Exploring the roles and potential therapeutic strategies of inflammation and metabolism in the pathogenesis of vitiligo: a mendelian randomization and bioinformatics-based investigation.

Introduction: Vitiligo, a common autoimmune acquired pigmentary skin disorder, poses challenges due to its unclear pathogenesis. Evidence suggests inflammation and metabolism's pivotal roles in its onset and progression. This study aims to elucidate the causal relationships between vitiligo and inflammatory proteins, immune cells, and metabolites, exploring bidirectional associations and potential drug targets. Methods: Mendelian Randomization (MR) analysis encompassed 4,907 plasma proteins, 91 inflammatory proteins, 731 immune cell features, and 1400 metabolites. Bioinformatics analysis included Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Subnetwork discovery and hub protein identification utilized the Molecular Complex Detection (MCODE) plugin. Colocalization analysis and drug target exploration, including molecular docking validation, were performed. Results: MR analysis identified 49 proteins, 39 immune cell features, and 59 metabolites causally related to vitiligo. Bioinformatics analysis revealed significant involvement in PPI, GO enrichment, and KEGG pathways. Subnetwork analysis identified six central proteins, with Interferon Regulatory Factor 3 (IRF3) exhibiting strong colocalization evidence. Molecular docking validated Piceatannol's binding to IRF3, indicating a stable interaction. Conclusion: This study comprehensively elucidates inflammation, immune response, and metabolism's intricate involvement in vitiligo pathogenesis. Identified proteins and pathways offer potential therapeutic targets, with IRF3 emerging as a promising candidate. These findings deepen our understanding of vitiligo's etiology, informing future research and drug development endeavors.

Carrageenan maintains the contractile phenotype of vascular smooth muscle cells by increasing macromolecular crowding in vitro.

BACKGROUND: The contractile phenotype of vascular smooth muscle cells (VSMCs) results in good diastolic and contractile capacities, and its altered function is the main pathophysiological basis for diseases such as hypertension. VSMCs exist as a synthetic phenotype in vitro, making it challenging to maintain a contractile phenotype for research. It is widely recognized that the common medium in vitro is significantly less crowded than in the in vivo environment. Additionally, VSMCs have a heightened sense for detecting changes in medium crowding. However, it is unclear whether macromolecular crowding (MMC) helps maintain the VSMCs contractile phenotype. PURPOSE: This study aimed to explore the phenotypic, behavioral and gene expression changes of VSMCs after increasing the crowding degree by adding carrageenan (CR). METHODS: The degree of medium crowding was examined by a dynamic light scattering assay; VSMCs survival and activity were examined by calcein/PI cell activity and toxicity and CCK-8 assays; VSMCs phenotypes and migration were examined by WB and wound healing assays; and gene expression was examined by transcriptomic analysis and RT-qPCR. RESULTS: Notably, 225 µg/mL CR significantly increased the crowding degree of the medium and did not affect cell survival. Simultaneously, CR significantly promoted the contraction phenotypic marker expression in VSMCs, shortened cell length, decreased cell proliferation, and inhibited cell migration. CR significantly altered gene expression in VSMCs. Specifically, 856 genes were upregulated and 1207 genes were downregulated. These alterations primarily affect the cellular ion channel transport, microtubule movement, respiratory metabolism, amino acid transport, and extracellular matrix synthesis. The upregulated genes were primarily involved in the cytoskeleton and contraction processes of VSMCs, whereas the downregulated genes were mainly involved in extracellular matrix synthesis. CONCLUSIONS: The in vitro study showed that VSMCs can maintain the contractile phenotype by sensing changes in the crowding of the culture environment, which can be maintained by adding CR.

Low concentrations of TNF-α in vitro transform the phenotype of vascular smooth muscle cells and enhance their survival in a three-dimensional culture system.

BACKGROUND: Vascular smooth muscle cells (VSMCs) are commonly used as seed cells in tissue-engineered vascular constructions. However, their variable phenotypes and difficult to control functions pose challenges. This study aimed to overcome these obstacles using a three-dimensional culture system. METHODS: Calf VSMCs were administered tumor necrosis factor-alpha (TNF-α) before culturing in two- and three-dimensional well plates and polyglycolic acid (PGA) scaffolds, respectively. The phenotypic markers of VSMCs were detected by immunofluorescence staining and western blotting, and the proliferation and migration abilities of VSMCs were detected by CCK-8, EDU, cell counting, scratch, and Transwell assays. RESULTS: TNF-α rapidly decreased the contractile phenotypic markers and elevated the synthetic phenotypic markers of VSMCs, as well as markedly increasing the proliferation and migration ability of VSMCs under two- and three-dimensional culture conditions. CONCLUSIONS: TNF-α can rapidly induce a phenotypic shift in VSMCs and change their viability on PGA scaffolds.

Injectable and In Situ Formed Dual-Network Hydrogel Reinforced by Mesoporous Silica Nanoparticles and Loaded with BMP-4 for the Closure and Repair of Skull Defects.

Bone defects are a common and challenging orthopedic problem with poor self-healing ability and long treatment cycles. The difficult-to-heal bone defects cause a significant burden of medical expenses on patients. Currently, biomaterials with mechanical stability, long-lasting action, and osteogenic activity are considered as a suitable way to effectively heal bone defects. Here, an injectable double network (DN) hydrogel prepared using physical and chemical cross-linking methods is designed. The first rigid network is constructed using methylpropenylated hyaluronic acid (HAMA), while the addition of chitosan oligosaccharide (COS) forms a second flexible network by physical cross-linking. The mesoporous silica nanoparticles (MSN) loaded with bone morphogenetic protein-4 (BMP-4) were embedded into DN hydrogel, which not only enhanced the mechanical stability of the hydrogel, but also slowly released BMP-4 to achieve long-term skull repair. The designed composite hydrogel showed an excellent compression property and deformation resistance. In vitro studies confirmed that the HAMA/COS/MSN@BMP-4 hydrogel had good biocompatibility and showed great potential in supporting proliferation and osteogenic differentiation of mouse embryo osteoblast precursor (MC3T3-E1) cells. Furthermore, in vivo studies confirmed that the DN hydrogel successfully filled and closed irregular skull defect wounds, effectively promoted bone regeneration, and significantly promoted bone repair compared with the control group. In addition, HAMA/COS/MSN@BMP-4 hydrogel precursor solution can quickly form hydrogel in situ at the wound by ultraviolet light, which can be applied to the closure and repair of wounds of different shapes, which provides the new way for the treatment of bone defects.

Exosomes secreted from induced pluripotent stem cell ameliorate the lipopolysaccharide induced neuroinflammatory response via lncRNA-0949.

PURPOSE: To study the effect of exosomes derived from the induced pluripotent stem cells (iPSCs) in the neuroinflammatory response of microglia caused by lipopolysaccharide (LPS) and reveal the potential underlying mechanism. METHODS: A permanent microglia cell line HMO6 was activated by LPS. The features of exosomes were analyzed by nano flow cytometry, Western blot and transmission electron microscope. The RNA-seq was used to analyze the difference of noncoding RNA profiles between iPSC-Exos and HMO6 derived exosomes and proved that long no-coding RNA (lncRNA-0949) was highly expressed in the iPSC-Exos. Activated HMO6 cells were cocultured with iPSC-Exos in which lncRNA-0949 was overexpressed, knocked down or normally expressed. Quantitative real-time polymerase chain reaction (RT-qPCR), Enzyme-Linked Immunosorbent Assay and Western blot assay were adopted to analyze RNA and protein expression of inflammatory factors in HMO6 cells. RESULTS: The oxidative stress and inflammatory response of microglia were significantly attenuated with the iPSC derived exosomes treatment. LncRNA-0949 was effectively delivered into the HMO6 cells through the iPSC-Exos, which largely alleviated the production of malondialdehyde, IL-6, IL-1ß and TNF-α in HMO6 cells. Overexpression of lncRNA-0949 could enhance the anti-inflammatory effect of the iPSC-Exos, and knock-down of lncRNA-0949 impaired this availability. CONCLUSION: According to our results, lncRNA-0949 enriched exosomes from iPSC could potentially be used as a therapeutic strategy to prevent/treat neuroinflammatory diseases.

Macromolecular Crowding Enhances Matrix Protein Deposition in Tissue-Engineered Vascular Grafts.

Successful in vitro culture of small-diameter tissue-engineered vascular grafts (TEVGs) requires rapid deposition of biomacromolecules secreted by vascular smooth muscle cells in a polyglycolic acid mesh scaffold's three-dimensional (3D) porous environment. However, common media have lower crowding conditions than in vivo tissue fluids. In addition, during the early stages of construction, most of the biomolecules secreted by the cells into the medium are lost, which negatively affects the TEVG culture process. In this study, we propose the use of macromolecular crowding (MMC) to enhance medium crowding to improve the deposition and self-assembly efficiency of major biomolecules in the early stages of TEVG culture. The addition of carrageenan significantly increased the degree of MMC in the culture medium without affecting cell viability, proliferation, and metabolic activity. Protein analysis demonstrated that the deposition of collagen types I and III and fibronectin increased significantly in the cell layers of two-dimensional and 3D smooth muscle cell cultures after the addition of a MMC agent. Collagen type I in the culture medium decreased significantly compared with that in the medium without a MMC agent. Scanning electron microscopy demonstrated that MMC agents considerably enhanced the formation of matrix protein structures during the early stages of 3D culture. Hence, MMC modifies the crowding degree of the culture medium, resulting in the rapid formation of numerous matrix proteins and fiber structures. Impact Statement Small-diameter tissue-engineered vascular grafts (TEVGs) are one of the most promising means of treating cardiovascular diseases; however, the in vitro construction of TEVGs has some limitations, such as slow deposition of extracellular matrix (ECM), long culture period, and poor mechanical properties. We hypothesized that macromolecular crowding can increase the crowding of the culture medium to construct a more bionic microenvironment, which enhances ECM deposition in the medium to the cell layer and reduces collagen loss, accelerating and enhancing TEVG culture and construction in vitro.

Mechanism and role of mitophagy in the development of severe infection.

Mitochondria produce adenosine triphosphate and potentially contribute to proinflammatory responses and cell death. Mitophagy, as a conservative phenomenon, scavenges waste mitochondria and their components in the cell. Recent studies suggest that severe infections develop alongside mitochondrial dysfunction and mitophagy abnormalities. Restoring mitophagy protects against excessive inflammation and multiple organ failure in sepsis. Here, we review the normal mitophagy process, its interaction with invading microorganisms and the immune system, and summarize the mechanism of mitophagy dysfunction during severe infection. We highlight critical role of normal mitophagy in preventing severe infection.

Altered metabolism in right basal ganglia associated with asymptomatic neurocognitive impairment in HIV-infected individuals.

Background: Only few studies have focused on the metabolite differences between asymptomatic neurocognitive impairment (ANI) and cognitively normal people living with HIV (PLWH). The current study aims to examine whether brain metabolisms in basal ganglia (BG) by magnetic resonance spectroscopy (MRS) were potential to discriminate ANI from cognitively normal PLWH. Methods: According to neuropsychological (NP) test, 80 PLWH (37.4 ± 10.2 years) were divided into ANI group (HIV-ANI, n = 31) and NP normal group (HIV-normal, n = 49). Brain metabolisms by MRS from right BG were compared between groups, including N-acetylaspartate and N-acetyl aspartylglutamate (tNAA), creatine and phosphocreatine (tCr), and choline-containing compounds (tCho). A total value of three metabolites were introduced. All brain metabolisms were evaluated as its percentage of total. Furthermore, correlations between MRS and NP and clinical measures were evaluated. A logistic regression model was applied, and the AUC values for the model and the continuous factors were compared using receiver operating curve (ROC) analysis. Results: Compared to HIV-normal group, tNAA/total was lower and tCr/total was higher in the HIV-ANI group (P < 0.05). Both tNAA/total and tCr/total values were correlated with NP score (P < 0.05), especially in verbal fluency, speed of information processing, learning, and recall (P < 0.05). The logistic model included BG-tCr/total, current CD4 and infection years of PLWH. The AUC value for the BG-tCr/total was 0.696 and was not significantly lower than that for logistic model (P < 0.01). Conclusion: The altered brain metabolites in the right BG were found in the ANI group compared to PLWH with normal cognition, and further associated with NP deficits. The current findings indicated that brain metabolites assessed by MRS has the potential to discriminate ANI from cognitively normal PLWH.

A Central Auditory Test reveals differences between drug treatment regimens in adults living with HIV.

OBJECTIVE: This exploratory study examined whether central auditory tests show differences between people living with HIV (PLWH) treated with two predominant antiretroviral drug therapy (ART) regimens. DESIGN: Cross-sectional. STUDY SAMPLE: 253 PLWH (mean age 39.8 years) from the Shanghai Public Health Clinical Centre, China. METHODS: The Hearing in Noise Test speech reception threshold (SRT) assessed central auditory function and the Montreal Cognitive Assessment (MoCA) assessed cognition. The relationship between ART regimen and SRT was evaluated with multivariable linear regression incorporating age, HIV duration, and peripheral hearing ability. Multivariable logistic regression was used to ascertain if SRT and ART regimen predicted MoCA impairment. RESULTS: The two predominant ART regimens differed by one drug (zidovudine or tenofovir). Participants taking the zidovudine-containing regimen had poorer SRT performance (p=.012) independent of age and hearing thresholds. MoCA scores did not differ between drug regimens, but a negative relationship was found between SRT and MoCA impairment (p=.048). CONCLUSIONS: ART regimens differed in their association with central auditory test performance likely reflecting neurocognitive changes in PLWH taking the zidovudine-containing regimen. Central auditory test performance also marginally predicted cognitive impairment, supporting further assessment of central auditory tests to detect neurocognitive deficits in PLWH.

Co-Occurrence of tet(X4) and blaNDM-5 in Escherichia coli Isolates of Inpatient Origin in Guangzhou, China.

Tigecycline, one of the last-resort therapeutic options for complicated infections caused by multidrug-resistant pathogens, especially carbapenem-resistant Enterobacterales and Acinetobacter in recent years. The emergence of antibiotic-resistant bacteria and antibiotic-resistant genes has threatened the effectiveness of antibiotics and public health with the excessive use of antibiotics in clinics. However, the emergence and dissemination of high-level mobile tigecycline-resistance gene tet(X) is challenging for clinical effectiveness of antimicrobial agent. This study aimed to characterize an E. coli strain T43, isolated from an inpatient in a teaching hospital in China. The E. coli T43 was resistant to almost all antimicrobials except colistin and consisted of a 4,774,080 bp chromosome and three plasmids. Plasmids pT43-1 and pT43-2 contained tigecycline-resistance gene tet(X4). Plasmid pT43-1 had a size of 152,423 bp with 51.05% GC content and harbored 151 putative open reading frames. pT43-1 was the largest plasmid in strain T43 and carried numerous resistance genes, especially tigecycline resistance gene tet(X4) and carbapenemase resistance gene blaNDM-5. The tet(X) gene was associated with IS26. Co-occurrence of numerous resistance genes in a single plasmid possibly contributed to the dissemination of these genes under antibiotics stress. It might explain the presence of clinically crucial resistance genes tet(X) and blaNDM-5 in clinics. This study suggested the applicable use of antibiotics and continued surveillance of tet(X) and blaNDM-5 in clinics are imperative.

PRP significantly promotes the adhesion and migration of vascular smooth muscle cells on stent material.

BACKGROUND: The adhesion and survival state of cells on scaffold material is a major problem in tissue-engineered blood vessel (TEBV) culture. Platelet-rich plasma (PRP) contains a large amount of biologically active factors and fibrin, which is expected to play an important role in TEBV culture. PURPOSE: To combine PRP with cells and scaffold material to promote cell adhesion and biological activity on the scaffold material. METHODS: The adhesion status and migration of SMCs under the optimal concentration suitable for SMC growth and the optimal concentration of PRP were examined by scanning electron microscopy, HE staining, CCK-8 assays, qPCR, WB, and other experimental methods and compared with those under the conventional culture (20% FBS); finally, the effect of PRP on the deposition of ECM in vascular tissue engineering culture was verified by three-dimensional culture. RESULTS: PRP at 20% is a suitable concentration for SMCs. Compared with the control group, the 20% PRP group had better migration, and the number of SMC adhesions was significantly higher than that of the control group. In addition, collagen deposition in the experimental group was significantly higher than that in the control group. CONCLUSION: PRP (20%) can promote SMC adhesion, migration, and collagen deposition on the scaffold material.

Development and validation of a deep learning model for multicategory pneumonia classification on chest computed tomography: a multicenter and multireader study.

Background: Accurate diagnosis of pneumonia is vital for effective disease management and mortality reduction, but it can be easily confused with other conditions on chest computed tomography (CT) due to an overlap in imaging features. We aimed to develop and validate a deep learning (DL) model based on chest CT for accurate classification of viral pneumonia (VP), bacterial pneumonia (BP), fungal pneumonia (FP), pulmonary tuberculosis (PTB), and no pneumonia (NP) conditions. Methods: In total, 1,776 cases from five hospitals in different regions were retrospectively collected from September 2019 to June 2023. All cases were enrolled according to inclusion and exclusion criteria, and ultimately 1,611 cases were used to develop the DL model with 5-fold cross-validation, with 165 cases being used as the external test set. Five radiologists blindly reviewed the images from the internal and external test sets first without and then with DL model assistance. Precision, recall, F1-score, weighted F1-average, and area under the curve (AUC) were used to evaluate the model performance. Results: The F1-scores of the DL model on the internal and external test sets were, respectively, 0.947 [95% confidence interval (CI): 0.936-0.958] and 0.933 (95% CI: 0.916-0.950) for VP, 0.511 (95% CI: 0.487-0.536) and 0.591 (95% CI: 0.557-0.624) for BP, 0.842 (95% CI: 0.824-0.860) and 0.848 (95% CI: 0.824-0.873) for FP, 0.843 (95% CI: 0.826-0.861) and 0.795 (95% CI: 0.767-0.822) for PTB, and 0.975 (95% CI: 0.968-0.983) and 0.976 (95% CI: 0.965-0.986) for NP, with a weighted F1-average of 0.883 (95% CI: 0.867-0.898) and 0.846 (95% CI: 0.822-0.871), respectively. The model performed well and showed comparable performance in both the internal and external test sets. The F1-score of the DL model was higher than that of radiologists, and with DL model assistance, radiologists achieved a higher F1-score. On the external test set, the F1-score of the DL model (F1-score 0.848; 95% CI: 0.824-0.873) was higher than that of the radiologists (F1-score 0.541; 95% CI: 0.507-0.575) as was its precision for the other three pneumonia conditions (all P values <0.001). With DL model assistance, the F1-score for FP (F1-score 0.541; 95% CI: 0.507-0.575) was higher than that achieved without assistance (F1-score 0.778; 95% CI: 0.750-0.807) as was its precision for the other three pneumonia conditions (all P values <0.001). Conclusions: The DL approach can effectively classify pneumonia and can help improve radiologists' performance, supporting the full integration of DL results into the routine workflow of clinicians.

An acupuncture manipulation classification system based on three-axis attitude sensor and computer vision. / ä¸€ç§åŸºäºŽä¸‰è½´å§¿æ€ä¼ æ„Ÿå™¨å’Œè®¡ç®—æœºè§†è§‰çš„é’ˆåˆºæ‰‹æ³•åˆ†ç±»ç³»ç»Ÿ.

OBJECTIVES: To explore the action characteristics of acupuncture manipulations by combining visual and sensor technique, so as to improve the identification and classification accuracy of acupuncture manipulations and to quantificate the classifiations. METHODS: In this paper, the time domain features of acupuncture physical parameters and dynamic gesture features in the video of acupuncture manipulations are combined together to identify and classify acupuncture techniques. The acupuncture needle manipulation processes of 2 acupuncture experts and 3 young acupuncturists were selected as the study objects. The collected data included 4 basic manipulation techniques：lifting-thrusting reinforcing, lifting- thrusting reducing, twisting reinforcing and twisting reducing methods, all of which were performed by right-handed doctors. During acupuncture manipulation, a three-axis attitude sensor was used to acquire finger moving acceleration velocity and needle-rotating angle velocity, followed by analyzing the parameters of hand-moving velocity, amplitude, strength and angle. The mapping relationship among physical parameters and different manipulating methods was formed in time domain. The computer vision technology was employed to extract the spatio-temporal features of the acupuncture manipulation video images, and a hybrid model of three-dimensional convolutional neural network (3D CNN) and long- and short-term memory (LSTM) neural network were used for the recognition and classification of dynamic gestures of hand in acupuncture manipulation videos. Then the time-domain features of physical parameters were combined with the dynamic gestures in the classification process, with the manipulation classification realized. RESULTS: In performing the lift-thrusting reinforcing method, the needle insertion speed was faster and the force was larger, while the needle lifting speed was slower and the force was smaller. And in performing the lift-thrusting reducing method, the needle lifting speed was faster, the force was stronger, and the needle insertion speed was slower and the force was smaller. In the performance of twisting reinforcing, the leftward twisting force was bigger and the rotation amplitude was larger, while in performing the reducing method, the rightward twisting force was larger and the rotation amplitude was larger. When using the mean value of time of acceleration, speed, and amplitude as the basis of discrimination, the accuracy rates of lifting-thrusting reinforcing and reducing were 95.56% and 93.33%, while those of the two twisting manipulations were 95.56% and 91.11%, respectively. Compared with the classification method that only uses the sensor to obtain the manipulation information, the recognition accuracy was significantly improved. CONCLUSIONS: The acupuncture manipulation classification system can achieve quantitative analysis of physical parameters and dynamic recognition of acupuncture techniques, providing a certain foundation for the quantification and inheritance of acupuncture techniques.

Weaning difficulty after severe pneumonia in adult-onset mitochondrial myopathy with A3243G mutation in the mitochondrial tRNA gene: A case report.

Background: Mitochondrial myopathy is a group of diseases caused by abnormal mitochondrial structure or function. The mitochondrial myopathy impacts muscles of the whole body and exhibits variable symptoms. Respiratory muscle deficits deteriorate pulmonary function in patients with severe pneumonia. Case presentation: We report the case of a male patient with severe pneumonia-induced respiratory failure. He was abnormally dependent invasive ventilator-assisted ventilation after his condition had improved. Then we found abnormal ventilator waveform and a decline in muscle strength of him. Mitochondrial myopathy was ultimately confirmed by muscle pathological biopsy and body fluid genetic testing. Vitamin B complex, coenzyme Q10, Neprinol AFD, l-arginine, and MITO-TONIC were used to improve mitochondrial function and muscle metabolism. After treatment, discomfort associated with chest tightness, fatigue, cough, and sputum disappeared, and the patient was discharged. Conclusion: This case presented an uncommon cause of difficult weaning and extubation-acute onset of mitochondrial myopathy. Muscle biopsy and genetic testing of body fluid are essential for diagnosing mitochondrial myopathy. The A3243G mutation in the MT-TL1 gene of mitochondrial DNA contributes to pathogenesis of this case.

BRISC is required for optimal activation of NF-κB in Kupffer cells induced by LPS and contributes to acute liver injury.

BRISC (BRCC3 isopeptidase complex) is a deubiquitinating enzyme that has been linked with inflammatory processes, but its role in liver diseases and the underlying mechanism are unknown. Here, we investigated the pathophysiological role of BRISC in acute liver failure using a mice model induced by D-galactosamine (D-GalN) plus lipopolysaccharide (LPS). We found that the expression of BRISC components was dramatically increased in kupffer cells (KCs) upon LPS treatment in vitro or by the injection of LPS in D-GalN-sensitized mice. D-GalN plus LPS-induced liver damage and mortality in global BRISC-null mice were markedly attenuated, which was accompanied by impaired hepatocyte death and hepatic inflammation response. Constantly, treatment with thiolutin, a potent BRISC inhibitor, remarkably alleviated D-GalN/LPS-induced liver injury in mice. By using bone marrow-reconstituted chimeric mice and cell-specific BRISC-deficient mice, we demonstrated that KCs are the key effector cells responsible for protection against D-GalN/LPS-induced liver injury in BRISC-deficient mice. Mechanistically, we found that hepatic and circulating levels of TNF-α, IL-6, MCP-1, and IL-1ß, as well as TNF-α- and MCP-1-producing KCs, in BRISC-deleted mice were dramatically decreased as early as 1 h after D-GalN/LPS challenge, which occurred prior to the elevation of the liver injury markers. Moreover, LPS-induced proinflammatory cytokines production in KCs was significantly diminished by BRISC deficiency in vitro, which was accompanied by potently attenuated NF-κB activation. Restoration of NF-κB activation by two small molecular activators of NF-κB p65 effectively reversed the suppression of cytokines production in ABRO1-deficient KCs by LPS. In conclusion, BRISC is required for optimal activation of NF-κB-mediated proinflammatory cytokines production in LPS-treated KCs and contributes to acute liver injury. This study opens the possibility to develop new strategies for the inhibition of KCs-driven inflammation in liver diseases.

[Predictive model of early urinary continence recovery based on prostate gland MRI parameters after laparoscopic radical prostatectomy].

OBJECTIVE: Constructing a predictive model for urinary incontinence after laparoscopic radical prostatectomy (LRP) based on prostatic gland related MRI parameters. METHODS: In this study, 202 cases were included. All the patients were diagnosed with prostate cancer by prostate biopsy and underwent LRP surgery in Peking University Third Hospital. The preoperative MRI examination of all the patients was completed within 1 week before the prostate biopsy. Prostatic gland related parameters included prostate length, width, height, prostatic volume, intravesical prostatic protrusion length (IPPL), prostate apex shape, etc. From the first month after the operation, the recovery of urinary continence was followed up every month, and the recovery of urinary continence was based on the need not to use the urine pad all day long. Logistic multivariate regression analysis was used to analyze the influence of early postoperative recovery of urinary continence. Risk factors were used to draw the receiver operator characteristic (ROC) curves of each model to predict the recovery of postoperative urinary continence, and the difference of the area under the curve (AUC) was compared by DeLong test, and the clinical net benefit of the model was evaluated by decision curve analysis (DCA). RESULTS: The average age of 202 patients was 69.0 (64.0, 75.5) years, the average prostate specific antigen (PSA) before puncture was 12.12 (7.36, 20.06) µg/L, and the Gleason score < 7 points and ≥ 7 points were 73 cases (36.2%) and 129 cases (63.9%) respectively, with 100 cases (49.5%) at T1/T2 clinical stage, and 102 cases (50.5%) at T3 stage. The prostatic volume measured by preoperative MRI was 35.4 (26.2, 51.1) mL, the ratio of the height to the width was 0.91 (0.77, 1.07), the membranous urethral length (MUL) was 15 (11, 16) mm, and the IPPL was 2 (0, 6) mm. The prostatic apex A-D subtypes were 67 cases (33.2%), 80 cases (39.6%), 24 cases (11.9%) and 31 cases (15.3%), respectively. The training set and validation set were 141 cases and 61 cases, respectively. The operations of all the patients were successfully completed, and the urinary continence rate was 59.4% (120/202) in the 3 months follow-up. The results of multivariate analysis of the training set showed that the MUL (P < 0.001), IPPL (P=0.017) and clinical stage (P=0.022) were independent risk factors for urinary incontinence in the early postoperative period (3 months). The nomogram and clinical decision curve were made according to the results of multivariate analysis. The AUC value of the training set was 0.885 (0.826, 0.944), and the AUC value of the validation set was 0.854 (0.757, 0.950). In the verification set, the Hosmer-Lemeshow goodness-of-fit test was performed on the model, and the Chi-square value was 5.426 (P=0.711). CONCLUSION: Preoperative MUL, IPPL, and clinical stage are indepen-dent risk factors for incontinence after LRP. The nomogram developed based on the relevant parameters of MRI glands can effectively predict the recovery of early urinary continence after LRP. The results of this study require further large-scale clinical research to confirm.

[Near-infrared targeted probe designed for intraoperative imaging of prostatic neurovascular bundles].

OBJECTIVE: To investigate the imaging effect of a near-infrared fluorescent targeted probe ICG-NP41 on the neurovascular bundles (NVB) around the prostate in rats. METHODS: A near-infrared fluorescent targeted probe ICG-NP41 was synthesized. An animal model for NVB imaging was established using Sprague-Dawley rats (250-400 g). Experiments were conducted using a custom-built near-infrared windowⅡ(NIR-Ⅱ) small animal in vivo imaging system, and images collected were processed using ImageJ and Origin. The fluorescence signal data were statistically analyzed using GraphPad Prism. The signal-to-background ratio (SBR) for NVB was quantitatively calculated to explore the effective dosage and imaging time points. Finally, paraffin pathology sections and HE staining were performed on the imaging structures. RESULTS: Except for rats in the control group (n=2), right-sided NVB of the rats injected with ICG-NP41 (n=2 per group) were all observed in NIR-Ⅱ fluorescence mode 2 h and 4 h after administration. At 2 h and 4 h, average SBR of cavernous nerve in 2 mg/kg group in fluorescence mode was 1.651±0.142 and 1.619±0.110, respectively, both higher than that in white light mode (1.111±0.036), with no significant difference (P>0.05); average SBR of 4 mg/kg group in fluorescence mode were 1.168±0.066 and 1.219±0.118, respectively, both higher than that in white light mode (1.081±0.040), with no significant difference (P>0.05). At 2 h and 4 h, the average SBR of 2 mg/kg and 4 mg/kg groups in fluorescence mode were higher than that of the control group (SBR=1), the average SBR of the 2 mg/kg group was higher than that of the 4 mg/kg group, and all the above with no significant difference (P>0.05). The average diameter of the nerve measured by full width at half maxima method was about (178±15) µm. HE staining of paraffin sections showed the right major pelvic ganglion. CONCLUSION: The near-infrared fluorescent targeted probe ICG-NP41 can be used for real-time imaging of the NVB around the prostate in rats, providing a potential feasible solution for localizing NVB in real time during nerve-sparing radical prostatectomy.

Reconfigurable Photonic Crystal Reversibly Exhibiting Single and Double Structural Colors.

Unlike absorption-based colors of dyes and pigments, reflection-based colors of photonic crystals, so called "structural colors", are responsive to external stimuli, but can remain unfaded for over ten million years, and therefore regarded as a next-generation coloring mechanism. However, it is a challenge to rationally design the spectra of structural colors, where one structure gives only one reflection peak defined by Bragg's law, unlike those of absorption-based colors. Here, we report a reconfigurable photonic crystal that exhibits single-peak and double-peak structural colors. This photonic crystal is composed of a colloidal nanosheet in water, which spontaneously adopts a layered structure with single periodicity (407 nm). After a temperature-gradient treatment, the photonic crystal segregates into two regions with shrunken (385 nm) and expanded (448 nm) periodicities, and thus exhibits double reflection peaks that are blue- and red-shifted from the original one, respectively. Notably, the transition between the single-peak and double-peak states is reversible.

An uncertainty-aware self-training framework with consistency regularization for the multilabel classification of common computed tomography signs in lung nodules.

Background: Computed tomography (CT) signs of lung nodules play an important role in indicating lung nodules' malignancy, and accurate automatic classification of these signs can help doctors improve their diagnostic efficiency. However, few relevant studies targeting multilabel classification (MLC) of nodule signs have been conducted. Moreover, difficulty in obtaining labeled data also restricts this avenue of research to a large extent. To address these problems, a multilabel automatic classification system for nodule signs is proposed, which consists of a 3-dimensional (3D) convolutional neural network (CNN) and an efficient new semi-supervised learning (SSL) framework. Methods: Two datasets were used in our experiments: Lung Nodule Analysis 16 (LUNA16), a public dataset for lung nodule classification, and a private dataset of nodule signs. The private dataset contains 641 nodules, 454 of which were annotated with 6 important signs by radiologists. Our classification system consists of 2 main parts: a 3D CNN model and an SSL method called uncertainty-aware self-training framework with consistency regularization (USC). In the system, supervised training is performed with labeled data, and simultaneously, an uncertainty-and-confidence-based strategy is used to select pseudo-labeled samples for unsupervised training, thus jointly realizing the optimization of the model. Results: For the MLC of nodule signs, our proposed 3D CNN achieved satisfactory results with a mean average precision (mAP) of 0.870 and a mean area under the curve (AUC) of 0.782. In semi-supervised experiments, compared with supervised learning, our proposed SSL method could increase the mAP by 7.6% (from 0.730 to 0.806) and the mean AUC by 8.1% (from 0.631 to 0.712); it thus efficiently utilized the unlabeled data and achieved superior performance improvement compared to the recently advanced methods. Conclusions: We realized the optimal MLC of lung nodule signs with our proposed 3D CNN. Our proposed SSL method can also offer an efficient solution for the insufficiency of labeled data that may exist in the MLC tasks of 3D medical images.

Optimization and validation of voxel size-related radiomics variability by combatting batch effect harmonization in pulmonary nodules: a phantom and clinical study.

Background: Broad generalization of radiomics-assisted models may be impeded by concerns about variability. This study aimed to evaluate the merit of combatting batch effect (ComBat) harmonization in reducing the variability of voxel size-related radiomics in both phantom and clinical study in comparison with image resampling correction method. Methods: A pulmonary phantom with 22 different types of nodules was scanned by computed tomography (CT) with different voxel sizes. The variability of voxel size-related radiomics features was evaluated using concordance correlation coefficient (CCC), dynamic range (DR), and intraclass correlation coefficient (ICC). ComBat and image resampling compensation methods were used to reduce variability of voxel size-related radiomics. The percentage of robust radiomics features was compared before and after optimization. Pathologically differential diagnosis of invasive adenocarcinoma (IAC) from adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) (AIS-MIA group) was used for clinical validation in 134 patients. Results: Before optimization, the number of excellent features in the phantom and clinical data was 26.12% and 32.31%, respectively. The excellent features were increased after image resampling and ComBat correction. For clinical optimization, the effect of the ComBat compensation method was significantly better than that of image resampling, with excellent features reaching 90.96% and poor features only amounting to 4.96%. In addition, the hierarchical clustering analysis showed that the first-order and shape features had better robustness than did texture features. In clinical validation, the area under the curve (AUC) of the testing set was 0.865 after ComBat correction. Conclusions: The ComBat harmonization can optimize voxel size-related CT radiomics variability in pulmonary nodules more efficiently than image resampling harmonization.