Distributed visual positioning for surgical instrument tracking.

In clinical operations, it is crucial for surgeons to know the location of the surgical instrument. Traditional positioning systems have difficulty dealing with camera occlusion, marker occlusion, and environmental interference. To address these issues, we propose a distributed visual positioning system for surgical instrument tracking in surgery. First, we design the marker pattern with a black and white triangular grid and dot that can be adapted to various instrument surfaces and improve the marker location accuracy of the feature. The cross-points in the marker are the features that each feature has a unique ID. Furthermore, we proposed detection and identification for the position-sensing marker to realize the accurate location and identification of features. Second, we introduce multi Perspective-n-Point (mPnP) method, which fuses feature coordinates from all cameras to deduce the final result directly by the intrinsic and extrinsic parameters. This method provides a reliable initial value for the Bundle Adjustment algorithms. During instrument tracking, we assess the motion state of the instrument and select either dynamic or static Kalman filtering to mitigate any jitter in the instrument's movement. The core algorithms comparison experiment indicates our positioning algorithm has a lower reprojection error comparison to the mainstream algorithms. A series of quantitative experiments showed that the proposed system positioning error is below 0.207 mm, and the run time is below 118.842 ms. The results demonstrate the tremendous clinical application potential of our system providing accurate positioning of instruments promoting the efficiency and safety of clinical surgery.

Efficient intraoral photogrammetry using self-identifying projective invariant marker.

PURPOSE: The re-measurement of full-arch implant digital impressions is an important step in denture restoration. This paper provides an efficient oral photogrammetry technology using projective invariant marker, applied in the re-measurement of full-arch implant digital impressions. METHODS: We have developed a self-recognizing marker with projection invariance, along with its detection code. The marker is installed on the scanning body and used for photogrammetric measurements. Triangulation is utilized to determine the 3D coordinates of the marker, followed by a series of post-processing steps to obtain more accurate 3D coordinates. RESULTS: The experimental data indicate that the optimal working distance is between 200 and 250 mm, with a minimum measurement error of less than 0.05 mm and an average measurement error of 0.10 mm. The measurement time is less than 2 min. CONCLUSIONS: The experimental results show that the photogrammetric system can obtain reliable positions of full-arch implants with efficient photogrammetry, without the need to enter the patient's oral cavity, and has potential clinical application value.

L-cystathionine protects against oxidative stress and DNA damage induced by oxidized low-density lipoprotein in THP-1-derived macrophages.

Introduction: Oxidative stress in monocyte-derived macrophages is a significant pathophysiological process in atherosclerosis. L-cystathionine (L-Cth) acts as a scavenger for oxygen free radicals. However, the impact of L-Cth on macrophage oxidative stress during atherogenesis has remained unclear. This study aimed to investigate whether L-Cth affects oxidative stress in THP-1-derived macrophages and its subsequent effects on DNA damage and cell apoptosis. Methods: We established a cellular model of oxLDL-stimulated macrophages. The content of superoxide anion, H2O2, NO, and H2S in the macrophage were in situ detected by the specific fluorescence probe, respectively. The activities of SOD, GSH-Px, and CAT were measured by colorimetrical assay. The protein expressions of SOD1, SOD2, and iNOS were detected using western blotting. The DNA damage and apoptosis in the macrophage was evaluated using an fluorescence kit. Results: The results demonstrated that oxLDL significantly increased the content of superoxide anion and H2O2, the expression of iNOS protein, and NO production in macrophages. Conversely, oxLDL decreased the activity of antioxidants GSH-Px, SOD, and CAT, and downregulated the protein expressions of SOD1 and SOD2 in macrophages. However, treatment with L-Cth reduced the levels of superoxide anion, H2O2, and NO, as well as the protein expression of iNOS induced by oxLDL. Moreover, L-Cth treatment significantly enhanced GSH-Px, SOD, and CAT activity, and upregulated the expressions of SOD1 and SOD2 proteins in macrophages treated with oxLDL. Furthermore, both L-Cth supplementation and activation of endogenous L-Cth production suppressed DNA damage and cell apoptosis in oxLDL-injured macrophages, whereas inhibition of endogenous L-Cth exacerbated the deleterious effects of oxLDL. Conclusion: These findings suggest that L-Cth exerts a pronounced inhibitory effect on the oxidative stress, subsequent DNA damage and cell apoptosis in oxLDL-stimulated THP-1 monocytes. This study deepens our understanding of the pathogenesis of macrophage-related cardiovascular pathology.

Ent-eudesmane sesquiterpenoids from the Chinese liverwort Chiloscyphus polyanthus.

- Seven previously undescribed ent-eudesmane sesquiterpenoids (1-7), as well as seven known analogs (8-14), were isolated from the Chinese liverwort Chiloscyphus polyanthus var. rivularis. Their structures were established based on comprehensive spectroscopy analysis, electronic circular dichroism calculations, as well as biosynthetic considerations. The cytotoxicity against HepG2 (Human hepatocellular carcinomas) cancer cell line, and antifungal activity against Candida albicans SC5314 of all isolated ent-eudesmane sesquiterpenoids were preliminarily tested, results showed that the tested compounds did not display obvious cytotoxicity and antifungal activities under the tested concentration.

Deep learning-assisted diagnosis of femoral trochlear dysplasia based on magnetic resonance imaging measurements.

BACKGROUND: Femoral trochlear dysplasia (FTD) is an important risk factor for patellar instability. Dejour classification is widely used at present and relies on standard lateral X-rays, which are not common in clinical work. Therefore, magnetic resonance imaging (MRI) has become the first choice for the diagnosis of FTD. However, manually measuring is tedious, time-consuming, and easily produces great variability. AIM: To use artificial intelligence (AI) to assist diagnosing FTD on MRI images and to evaluate its reliability. METHODS: We searched 464 knee MRI cases between January 2019 and December 2020, including FTD (n = 202) and normal trochlea (n = 252). This paper adopts the heatmap regression method to detect the key points network. For the final evaluation, several metrics (accuracy, sensitivity, specificity, etc.) were calculated. RESULTS: The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the AI model ranged from 0.74-0.96. All values were superior to junior doctors and intermediate doctors, similar to senior doctors. However, diagnostic time was much lower than that of junior doctors and intermediate doctors. CONCLUSION: The diagnosis of FTD on knee MRI can be aided by AI and can be achieved with a high level of accuracy.

Image-guided navigation system for minimally invasive total hip arthroplasty (MITHA) using an improved position-sensing marker.

PURPOSE: Minimally invasive total hip arthroplasty (MITHA) is a treatment for hip arthritis, and it causes less tissue trauma, blood loss, and recovery time. However, the limited incision makes it difficult for surgeons to perceive the instruments' location and orientation. Computer-assisted navigation systems can help improve the medical outcome of MITHA. Directly applying existing navigation systems for MITHA, however, suffers from problems of bulky fiducial marker, severe feature-loss, multiple instruments tracking confusion, and radiation exposure. To tackle these problems, we propose an image-guided navigation system for MITHA using a novel position-sensing marker. METHODS: A position-sensing marker is proposed to serve as the fiducial marker with high-density and multi-fold ID tags. It results in less feature span and enables the use of ID for each feature, overcoming the problem of bulky fiducial markers and multiple instruments tracking confusion. And the marker can be recognized even when a large part of locating features is obscured. As for the elimination of intraoperative radiation exposure, we propose a point-based method to achieve patient-image registration based on anatomical landmarks. RESULTS: Quantitative experiments are conducted to evaluate the feasibility of our system. The accuracy of instrument positioning is achieved at 0.33 ± 0.18 mm, and that of patient-image registration is achieved at 0.79 ± 0.15 mm. And qualitative experiments are also performed, verifying that our system can be used in compact surgical spatial volume and can address severe feature-loss and tracking confusion problems. In addition, our system does not require any intraoperative medical scans. CONCLUSION: Experimental results indicate that our proposed system can assist surgeons without larger space occupations, radiation exposure, and extra incision, showing its potential application value in MITHA.

NVX-CoV2373 vaccination induces functional SARS-CoV-2-specific CD4+ and CD8+ T cell responses.

NVX-CoV2373 is an adjuvanted recombinant full-length SARS-CoV-2 spike trimer protein vaccine demonstrated to be protective against COVID-19 in efficacy trials. Here we demonstrate that vaccinated individuals made CD4+ T cell responses after 1 and 2 doses of NVX-CoV2373, and a subset of individuals made CD8+ T cell responses. Characterization of the vaccine-elicited CD8+ T cells demonstrated IFN-γ production. Characterization of the vaccine-elicited CD4+ T cells revealed both circulating T follicular helper (cTfh) cells and Th1 cells (IFN-γ+, TNF-α+, and IL-2+) were detectable within 7 days of the primary immunization. Spike-specific CD4+ T cells were correlated with the magnitude of the later SARS-CoV-2-neutralizing antibody titers, indicating that robust generation of CD4+ T cells, capable of supporting humoral immune responses, may be a key characteristic of NVX-CoV2373 that utilizes Matrix-M adjuvant.

Unprecedented 4,9-Seco-Oplopanane and Seven Drimane Sesquiterpenoids from the Chinese Liverwort Lejeunea flava (Sw.) Nees.

An unprecedented 4,9-seco-oplopanane (1), two undescribed drimane epimers (2 and 3), and five known drimane sesquiterpenoids (4-8) were isolated from the Chinese liverwort Lejeunea flava (Sw.) Nees. The structures of the new sesquiterpenoids were determined using nuclear magnetic resonance spectroscopy, electronic circular dichroism calculations, and single-crystal X-ray diffraction measurements. The inhibitory capacity of the new compounds against nitric oxide production in lipopolysaccharide-induced RAW 264.7 murine macrophages, along with the cytotoxicity of the new compounds against A549 and HepG-2 human cancer cell lines, were discussed.

Pinguisane Sesquiterpenoids from the Chinese Liverwort Trocholejeunea sandvicensis and Their Anti-Inflammatory Activity.

Nine new pinguisane sesquiterpenoid compounds, 1-9, including a highly oxygenated compound (1) and two amides (7 and 8), along with three known compounds (10, 11, and 12), were isolated from the Chinese liverwort Trocholejeunea sandvicensis Mizut (Lejeuneaceae). The structures of these compounds were determined by analysis of IR, UV, HRESIMS, NMR spectroscopic data, electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis. Inhibitory effects against lipopolysaccharide (LPS)-induced NO production in RAW 264.7 murine macrophages indicated that the maximum inhibition rates of NO production of compounds 1, 9, and 10 were 83.15%, 83.54%, and 96.28% under the nontoxic tested concentration, respectively. Compound 9 also displayed moderate anti-inflammatory activity in vivo in a CuSO4-induced transgenic zebrafish model.

Depletion of high-content CD14+ cells from apheresis products is critical for successful transduction and expansion of CAR T cells during large-scale cGMP manufacturing.

With the US Food and Drug Administration (FDA) approval of four CD19- and one BCMA-targeted chimeric antigen receptor (CAR) therapy for B cell malignancies, CAR T cell therapy has finally reached the status of a medicinal product. The successful manufacturing of autologous CAR T cell products is a key requirement for this promising treatment modality. By analyzing the composition of 214 apheresis products from 210 subjects across eight disease indications, we found that high CD14+ cell content poses a challenge for manufacturing CAR T cells, especially in patients with non-Hodgkin's lymphoma and multiple myeloma caused by the non-specific phagocytosis of the magnetic beads used to activate CD3+ T cells. We demonstrated that monocyte depletion via rapid plastic surface adhesion significantly reduces the CD14+ monocyte content in the apheresis products and simultaneously boosts the CD3+ content. We established a 40% CD14+ threshold for the stratification of apheresis products across nine clinical trials and demonstrated the effectiveness of this procedure by comparing manufacturing runs in two phase 1 clinical trials. Our study suggests that CD14+ content should be monitored in apheresis products, and that the manufacturing of CAR T cells should incorporate a step that lessens the CD14+ cell content in apheresis products containing more than 40% to maximize the production success.

Terpenoids from Chinese Liverworts Scapania spp.

An investigation of the chemical composition of Chinese liverworts led to the isolation of six new caged clerodane-type diterpenoids, scaparins A-C (1-3) from Scapania koponenii and scaparins D-F (4-6) from S. verrucosa. An unknown ent-trachylobane diterpenoid (7) and three known terpenoid derivatives (8-10) were obtained from S. verrucosa. The structures of the compounds were established on the basis of physical data (IR, UV, HRESIMS, and 1D and 2D NMR), and the absolute configurations were unequivocally confirmed by comparison of the experimental and calculated electronic circular dichroism spectra. Preliminary bioassays showed that compounds 1-7 exhibited moderate to weak quinone reductase-inducing activity in Hepa-1c1c7 cells.

Sacculatane diterpenoids from the Chinese liverwort Pellia epiphylla with protection against H2O2-induced apoptosis of PC12 cells.

Eight previously undescribed sacculatane diterpenoids, epiphyllins A-H, and one unknown bibenzyl-based isopentene along with seven known compounds were isolated from the Chinese liverwort Pellia epiphylla (L.) Corda. Their structures were established unequivocally on the basis of spectroscopic data and CD measurement. The quinine reductase-inducing activity evaluation demonstrated that epiphyllins A-D, 1ß-hydroxysacculatanolide and pellianolactone B displayed moderate antioxidant effect. Further investigation of pellianolactone B revealed its protective effects on H2O2-induced oxidative insults and apoptosis in PC12 cells.

Endoscopic thyroidectomy along with bilateral central neck dissection (ETBC) increases the risk of transient hypoparathyroidism for patients with thyroid carcinoma.

Increasing number of patients with thyroid carcinoma, especially young female patients, prefer to choose endoscopic thyroidectomy with bilateral central neck dissection (ETBC) for perfect cosmetic effects. However, the incidence of hypoparathyroidism after ETBC has not been well studied. Ninety six patients with papillary thyroid carcinoma were enrolled. All patients, including 49 ETBC and 47 open surgery patients, underwent total thyroidectomy with bilateral central neck dissection (CND). Some patients also underwent lateral neck dissection simultaneously. The incidence of hypoparathyroidism and parathyroid hormone (PTH) level were examined. Patients in the open surgery group had more advanced lesions, with larger tumor (p = 0.000), older age (p = 0.000), and more serious local involvement. The dissection extent of the open group was significantly larger than that of the ETBC group (p = 0.006). In contrast, the ETBC group with less dissection extent showed a significantly higher incidence of transient hypoparathyroidism than the open group (59.2 vs. 29.6 %, p = 0.004). The average PTH decline of the ETBC group was significantly higher than that of the open group on postoperative day 1 (POD1) (32.1 vs. 21.6 pg/ml, p = 0.010). Furthermore, the ETBC group had a significantly higher portion of patients with a PTH <10 pg/ml on POD1 (p = 0.001). One patient in the ETBC group developed permanent hypoparathyroidism. Autotransplantation and inadvertent removal rates of parathyroid did not differ between the two groups. Although generally considered a safe method for patients with thyroid carcinoma, ETBC may increase the risk of transient hypoparathyroidism compared with conventional open surgery.

The tumor suppressor PTEN has a critical role in antiviral innate immunity.

The gene encoding PTEN is one of the most frequently mutated tumor suppressor-encoding genes in human cancer. While PTEN's function in tumor suppression is well established, its relationship to anti-microbial immunity remains unknown. Here we found a pivotal role for PTEN in the induction of type I interferon, the hallmark of antiviral innate immunity, that was independent of the pathway of the kinases PI(3)K and Akt. PTEN controlled the import of IRF3, a master transcription factor responsible for IFN-ß production, into the nucleus. We further identified a PTEN-controlled negative phosphorylation site at Ser97 of IRF3 and found that release from this negative regulation via the phosphatase activity of PTEN was essential for the activation of IRF3 and its import into the nucleus. Our study identifies crosstalk between PTEN and IRF3 in tumor suppression and innate immunity.

Downregulation of Endogenous Hydrogen Sulfide Pathway Is Involved in Mitochondrion-Related Endothelial Cell Apoptosis Induced by High Salt.

BACKGROUND: The study aimed to investigate whether endogenous H2S pathway was involved in high-salt-stimulated mitochondria-related vascular endothelial cell (VEC) apoptosis. METHODS: Cultured human umbilical vein endothelial cells (HUVECs) were used in the study. H2S content in the supernatant was detected. Western blot was used to detect expression of cystathionine gamma-lyase (CSE), cleaved-caspase-3, and mitochondrial and cytosolic cytochrome c (cytc). Fluorescent probes were used to quantitatively detect superoxide anion generation and measure the in situ superoxide anion generation in HUVEC. Mitochondrial membrane pore opening, mitochondrial membrane potential, and caspase-9 activities were measured. The cell apoptosis was detected by cell death ELISA and TdT-mediated dUTP nick end labeling (TUNEL) methods. RESULTS: High-salt treatment downregulated the endogenous VEC H2S/CSE pathway, in association with increased generation of oxygen free radicals, decreased mitochondrial membrane potential, enhanced the opening of mitochondrial membrane permeability transition pore and leakage of mitochondrial cytc, activated cytoplasmic caspase-9 and caspase-3 and subsequently induced VEC apoptosis. However, supplementation of H2S donor markedly inhibited VEC oxidative stress and mitochondria-related VEC apoptosis induced by high salt. CONCLUSION: H2S/CSE pathway is an important endogenous defensive system in endothelial cells antagonizing high-salt insult. The protective mechanisms for VEC damage might involve inhibiting oxidative stress and protecting mitochondrial injury.

L-cystathionine inhibits oxidized low density lipoprotein-induced THP-1-derived macrophage inflammatory cytokine monocyte chemoattractant protein-1 generation via the NF-κB pathway.

This study aimed to explore whether and how L-cystathionine had any regulatory effect on the inflammatory response in THP-1-derived macrophages cultured in vitro under oxidized low-density lipoprotein (ox-LDL) stimulation. The human monocyte line THP-1 cell was cultured in vitro and differentiated into macrophages after 24 hours of PMA induction. Macrophages were pretreated with L-cystathionine and then treated with ox-LDL. The results showed that compared with the controls, ox-LDL stimulation significantly upregulated the expression of THP-1-derived macrophage MCP-1 by enhancing NF-κB p65 phosphorylation, nuclear translocation and DNA binding with the MCP-1 promoter. Compared with the ox-LDL group, 0.3 mmol/L and 1.0 mmol/L L-cystathionine significantly inhibited the expression of THP-1-derived macrophage MCP-1. Mechanistically, 0.3 mmol/L and 1.0 mmol/L L-cystathionine suppressed phosphorylation and nuclear translocation of the NF-κB p65 protein, as well as the DNA binding activity and DNA binding level of NF-κB with the MCP-1 promoter, which resulted in a reduced THP-1-derived macrophage MCP-1 generation. This study suggests that L-cystathionine could inhibit the expression of MCP-1 in THP-1-derived macrophages induced by ox-LDL via inhibition of NF-κB p65 phosphorylation, nuclear translocation, and binding of the MCP-1 promoter sequence after entry into the nucleus.

Down-regulated CBS/H2S pathway is involved in high-salt-induced hypertension in Dahl rats.

BACKGROUND: The study was designed to explore the significance of endogenous H2S in the development of high-salt-induced hypertension in rats. METHODS: High-salt-induced hypertension rat model was made by feeding Dahl rat high-salt diet containing 8% NaCl for 8 weeks with SD rats as control. SBP and aorta structure in rats were observed. Endogenous H2S content and expression of cystathionine ß-lyase (CBS), cystathionine γ-lyase and mercaptopyruvate sulfurtransferase in renal tissues were detected. Mechanisms for the impact of high-salt on CBS/H2S in renal tissues were studied, targeting HIF-1α pathway. The effect of H2S on RAS in serum and renal tissue of rats were tested. RESULTS: High-salt reduced endogenous H2S content and inhibited the expression of CBS in renal tissue in salt-sensitive Dahl rats. H2S donor, however, inhibited salt-sensitive hypertension, reversed aortic structural remodeling and inhibited activation of the RAS system in renal tissues in Dahl rats. Expression of HIF-1α was decreased but expression of PHD2 was increased in renal tissue of Dahl rats with high-salt diet, whereas they did not alter in renal tissue of SD rats with high-salt diet. Ex vivo experiment showed that inhibitor of HIF-1α degradation could rescue down-regulated CBS/H2S pathway in renal tissue of Dahl rats with high-salt. In contrast, inhibitor of HIF-1α activity decreased the CBS/H2S pathway in the renal tissue of SD rats treated with high-salt. CONCLUSIONS: Down-regulated CBS/H2S pathway in renal tissues under high-salt insult might be an important pathogenesis of salt-sensitive hypertension.

L-cystathionine inhibits the mitochondria-mediated macrophage apoptosis induced by oxidized low density lipoprotein.

This study was designed to investigate the regulatory role of l-cystathionine in human macrophage apoptosis induced by oxidized low density lipoprotein (ox-LDL) and its possible mechanisms. THP-1 cells were induced with phorbol 12-myristate 13-acetate (PMA) and differentiated into macrophages. Macrophages were incubated with ox-LDL after pretreatment with l-cystathionine. Superoxide anion, apoptosis, mitochondrial membrane potential, and mitochondrial permeability transition pore (MPTP) opening were examined. Caspase-9 activities and expression of cleaved caspase-3 were measured. The results showed that compared with control group, ox-LDL treatment significantly promoted superoxide anion generation, release of cytochrome c (cytc) from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and cell apoptosis, in addition to reduced mitochondrial membrane potential as well as increased MPTP opening. However, 0.3 and 1.0 mmol/L l-cystathionine significantly reduced superoxide anion generation, increased mitochondrial membrane potential, and markedly decreased MPTP opening in ox-LDL + l-cystathionine macrophages. Moreover, compared to ox-LDL treated-cells, release of cytc from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and apoptosis levels in l-cystathionine pretreated cells were profoundly attenuated. Taken together, our results suggested that l-cystathionine could antagonize mitochondria-mediated human macrophage apoptosis induced by ox-LDL via inhibition of cytc release and caspase activation.

Hydrogen sulfide suppresses oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 generation from macrophages via the nuclear factor κB (NF-κB) pathway.

This study was designed to examine the role of hydrogen sulfide (H2S) in the generation of oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 (MCP-1) from macrophages and possible mechanisms. THP-1 cells and RAW macrophages were pretreated with sodium hydrosulfide (NaHS) and hexyl acrylate and then treated with ox-LDL. The results showed that ox-LDL treatment down-regulated the H2S/cystathionine-ß-synthase pathway, with increased MCP-1 protein and mRNA expression in both THP-1 cells and RAW macrophages. Hexyl acrylate promoted ox-LDL-induced inflammation, whereas the H2S donor NaHS inhibited it. NaHS markedly suppressed NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter in ox-LDL-treated macrophages. Furthermore, NaHS decreased the ratio of free thiol groups in p65, whereas the thiol reductant DTT reversed the inhibiting effect of H2S on the p65 DNA binding activity. Most importantly, site-specific mutation of cysteine 38 to serine in p65 abolished the effect of H2S on the sulfhydration of NF-κB and ox-LDL-induced NF-κB activation. These results suggested that endogenous H2S inhibited ox-LDL-induced macrophage inflammation by suppressing NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter. The sulfhydration of free thiol group on cysteine 38 in p65 served as a molecular mechanism by which H2S inhibited NF-κB pathway activation in ox-LDL-induced macrophage inflammation.