated. The tibial tunnel was replaced in all patients using the same method (with reference to the tibial capsular reflection and the posterior septum). The placement of the tibial tunnel was assessed using X-ray fluoroscopy intraoperatively and computed tomography and three-dimensional reconstruction postoperatively. RESULTS: All fibres in the tibial insertion of the PCL in the 12 cadaveric specimens were located in the posteromedial compartment, adjacent to the posterior septum. The inferior border of the PCL insertion is adjacent to the tibial capsular reflection, which is attached at the champagne glass drop-off of the posterior tibia. In our previous cases, none of the patients experienced postoperative or intraoperative complications such as neurovascular injury, and the angle between the pin and the PCL facet was 93.1 ± 3.9° as measured on intraoperative radiographs. The mean distance from the centre of the tibial tunnel outlet to the inferior border of the PCL insertion was 5.6 ± 1.1 mm, and the distance from the centre of the tibial tunnel outlet to the outer border of the PCL insertion as a percentage of the length of the inferior border of PCL insertion was 42.2 ± 6.3%. CONCLUSION: The tibial capsular reflection and septum in the posterior compartment are safe and reliable soft-tissue landmark for tibial tunnel drilling in PCLR. LEVEL OF EVIDENCE: Level Ⅳ.

3.
Heliyon ; 10(5): e27196, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38486782

RESUMO

Various preclinical and a limited number of clinical studies of CAR-NK cells have shown promising results: efficient elimination of target cells without side effects similar to CAR-T therapy. However, the homing and infiltration abilities of CAR-NK cells are poor due to the inhibitory tumor microenvironment. From the perspective of clinical treatment strategies, combined with the biological and tumor microenvironment characteristics of NK cells, CAR-NK combination therapy strategies with anti-PD-1/PD-L1, radiotherapy and chemotherapy, kinase inhibitors, proteasome inhibitors, STING agonist, oncolytic virus, photothermal therapy, can greatly promote the proliferation, migration and cytotoxicity of the NK cells. In this review, we will summarize the targets selection, structure constructions and combinational therapies of CAR-NK cells for tumors to provide feasible combination strategies for overcoming the inhibitory tumor microenvironment and improving the efficacy of CAR-NK cells.

4.
Int J Biol Sci ; 20(5): 1578-1601, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481806

RESUMO

Background: The application of chimeric antigen receptor (CAR) NK cells in solid tumors is hindered by lack of tumor-specific targets and inefficient CAR-NK cell efficacy. Claudin-6 (CLDN6) has been reported to be overexpressed in ovarian cancer and may be an attractive target for CAR-NK cells immunotherapy. However, the feasibility of using anti-CLDN6 CAR-NK cells to treat ovarian cancer remains to be explored. Methods: CLDN6 expression in primary human ovarian cancer, normal tissues and cell lines were detected by immunohistochemistry and western blot. Two types of third-generation CAR NK-92MI cells targeting CLDN6, CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) and CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB) were constructed by lentivirus transfection, sorted by flow cytometry and verified by western blot and qPCR. OVCAR-3, SK-OV-3, A2780, Hey and PC-3 cells expressing the GFP and luciferase genes were transduced. Subcutaneous and intraperitoneal tumor models were established via NSG mice. The ability of CLDN6-CAR NK cells to kill CLDN6-positive ovarian cancer cells were evaluated in vitro and in vivo by live cell imaging and bioluminescence imaging. Results: Both CLDN6-CAR1 and CLDN6-CAR2 NK-92MI cells could specifically killed CLDN6-positive ovarian cancer cells (OVCAR-3, SK-OV-3, A2780 and Hey), rather than CLDN6 negative cell (PC-3), in vitro. CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) exhibited stronger cytotoxicity than CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB). Furthermore, CLDN6-CAR1 NK cells could effectively eliminate ovarian cancer cells in subcutaneous and intraperitoneal tumor models. More importantly, CAR-NK cells combined with immune checkpoint inhibitors, anti-PD-L1, could synergistically enhance the antitumor efficacy of CLDN6-targeted CAR-NK cells. Conclusions: These results indicate that CLDN6-CAR NK cells possess strong antitumor activity and represent a promising immunotherapeutic modality for ovarian cancer.


Assuntos
Claudinas , Neoplasias Ovarianas , Receptores de Antígenos Quiméricos , Humanos , Animais , Camundongos , Feminino , Receptores de Antígenos Quiméricos/genética , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/metabolismo , Linhagem Celular Tumoral , Apoptose , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Antígenos CD28/metabolismo , Células Matadoras Naturais , Imunoterapia/métodos , Imunoterapia Adotiva/métodos
5.
Adv Sci (Weinh) ; : e2309126, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477425

RESUMO

Along with the increasing integration density and decreased feature size of current semiconductor technology, heterointegration of the Si-based devices with diamond has acted as a promising strategy to relieve the existing heat dissipation problem. As one of the heterointegration methods, the microwave plasma chemical vapor deposition (MPCVD) method is utilized to synthesize large-scale diamond films on a Si substrate, while distinct structures appear at the Si-diamond interface. Investigation of the formation mechanisms and modulation strategies of the interface is crucial to optimize the heat dissipation behaviors. By taking advantage of electron microscopy, the formation of the epitaxial ß-SiC interlayer is found to be caused by the interaction between the anisotropically sputtered Si and the deposited amorphous carbon. Compared with the randomly oriented ß-SiC interlayer, larger diamond grain sizes can be obtained on the epitaxial ß-SiC interlayer under the same synthesis condition. Moreover, due to the competitive interfacial reactions, the epitaxial ß-SiC interlayer thickness can be reduced by increasing the CH4 /H2 ratio (from 3% to 10%), while further increase in the ratio (to 20%) can lead to the broken of the epitaxial relationship. The above findings are expected to provide interfacial design strategies for multiple large-scale diamond applications.

6.
ACS Nano ; 18(10): 7610-7617, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38426715

RESUMO

The quest for solar-blind photodetectors (SBPDs) with exceptional optoelectronic properties for imaging applications has prompted the investigation of SBPD arrays. Ga2O3, characterized by its ultrawide bandgap and low growth cost, has emerged as a promising material for solar-blind detection. In this study, SBPD arrays were fabricated by weaving Sn-doped ß-Ga2O3 microbelts (MBs). These MBs, which have a conductive core surrounded by a high-resistivity depletion surface layer resulting from the segregation of Sn and oxygen, are woven into a grid structure. Each intersection of the MBs functions as a photodetector pixel, with the intersecting MBs serving as the output electrodes of the pixel. This design simplifies the readout circuit for the photodetector array. The solar-blind photodetector array demonstrates superior solar-blind detection performance, including a dark current of 0.5 pA, a response time of 38.8 µs, a light/dark current ratio of 108, and a responsivity of 300 A/W. This research may provide a feasible strategy for the fabrication of photodetector arrays, thus pushing forward the application of photodetectors in imaging.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38420729

RESUMO

STUDY DESIGN: Anatomical study. OBJECTIVE: This study aimed to elaborate on the anatomical characteristics of the medial branch of the lumbar dorsal rami and to discuss its possible clinical significance. SUMMARY OF BACKGROUND DATA: Radiofrequency ablation targeting the medial branch of the lumbar dorsal rami has been increasingly used in the clinical management of facetogenic low back pain (FLBP). Nonetheless, attention is also being given to complications such as atrophy of the lumbar soft tissues and muscles. Therefore, a more detailed understanding of the innervation pattern on the facet joint may improve the precision of nerve ablation therapy for FLBP. METHODS: An anatomical study of 8 human specimens was carried out. The anatomic characteristics of the medial branch were observed and recorded. RESULTS: The medial branch originates from the lumbar dorsal rami, running close to the root of the posterolateral side of the superior articular process of the inferior cone. When passed through the mamillo-accessory ligament, it turns direction to the medial and caudal side, running in the multifidus muscle. In our study, each medial branch sent out 2-5 branches along the way. All the medial branches in L1-L4 gave off 1-2 small branches when crossing the facet joint and innervated the joint of the lower segment. Nineteen medial branches (23.75%) gave off recurrent branches to innervate the joint at the upper segment. CONCLUSION: The anatomical features of the medial branch remain similar in each lumbar segment. There are two types of joint branches, including the articular fibers that emanate from the medial branch as it runs along the medial border of the facet joint, and the recurrent branch from the medial branch that innervates the upper facet joint. Moreover, an anastomotic branch was found in the medial branches between different segments.

8.
BMC Musculoskelet Disord ; 25(1): 73, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238705

RESUMO

BACKGROUND: Lowering the exit position of the tibial tunnel can improve the clinical efficacy of posterior cruciate ligament (PCL) reconstruction, however, there is no unified positioning standard. This study aimed to use novel soft tissue landmarks to create a low tunnel. METHODS: A total of 14 human cadaveric knees and 12 patients with PCL injury were included in this study. Firstly, we observed the anatomical position between the PCL, posterior septum, and other tissue, and evaluated the relationship between the center of the low tibial tunnel (SP tunnel) and posterior septum and distal reflection of posterior capsule, and using computed tomography (CT) to evaluate distance between the center of the SP tunnel with bony landmarks. Then, evaluated the blood vessels content in the posterior septum with HE staining. Finally, observed the posterior septum and distal reflection of the posterior capsule under arthroscopy to explore the clinical feasibility of creating a low tibial tunnel, and assessed the risk of surgery by using ultrasound to detect the distance between the popliteal artery and the posterior edge of tibial plateau bone cortex. RESULTS: In all 14 cadaveric specimens, the PCL tibial insertions were located completely within the posterior medial compartment of the knee. The distance between the center of the SP tunnel and the the articular surface of tibial plateau was 9.4 ± 0.4 mm. All SP tunnels retained an intact posterior wall, which was 1.6 ± 0.3 mm from the distal reflection of the posterior capsule. The distances between the center of the SP tunnel and the the articular surface of tibial plateau, the champagne glass drop-off were 9.2 ± 0.4 mm (ICC: 0.932, 95%CI 0.806-0.978) and 1.5 ± 0.2 mm (ICC:0.925, 95%CI 0.788-0.975) in CT image. Compared with the posterior capsule, the posterior septum contained more vascular structures. Last, all 12 patients successfully established low tibial tunnels under arthroscopy, and the distance between the posterior edge of tibial plateau bone cortex and the popliteal artery was 7.8 ± 0.3, 9.4 ± 0.4 and 7.4 ± 0.3 mm at 30°, 60° and 90° flexion angels after filling with water and supporting with shaver in posterior-medial compartment of knee joint. CONCLUSIONS: A modified low tibial tunnel could be established in the PCL anatomical footprint by using the posterior septum and posterior capsule as landmarks.


Assuntos
Reconstrução do Ligamento Cruzado Posterior , Ligamento Cruzado Posterior , Humanos , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Extremidade Inferior/cirurgia , Cadáver , Ligamento Cruzado Posterior/diagnóstico por imagem , Ligamento Cruzado Posterior/cirurgia , Fêmur/cirurgia
9.
Org Lett ; 26(4): 769-774, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38047613

RESUMO

An efficient cobalt-catalyzed asymmetric reductive amination of ketones with hydrazides has been realized, directly producing valuable chiral hydrazines in high yields and enantioselectivities (up to 98% enantiomeric excess).

10.
J Med Chem ; 66(24): 16843-16868, 2023 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-38079530

RESUMO

Survivin is a novel attractive target for cancer therapy; however, it is considered undruggable because it lacks enzymatic activities. Herein, we describe our efforts toward the discovery of a novel series of 4,11-dioxo-4,11-dihydro-1H-anthra[2,3-d]imidazol-3-ium derivatives as survivin inhibitors by targeting ILF3/NF110. Intensive structural modifications led us to identify a lead compound AQIM-I, which remarkably inhibited nonsmall cell lung cancer cells A549 with an IC50 value of 9 nM and solid tumor cell proliferation with more than 700-fold selectivity against human normal cells. Further biological studies revealed that compound AQIM-I significantly inhibited survivin expression and colony formation and induced ROS production, apoptosis, cell cycle arrest, DNA damage, and autophagy. Furthermore, the promoter-luciferase reporter assay showed that AQIM-I attenuated the survivin promoter activity enhanced by the overexpression of ILF3/NF110 in a concentration-dependent manner, and specific binding (KD = 163 nM) of AQIM-I to ILF3/NF110 was detected by surface plasmon resonance.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Survivina/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Apoptose , Proteínas Inibidoras de Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Proteínas do Fator Nuclear 90/genética , Proteínas do Fator Nuclear 90/metabolismo
11.
Front Immunol ; 14: 1287367, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38143742

RESUMO

Background and aims: The co-infection of hepatitis B (HBV) patients with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis and thus drastically worsens the course of the disease. Therapy options for HBV/HDV patients are still limited. Here, we investigated the potential of natural killer (NK) cells that are crucial drivers of the innate immune response against viruses to target HDV-infected hepatocytes. Methods: We established in vitro co-culture models using HDV-infected hepatoma cell lines and human peripheral blood NK cells. We determined NK cell activation by flow cytometry, transcriptome analysis, bead-based cytokine immunoassays, and NK cell-mediated effects on T cells by flow cytometry. We validated the mechanisms using CRISPR/Cas9-mediated gene deletions. Moreover, we assessed the frequencies and phenotype of NK cells in peripheral blood of HBV and HDV superinfected patients. Results: Upon co-culture with HDV-infected hepatic cell lines, NK cells upregulated activation markers, interferon-stimulated genes (ISGs) including the death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), produced interferon (IFN)-γ and eliminated HDV-infected cells via the TRAIL-TRAIL-R2 axis. We identified IFN-ß released by HDV-infected cells as an important enhancer of NK cell activity. In line with our in vitro data, we observed activation of peripheral blood NK cells from HBV/HDV co-infected, but not HBV mono-infected patients. Conclusion: Our data demonstrate NK cell activation in HDV infection and their potential to eliminate HDV-infected hepatoma cells via the TRAIL/TRAIL-R2 axis which implies a high relevance of NK cells for the design of novel anti-viral therapies.


Assuntos
Carcinoma Hepatocelular , Hepatite D , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/metabolismo , Ligantes , Hepatite D/metabolismo , Interferons/metabolismo , Vírus Delta da Hepatite/genética , Células Matadoras Naturais , Fatores de Necrose Tumoral/metabolismo , Apoptose , Neoplasias Hepáticas/metabolismo
12.
JACS Au ; 3(11): 2981-2986, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38034968

RESUMO

Based on an amino-group-assisted coordination strategy and a proton-shuttle-activated outer-sphere mode, the cobalt-catalyzed asymmetric hydrogenation of α-primary amino ketones has been developed, resulting in the efficient synthesis of chiral vicinal amino alcohols bearing functionalized aryl rings in high yields and enantioselectivities (up to 99% enantiomeric excess (ee)) within 0.5 h.

13.
Sci Adv ; 9(47): eadj0123, 2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-37992178

RESUMO

Transcriptional dysregulation is a recurring pathogenic hallmark and an emerging therapeutic vulnerability in ovarian cancer. Here, we demonstrated that ovarian cancer exhibited a unique dependency on the regulatory machinery of transcriptional termination, particularly, cleavage and polyadenylation specificity factor (CPSF) complex. Genetic abrogation of multiple CPSF subunits substantially hampered neoplastic cell viability, and we presented evidence that their indispensable roles converged on the endonuclease CPSF3. Mechanistically, CPSF perturbation resulted in lengthened 3'-untranslated regions, diminished intronic polyadenylation and widespread transcriptional readthrough, and consequently suppressed oncogenic pathways. Furthermore, we reported the development of specific CPSF3 inhibitors building upon the benzoxaborole scaffold, which exerted potent antitumor activity. Notably, CPSF3 blockade effectively exacerbated genomic instability by down-regulating DNA damage repair genes and thus acted in synergy with poly(adenosine 5'-diphosphate-ribose) polymerase inhibition. These findings establish CPSF3-dependent transcriptional termination as an exploitable driving mechanism of ovarian cancer and provide a promising class of boron-containing compounds for targeting transcription-addicted human malignancies.


Assuntos
Recidiva Local de Neoplasia , Neoplasias Ovarianas , Feminino , Humanos , Fator de Especificidade de Clivagem e Poliadenilação/genética , Fator de Especificidade de Clivagem e Poliadenilação/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética
14.
BMC Anesthesiol ; 23(1): 284, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37608257

RESUMO

BACKGROUND: Cognitive decline following surgery is a common concern among elderly individuals. Leukocyte telomere length (LTL) can be assessed as a biological clock connected to an individual lifespan. However, the mechanisms causing this inference are still not fully understood. As a result of this, LTL has the potential to be useful as an aging-related biomarker for assessing delayed neurocognitive recovery (dNCR) and related diseases. METHODS: For this study, 196 individuals over 60 who were scheduled due to major non-cardiac surgical operations attended neuropsychological testing before surgery, followed by additional testing one week later. The finding of dNCR was based on a measured Z-score ≤ -1.96 on two or more separate tests. The frequency of dNCR was presented as the primary outcome of the study. Secondly, we evaluated the association between dNCR and preoperative LTL. RESULTS: Overall, 20.4% [40/196; 95% confidence interval (CI), 14.7-26.1%] of patients exhibited dNCR 1-week post-surgery. Longer LTL was identified as a predictor for the onset of early cognitive impairment resulting in postoperative cognitive decline [odds ratio (OR), 14.82; 95% CI, 4.01-54.84; P < 0.001], following adjustment of age (OR, 12.33; 95% CI, 3.29-46.24; P < 0.001). The dNCR incidence based on LTL values of these patients, the area under the receiver operating characteristic (ROC) curve was 0.79 (95% CI, 0.722-0.859; P < 0.001). At an optimal cut-off value of 0.959, LTL values offered respective specificity and sensitivity values of 64.7% and 87.5%. CONCLUSIONS: In summary, the current study revealed that the incidence of dNCR was strongly associated with prolonged LTL. Furthermore, this biomarker could help identify high-risk patients and offer insight into the pathophysiology of dNCR.


Assuntos
Envelhecimento , Disfunção Cognitiva , Idoso , Humanos , Estudos Retrospectivos , Leucócitos , Telômero
15.
Cell Rep ; 42(7): 112797, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37436890

RESUMO

Chimeric antigen receptor (CAR) T cell therapy lacks persistent efficacy with "on-target, off-tumor" toxicities for treating solid tumors. Thus, an antibody-guided switchable CAR vector, the chimeric Fc receptor CD64 (CFR64), composed of a CD64 extracellular domain, is designed. T cells expressing CFR64 exert more robust cytotoxicity against cancer cells than CFR T cells with high-affinity CD16 variant (CD16v) or CD32A as their extracellular domains. CFR64 T cells also exhibit better long-term cytotoxicity and resistance to T cell exhaustion compared with conventional CAR T cells. With trastuzumab, the immunological synapse (IS) established by CFR64 is more stable with lower intensity induction of downstream signaling than anti-HER2 CAR T cells. Moreover, CFR64 T cells exhibit fused mitochondria in response to stimulation, while CARH2 T cells contain predominantly punctate mitochondria. These results show that CFR64 T cells may serve as a controllable engineered T cell therapy with prolonged persistence and long-term antitumor activity.


Assuntos
Neoplasias , Linfócitos T , Humanos , Linhagem Celular Tumoral , Imunoterapia Adotiva/métodos , Neoplasias/terapia , Receptores Fc , Trastuzumab , Ensaios Antitumorais Modelo de Xenoenxerto , Animais
16.
J Org Chem ; 88(11): 7601-7606, 2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37125776

RESUMO

TBAJ-587, an analogue of the antituberculosis drug bedaquiline (BDQ), bearing a diarylquinoline skeleton retains the high bacterial potency, is less toxic, and has a better pharmacokinetic profile than the parent molecule, which has entered phase I clinical trials. In contrast to its fascinating bioactivity, however, the highly efficient synthesis of this molecule is still an unsolved challenge. Herein, the first asymmetric synthesis of TBAJ-587 based on a synergistic Li/Li bimetallic system is reported. The product could be obtained in an excellent yield of 90% and an enantiomeric ratio (er) of 80:20. Furthermore, the reaction could be conducted on a 5 g scale, and the product was obtained with 99.9:0.1 er after a simple recrystallization. The realization of this protocol will greatly aid the demand for clinical drug production.


Assuntos
Antituberculosos , Mycobacterium tuberculosis , Antituberculosos/farmacologia , Íons
17.
Eur Spine J ; 32(6): 2093-2100, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37131000

RESUMO

PURPOSE: The purpose of this study was to evaluate the efficacy of sinuvertebral nerve blocks in the diagnosis of discogenic low back pain. PATIENTS AND METHODS: In this retrospective cohort study, the data of 48 patients with high clinical suspicion of discogenic low back pain from L4/5 who received nerve block treatment from 2017 to 2018 were collected. Twenty-four patients received discoblock (L4/5 intradiscal injection of 1 ml 0.5% lidocaine) and another 24 patients received the sinuvertebral nerve block(L4/5 intervertebral space injection of 0.5 ml 0.5% lidocaine bilaterally). Percutaneous endoscopic radiofrequency thermal annuloplasty was performed in patients who responded to the diagnostic block. The visual analogue scale scores and Oswestry Disability Index scores in both groups before and 1, 3, and 12 months after surgery were compared. RESULTS: Ten patients with a negative diagnostic block did not undergo surgery. Eighteen patients in the discoblock group and 20 patients in the sinuvertebral nerve block group showed a positive response and were evaluated. There were no differences in visual analogue scale or Oswestry Disability Index scores between the two cohorts at baseline or at all time points postsurgery (all p > 0.05). When comparing baseline values to all time points postsurgery improved visual analogue scale scores, and Oswestry Disability Index scores were observed within both cohorts (all p < 0.05). CONCLUSION: The effect of sinuvertebral nerve block as a diagnostic tool for discogenic low back pain is similar to that of discoblock, and it is a promising tool that deserves further study.


Assuntos
Deslocamento do Disco Intervertebral , Disco Intervertebral , Dor Lombar , Bloqueio Nervoso , Humanos , Dor Lombar/diagnóstico , Dor Lombar/etiologia , Dor Lombar/tratamento farmacológico , Estudos Retrospectivos , Lidocaína/uso terapêutico , Injeções , Vértebras Lombares/cirurgia , Resultado do Tratamento , Deslocamento do Disco Intervertebral/cirurgia
19.
Angew Chem Int Ed Engl ; 62(26): e202303488, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37043303

RESUMO

Using the diphosphine-cobalt-zinc catalytic system, an efficient asymmetric hydrogenation of internal simple enamides has been realized. In particular, the Ph-BPE ligand can achieve convergent asymmetric hydrogenation of E/Z-substrates. High yields and excellent enantioselectivities were obtained for both acyclic and cyclic enamides bearing α-alkyl-ß-aryl, α-aryl-ß-aryl, and α-aryl-ß-alkyl substituents. Hydrogenated products can be applied for the synthesis of useful chiral drugs such as Arfromoterol, Rotigotine, and Norsertraline. In addition, reasonable catalytic mechanism and stereocontrol mode are proposed based on DFT calculations.


Assuntos
Cobalto , Hidrogenação , Estereoisomerismo , Catálise
20.
Spine J ; 23(8): 1223-1233, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37031892

RESUMO

BACKGROUND CONTEXT: Discogenic low-back pain (DLBP) is one of the primary causes of low back pain (LBP) and is associated with internal disc disruptions and is mainly transmitted by the sinuvertebral nerve (SVN). The lack of a universal understanding of the anatomical characteristics of the SVN has compromised surgical treatment for DLPB. PURPOSE: This study aims to elaborate on the anatomical characteristics of the SVN and to discuss their possible clinical significance. STUDY DESIGN: The SVNs were dissected and immunostained in ten human lumbar specimens. METHODS: The SVNs at the segments from L1-L2 to L5-S1 in ten human cadavers were studied, and the number, origin, course, diameter, anastomotic branches, and branching points of the SVNs were documented. Three longitudinal and five transverse zones were defined in the dorsal coronal plane of the vertebral body and disc. The vertebrae were divided longitudinally as follows: the region between the medial edges of the bilateral pedicles is divided into three equal parts, the middle third is zone I and the lateral third on both sides are zones II; the areas lateral to the medial margin of the pedicle were zones III. The transverse zones were designated as follows: (a)superior margin of the vertebral body to superior margin of the pedicle; (b) between superior and inferior margins of the pedicle; (c) inferior margin of the pedicle to inferior margin of the vertebral body; (d) superior margin of the disc to the midline of the disc; and (e) midline of the disc to the inferior margin of the disc. The distribution characteristics of SVNs in various zones were recorded, and tissue sections were immunostained with anti-NF 200 and anti-PGP 9.5. RESULTS: The SVNs are divided into main trunks and deputy branches, with 109 main trunks and 451 deputy branches identified in the 100 lumbar intervertebral foramens (IVFs). The main trunks of the SVN originate from the spinal nerve and/or the communicating branch, but the deputy branch originating from both roots was not observed. All the main trunks and deputy branches of the SVNs originate from the posterolateral disc (III d and III e). The deputy branches of the SVN primarily innervate the posterolateral aspect of the intervertebral disc (III d 46.78%, III e 36.36%) and the subpedicular vertebral body (III c 16.85%). The main trunk of the SVNs passes primarily through the subpedicular vertebral body (III c 96.33%) and divides into ascending, transverse, and descending branches in the IVF: III c (23/101, 22.77%) or spinal canal: II c (73/101, 72.28%), II d (3/101, 2.97%), II b (2/101, 1.98%). The main trunk possesses extensive innervation, and except for the most medial discs (I d and I e), it almost dominates all other zones of the spinal canal. At the segments from L1-L2 to L5-S1, 39 ipsilateral anastomoses connecting the ascending branch to the main trunk or spinal nerve at the upper level were observed, with one contralateral anastomosis observed at L5. CONCLUSION: The zone distribution characteristics of SVNs are similar across all levels. Comparatively, the proportion of double-root origin and the number of insertion points of the SVNs increased at the lower level. The three types of anastomosis offer connections between SVNs at the same level and at different levels. The posteromedial disc is innervated by corresponding and subjacent main trunks, with the posterolateral disc mainly innervated by the deputy branch. CLINICAL SIGNIFICANCE: Detailed information and zone distribution characteristics of the lumbar SVNs can help improve clinicians' understanding of DLBP and improve the effectiveness of treatments targeting the SVNs.


Assuntos
Relevância Clínica , Dor Lombar , Humanos , Vértebras Lombares/cirurgia , Nervos Espinhais , Região Lombossacral , Dor Lombar/etiologia
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