Circulating Concentrations of advanced Glycation end Products, Carboxymethyl Lysine and Methylglyoxal are Associated With Renal Function in Individuals With Diabetes.

OBJECTIVE: Diabetic kidney disease (DKD) is one of the most severe chronic complications of diabetes and is associated with higher level of advanced glycation end products (AGEs). The aim of this study was to investigate the diagnostic potential of combined detection of multiple serum AGEs in diagnosing DKD. METHODS: Serum AGEs, Nε-(carboxymethyl) lysine (CML), Nε-(carboxyethyl) lysine, and methylglyoxal (MGO) levels were measured by enzyme-linked immunosorbent assay in 176 individuals with type 2 diabetes. Participants were classified into normoalbuminuria, microalbuminuria, and macroalbuminuria group according to their urinary albumin to creatinine ratio (UACR). RESULTS: Higher serum AGEs levels were found to be positively correlated with U-Alb, UACR, and blood urea nitrogen in the study of 176 individuals with type 2 diabetes. CML and MGO levels were positively correlated with U-Alb, UACR, blood urea nitrogen, Scr, and uric acid, and negatively correlated with estimated glomerular filtration rate (P < .05). Multivariate logistic regression analysis showed that elevated levels of AGEs, CML, and MGO were independent risk factors for the progression of DKD (odds ratio = 1.861, 1.016, 7.607, P < .01). The sensitivity, specificity, and area under receiver operating characteristic curve of combined detection of AGEs, MGO, and CML were higher than those of three individual detections (area under the curve = 0.952, 0.772, 0.868, 0905, respectively, P < .05). CONCLUSION: The combined detection of AGEs, CML, and MGO may improve the reliability of early diagnosis of DKD.

Association Between Immunoglobulin G4-Related Ophthalmic Disease and Nonlymphoid Malignancy Case Series and Comprehensive Review of the Literature.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) and immunoglobulin G4-related ophthalmic disease (IgG4-ROD) complicated with nonlymphoid malignancy (NL-malignancy) are rare. No exact relationship between IgG4-RD and NL-malignancies has been established yet, and there have been few reports of different types of IgG4-ROD and related malignancies. METHODS: We retrospectively reviewed medical records of patients diagnosed with IgG4-RD and NL-malignancy, whichever occurred first, from January 2015 to March 2021. In addition, the literature on the relationship between IgG4-ROD and NL-malignancy was reviewed. RESULTS: There were 115 patients diagnosed with IgG4-RD, and 10 patients were enrolled in the study with NL-malignancy. Three patients were diagnosed with IgG4-ROD. One patient reported a previous history of cancer, and the other 2 patients developed cancer at or after the diagnosis of IgG4-RD. The 3 patients' cancers were located in the lung, gastrointestinal tract, and thyroid. CONCLUSIONS: There may be potential malignancy occurrence during follow-up of IgG4-RD patients, especially among elderly patients. In addition, IgG4-RD could be a paraneoplastic syndrome at or before the diagnosis of malignancy.

Nutritional Value and Structure Characterization of Protein Components of Corylus mandshurica Maxim.

Alternative protein sources for the human diet may help overcome the growing food pressure. Plants with abundant resources and high protein content are potential sources. In this article, graded proteins and isolated proteins from Corylus mandshurica Maxim kernels were extracted by the Osborne procedure and the alkali-solution and acid-isolation method, respectively, and the contents of the five proteins, and the differences in nutritional value and structural properties of the main proteins, were investigated. Amino acid analysis revealed that the total essential amino acids in the five proteins ranged from 249.58 to 324.52 mg/g. The essential amino acid profiles in the proteins were similar to those of FAO/WHO except for the alcohol-soluble protein. The essential amino acid indices ranged from 58.59 to 72.19 and the biological values ranged from 52.16 to 66.99, and the highest nutritional indices were found for the isolate and water-soluble protein, which were 41.68 and 55.78, respectively. The molecular weight pattern distribution of the protein isolates of the Corylus mandshurica Maxim kernel was more similar to that of the water-soluble proteins by SDS-PAGE. The ß-sheet and α-helix were the main secondary structures in the two protein fractions. The fluorescence spectra showed that the maximum fluorescence intensity of the two proteins and their λmax were also somewhat different. From the perspective of microscopic morphology, the two proteins are mainly compact and irregular lamellar structures, but the surface of the water-soluble protein is more flat and regular. Both proteins have good solubility, and the water-soluble protein has higher solubility. In general, the protein isolates of the Corylus mandshurica Maxim kernel and the water-soluble protein showed their potential as plant protein resources.

Formation and In Vitro Simulated Digestion Study of Gelatinized Korean Pine Seed Oil Encapsulated with Calcified Wax.

Natural waxes have demonstrated exceptional potential as oil gels for saturated and trans fatty acids, but their application has been limited by issues such as temperature sensitivity, lack of stability and durability, and compatibility. In this study, three types of wax (Beeswax (BW), Rice bran wax (RBW), and Carnauba wax (CW)) were combined with calcium hydroxide to produce calcified wax. The calcified Korean pine seed oil gel obtained by heating and stirring with Korean pine seed oil is responsive to temperature and has environmental adaptability. The effects of critical gel concentration, temperature regulation, texture properties, microstructure, oil-holding capacity, and FT-IR on the quality parameters of oil gel were investigated. Additionally, an in vitro digestion model was developed to comprehend the decomposition rate of fat during gel structure digestion and transportation. The results demonstrated a close correlation between the critical gelation concentration and calcium ion content. Furthermore, after calcification, the hardness followed the order BW > CW > RBW. Moreover, there was an approximate 10 °C increase in wax melting point. Conversely, BW:Ca exhibited the lowest oil leakage. The microstructures revealed that the oil gels formed post-wax calcification exhibited similar fractal dimension (Db) values (<7 µm), and the intermolecular forces were characterized by van der Waals forces, which were consistent with those observed in the non-calcified group. In conjunction with the vitro digestion simulation, our findings demonstrated that RBW and CW oil gels gradually released 20%, 35%, and 35% of free fatty acids (FFA) within the initial 30 min of intestinal digestion. Importantly, the FFA release rate was significantly attenuated, thereby providing a foundation for developing wax-based gel processed foods that facilitate gentle energy release benefits for healthy weight management.

A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IA1 with LVSI, IA2): study protocol of the LAUNCH 1 trial.

BACKGROUND: A retrospective study and a randomized controlled trial published in a high quality journal in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology, therefore this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stage IA1 with LVSI, IA2) patient survival under stringent operation standards and consistent tumor-free technique. This paper reports the rationale, design, and implementation of the trial. METHODS: This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 690 patients with stage IA1 (with intravascular), and IA2 cervical cancer will be enrolled over a period of three years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed-up for at least five years. The primary endpoint will be 5-year progression-free survival. Secondary endpoints will include 5-year overall survival rates, recurrence rates, operation time, intraoperative blood loss, surgery-related complications, and quality of life. DISCUSSION: The results of the trial will provide valuable evidence for guiding clinical decision of choosing appropriate treatment strategies for stage IA1 (LVSI) and stage IA2 cervical cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04934982 , Registered on 22 June 2021).

Association of platelet count with mortality in patients with infectious diseases in intensive care unit: a multicenter retrospective cohort study.

Platelets play important roles in thrombosis, hemostasis, inflammation, and infection. We aimed to evaluate the association between platelet count and its variation trend and prognosis of patient with infectious diseases in intensive care units (ICUs). This retrospective cohort study extracted 4,251 critically ill adult patients with infectious diseases from the eICU Collaborative Research Database, whose platelet counts were measured daily during the first 7 days after admission. In the survivors, platelet counts decreased in the first days after admission, reached a nadir on day 3, and then returned and continued to rise above the admission value. In non-survivors, the platelet counts decreased after admission, without a subsequent upturn. We defined three subgroups according to the nadir platelet counts within 7 days: ≤50, 50-130, and ≥130 × 109/L, corresponding to high, intermediate, and low ICU mortality. A decreased platelet count was associated with increased ICU mortality (intermediate vs. low: 1.676 [1.285-2.187]; high vs. low: 3.632 [2.611-5.052]). In conclusion, during the first 7 days, platelet counts decreased after ICU admission, while increased subsequently in the survivors but not in the non-survivors. ICU mortality risk increased as nadir platelet count decreased below 130 × 109/L, and further boosted when it reached below 50 × 109/L.

Calibration method of multi-projector display system with extra-large FOV and quantitative registration accuracy analysis.

The calibration of multi-projector display with extra-large field of view (FOV) and quantitative registration analysis for realizing perfect visual splicing is crucial and difficult. In this paper, we present a novel calibration method to realize the seamless splicing for a multi-projector display system with extra-large FOV. The display consists of 24 projectors, covering the range of 360 degrees in the longitude direction and 210 degrees in the latitude direction. A wide-angle camera fixed on a rotating optical system is used to scan the entire display scene and establish point-to-point correspondence between projector pixels and spatial points using the longitude and latitude information. Local longitude table and latitude table are established on the target of the wide-angle camera. A deterministic method is proposed to locate the North Pole of the display. The local tables corresponding to different camera views can be unified based on the image of the North Pole to form global longitude and latitude tables of arbitrary free-form surface. The mapping between the projector pixels and the camera pixels is established by inverse projection technique, and then each pixel of each projector can be appointed a pair of unique longitude and latitude values. A quantitative registration accuracy analysis method is proposed for multi-projector display system, in which, three-frequency temporal unwrapping method based on coded longitude and latitude values is applied to calculate the registration accuracy. Experiments prove that the registration error of the multi-projector system is less than 0.4 pixels.

High-speed 3D shape measurement using a rotary mechanical projector.

In this paper, a fast rotary mechanical projector (RMP) is designed and manufactured for high-speed 3D shape measurement. Compared with the common high-speed projectors, RMP has a good performance in high-speed projection, which can obtain high quality projected fringes with shorter camera exposure time by using the error diffusion binary coding method and chrome plating technology. The magnitude, acceptability of systemic projection error is analyzed and quantified in detail. For the quantified error, the probability distribution function (PDF) algorithm is introduced to correct the error. Corrected projection error is reduced to more than one third of the original error. Subsequently, a monocular measurement system composed of the RMP and a single camera is constructed. The combination of the RMP device and PDF algorithm ensure the accuracy of a corresponding 3D shape measurement system. Experiments have demonstrated that the proposed solution has a good performance for the 3D measurement of high-speed scenes.

Long-read genome sequencing identifies causal structural variation in a Mendelian disease.

PurposeCurrent clinical genomics assays primarily utilize short-read sequencing (SRS), but SRS has limited ability to evaluate repetitive regions and structural variants. Long-read sequencing (LRS) has complementary strengths, and we aimed to determine whether LRS could offer a means to identify overlooked genetic variation in patients undiagnosed by SRS.MethodsWe performed low-coverage genome LRS to identify structural variants in a patient who presented with multiple neoplasia and cardiac myxomata, in whom the results of targeted clinical testing and genome SRS were negative.ResultsThis LRS approach yielded 6,971 deletions and 6,821 insertions > 50 bp. Filtering for variants that are absent in an unrelated control and overlap a disease gene coding exon identified three deletions and three insertions. One of these, a heterozygous 2,184 bp deletion, overlaps the first coding exon of PRKAR1A, which is implicated in autosomal dominant Carney complex. RNA sequencing demonstrated decreased PRKAR1A expression. The deletion was classified as pathogenic based on guidelines for interpretation of sequence variants.ConclusionThis first successful application of genome LRS to identify a pathogenic variant in a patient suggests that LRS has significant potential for the identification of disease-causing structural variation. Larger studies will ultimately be required to evaluate the potential clinical utility of LRS.

Enhanced entomopathogenic nematode yield and fitness via addition of pulverized insect powder to solid media.

Beneficial nematodes are used as biological control agents. Low-cost mass production of entomopathogenic nematodes (EPNs) is an important prerequisite toward their successful commercialization. EPNs can be grown via in vivo methods or in sold or liquid fermentation. For solid and liquid approaches, media optimization is paramount to maximizing EPN yield and quality. In solid media, the authors investigated the effects of incorporating pulverized insect powder from larvae of three insects (Galleria mellonella, Tenebrio molitor, and Lucillia sericata) at three dose levels (1, 3, and 5%). The impact of insect powder was assessed on infective juvenile (IJ) yield in solid media. Additionally, IJs produced in solid culture were subsequently assessed for virulence, and progeny production in a target insect, Spodoptera litura. The dose level of larval powder had a significant effect on IJ yield in both trials, whereas insect type had significant effect on IJ yield in trial 1 but not in trial 2. The maximum solid culture yield was observed in T. molitor powder at the highest dose in both trials. Moreover, the time-to-death in S. litura was substantially shortened in trial 1 and in trial 2 when IJs from the T. molitor powder treatment were applied. There was no significant effect of combining two insect powders relative to addition of powder from a single insect species. These findings indicate that addition of insect powder to solid media leads to high mass production yields, and the fitness of the IJs produced (e.g., in virulence and reproductive capacity) can be enhanced as well.Beneficial nematodes are used as biological control agents. Low-cost mass production of entomopathogenic nematodes (EPNs) is an important prerequisite toward their successful commercialization. EPNs can be grown via in vivo methods or in sold or liquid fermentation. For solid and liquid approaches, media optimization is paramount to maximizing EPN yield and quality. In solid media, the authors investigated the effects of incorporating pulverized insect powder from larvae of three insects (Galleria mellonella, Tenebrio molitor, and Lucillia sericata) at three dose levels (1, 3, and 5%). The impact of insect powder was assessed on infective juvenile (IJ) yield in solid media. Additionally, IJs produced in solid culture were subsequently assessed for virulence, and progeny production in a target insect, Spodoptera litura. The dose level of larval powder had a significant effect on IJ yield in both trials, whereas insect type had significant effect on IJ yield in trial 1 but not in trial 2. The maximum solid culture yield was observed in T. molitor powder at the highest dose in both trials. Moreover, the time-to-death in S. litura was substantially shortened in trial 1 and in trial 2 when IJs from the T. molitor powder treatment were applied. There was no significant effect of combining two insect powders relative to addition of powder from a single insect species. These findings indicate that addition of insect powder to solid media leads to high mass production yields, and the fitness of the IJs produced (e.g., in virulence and reproductive capacity) can be enhanced as well.

Activation of the nuclear factor-κB pathway during postnatal lung inflammation preserves alveolarization by suppressing macrophage inflammatory protein-2.

A significant portion of lung development is completed postnatally during alveolarization, rendering the immature lung vulnerable to inflammatory stimuli that can disrupt lung structure and function. Although the NF-κB pathway has well-recognized pro-inflammatory functions, novel anti-inflammatory and developmental roles for NF-κB have recently been described. Thus, to determine how NF-κB modulates alveolarization during inflammation, we exposed postnatal day 6 mice to vehicle (PBS), systemic lipopolysaccharide (LPS), or the combination of LPS and the global NF-κB pathway inhibitor BAY 11-7082 (LPS + BAY). LPS impaired alveolarization, decreased lung cell proliferation, and reduced epithelial growth factor expression. BAY exaggerated these detrimental effects of LPS, further suppressing proliferation and disrupting pulmonary angiogenesis, an essential component of alveolarization. The more severe pathology induced by LPS + BAY was associated with marked increases in lung and plasma levels of macrophage inflammatory protein-2 (MIP-2). Experiments using primary neonatal pulmonary endothelial cells (PEC) demonstrated that MIP-2 directly impaired neonatal PEC migration in vitro; and neutralization of MIP-2 in vivo preserved lung cell proliferation and pulmonary angiogenesis and prevented the more severe alveolar disruption induced by the combined treatment of LPS + BAY. Taken together, these studies demonstrate a key anti-inflammatory function of the NF-κB pathway in the early alveolar lung that functions to mitigate the detrimental effects of inflammation on pulmonary angiogenesis and alveolarization. Furthermore, these data suggest that neutralization of MIP-2 may represent a novel therapeutic target that could be beneficial in preserving lung growth in premature infants exposed to inflammatory stress.

Prognostic value of lymph node ratio in survival of patients with locally advanced rectal cancer.

BACKGROUND: The lymph node ratio (LNR) has been shown to be an important prognostic factor in patients with gastric, breast, pancreatic and colorectal cancer. We investigated the prognostic impact of the LNR in addition to TNM classification in patients with locally advanced rectal cancer. METHODS: We retrospectively analyzed patients who underwent curative resection for locally advanced rectal cancer between July 2005 and December 2010. We determined the LNR cutoff value using a receiver operating characteristic curve. The Kaplan-Meier method was used to estimate survival curves, while Cox regression analyses were used to evaluate the relationship between LNR and survival. RESULTS: We included 180 patients aged 28-83 years with median follow-up of 41.8 months. The median number of lymph nodes examined and lymph nodes involved were 11.5 and 4, respectively, and the median LNR was 0.366. An LNR of 0.19 (19%) was the cutoff point to separate patients with regard to median overall survival. Median overall survival was 64.2 months for patients with an LNR of 0, 59.1 for an LNR of 0.19 or less and 37.6 for an LNR greater than 0.19 (p = 0.004). The median disease-free survival was 32.9 months for patients with an LNR of 0, 30.4 for an LNR of 0.19 or less and 17.8 for an LNR greater than 0.19 (p = 0.002). CONCLUSION: Our results suggest that LNR should be considered an additional prognostic factor in patients with locally advanced rectal cancer.

CONTEXTE: Il a été démontré que le ratio de ganglions lymphatiques positifs est un important facteur pronostique chez les patients atteints de cancer de l'estomac, de cancer du sein, de cancer du pancréas et de cancer colorectal. Nous avons étudié l'incidence pronostique de l'utilisation de ce ratio en plus de la classification TNM chez les patients présentant un cancer du rectum localement avancé. MÉTHODES: Nous avons analysé rétrospectivement des patients ayant subi une résection curative visant à traiter un cancer du rectum localement avancé entre juillet 2005 et décembre 2010. Nous avons déterminé la valeur seuil du ratio de ganglions lymphatiques positifs à l'aide d'une courbe caractéristique de la performance. La méthode de Kaplan-Meyer a été utilisée pour estimer les courbes de survie, tandis que le modèle de régression des hasards proportionnels de Cox a servi à évaluer la corrélation entre le ratio à l'étude et la survie. RÉSULTATS: Notre étude a porté sur 180 patients de 28 à 83 ans dont la durée médiane du suivi était de 41,8 mois. Les nombres médians de ganglions lymphatiques examinés et de ganglions lymphatiques positifs étaient de 11,5 et 4, respectivement, et le ratio médian de ganglions lymphatiques positifs était de 0,366. Nous avons utilisé une valeur seuil de 0,19 (19 %) pour séparer les patients en ce qui a trait à la survie globale médiane. Cette mesure était de 64,2 mois pour les patients présentant un ratio de 0, de 59,1 mois pour ceux présentant un ratio de 0,19 ou moins, et de 37,6 mois pour ceux dont le ratio était supérieur à 0,19 (p = 0,004). La survie sans récidive médiane était de 32,9 mois pour les patients présentant un ratio de 0, de 30,4 mois pour ceux présentant un ratio de 0,19 ou moins, et de 17,8 mois pour ceux dont le ratio était supérieur à 0,19 (p = 0,002). CONCLUSION: Nos résultats indiquent que le ratio de ganglions lymphatiques positifs devrait être envisagé comme facteur pronostique supplémentaire pour les patients atteints d'un cancer du rectum localement avancé.

YOLO-B:An infrared target detection algorithm based on bi-fusion and efficient decoupled.

The YOLO-B infrared target detection algorithm is proposed to address the problems of incomplete extraction of detailed features and missed and wrong detection of infrared targets by YOLOv5s. The algorithm improves the SPPF of YOLOv5s feature extraction network by proposing the CSPPF structure to increase the sensory field of the model. The Bifusion Neck structure is invoked to fuse the shallow location information with deep semantic information to enhance the feature extraction capability of the model. Taking fully into account the different information of concern for classification and localization, the efficient decoupled head is used as the prediction head of this algorithm, which reduces the latency while maintaining the accuracy. WIoUv3 loss is used as a bounding box regression loss function to reduce the harmful gradient generated by low-quality examples and reduce the competitiveness of high-quality anchor frames. Comparative experiments were conducted for each of the four improvement points, and the experimental results showed that each improvement point had the highest detection accuracy in the comparative experiments of the same category. All improvement points are fused in turn and ablation experiments are performed. The YOLO-B algorithm improves 1.9% in accuracy, 7.3% in recall, 3.8% in map_0.5, and 4.6% in map_0.5:0.95 compared to YOLOv5s. When compared with YOLOv7 and YOLOv8s, the proposed algorithm has better performance in terms of the number of parameters and detection accuracy.

Overexpression of SYNGAP1 suppresses the proliferation of rectal adenocarcinoma via Wnt/ß-Catenin signaling pathway.

Rectal adenocarcinoma (READ) is a common malignant tumor of the digestive tract. Growing studies have confirmed Ras GTPase-activating proteins are involved in the progression of several tumors. This study aimed to explore the expression and function of Ras GTPase-activating proteins in READ. In this study, we analyzed RNA sequencing data from 165 patients with READ and 789 normal tissue samples, identifying 5603 differentially expressed genes (DEGs), including 2937 upregulated genes and 2666 downregulated genes. Moreover, we also identified two dysregulated genes, RASA4 and SYNGAP1, among six Ras GTPase-activating proteins. High NF1 expression was associated with longer overall survival, while high SYNGAP1 expression showed a trend towards extended overall survival. Further analysis revealed the mutation frequency and copy number variations of Ras GTPase-activating proteins in various cancer samples. Additionally, DNA methylation analysis demonstrated a negative correlation between DNA methylation of Ras GTPase-activating proteins and their expression. Moreover, among Ras GTPase-activating proteins, we focused on SYNGAP1, and experimental validation confirmed that the overexpression of SYNGAP1 in READ significantly suppressed READ cell proliferation and increased apoptosis via regulating the Wnt/ß-Catenin signaling pathway. These findings underscored the potential significance of SYNGAP1 in READ and provide new insights for further research and treatment.

Multi-parametric Retinal Microvascular Functional Perfusion Imaging Based on Dynamic Fundus Fluorescence Angiography.

Retinal microvascular disease has caused serious visual impairment widely in the world, which can be hopefully prevented via early and precision microvascular hemodynamic diagnosis. Due to artifacts from choroidal microvessels and tiny movements, current fundus microvascular imaging techniques including fundus fluorescein angiography (FFA) precisely identify retinal microvascular microstructural damage and abnormal hemodynamic changes difficulty, especially in the early stage. Therefore, this study proposes an FFA-based multi-parametric retinal microvascular functional perfusion imaging (RM-FPI) scheme to assess the microstructural damage and quantify its hemodynamic distribution precisely. Herein, a spatiotemporal filter based on singular value decomposition combined with a lognormal fitting model was used to remove the above artifacts. Dynamic FFAs of patients (n = 7) were collected first. The retinal time fluorescence intensity curves were extracted and the corresponding perfusion parameters were estimated after decomposition filtering and model fitting. Compared with in vivo results without filtering and fitting, the signal-to-clutter ratio of retinal perfusion curves, average contrast, and resolution of RM-FPI were up to 7.32 ± 0.43 dB, 14.34 ± 0.24 dB, and 11.0 ± 2.0 µm, respectively. RM-FPI imaged retinal microvascular distribution and quantified its spatial hemodynamic changes, which further characterized the parabolic distribution of local blood flow within diameters ranging from 9 to 400 µm. Finally, RM-FPI was used to quantify, visualize, and diagnose the retinal hemodynamics of retinal vein occlusion from mild to severe. Therefore, this study provided a scheme for early and precision diagnosis of retinal microvascular disease, which might be beneficial in preventing its development.

Increased tumor-associated mast cells facilitate thyroid cancer progression by inhibiting CD8+ T cell function through galectin-9.

As an important component of solid tumors, mast cells show specific phenotypes in various tumor microenvironments. However, the precise mechanism of mast cell accumulation and the phenotypic features of thyroid cancer (TC) remain largely unknown. Here, we found that mast cells were obviously recruited to tumor tissue by TC-derived stem cell factor (SCF). With tumor progression, mast cell levels increased gradually. In addition, intratumoral mast cells expressed higher levels of the immunosuppressive molecule galectin-9, which effectively suppresses CD8+ T-cell antitumor immunity in vitro. Blocking galectin-9 on tumor-infiltrating mast cells reversed the immunosuppression of CD8+ T cells. In conclusion, our data elucidated novel protumorigenic and immunosuppressive roles of mast cells in TC. In addition, our results indicated that blocking mast cells may impede tumor progression and ameliorate the prognosis of TC patients.

Impacts of Plant-derived Secondary Metabolites for Improving Flora in Type 2 Diabetes.

BACKGROUND: Diabetes has become a problem that plagues public healthcare systems. Recent studies have shown that intestinal flora exerts positive therapeutic effects on metabolic diseases, and plant-derived secondary metabolites are safe, effective and easy to prepare and also have an impact on intestinal flora and diabetes; these drugs have rarely been reviewed before as a class of drugs for diabetes, especially focusing on the intestinal flora. Therefore, studying the relationship between plant-derived secondary metabolites and diabetes mellitus is crucial. OBJECTIVE: The objective of this study is to summarize and investigate the therapeutic mechanism of drugs extracted from natural plants effects on type 2 diabetes mellitus. METHODS: The relationship between flora and type 2 diabetes was investigated by reviewing the recent experimental literature, and the pathways available for natural plant-derived secondary metabolites in the treatment of type 2 diabetes were summarized. RESULTS: The therapeutic mechanisms of common plant-derived secondary metabolites for type 2 diabetes were summarized with a focus on the prebiotic efficacy of natural plant-derived secondary metabolites and the modulation of intestinal flora, and the mechanisms through which plantderived secondary metabolites treat type 2 diabetes via effects on intestinal flora are further reviewed. CONCLUSION: Common plant-derived secondary metabolites can play a role in regulating bacteria in the intestinal tract by enriching beneficial bacteria and removing harmful bacteria to achieve their therapeutic effect on type 2 diabetes. In addition, due to their excellent ability to regulate intestinal flora, plant-derived secondary metabolites may also have excellent efficacy in cancer and obesity, among other diseases.

Oral administration of kynurenic acid delays the onset of type 2 diabetes in Goto-Kakizaki rats.

Kynurenic acid (KYNA) is an endogenous catabolite of tryptophan that has been found to demonstrate neuroprotective properties in psychiatric disorders. Recently, accumulating data have suggested that KYNA may also play a significant role in various metabolic diseases by stimulating energy metabolism in adipose tissue and muscle. However, whether KYNA can serves as an anti-diabetes agent has yet to be studied. In this study, we investigated the potential anti-diabetic effects of administering KYNA orally through drinking water in pre-diabetic Goto-Kakizaki rats and examined how this treatment may influence energy metabolism regulation within the liver. We found that hyperglycemic Goto-Kakizaki rats showed lower plasmatic KYNA levels compared to normal rats. Oral administration of KYNA significantly delayed the onset of diabetes in Goto-Kakizaki rats compared to untreated animals. Moreover, we found that KYNA treatment significantly increased respiration exchange ratio and promoted the energy expenditure by stimulating the expression of uncoupling protein (UCP). We confirmed that KYNA stimulated the UCP expression in HepG2 cells and mouse hepatocytes at mRNA and protein levels. Our study reveals that KYNA could potentially act as an anti-diabetic agent and KYNA-induced UCP upregulation is closely associated with the regulation of energy metabolism. These results provide further evidence for the therapeutic potential of KYNA in diabetes.

Transcriptome and Pathway Analysis Reveals that Adipose-derived Stem Cells Target Inflammatory Factors and Delay the Progression of Diabetic Liver Disease.

BACKGROUND: Diabetic liver disease is one of the main complications that leads to the aggravation of diabetes, but it has not received sufficient attention. This study aimed to provide a better understanding of the altered molecular networks in in diabetic rats with liver damage after stem cell therapy. To a certain extent, our research would be instructive, since almost no studies of this kind have been performed on patients with diabetic liver disease after stem cell therapy. METHODS: Streptozotocin-induced diabetic rats were treated with adipose-derived stem cells. RNA-Seq analysis was performed on the liver tissues of these animals, and key pathway factors were further identified and validated. RESULTS: RNA-Seq analysis revealed numerous affected signaling pathways and functional categories. The results showed that the network of dual specificity phosphatase 1 (DUSP1), an oxidative stress-related gene, was prominently activated in the liver after stem cell therapy, and the enrichment of genes associated with liver damage, steatosis and fibrosis was also detected. The extracellular regulated protein kinase (ERK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway may be involved in this process by regulating the nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. CONCLUSIONS: These data provide novel insights into liver biology, suggest common alterations in the molecular networks during diabetic liver damage, and show the advantages of stem cell therapy, indicating its further application potential for early treatment of diabetic liver damage and delaying the progression of liver fibrosis in the later stage.

Influence of Appropriate Empirical Antibiotic Treatment on the Prognosis of ICU Patients with HAP Caused by Carbapenem-Resistant Gram-Negative Bacteria.

Purpose: In patients with carbapenem-resistant Gram-negative bacteria (CRGNB) infection, the impact of appropriate empirical antibiotic treatment (AEAT) initialized before culture results were available remains controversial. We aimed to investigate the effect of AEAT on the prognosis of critically ill patients with hospital-acquired pneumonia (HAP) caused by CRGNB. Patients and Methods: Patients with CRGNB-infected HAP and received empirical antibiotic treatment (EAT) for at least 3 days in the intensive care unit (ICU) of a tertiary teaching hospital in China from February 2017 to September 2021 were included in the retrospective cohort study. Patients were categorized into AEAT and inappropriate empirical antibiotic treatment (IEAT) groups based on whether they received EAT covering CRGNB. The associations of AEAT with ICU and 28-day mortality were assessed using multivariable logistic regression model. Results: A total of 94 patients were enrolled, including 29 patients in AEAT group and 65 patients in IEAT group. Patients in AEAT group had a higher Sequential Organ Failure Assessment (SOFA) score (P = 0.003), levels of procalcitonin (PCT) (P = 0.001), and lactic acid (LAC) (P = 0.026); while patients in the IEAT group had a higher platelet count (PLT) (P = 0.001). There was no significant difference in the length of ICU stay between the two groups (P = 0.051). Compared with IEAT, AEAT was associated with an increased risk of 28-day mortality in the univariable logistic regression model (OR: 2.618, 95% CI: 1.063-6.448). However, after adjusted for SOFA score, PLT, PCT, and LAC level, the association between AEAT and 28-day mortality diminished (OR: 1.028, 95% CI: 0.353-2.996). AEAT showed no significant association with ICU mortality in neither univariable (OR: 1.167, 95% CI: 0.433-3.142) nor multivariable (OR: 0.357, 95% CI: 0.097-1.320) models. Conclusion: AEAT showed no significant influence on ICU or 28-day mortality in critically ill patients with HAP caused by CRGNB infection.