[Preoperative prediction of HER-2 expression status in breast cancer based on MRI radiomics model].

Objective: This study aims to explore the predictive value of T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC), and early-delayed phases enhanced magnetic resonance imaging (DCE-MRI) radiomics prediction model in determining human epidermal growth factor receptor 2 status in breast cancer. Methods: A retrospective study was conducted, involving 187 patients with confirmed breast cancer by postsurgical pathology at Zhenjiang First People's Hospital during January 2021 and May 2023. Immunohistochemistry or fluorescence in situ hybridization was used to determine the HER-2 status of these patients, with 48 cases classified as HER-2 positive and 139 cases as HER-2 negative. The training set was used to construct the prediction models and the validation set was used to verify the prediction models. Layers of T2WI, ADC, and early-delayed phase DCE-MRI images were used to delineate the volumeof interest and 960 radiomic features were extracted from each case using Pyradiomic. After screening and dimensionality reduction by intraclass correlation coefficient, Pearson correlation analysis, least absolute shrinkage, and selection operator, the radiomics labels were established. Logistic regression analysis was used to construct the T2WI radiomics model, ADC radiomics model, DCE-2 radiomics model, DCE-6 radiomics model, and the joint sequence radiomics model to predict the HER-2 expression status of breast cancer, respectively. Based on the clinical, pathological, and MRI image characteristics of patients, univariate and multivariate logistic regression analysis wasused to construct a clinicopathological MRI feature model. The radscore of every patient and the clinicopathological MRI features which were statistically significant after screening were used to construct a nomogram model. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of each model and the decision curve analysis wasused to evaluate the clinical usefulness. Results: The T2WI, ADC, DCE-2, DCE-6, and joint sequence radiomics models, the clinicopathological MRI feature model, and the nomogram model were successfully constructed to predict the expression status of HER-2 in breast cancer. ROC analysis showed that in the training set and validation set, the areas under the curve (AUC) of the T2WI radiomics model were 0.797 and 0.760, of the ADC radiomics model were 0.776 and 0.634, of the DCE-2 radiomics model were 0.804 and 0.759, of the DCE-6 radiomics model were 0.869 and 0.798, of the combined sequence radiomics model were 0.908 and 0.847, of the clinicopathological MRI feature model were 0.703 and 0.693, and of the nomogram model were 0.938 and 0.859, respectively. In the training set, the combined sequence radiomics model outperformed the clinicopathological features model (P＜0.001). In the training and validation sets, the nomogram outperformed the clinicopathological features model (P＜0.05). In addition, the diagnostic performance of the nomogram was better than that of the four single-modality radiomics models in the training cohort (P＜0.05) and was better than that of DCE-2 and ADC models in the validation cohort (P＜0.05). Decision curve analysis indicated that the value of individualized prediction models was higher than clinical and pathological prediction models in clinical practice. The calibration curve showed that the multimodal radiomics model had a high consistency with the actual results in predicting HER-2 expression. Conclusions: T2WI, ADC and early-delayed phase DCE-MRI imaging histology models for HER-2 expression status in breast cancer are expected to provide a non-invasive virtual pathological basis for decision-making on preoperative neoadjuvant regimens in breast cancer.

[The method of determination for 2, 3-Butanedione in the air of workplace by high performance liquid chromatography with derivatization].

Objective: To establish a method for the determination of 2, 3-Butanedione (BUT) in the air of workplace, which including the process of collection by absorption in phosphoric acid aqueous solution and the process of analysis and detection by high performance liquid chromatography with derivatization. Methods: In October 2022, a porous glass plate absorption tube containing 10 ml of 0.01% phosphoric acid solution was used to collect BUT in the air of the workplace at a flow rate of 0.2 L/min. The absorption solution was derived by 2, 4-dinitrophenylhydrazine for 75 min and separated on a SB-C18 column (250 mm×4.6 mm, 5 µm) . At the column temperature of 30 ℃, the mixture of acetonitrile-water (V∶V, 1∶1) was eluted at the flow rate of 1.0 ml/min. It was detected by UV detector (λ=365 nm) , qualitatived by retention time and quantitatived by external standard. Results: It showed that BUT in phosphoric acid aqueous solution could be stored for at least 7 d at 4 ℃. There was a linear relationship within the determination range of 0.05-6.00 µg/ml, the linear regression equation was y=89.610x+0.133, r=0.9999. The sampling absorption efficiencies were 98.33%-100.00%, the detection limit of the method was 0.005 µg/ml, the minimum detection concentration was 0.016 mg/m(3) (based on V(0)=3.0 L) . The recovery rates were 95.96%-102.44%, the intra batch precision were 4.36%-7.78%, and the inter batch precision were 4.96%-6.06%. Conclusion: The method has the advantages of simple operation, high sensitivity and good accuracy. It can prevent the loss and degradation of BUT. It can be used for the determination of BUT in the air of workplace.

Evaluation of restriction and Cas endonuclease kinetics using matrix-insensitive magnetic biosensors.

The enzymatic actions of endonucleases in vivo can be altered due to bound substrates and differences in local environments, including enzyme concentration, pH, salinity, ionic strength, and temperature. Thus, accurate estimation of enzymatic reactions in vivo using matrix-dependent methods in solution can be challenging. Here, we report a matrix-insensitive magnetic biosensing platform that enables the measurement of endonuclease activity under different conditions with varying pH, salinity, ionic strength, and temperature. Using biosensor arrays and orthogonal pairs of oligonucleotides, we quantitatively characterized the enzymatic activity of EcoRI under different buffer conditions and in the presence of inhibitors. To mimic a more physiological environment, we monitored the sequence-dependent star activity of EcoRI under unconventional conditions. Furthermore, enzymatic activity was measured in cell culture media, saliva, and serum. Last, we estimated the effective cleavage rates of Cas12a on anchored single-strand DNAs using this platform, which more closely resembles in vivo settings. This platform will facilitate precise characterization of restriction and Cas endonucleases under various conditions.

Intraosseous schwannoma of the mandible: new case series, literature update, and proposal of a classification.

Intraosseous schwannoma of the mandible is rare, with diagnostic and therapeutic challenges. The aims of this study were to report new cases of intraosseous schwannoma of the mandible and to propose a clinical classification, providing suggestions for treatment methods. The cases of 13 patients treated at the authors' hospital and 86 cases reported previously in the literature were reviewed. The most common clinical feature was facial swelling (60/93). The rate of cortical thinning or expansion was 44.8% (43/96); widening of the inferior alveolar nerve canal on radiographs was observed in 15 patients.

Effects of personalized oral exercises on swallowing function among patients with oral cancer after free flap transplantation: a cluster randomized controlled trial.

Dysphagia is a common complication in patients with oral cancer who have undergone free flap transplantation. The aim of this cluster randomized controlled trial was to evaluate the effect of personalized oral exercises on swallowing function in this group of patients. Eligible patients were randomly assigned to the intervention (n = 34) or control (n = 34) group. Intervention group patients received personalized oral exercises starting on day 6 after surgery. Swallowing function was evaluated on days 6 and 15, and at 1 month postoperative using the Mann Assessment of Swallowing Ability-Oral Cancer tool (MASA-OC). On day 15 and at 1 month after surgery, the total MASA-OC score (P = 0.003, P < 0.001) and the mouth opening (P = 0.001, P < 0.001) and lip seal (both P < 0.001) item scores showed a significantly greater improvement in the intervention group than in the control group. Moreover, the changes in salivation (P < 0.001) and tongue movement (P = 0.025) scores at 1 month after surgery were significantly greater in the intervention group than in the control group. There was no significant difference between the groups in the change in tongue strength scores on day 15 or at 1 month postoperative (P = 0.476, P = 0.223). Personalized oral exercises can improve swallowing function in patients with oral cancer after free flap transplantation.

Secondary ear reconstruction based on the Nagata method after unsatisfactory microtia surgery outcomes.

BACKGROUND: Follow-up studies on auricular reconstruction procedures have reported postoperative complications; some of which can only be reversed with revision surgery. This study aims to provide a feasible surgical strategy based on the Nagata method for patients requiring secondary revision and verify mid-term aesthetic outcomes. METHODS: Secondary auricular reconstructions based on the Nagata method were performed on seven patients seeking secondary revision between 2017 and 2021. Scores of a five-point Likert scale and artificial intelligence ratings based on convolutional nerve networks were used as outcome measures. RESULTS: Five patients underwent complete two-stage ear reconstruction, and the other two patients underwent the first-stage microtia procedure only. Few complications were observed, except in Case 4; this patient required an additional minor surgery after frame exposure 6 weeks after the first-stage procedure. All revised ears showed clear anatomical structures, and all patients were satisfied with the aesthetic results. Statistical analysis showed a significant increase in postoperative versus preoperative scores by convolutional neural network models (p < 0.05). Cases 5 and 6, which involved projection surgeries only, had decreased artificial intelligence appearance scores postoperatively. CONCLUSION: After adequate preoperative evaluation, secondary auricle reconstruction based on the Nagata method can achieve reliable aesthetic outcomes with few complications. CLINICAL TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov ID: NCT05604456.

Real-time temperature correction for magnetoresistive biosensors integrated with temperature modulator.

Magnetoresistance-based biosensors utilize changes in electrical resistance upon varying magnetic fields to measure biological molecules or events involved with magnetic tags. However, electrical resistance fluctuates with temperature. To decouple unwanted temperature-dependent signals from the signal of interest, various methods have been proposed to correct signals from magnetoresistance-based biosensors. Yet, there is still a need for a temperature correction method capable of instantaneously correcting signals from all sensors in an array, as multiple biomarkers need to be detected simultaneously with a group of sensors in a central laboratory or point-of-care setting. Here we report a giant magnetoresistive biosensor system that enables real-time temperature correction for individual sensors using temperature correction coefficients obtained through a temperature sweep generated by an integrated temperature modulator. The algorithm with individual temperature correction coefficients obviously outperformed that using the average temperature correction coefficient. Further, temperature regulation did not eliminate temperature-dependent signals completely. To demonstrate that the method can be used in biomedical applications where large temperature variations are involved, binding kinetics experiments and melting curve analysis were conducted with the temperature correction method. The method successfully removed all temperature-dependent artifacts and thus produced more precise kinetic parameters and melting temperatures of DNA hybrids.

[Application of methylene blue near-infrared fluorescence imaging for oral sentinel lymph node mapping in rats].

OBJECTIVE: To explore the concentration range and penetration depth of methylene blue near-infrared fluorescence imaging, and to clarify the role of methylene blue in oral lymphatic drainage and sentinel lymph node localization, so as to lay a foundation for the potential research and application of sentinel lymph node in oral cancer. METHODS: 10% (mass fraction) methylene blue injection was diluted into 29 different concentrations with 0.9% (mass fraction) normal saline, and the concentration range of methylene blue near-infrared fluorescence imaging was determined by near-infrared fluorescence imager. The maximum penetration depth of methylene blue near-infrared fluorescence was determined by covering pigskin with different thicknesses (1, 2, 3, 4 and 5 mm) in methylene blue solution. 0.2 mL methylene blue solution was injected into the submucosal 0.5 cm at the lateral margin of tongue on one side of the rats. The near-infrared fluorescence imager was used for continuously monitoring for 3 hours. The first near-infrared fluorescence hotspot was identified as sentinel lymph node and labeled by percutaneous observation. The rats were then sacrificed and dissected in the head and neck. Near-infrared fluorescence imaging was performed again to observe whether the fluorescent tissue was consistent with the labeled fluorescent hotspot in vitro, and the presence of lymphoid tissue was confirmed by pathological examination after resection. RESULTS: Except that no fluorescence signals were detected in the blank control groups, the fluorescence intensity of methylene blue increased first and then decreased with its solution concentration decreased. When the concentration of methylene blue was diluted to the picomole level, the fluorescence signal could still be detected. The maximum penetration depth of methylene blue fluorescence was 4 mm. Methylene blue near-infrared fluorescence could be localized in oral lymphatic drainage and sentinel lymph node. The fluorescence was sustained for more than 3 hours after methylene blue injection. Methylene blue solution concentrations of 3.34 mmol/L, 6.68 mmol/L, 13.37 mmol/L and 26.74 mmol/L were selected in the rats to map sentinel lymph node by near-infrared fluorescence. CONCLUSION: Methylene blue near-infrared fluorescence has a certain penetrating ability and can transcuta-neously map the sentinel lymph node and their associated lymphatic vessels in rats, which is expected to be further applied in the study of sentinel lymph node in oral cancer.

[Application value of whole exon sequencing and immune related indicators in the precision treatment of oral squamous cell carcinoma].

OBJECTIVE: To explore the significance and feasibility of whole exon sequencing and immune related indexes in personalized precision treatment of oral squamous cell carcinoma (OSCC). METHODS: We retrospectively screened the patients who underwent surgery for oral cancer in Peking University Hospital of Stomatology and underwent genetic and immune biomarkers tests between January 2021 and June 2022. Combined with the clinicopathological characteristics of patients, potential targeted drugs and immunotherapy drugs were screened to evaluate the possibility of gene testing benefiting OSCC. The main evaluation indicators included the number of gene mutations, combined positive score (CPS), tumor mutation burden (TMB), microsatellite sequence status and human leukocyte antigen B (HLA-B) locus. Excel was used for statistical analysis. RESULTS: A total of 10 patients were enrolled and 9 were included in this study, including 6 males and 3 females, with an average age of (55.44±9.59) years. The tumor location was buccal (5 cases), tongue (3 cases) and gingival (1 case). The results of genetic testing showed that 3 (33.3%) patients had no gene mutations in the tumor tissue, 5 (55.6%) patients had unique TP53 gene mutations, and 1 (11.1%) patient had TP53 and CHEK1 mutations. However, no drugs were available for targeted therapy of the mutated genes. The genetic tumor gene testing results showed that no genetic tumor gene was found in all the patients, suggesting that OSCC had a low possibi-lity of hereditary tumor. In terms of immune efficacy related markers, CPS test results showed that 8 patients had CPS≥1. TMB detection results showed that the median value of TMB value was 0.72 mutations/Mb, and the range was 0 to 4.32 mutations/Mb. The negative and positive control results of microsatellite sequence status were consistent, indicating that all the tumor tissues detected were microsatellite stability. The results of HLA-B detection showed that only one patient had B62 gene mutation, suggesting that the B44 and B62 related genotypes of HLA-B in OSCC tissue samples were low. CONCLUSION: The present results do not support the wide application and promotion of genetic testing and immune related indexes in OSCC.

Field-free spin-orbit torque switching assisted by in-plane unconventional spin torque in ultrathin [Pt/Co]N.

Electrical manipulation of magnetization without an external magnetic field is critical for the development of advanced non-volatile magnetic-memory technology that can achieve high memory density and low energy consumption. Several recent studies have revealed efficient out-of-plane spin-orbit torques (SOTs) in a variety of materials for field-free type-z SOT switching. Here, we report on the corresponding type-x configuration, showing significant in-plane unconventional spin polarizations from sputtered ultrathin [Pt/Co]N, which are either highly textured on single crystalline MgO substrates or randomly textured on SiO2 coated Si substrates. The unconventional spin currents generated in the low-dimensional Co films result from the strong orbital magnetic moment, which has been observed by X-ray magnetic circular dichroism (XMCD) measurement. The x-polarized spin torque efficiency reaches up to -0.083 and favors complete field-free switching of CoFeB magnetized along the in-plane charge current direction. Micromagnetic simulations additionally demonstrate its lower switching current than type-y switching, especially in narrow current pulses. Our work provides additional pathways for electrical manipulation of spintronic devices in the pursuit of high-speed, high-density, and low-energy non-volatile memory.

Rapid, Point-of-Care Host-Based Gene Expression Diagnostics Using Giant Magnetoresistive Biosensors.

Host-based gene expression analysis is a promising tool for a broad range of clinical applications, including rapid infectious disease diagnostics and real-time disease monitoring. However, the complex instrumentation requirements and slow turnaround-times associated with traditional gene expression analysis methods have hampered their widespread adoption at the point-of-care (POC). To overcome these challenges, we have developed an automated and portable platform that utilizes polymerase chain reaction (PCR) and giant magnetoresistive (GMR) biosensors to perform rapid multiplexed, targeted gene expression analysis at the POC. As proof-of-concept, we utilized our platform to amplify and measure the expression of four genes (HERC5, HERC6, IFI27, and IFIH1) that were previously shown to be upregulated in hosts infected with influenza viruses. The compact instrument conducted highly automated PCR amplification and GMR detection to measure the expression of the four genes in multiplex, then utilized Bluetooth communication to relay results to users on a smartphone application. To validate the platform, we tested 20 cDNA samples from symptomatic patients that had been previously diagnosed as either influenza-positive or influenza-negative using a RT-PCR virology panel. A non-parametric Mann-Whitney test revealed that day 0 (day of symptom onset) gene expression was significantly different between the two groups (p < 0.0001, n = 20). Hence, we preliminarily demonstrated that our platform could accurately discriminate between symptomatic influenza and non-influenza populations based on host gene expression in ∼30 min. This study not only establishes the potential clinical utility of our proposed assay and device for influenza diagnostics but it also paves the way for broadscale and decentralized implementation of host-based gene expression diagnostics at the POC.

A magnetic hydrogel for the efficient retrieval of kidney stone fragments during ureteroscopy.

Only 60-75% of conventional kidney stone surgeries achieve complete stone-free status. Up to 30% of patients with residual fragments <2 mm in size experience subsequent stone-related complications. Here we demonstrate a stone retrieval technology in which fragments are rendered magnetizable with a magnetic hydrogel so that they can be easily retrieved with a simple magnetic tool. The magnetic hydrogel facilitates robust in vitro capture of stone fragments of clinically relevant sizes and compositions. The hydrogel components exhibit no cytotoxicity in cell culture and only superficial effects on ex vivo human urothelium and in vivo mouse bladders. Furthermore, the hydrogel demonstrates antimicrobial activity against common uropathogens on par with that of common antibiotics. By enabling the efficient retrieval of kidney stone fragments, our method can lead to improved stone-free rates and patient outcomes.

Observation of anti-damping spin-orbit torques generated by in-plane and out-of-plane spin polarizations in MnPd3.

Large spin-orbit torques (SOTs) generated by topological materials and heavy metals interfaced with ferromagnets are promising for next-generation magnetic memory and logic devices. SOTs generated from y spin originating from spin Hall and Edelstein effects can realize field-free magnetization switching only when the magnetization and spin are collinear. Here we circumvent the above limitation by utilizing unconventional spins generated in a MnPd3 thin film grown on an oxidized silicon substrate. We observe conventional SOT due to y spin, and out-of-plane and in-plane anti-damping-like torques originated from z spin and x spin, respectively, in MnPd3/CoFeB heterostructures. Notably, we have demonstrated complete field-free switching of perpendicular cobalt via out-of-plane anti-damping-like SOT. Density functional theory calculations show that the observed unconventional torques are due to the low symmetry of the (114)-oriented MnPd3 films. Altogether our results provide a path toward realization of a practical spin channel in ultrafast magnetic memory and logic devices.

Longitudinal analysis of anti-SARS-CoV-2 neutralizing antibody (NAb) titers in vaccinees using a novel giant magnetoresistive (GMR) assay.

The COVID-19 pandemic has highlighted the need to monitor important correlates of immunity on a population-wide level. To this end, we have developed a competitive assay to assess neutralizing antibody (NAb) titer on the giant magnetoresistive (GMR) biosensor platform. We compared the clinical performance of our biosensor with established techniques such as Ortho's VITROS Anti-SARS-CoV-2 IgG Quantitative Antibody test. Results obtained between the VITROS test and the GMR assay showed correlation (r = -0.93). We then validated the assay with patient plasma samples that had been tested using focus reduction neutralization testing (FRNT). The results obtained from our GMR assay exhibit a previously identified trend of increased NAb titers 2 weeks post-vaccination. We further evaluated NAb titers 6 months post-vaccination and observed waning neutralizing antibody titers over that time in vaccinated patients. In addition, we calibrated our assay to an arbitrary unit (IU/mL) using World Health Organization (WHO) reference plasma provided by the National Institute of Biological Standards and Control (NIBSC). Our biosensor provides highly specific and sensitive results in serum and plasma with analytical, clinical, and point-of-care (POC) applications due to quick turnaround times on samples and the cost-effectiveness of the platform.

Point-of-Care Testing of Enzyme Polymorphisms for Predicting Hypnotizability and Postoperative Pain.

Hypnotizability is a stable trait that moderates the benefit of hypnosis for treating pain, but limited availability of hypnotizability testing deters widespread use of hypnosis. Inexpensive genotyping of four single-nucleotide polymorphisms in the catechol-o-methyltransferase (COMT) gene was performed using giant magnetoresistive biosensors to determine if hypnotizable individuals can be identified for targeted hypnosis referrals. For individuals with the proposed optimal COMT diplotypes, 89.5% score highly on the Hypnotic Induction Profile (odds ratio, 6.12; 95% CI, 1.26-28.75), which identified 40.5% of the treatable population. Mean hypnotizability scores of the optimal group were significantly higher than the total population (P = 0.015; effect size = 0.60), an effect that was present in women (P = 0.0015; effect size = 0.83), but not in men (P = 0.28). In an exploratory cohort, optimal individuals also reported significantly higher postoperative pain scores (P = 0.00030; effect size = 1.93), indicating a greater need for treatment.

Accurate occlusion-driven maxillary reconstruction with deep circumflex iliac artery flap using computer-assisted techniques and intraoral anastomosis: a case series.

The aim of this study was to evaluate the feasibility and accuracy of occlusion-driven maxillary reconstruction with the deep circumflex iliac artery (DCIA) flap, using computer-assisted design and manufacturing (CAD/CAM) technology and intraoral anastomosis. The data of 11 patients who underwent occlusion-driven maxillary reconstruction with this method between December 2018 and December 2020 in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology were reviewed retrospectively. Postoperative complications and functional and aesthetic outcomes were recorded. The accuracy of the postoperative restoration was assessed using Geomagic Control 2014. Reconstruction was successful in nine patients; all were satisfied with their aesthetic and functional outcomes. One patient underwent extraoral anastomosis after failure of intraoral anastomosis. In another patient, the DCIA flap had to be removed after the operation because of flap failure. Among the 10 patients with DCIA flap success, colour map analysis showed a mean deviation of 0.40 ± 0.08 mm between the preoperative and postoperative craniomaxillary models. Thus, occlusion-driven maxillary reconstruction with the DCIA flap, using CAD/CAM technology and intraoral anastomosis, appears to be a feasible and accurate method for the repair of maxillary defects.

Bone resorption after maxillary reconstruction with the vascularized free iliac flap.

The aim of this study was to evaluate the resorption of the iliac bone after maxillary reconstruction with a vascularized free iliac flap. Twenty-seven patients with maxillary defects who underwent maxillary reconstruction with the vascularized free iliac flap between January 2017 and January 2021 were included. Computed tomography (CT) images taken at 1 week, approximately 6 months, and 1 year after the surgery were used for evaluation. The total iliac bone thickness and height, cortical bone thickness, and cancellous bone density were measured in the CT images. Compared with 1 week after the surgery, the total thickness and height of the iliac bone were reduced significantly 1 year after the surgery, and the cortical bone thickness and cancellous bone density were reduced significantly at 6 months and 1 year after the surgery. Compared with 6 months after the surgery, cancellous bone density was reduced significantly 1 year after the surgery. In conclusion, during the first year after maxillary reconstruction with a vascularized free iliac flap, there was significant resorption of iliac bone, including the total iliac bone thickness and height, the cortical bone thickness, and the cancellous bone density.

Development and Validation of a Risk Assessment Model for Pulmonary Nodules Using Plasma Proteins and Clinical Factors.

BACKGROUND: Deficiencies in risk assessment for patients with pulmonary nodules (PNs) contribute to unnecessary invasive testing and delays in diagnosis. RESEARCH QUESTION: What is the accuracy of a novel PN risk model that includes plasma proteins and clinical factors? How does the accuracy compare with that of an established risk model? STUDY DESIGN AND METHODS: Based on technology using magnetic nanosensors, assays were developed with seven plasma proteins. In a training cohort (n = 429), machine learning approaches were used to identify an optimal algorithm that subsequently was evaluated in a validation cohort (n = 489), and its performance was compared with the Mayo Clinic model. RESULTS: In the training set, we identified a support vector machine algorithm that included the seven plasma proteins and six clinical factors that demonstrated an area under the receiver operating characteristic curve of 0.87 and met other selection criteria. The resulting risk reclassification model (RRM) was used to recategorize patients with a pretest risk of between 10% and 84%, and its performance was assessed across five risk strata (low, ≤ 10%; moderate, 10%-34%; intermediate, 35%-70%; high, 71%-84%; very high, > 85%). Stratification by the RRM decreased the proportion of intermediate-risk patients from 26.7% to 10.8% (P < .001) and increased the low-risk and high-risk strata from 16.8% to 21.9% (P < .001) and from 3.7% to 12.1% (P < .001), respectively. Among patients classified as low risk by the RRM and Mayo Clinic model, the corresponding true-negative to false-negative ratios were 16.8 and 19.5, respectively. Among patients classified as very high risk by the RRM and Mayo Clinic model, the corresponding true-positive to false-positive ratios were 28.5 and 17.0, respectively. Compared with the Mayo Clinic model, the RRM provided higher specificity at the low-risk threshold and higher sensitivity at the very high-risk threshold. INTERPRETATION: The RRM accurately reclassified some patients into low-risk and very high-risk categories, suggesting the potential to improve PN risk assessment.

[Role of hyperglycemia-induced 5-hydroxytryptamine degradation of hepatic stellate cells in hepatic inflammation and fibrosis induced by type 2 diabetes mellitus].

OBJECTIVE: To explore the role of 5-hydroxytryptamine (5-HT) in type 2 diabetes mellitus (T2DM)-related hepatic inflammation and fibrosis. METHODS: Male C57BL/6J mice were used to establish T2DM model by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. Then, the mice with hyperglycemia were still fed with high-fat diet for nine weeks, and treated with or without 5-HT2A receptor (5-HT2AR) antagonist sarpogrelate hydrochloride (SH) and 5-HT synthesis inhibitor carbidopa (CDP) (alone or in combination). To observe the role of 5-HT in the myofibroblastization of hepa-tic stellate cells (HSCs), human HSCs LX-2 were exposed to high glucose, and were treated with or without SH, CDP or monoamine oxidase A (MAO-A) inhibitor clorgiline (CGL). Hematoxylin & eosin and Masson staining were used to detect the pathological lesions of liver tissue section, immunohistochemistry and Western blot were used to analyze protein expression, biochemical indicators were measured by ELISA or enzyme kits, and levels of intracellular reactive oxygen species (ROS) were detected by fluorescent probe. RESULTS: There were up-regulated expressions of 5-HT2AR, 5-HT synthases and MAO-A, and elevated levels of 5-HT in the liver of the T2DM mice. In addition to reduction of the hepatic 5-HT levels and MAO-A expression, treatment with SH and CDP could effectively ameliorate liver lesions in the T2DM mice, both of which could ameliorate hepatic injury and steatosis, significantly inhibit the increase of hepatic ROS (H2O2) levels to alleviate oxidative stress, and markedly suppress the production of transforming growth factor ß1 (TGF-ß1) and the development of inflammation and fibrosis in liver. More importantly, there was a synergistic effect between SH and CDP. Studies on LX-2 cells showed that high glucose could induce up-regulation of 5-HT2AR, 5-HT synthases and MAO-A expression, increase intracellular 5-HT level, increase the production of ROS, and lead to myofibroblastization of LX-2, resulting in the increase of TGF-ß1 synthesis and production of inflammatory and fibrosis factors. The effects of high glucose could be significantly inhibited by 5-HT2AR antagonist SH or be markedly abolished by mitochondrial 5-HT degradation inhibitor CGL. In addition, SH significantly suppressed the up-regulation of 5-HT synthases and MAO-A induced by high glucose in LX-2. CONCLUSION: Hyperglycemia-induced myofibroblastization and TGF-ß1 production of HSCs, which leads to hepatic inflammation and fibrosis in T2DM mice, is probably due to the up-regulation of 5-HT2AR expression and increase of 5-HT synthesis and degradation, resulting in the increase of ROS production in mitochondria. Among them, 5-HT2AR is involved in the regulation of 5-HT synthases and MAO-A expression.