Analysis of status and influencing factors of mental health in patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder with varied clinical courses and prognoses, not only did the patients suffer from physical impairment, but also various physical and psychiatric comorbidities. Growing evidence have suggested that mental disorders in SLE patients, can lead to various adverse consequences. AIM: To explored the features and influencing factors of mental health in patients with SLE and clarifying the correlations between mental health and personality characteristics and perceived social support. The results would provide a basis for psychological intervention in patients with SLE. METHODS: The clinical data of 168 patients with SLE admitted at the First Affiliated Hospital of Hainan Medical University between June 2020 and June 2022 were collected. Psychological assessment and correlation analysis were conducted using the Symptom Checklist-90 (SCL-90) and Perceived Social Support Scale, and the collected data were compared with the national norms in China. The relevant factors influencing mental health were identified by statistical analysis. A general information questionnaire, the Revised Life Orientation Test, and Short-Form 36-Item Health Survey were employed to assess optimism level and quality of life (QoL), respectively. RESULTS: Patients with SLE obtained higher scores for the somatization, depression, anxiety, and phobic anxiety subscales than national norms (P < 0.05). A correlation was identified between total social support and total SCL-90 score or each subscale (P < 0.05). The factors significantly affecting patients' mental health were hormone dosage and disease activity index (DAI) (P < 0.05). The average optimism score of patients with SLE was 14.36 ± 4.42, and 30 cases were in the middle and lower levels. A positive correlation was found between optimism level and QoL scores. CONCLUSION: Patients with SLE develop psychological disorders at varying degrees, which are significantly influenced by hormone dosage and DAI. Patients' mental health should be closely monitored during clinical diagnosis and treatment and provided adequate support in establishing positive, healthy thinking and behavior patterns and improving their optimism level and QoL.

Study on the Shear Strength of Loess Solidified by Guar Gum and Basalt Fiber.

Loess is widely distributed in the northwest and other regions, and its unique structural forms such as large pores and strong water sensitivity lead to its collapsibility and collapse, which can easily induce slope instability. Guar gum and basalt fiber are natural green materials. For these reasons, this study investigated the solidification of loess by combining guar gum and basalt fiber and analyzed the impact of the guar gum content, fiber length, and fiber content on the soil shearing strength. Using scanning electron microscopy (SEM), the microstructure of loess was examined, revealing the synergistic solidification mechanism of guar gum and basalt fibers. On this basis, a shear strength model was established through regression analysis with fiber length, guar gum content, and fiber content. The results indicate that adding guar gum and basalt fiber increases soil cohesion, as do fiber length, guar gum content, and fiber content. When the fiber length was 12 mm, the fiber content was 1.00%, and the guar gum content was equal to 0.50%, 0.75%, or 1.00%, the peak strength of the solidified loess increased by 82.80%, 85.90%, and 90.40%, respectively. According to the shear strength model, the predicted and test data of the shear strength of solidified loess are evenly distributed on both sides of parallel lines, indicating a good fit. These findings are theoretically significant and provide practical guidance for loess solidification engineering.

Permeability and Disintegration Characteristics of Loess Solidified by Guar Gum and Basalt Fiber.

Loess has the characteristics of loose, large pore ratio, and strong water sensitivity. Once it encounters water, its structure is damaged easily and its strength is degraded, causing a degree of subgrade settlement. The water sensitivity of loess can be evaluated by permeability and disintegration tests. This study analyzes the effects of guar gum content, basalt fiber content, and basalt fiber length on the permeability and disintegration characteristics of solidified loess. The microstructure of loess was studied through scanning electron microscopy (SEM) testing, revealing the synergistic solidification mechanism of guar gum and basalt fibers. A permeability model was established through regression analysis with guar gum content, confining pressure, basalt fiber content, and length. The research results indicate that the addition of guar gum reduces the permeability of solidified loess, the addition of fiber improves the overall strength, and the addition of guar gum and basalt fiber improves the disintegration resistance. When the guar gum content is 1.00%, the permeability coefficient and disintegration rate of solidified soil are reduced by 50.50% and 94.10%, respectively. When the guar gum content is 1.00%, the basalt fiber length is 12 mm, and the fiber content is 1.00%, the permeability of the solidified soil decreases by 31.9%, and the disintegration rate is 4.80%. The permeability model has a good fitting effect and is suitable for predicting the permeability of loess reinforced with guar gum and basalt fiber composite. This research is of vital theoretical worth and great scientific significance for guidelines on practicing loess solidification engineering.

Artificial intelligence automatic measurement technology of lumbosacral radiographic parameters.

Background: Currently, manual measurement of lumbosacral radiological parameters is time-consuming and laborious, and inevitably produces considerable variability. This study aimed to develop and evaluate a deep learning-based model for automatically measuring lumbosacral radiographic parameters on lateral lumbar radiographs. Methods: We retrospectively collected 1,240 lateral lumbar radiographs to train the model. The included images were randomly divided into training, validation, and test sets in a ratio of approximately 8:1:1 for model training, fine-tuning, and performance evaluation, respectively. The parameters measured in this study were lumbar lordosis (LL), sacral horizontal angle (SHA), intervertebral space angle (ISA) at L4-L5 and L5-S1 segments, and the percentage of lumbar spondylolisthesis (PLS) at L4-L5 and L5-S1 segments. The model identified key points using image segmentation results and calculated measurements. The average results of key points annotated by the three spine surgeons were used as the reference standard. The model's performance was evaluated using the percentage of correct key points (PCK), intra-class correlation coefficient (ICC), Pearson correlation coefficient (r), mean absolute error (MAE), root mean square error (RMSE), and box plots. Results: The model's mean differences from the reference standard for LL, SHA, ISA (L4-L5), ISA (L5-S1), PLS (L4-L5), and PLS (L5-S1) were 1.69°, 1.36°, 1.55°, 1.90°, 1.60%, and 2.43%, respectively. When compared with the reference standard, the measurements of the model had better correlation and consistency (LL, SHA, and ISA: ICC = 0.91-0.97, r = 0.91-0.96, MAE = 1.89-2.47, RMSE = 2.32-3.12; PLS: ICC = 0.90-0.92, r = 0.90-0.91, MAE = 1.95-2.93, RMSE = 2.52-3.70), and the differences between them were not statistically significant (p > 0.05). Conclusion: The model developed in this study could correctly identify key vertebral points on lateral lumbar radiographs and automatically calculate lumbosacral radiographic parameters. The measurement results of the model had good consistency and reliability compared to manual measurements. With additional training and optimization, this technology holds promise for future measurements in clinical practice and analysis of large datasets.

Preparation, Structures, Photoluminescence and Semiconductive Properties of Two Novel Lanthanide Mercury Materials with a 3-D Framework Structure.

Two novel lanthanide mercury materials, [Gd(IA)3(H3O)2Hg3Br6]n·2nCl (1) and [La(IA)3(H3O)2Hg3Br6]n·2nCl (2) (IA = isonicotinic anion), have been prepared under solvothermal conditions and characterized by single-crystal X-ray diffraction techniques. They are isomorphic and characterized by a three-dimensional (3-D) framework structure. The lanthanide ions are bound by eight oxygen atoms to exhibit a square antiprismatic geometry. The solid-state photoluminescence experiment discovers that compound 1 shows a strong emission in the red region. Compound 1 possesses CIE (Commission Internationale de I'Éclairage) chromaticity coordinates of 0.7347 and 0.2653. Its CCT (correlated color temperature) is 6514 K. Compound 2 displays yellow photoluminescence and it has CIE chromaticity coordinates of 0.4411 and 0.5151. The CCT of compound 2 is 3633 K. Solid-state UV/Vis diffuse reflectance spectra revealed that their semiconductor band gaps are 2.16 eV and 2.85 eV, respectively.

Rickettsia symbionts spread via mixed mode transmission, increasing female fecundity and sex ratio shift by host hormone modulating.

Heritable symbionts are common among animals in nature, but the molecular mechanisms underpinning symbiont invasions of host populations have been elusive. In this study, we demonstrate the spread of Rickettsia in an invasive agricultural pest, the whitefly Bemisia tabaci Mediterranean (MED), across northeastern China from 2018 to 2023. Here, we show that the beneficial symbiont Rickettsia spreads by manipulating host hormone signals. Our analyses suggest that Rickettsia have been horizontally acquired by B. tabaci MED from another invasive whitefly B. tabaci Middle East-Asia Minor 1 during periods of coexistence. Rickettsia is transmitted maternally and horizontally from female B. tabaci MED individuals. Rickettsia infection enhances fecundity and results in female bias among whiteflies. Our findings reveal that Rickettsia infection stimulates juvenile hormone (JH) synthesis, in turn enhancing fecundity, copulation events, and the female ratio of the offspring. Consequently, Rickettsia infection results in increased whitefly fecundity and female bias by modulating the JH pathway. More female progeny facilitates the transmission of Rickettsia. This study illustrates that the spread of Rickettsia among invasive whiteflies in northeastern China is propelled by host hormone regulation. Such symbiont invasions lead to rapid physiological and molecular evolution in the host, influencing the biology and ecology of an invasive species.

Prescription glucocorticoid medication and iridocyclitis are associated with an increased risk of senile cataract occurrence: a Mendelian randomization study.

Iridocyclitis and the use of glucocorticoid medication have been widely studied as susceptibility factors for cataracts. However, the causal relationship between them remains unclear. This study aimed to investigate the causal relationship between the development of iridocyclitis and the genetic liability of glucocorticoid medication use on the risk of senile cataracts occurrence by performing Two-sample Mendelian randomization (MR) analyses. Instrumental variables (IVs) significantly associated with exposure factors (P < 5 × 10-8) were identified using published genome-wide association data from the FinnGen database and UK Biobank. Reliability analyses were conducted using five approaches, including inverse-variance weighted (IVW), MR-Egger regression, simple median, weighted median, and weighted mode. A sensitivity analysis using the leave-one-out method was also performed. Genetic susceptibility to glucocorticoid use was associated with an increased risk of developing senile cataracts (OR, 1.10; 95% CI, 1.02-1.17; P < 0.05). Moreover, iridocyclitis was significantly associated with a higher risk of developing senile cataracts (OR, 1.03; 95% CI, 1.01-1.05; P < 0.05). Nonetheless, some heterogeneity in the IVs was observed, but the MR results remained consistent after penalizing for outliers. The estimates were consistent in multivariate analyses by adjusting for body mass index (BMI) and diabetes mellitus type 2 (T2DM). This study provides new insights into the prevention and management of senile cataracts by highlighting the increased risk associated with iridocyclitis and the use of glucocorticoids.

[Investigation of influencing factors and reference ranges for thyroid function in hospitalized preterm infants at the age of 7 days]. / 7æ—¥é¾„ä½é™¢æ—©äº§å„¿ç”²çŠ¶è ºåŠŸèƒ½å½±å“å› ç´ åŠå‚è€ƒå€¼èŒƒå›´æŽ¢è®¨.

OBJECTIVES: To investigate the influencing factors and reference ranges for thyroid function in preterm infants at the age of 7 days, with the aim of avoiding unnecessary clinical reexamination and intervention. METHODS: A retrospective analysis was performed for the data of 685 preterm infants from January 2020 to January 2023. According to gestational age and birth weight, they were divided into a high-risk group (gestational age <34 weeks or birth weight<2 000 g; 228 infants) and a low-risk group (gestational age ≥34 weeks and birth weight ≥2 000 g;457 infants). The influencing factors for thyroid function were analyzed, and 95% reference range was calculated. RESULTS: Gestational age, birth weight, birth season, sex, and assisted reproduction were the influencing factors for thyroid function (P<0.05). For the preterm infants in the high-risk group, the reference ranges of free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), and thyroid stimulating hormone (TSH) were 2.79-5.40 pmol/L, 8.80-25.64 pmol/L, 0.80-2.15 nmol/L, 50.06-165.09 nmol/L, and 0.80-18.57 µIU/mL, respectively. For those in the low-risk group, the reference ranges of these indicators were 3.08-5.93 pmol/L, 11.17-26.24 pmol/L, 1.02-2.27 nmol/L, 62.90-168.95 nmol/L, and 0.69-13.70 µIU/mL, respectively. FT3, FT4, TT3, and TT4 were positively correlated with gestational age (P<0.05); FT3, FT4, TT3, and TT4 were positively correlated with birth weight (P<0.05); TSH was negatively correlated with birth weight (P<0.05). CONCLUSIONS: Thyroid function in preterm infants at the age of 7 days is affected by the factors such as gestational age and birth weight, and the reference ranges of thyroid function in preterm infants at the age of 7 days should be established based on gestational age and birth weight.

N6-methyladenosine modified TGFB2 triggers lipid metabolism reprogramming to confer pancreatic ductal adenocarcinoma gemcitabine resistance.

Gemcitabine resistance is a major obstacle to the effectiveness of chemotherapy in pancreatic ductal adenocarcinoma (PDAC). Therefore, new strategies are needed to sensitize cancer cells to gemcitabine. Here, we constructed gemcitabine-resistant PDAC cells and analyzed them with RNA-sequence. Employing an integrated approach involving bioinformatic analyses from multiple databases, TGFB2 is identified as a crucial gene in gemcitabine-resistant PDAC and is significantly associated with poor gemcitabine therapeutic response. The patient-derived xenograft (PDX) model further substantiates the gradual upregulation of TGFB2 expression during gemcitabine-induced resistance. Silencing TGFB2 expression can enhance the chemosensitivity of gemcitabine against PDAC. Mechanistically, TGFB2, post-transcriptionally stabilized by METTL14-mediated m6A modification, can promote lipid accumulation and the enhanced triglyceride accumulation drives gemcitabine resistance by lipidomic profiling. TGFB2 upregulates the lipogenesis regulator sterol regulatory element binding factor 1 (SREBF1) and its downstream lipogenic enzymes via PI3K-AKT signaling. Moreover, SREBF1 is responsible for TGFB2-mediated lipogenesis to promote gemcitabine resistance in PDAC. Importantly, TGFB2 inhibitor imperatorin combined with gemcitabine shows synergistic effects in gemcitabine-resistant PDAC PDX model. This study sheds new light on an avenue to mitigate PDAC gemcitabine resistance by targeting TGFB2 and lipid metabolism and develops the potential of imperatorin as a promising chemosensitizer in clinical translation.

Development of a software system for surgical robots based on multimodal image fusion: study protocol.

Background: Surgical robots are gaining increasing popularity because of their capability to improve the precision of pedicle screw placement. However, current surgical robots rely on unimodal computed tomography (CT) images as baseline images, limiting their visualization to vertebral bone structures and excluding soft tissue structures such as intervertebral discs and nerves. This inherent limitation significantly restricts the applicability of surgical robots. To address this issue and further enhance the safety and accuracy of robot-assisted pedicle screw placement, this study will develop a software system for surgical robots based on multimodal image fusion. Such a system can extend the application range of surgical robots, such as surgical channel establishment, nerve decompression, and other related operations. Methods: Initially, imaging data of the patients included in the study are collected. Professional workstations are employed to establish, train, validate, and optimize algorithms for vertebral bone segmentation in CT and magnetic resonance (MR) images, intervertebral disc segmentation in MR images, nerve segmentation in MR images, and registration fusion of CT and MR images. Subsequently, a spine application model containing independent modules for vertebrae, intervertebral discs, and nerves is constructed, and a software system for surgical robots based on multimodal image fusion is designed. Finally, the software system is clinically validated. Discussion: We will develop a software system based on multimodal image fusion for surgical robots, which can be applied to surgical access establishment, nerve decompression, and other operations not only for robot-assisted nail placement. The development of this software system is important. First, it can improve the accuracy of pedicle screw placement, percutaneous vertebroplasty, percutaneous kyphoplasty, and other surgeries. Second, it can reduce the number of fluoroscopies, shorten the operation time, and reduce surgical complications. In addition, it would be helpful to expand the application range of surgical robots by providing key imaging data for surgical robots to realize surgical channel establishment, nerve decompression, and other operations.

Beneficial Effects of Concomitant Long-Acting Injectable Antipsychotics on Time to Rehospitalization in Patients With Treatment-Resistant Schizophrenia Receiving Clozapine: A Retrospective Cohort Study.

Introduction: This study aimed to assess the association between long-acting injectable (LAI) antipsychotic prescription and the risk of psychiatric hospitalization in patients with treatment-resistant schizophrenia (TRS) receiving clozapine.Methods: In this retrospective cohort study at a single tertiary psychiatric center, we analyzed rehospitalization hazard ratios (HRs) in refractory schizophrenia patients, classified by DSM-IV-TR and DSM-5 criteria. We examined various psychotropic regimens-clozapine with or without other oral antipsychotics (OAPs) or LAI antipsychotics. Subgroups were stratified by daily clozapine dosage and previous admissions.Results: A total of 719 patients were included in the study. Analyses were conducted on all the patients over 3- month, 6-month, and 1-year periods. Patients treated with a combination of clozapine and LAI antipsychotics (CLO + LAI) had a significantly higher number of previous hospitalizations (P = .003), and a higher daily dose of clozapine (P < .001) was found in the CLO + OAP group than in the CLO (monotherapy) group and the CLO + LAI group. Patients treated with LAI antipsychotic comedication had significantly lower HRs for rehospitalization in 1 year among 3 studied groups. Moreover, the protective effects of LAI antipsychotics were observed in all the subgroups stratified by daily clozapine dosage and number of previous admissions to represent disease severity.Conclusion: The combination of clozapine and LAI antipsychotics was associated with a significantly lower risk of rehospitalization compared to both the combination of clozapine and OAPs and clozapine monotherapy. The use of LAI antipsychotics should be considered to prevent rehospitalization in patients with TRS who are already being treated with clozapine.

Study of the Correlation between Streaming Video Platform Content on Food Production Processes and the Behavioral Intentions of Generation Z.

With an estimated 2.4 million cases of foodborne illnesses recorded annually in the UK alone, food safety has become a paramount concern among stakeholders. Modern technology has positioned streaming platforms as pivotal conduits for disseminating information. Channels such as YouTube offer detailed recordings of the food production process, granting consumers extensive visibility of the food journey from farm to table. This increased transparency not only promotes vigilant monitoring of food safety practices but also solicits consumer feedback regarding the public exposure to food processing videos. Based on the Theory of Planned Behavior (TPB), this study augments its framework with constructs, such as perceived trust, perceived risk, community experience, and brand identity, to evaluate Taiwan's Generation Z consumer behavioral intentions. With 226 valid responses amassed, structural equation modeling facilitated elucidation of the relationships among the constructs. This analysis yielded three salient insights. First, Generation Z's engagement with food processing videos on streaming platforms is positively correlated with their subsequent purchasing behavior. Second, enriched community experience was correlated with strengthened brand identification. Third, both perceived trust and perceived risk had a constructive impact on behavioral intentions within Gen Z's demographic data. Based on these outcomes, food industry enterprises should proactively develop and bolster community experiential value, thereby encouraging streaming platform users to transform into brand consumers and advocates.

Creation of memory-memory entanglement in a metropolitan quantum network.

Towards realizing the future quantum internet1,2, a pivotal milestone entails the transition from two-node proof-of-principle experiments conducted in laboratories to comprehensive multi-node set-ups on large scales. Here we report the creation of memory-memory entanglement in a multi-node quantum network over a metropolitan area. We use three independent memory nodes, each of which is equipped with an atomic ensemble quantum memory3 that has telecom conversion, together with a photonic server where detection of a single photon heralds the success of entanglement generation. The memory nodes are maximally separated apart for 12.5 kilometres. We actively stabilize the phase variance owing to fibre links and control lasers. We demonstrate concurrent entanglement generation between any two memory nodes. The memory lifetime is longer than the round-trip communication time. Our work provides a metropolitan-scale testbed for the evaluation and exploration of multi-node quantum network protocols and starts a stage of quantum internet research.

Prediction of carbon emissions in China's construction industry using an improved grey prediction model.

As a significant source of global energy consumption and greenhouse gas emissions, the construction industry garners widespread attention due to its high carbon emissions. Anticipating its development trends is crucial for energy conservation and emission reduction. In this paper, we utilize the carbon emission data from China's national and provincial construction sectors from 2012 to 2021, employ the grey prediction model optimized by the particle swarm optimization algorithm, coupled with a metabolic algorithm, to forecast the carbon emissions of the construction industry across China and its provinces. The results demonstrate that: (1) The dynamic grey prediction model combined with the metabolism algorithm has a better prediction effect than the classical model, and the relative error is reduced from 5.103 % to 0.874 %. (2) The carbon emissions of China's construction industry will continue to rise in the next decade, but the growth rate will decrease, and the proportion of indirect carbon emissions continues to increase. (3) There is a marked regional disparity in carbon emissions, with the eastern region exhibiting higher emission levels yet slower growth. In contrast, the western region has lower emission levels but experiences faster growth. These studies provide valuable insights for both the existing approaches to energy conservation and emission reduction, as well as for future policy improvements.

[Research progress in anti-tumor activity and nano-drug delivery system of piperlongumine].

Piperlongumine(PL), a natural alkaloid extracted from Piperis Longi Fructus, has attracted much attention in recent years because of its strong anti-tumor activity, little toxicity to normal cells, and excellent sensitizing effect combined with chemotherapy and radiotherapy, which endow PL with unique advantages as an anti-tumor drug. However, similar to other alkaloids, PL has low water solubility and poor bioavailability. To improve the application of PL in the clinical treatment of tumors, researchers have constructed various nano-drug delivery systems to increase the efficiency of PL delivery. This paper reviewed the physicochemical properties, anti-tumor mechanism, combined therapies, and nano-drug delivery systems of PL in recent years. The review aimed to provide a reference for further research on the anti-tumor effect and nano-drug delivery system of PL. Moreover, this review is expected to provide a reference for the development and application of PL in the anti-tumor therapies.

Association of osteoporotic fractures of femoral neck and femoral neck geometric parameters in native Chinese women.

BACKGROUND: Although it is generally believed that the femoral neck fracture is related to the femoral neck geometric parameters (FNGPs), the association between the risk of osteoporotic fracture of the femoral neck and FNGPs in native Chinese women is still unclear. METHODS: A total of 374 female patients (mean age 70.2 ± 9.32 years) with osteoporotic fracture of the femoral neck, and 374 non-fracture control groups were completely matched with the case group according to the age ratio of 1:1. Using DXA bone densitometer to measured eight FNGPs: the outer diameter (OD), cross-sectional area (CSA), cortical thickness (CT), endocortical diameter (ED), buckling ratio (BR), section modulus (SM), cross-sectional moment of inertia (CSMI), and compressive strength index (CSI) at the narrowest point of the femoral neck. RESULTS: Compared with the control group, the average values of OD (2.9%), ED (4.5%), and BR (26.1%) in the patient group significantly increased (p = 0.015 to < 0.001), while CSA (‒15.3%), CT (‒18.2%), SM (‒10.3%), CSMI (‒6.4%), and CSI (‒10.8%) significantly decreased (all p < 0.001). The prevalence of osteoporosis in the lumbar spine, femoral neck, and total hip was, respectively, 82%, 81%, and 65% in fracture patients. Cox proportional hazard model analysis showed that in the age adjusted model, the fracture hazard ratio (HR) of CSA, CT, BR, SM, and CSI significantly increased (HRs = 1.60‒8.33; 95% CI = 1.08‒16.6; all p < 0.001). In the model adjusted for age and femoral neck BMD, HRs of CT (HRs = 3.90‒8.03; 95% CI = 2.45‒15.1; all p < 0.001) and BR (HRs = 1.62‒2.60; 95% CI = 1.20‒5.44; all p < 0.001) were still significantly increased. CONCLUSION: These results suggest that the majority of osteoporotic fractures of the femoral neck of native Chinese women occur in patients with osteoporosis. CT thinning or BR increase of FNGPs may be independent predictors of fragility fracture of femoral neck in native Chinese women unrelated to BMD.

Sialic acid-based probiotic intervention in lactating mothers improves the neonatal gut microbiota and immune responses by regulating sialylated milk oligosaccharide synthesis via the gut-breast axis.

Human milk oligosaccharides (HMOs) are vital milk carbohydrates that help promote the microbiota-dependent growth and immunity of infants. Sialic acid (SA) is a crucial component of sialylated milk oligosaccharides (S-MOs); however, the effects of SA supplementation in lactating mothers on S-MO biosynthesis and their breastfed infants are unknown. Probiotic intervention during pregnancy or lactation demonstrates promise for modulating the milk glycobiome. Here, we evaluated whether SA and a probiotic (Pro) mixture could increase S-MO synthesis in lactating mothers and promote the microbiota development of their breastfed neonates. The results showed that SA+Pro intervention modulated the gut microbiota and 6'-SL contents in milk of maternal rats more than the SA intervention, which promoted Lactobacillus reuteri colonization in neonates and immune development. Deficient 6'-SL in the maternal rat milk of St6gal1 knockouts (St6gal1-/-) disturbed intestinal microbial structures in their offspring, thereby impeding immune tolerance development. SA+Pro intervention in lactating St6gal1± rats compromised the allergic responses of neonates by promoting 6'-SL synthesis and the neonatal gut microbiota. Our findings from human mammary epithelial cells (MCF-10A) indicated that the GPR41-PI3K-Akt-PPAR pathway helped regulate 6'-SL synthesis in mammary glands after SA+Pro intervention through the gut - breast axis. We further validated our findings using a human-cohort study, confirming that providing SA+Pro to lactating Chinese mothers increased S-MO contents in their breast milk and promoted gut Bifidobacterium spp. and Lactobacillus spp. colonization in infants, which may help enhance immune responses. Collectively, our findings may help alter the routine supplementation practices of lactating mothers to modulate milk HMOs and promote the development of early-life gut microbiota and immunity.

Lung cancer cell-intrinsic IL-15 promotes cell migration and sensitizes murine lung tumors to anti-PD-L1 therapy.

BACKGROUND: IL-15 plays a vital role in enhancing NK cell- and T-cell-mediated antitumor immune responses; however, the direct effect of IL-15 on tumor cells has not been fully elucidated. Herein, we investigated the effect of IL-15 on lung adenocarcinoma cells. METHODS: Silencing and overexpression techniques were used to modify endogenous IL-15 expression in tumor cells. Transwell assays were used to assess tumor cell migration and invasion; a live-cell analysis system was used to evaluate cell motility; cellular morphological changes were quantified by confocal fluorescence microscopy; the molecular mechanisms underlying the effect of IL-15 on tumor cells were analyzed by western blotting; and RhoA and Cdc42 activities were evaluated by a pulldown assay. NCG and C57BL/6 mouse models were used to evaluate the functions of IL-15 in vivo. RESULTS: Cancer cell-intrinsic IL-15 promoted cell motility and migration in vitro and metastasis in vivo via activation of the AKT-mTORC1 pathway; however, exogenous IL-15 inhibited cell motility and migration via suppression of the RhoA-MLC2 axis. Mechanistic analysis revealed that both the intracellular and extracellular IL-15-mediated effects required the expression of IL-15Rα by tumor cells. Detailed analyses revealed that the IL-2/IL-15Rß and IL-2Rγ chains were undetected in the complex formed by intracellular IL-15 and IL-15Rα. However, when exogenous IL-15 engaged tumor cells, a complex containing the IL-15Rα, IL-2/IL-15Rß, and IL-2Rγ chains was formed, indicating that the differential actions of intracellular and extracellular IL-15 on tumor cells might be caused by their distinctive modes of IL-15 receptor engagement. Using a Lewis lung carcinoma (LLC) metastasis model, we showed that although IL-15 overexpression facilitated the lung metastasis of LLC cells, IL-15-overexpressing LLC tumors were more sensitive to anti-PD-L1 therapy than were IL-15-wild-type LLC tumors via an enhanced antitumor immune response, as evidenced by their increased CD8+ T-cell infiltration compared to that of their counterparts. CONCLUSIONS: Cancer cell-intrinsic IL-15 and exogenous IL-15 differentially regulate cell motility and migration. Thus, cancer cell-intrinsic IL-15 acts as a double-edged sword in tumor progression. Additionally, high levels of IL-15 expressed by tumor cells might improve the responsiveness of tumors to immunotherapies.

[Clinical Application of Microwave Ablation in Potentially Resectable Colorectal Cancer With Simultaneously Multiple Liver Metastases].

Objective To analyze the clinical efficacy of microwave ablation in the colorectal cancer with simultaneously multiple liver metastases that was initially evaluated as potentially resectable. Methods The patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases treated in the Department of General Surgery of the First Affiliated Hospital of Hebei North University,the Center of Minimally Invasive Therapy in Oncology of Traditional Chinese and Western Medicine in Dongzhimen Hospital of Beijing University of Chinese Medicine,and the Second Department of General Surgery in the Fourth Hospital of Hebei Medical University from October 1,2018 to October 1,2020 were selected in this study.The general data,pathological features,treatment methods,and clinical efficacy of the patients were collected.According to the treatment methods,the patients were assigned into a surgical resection group(conversion therapy+laparoscopic primary resection+hepatectomy)and a microwave ablation group(conversion therapy+laparoscopic primary resection+microwave ablation).The surgical indicators(operation duration,time to first postoperative anal exhaust,hospital stay,etc.)and postoperative complications(anastomotic stenosis,anastomotic hemorrhage,incision infection,etc.)were compared between the two groups.The survival period was followed up,including the overall survival period and disease-free survival period,and the survival curves were drawn to analyze the clinical efficacy of the two treatment regimens. Results A total of 198 patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases were included in this study.Sixty-six patients were cured by neoadjuvant chemotherapy(FOLFOX or FOLFIRI),including 30 patients in the surgical resection group and 36 patients in the microwave ablation group(with 57 tumors ablated).After the first ablation,54(94.74%)tumors achieved complete ablation,and all of them reached no evidence of disease status after re-ablation.The microwave ablation group had shorter operation duration,less intraoperative blood loss,shorter time to first postoperative anal exhaust,shorter time of taking a liquid diet,shorter hospital stay,and lower hospitalization cost than the surgical resection group(all P<0.001).In addition,the microwave ablation group had lower visual analogue scale score(P<0.001)than the surgical resection group.The incidences of complications such as incision infection(P=0.740),anastomotic fistula(P=1.000),and anastomotic stenosis(P=1.000),the overall survival period(P=0.191),and the disease-free survival period(P=0.934)showed no significant differences between the two groups. Conclusions For patients with colorectal cancer with simultaneous multiple liver metastases initially assessed as potentially resectable,laparoscopic primary resection+surgical resection/microwave ablation after conversion therapy was safe,effective,and had similar survival outcomes.Microwave ablation outperformed surgical resection in postoperative recovery,economy,and tolerability,being worthy of clinical promotion.

Effect of glycotoxicity and lipotoxicity on carbohydrate antigen 19 - 9 in the patients with diabetes.

OBJECTIVES: In comparison to the subjects without diabetes, a greater concentration of serum carbohydrate antigen 19 - 9 (CA 19 - 9) was observed in the subjects with diabetes. Nevertheless, since the occurrence of abnormal CA 19 - 9 is not widespread among the whole diabetic population, this phenomenon has not attracted enough attention. The prevalence of abnormal CA 19 - 9 in hospitalized patients with diabetes was the focus of our research. METHOD: A total of 385 subjects with diabetes and 200 controls were enrolled and all had been tested the CA19-9 levels. Cases of cancers were excluded through examination and followup for 1 year. RESULTS: We found that the rate of patients with abnormal CA19-9 level was 8.3%. The rate of patients with abnormal CA19-9 level was 14.0% in the HbA1c ≥ 9% group, and 3.0% in the HbA1c < 9% group, 2.5% in the control group. There was no significant difference in the HbA1c < 9% group and the control group. A significant correlation between serum CA19-9 and both HbA1c and total cholesterol was observed, yet no difference in CRP level was observed between subjects with normal CA19-9 level and subjects with abnormal CA19-9 level. However, a significant difference in fasting C-peptide levels was observed between the two groups, p = 0.039. CONCLUSION: The percentage of patients with diabetes exhibiting elevated CA19-9 level is 14% in the HbA1c ≥ 9% diabetic patients, much higher than expected. The underlying mechanism may be related to islet injury caused by glycotoxicity and lipotoxicity. STRENGTHS AND LIMITATIONS OF THE STUDY: We studied the rate of hospitalized diabetic patients with elevated CA 19 - 9 which were characterized with poorly controlled blood glucose. We found that the elevation of CA 19 - 9 was unexpectedly high in diabetic inpatients without development to cancer. The limitation of this study is that the underlying mechanism is not sufficiently studied.