Analysis of Bifidobacterium animalis subsp. lactis BB-12 ® and Lactobacillus rhamnosus GG on underweight and malabsorption in premature infants

SUMMARY OBJECTIVE: This study aimed to explore and analyze the therapeutic effect of the combination of Bifidobacterium animalis subsp. lactis BB-12® and Lactobacillus rhamnosus GG on underweight and malabsorption in premature infants. METHODS: This is a retrospective study. The clinical data of 68 premature infants admitted to Beijing United Family Hospital (Private Secondary Comprehensive Hospital, Chaoyang District, Beijing, China) from January 2016 to January 2022 were analyzed retrospectively. Preterm infants less than 37 weeks of gestational age admitted to the neonatal intensive care unit were included in the study. Patients with intestinal malformations, necrotizing enterocolitis, etc., who require long-term fasting were excluded. A telephone follow-up was performed 3-6 months after discharge. They were classified as treatment groups A and B according to the treatment plan. The treatment group A included parenteral nutrition, enteral nutrition, etc. In treatment group B, based on treatment group A, the premature infants were treated with Bifidobacterium animalis subsp. lactis BB-12® and Lactobacillus rhamnosus GG. The time to regain birthweight and the weight on day 30 were compared between the two groups, as was the duration of transition from parenteral nutrition to total enteral nutrition. RESULTS: The time of weight regain birthweight in group B was shorter than that in group A (t=-2.560; t=-4.287; p<0.05). The increase of weight on day 30 in group B was significantly higher than that in group A (t=2.591; t=2.651; p<0.05). The time from parenteral nutrition to total enteral nutrition in group B was shorter than that in group A (z=-2.145; z=-2.236; p<0.05). CONCLUSION: In the treatment of premature infants, the combination of Bifidobacterium animalis subsp. lactis BB-12® and Lactobacillus rhamnosus GG can have a better therapeutic effect on the underweight and malabsorption of premature infants, and this treatment method can be popularized in clinics.

Association between handgrip strength and heart failure in adults aged 45 years and older from NHANES 2011-2014.

Growing evidence indicates that handgrip strength (HGS) is a conspicuous marker for assessing some diseases affecting middle-aged and elderly individuals. However, research regarding HGS and heart failure (HF) is sparse and controversial. Hence, we aimed to investigate the association between HGS and HF among adults aged 45 years and older in the United States. In this cross-sectional study, we included 4524 adults older than 45 years who were part of the National Health and Nutrition Examination Survey. A generalized additive model was used to estimate the association between HGS and HF. Age, gender, race, income, education, body mass index, smoking status, drinking status, diabetes, hypertension, stroke, vigorous physical activity, total energy intake, total protein intake, total sugars intake, and total fat intake covariates were adjusted using multiple regression models. And further subgroup analysis was conducted. We documented 189 cases of HF, including 106 men and 83 women. HGS was negatively associated with HF after adjusting for all the covariates (odds ratio = 0.97, 95% confidence interval = 0.96-0.99; P < 0.001). Compared with the lowest quintile, the highest quintile was associated with an 82% lower incidence of HF (odds ratio = 0.18, 95% confidence interval = 0.08-0.43; P < 0.001). Subgroup analysis showed that the results remained stable. In US adults older than 45, HGS was negatively associated with HF after adjusting for covariates. This finding had the potential to draw attention to the physiological and pathological effects of decreased muscle function on HF and may influence further prospective studies with intervention trials.

Fu-Huang ointment ameliorates impaired wound healing associated with diabetes through PI3K-AKT signalling pathway activation.

A diabetic ulcer (DU) is a dreaded and resistant complication of diabetes mellitus with high morbidity. Fu-Huang ointment (FH ointment) is a proven recipe for treating chronic refractory wounds; however, its molecular mechanisms of action are unclear. In this study, we identified 154 bioactive ingredients and their 1127 target genes in FH ointment through the public database. The intersection of these target genes with 151 disease-related targets in DUs resulted in 64 overlapping genes. Overlapping genes were identified in the PPI network and enrichment analyses. The PPI network identified 12 core target genes, whereas Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that upregulation of the PI3K/Akt signalling pathway was involved in the role of FH ointment in treating diabetic wounds. Molecular docking showed that 22 active compounds in FH ointment could enter the active pocket of PIK3CA. Molecular dynamics was used to prove the binding stability of the active ingredients and protein targets. We found that PIK3CA/Isobutyryl shikonin and PIK3CA/Isovaleryl shikonin combinations had strong binding energies. An in vivo experiment was conducted on PIK3CA, which was the most significant gene.This study comprehensively elucidated the active compounds, potential targets, and molecular mechanism of FH ointment application in treating DUs, and believed that PIK3CA is a promising target for accelerated healing.

Heat Shock Protein B7 Inhibits the Progression of Endometrial Carcinoma by Inhibiting PI3K/AKT/mTOR Pathway.

PURPOSE: To investigate the role and mechanism of action of Heat shock protein B7 (HSPB7) in endometrial carcinoma (EC). METHODS: GEPIA (Gene Expression Profiling Interactive Analysis) was used to analyze the expression and prognostic value of HSPB7 in TCGA data. HSPB7 mRNA and protein expression levels were detected by qRT-PCR and Western blot, respectively. EC cell proliferation, apoptosis, migration, and invasion were determined by colony formation, EdU, flow cytometry, and transwell assays. Mitochondrial membrane potential was determined using JC-1 probe. In addition, apoptosis-related and metastasis-related proteins were quantitatively evaluated. A gene set enrichment analysis of the signaling pathways by which HSPB7 influences EC was performed and the levels of enriched pathway-related proteins were evaluated. RESULTS: We first proved that HSPB7 was downregulated in EC tissues and HSPB7 levels were positively related to survival rates. In functional assays, HSPB7 overexpression suppressed the proliferation, migration, and invasion of EC cells and conversely promoted apoptosis. Moreover, HSPB7 overexpression decreased the mitochondrial membrane potential of EC cells significantly. Bioinformatics analyses revealed that the PI3K/AKT/mTOR pathway was significantly enriched in EC. HSPB7 inhibited the phosphorylation of the PI3K/AKT/mTOR pathway to reduce proliferation, migration and invasion, and increased apoptosis in EC cells. CONCLUSION: HSPB7 was downregulated in EC and influenced EC cell proliferation, invasion, migration, and apoptosis via the PI3K/AKT/mTOR signaling pathway. These findings provide a novel perspective for the development of EC treatment strategies.

Predict DLBCL patients' recurrence within two years with Gaussian mixture model cluster oversampling and multi-kernel learning.

BACKGROUND AND OBJECTIVE: Diffuse large B-cell lymphoma (DLBCL) is common in adults' non-Hodgkin's lymphoma. Relapse mainly occurs within two years after diagnosis and has a poor prognosis. Relapse after two years is less frequent and has a better prognosis. In this work, we constructed a relapse prediction model for diffuse large B-cell lymphoma patients within two years, expecting to provide a reference for Clinicians to implement individualized treatment. METHOD: We propose a secondary-level class imbalance method based on Gaussian mixture model (GMM) clustering resampling to balance the data. Then use a multi-kernel support vector machine(SVM) to inscribe heterogeneous clinical data. Finally, merging them to identify recurrence patients within two years. RESULTS: Among all the class imbalance methods in this work, Inverse Weighted -GMM +SMOTEENN has the best performance. Compared with NO-GMM (Directl use the SMOTEENN without the GMM clustering process), its Area Under the ROC Curve(AUC) increases by 8.75%, and ECE and brier scores decrease 2.07% and 3.09%, respectively. Among the four classification algorithms in this work, Multiple kernel learning (MKL) has the most minimized brier scores and expected calibration error(ECE), the largest AUC, accuracy, Recall, precision and F1, has the best discrimination and calibration. CONCLUSION: Our inverse weighted -GMM+SMOTEENN+MKL (GMM-SENN-MKL) method can handle data class imbalance and clinical heterogeneity data well and can be used to predict recurrence in DLBCL patients.

Activation of natural killer T cells contributes to Th1 bias in the murine liver after 14 d of ethinylestradiol exposure.

BACKGROUND: As the main component of oral contraceptives (OCs), ethinylestradiol (EE) has been widely applied as a model drug to induce murine intrahepatic cholestasis. The clinical counterpart of EE-induced cholestasis includes women who are taking OCs, sex hormone replacement therapy, and susceptible pregnant women. Taking intrahepatic cholestasis of pregnancy (ICP) as an example, ICP consumes the medical system due to its high-risk fetal burden and the impotency of ursodeoxycholic acid in reducing adverse perinatal outcomes. AIM: To explore the mechanisms and therapeutic strategies of EE-induced cholestasis based on the liver immune microenvironment. METHODS: Male C57BL/6J mice or invariant natural killer T (iNKT) cell deficiency (Jα18-/- mice) were administered with EE (10 mg/kg, subcutaneous) for 14 d. RESULTS: Both Th1 and Th2 cytokines produced by NKT cells increased in the liver skewing toward a Th1 bias. The expression of the chemokine/chemokine receptor Cxcr6/Cxcl16, toll-like receptors, Ras/Rad, and PI3K/Bad signaling was upregulated after EE administration. EE also influenced bile acid synthase Cyp7a1, Cyp8b1, and tight junctions ZO-1 and Occludin, which might be associated with EE-induced cholestasis. iNKT cell deficiency (Jα18-/- mice) robustly alleviated cholestatic liver damage and lowered the expression of the abovementioned signaling pathways. CONCLUSION: Hepatic NKT cells play a pathogenic role in EE-induced intrahepatic cholestasis. Our research improves the understanding of intrahepatic cholestasis by revealing the hepatic immune microenvironment and also provides a potential clinical treatment by regulating iNKT cells.

TMT-based proteomics analysis reveals the protective effect of Jueyin granules on imiquimod-induced psoriasis mouse model by causing autophagy.

BACKGROUND: Psoriasis is a chronic relapsing inflammatory skin disease that may markedly influence the patients' physical health and mental condition. According to animal models and clinical researches, it has been proved that Jueyin granules (JYG), a Chinese formula comprised of seven kinds of Traditional Chinese Medicine (TCM), is a therapeutic agent for treating psoriasis, while the specific mechanisms of the anti-inflammation effects of JYG have not been fully elucidated. OBJECTIVE: To uncover the underlying mechanisms of the action of JYG on psoriasis by proteomics clues. MATERIALS AND METHODS: Differentially expressed proteins (DEPs) were explored by tandem mass tag (TMT)-based quantitative proteomics analysis after JYG treatment (administered intragastrically for 12 days). Bioinformatics analysis of DEPs was conducted through hierarchical clustering, volcano plot, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Major DEPs were further identified by enzyme-linked immunoassay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR). RESULTS: Ninety-five DEPs were identified, including 57 up-regulated and 38 down-regulated proteins, between imiquimod (IMQ) and IMQ+JYG groups. GO analysis indicated that DEPs were mainly associated with keratin filament, intermediate filament, extracellular exosome, extracellular space, innate immune response, keratinization, and keratinocyte differentiation. The KEGG pathway analysis manifested that estrogen signaling pathway, cholesterol metabolism, fat digestion, absorption, peroxisome proliferator-activated receptor (PPAR), and interleukin (IL)-17 signaling pathway might be the paramount pathways, through which JYG functioned on psoriasis. Furthermore, we determined that JYG could regulate macrophage and CD4+ T cell phenotypes by inducing autophagy. CONCLUSIONS: JYG may induce autophagy by up-regulating ApoA1 and inhibit the infiltration of CD4+ T cells and macrophages, thereby alleviating IMQ-induced psoriatic inflammation.

Value of Magnifying Chromoendoscopy and Magnifying Optical Enhancement Technology in Classifying Colorectal Polyps: A Prospective Controlled Study.

BACKGROUND AND AIMS: Magnifying chromoendoscopy (ME-CE) through the observation of pit patterns is a productive way to distinguish between neoplastic and nonneoplastic polyps. Magnifying optical enhancement technology (ME-OE) is an emerging virtual chromoendoscopy imaging technology and appeared to be a promising approach. However, this information is currently not available. This study is aimed at comparing the differential diagnostic value of ME-CE and OE for neoplastic and nonneoplastic polyps. Patients and Methods. Consecutive patients undergoing colonoscopy were randomized (1 : 1) into examination by ME-OE or ME-CE. Histopathological findings were utilized as the reference standard. Accuracy, sensitivity, specificity, and positive and negative predictive values of two endoscopy methods were compared using ME-OE (were classified according to the JNET classification) and ME-CE (were classified according to the Kudo pit pattern classification), respectively, and the time to predict the histological polyp type was compared. And the agreements between the pathological and clinical diagnosis by ME-OE or ME-CE were analyzed. RESULTS: A total of 365 polyps were found in the 220 patients included (ME-OE: 185; ME-CE: 180.202 had nonneoplastic polyps, 163 had neoplastic polyps). The diagnostic accuracy of ME-OE was higher than that of ME-CE (93% vs. 92%, p > 0.05). The average diagnosis time was lower in ME-OE than ME-CE (83 ± 26.4 s vs. 194 ± 17.7 s, p < 0.001). The agreements between the pathological and clinical diagnosis were at least substantial in both groups. CONCLUSION: ME-OE was superlative to ME-CE in predicting the histology of polyps. OE devoted classification would possibly similarly enhance the endoscopist performance. The trial is registered with ChiCT2000032075.

Probability calibration-based prediction of recurrence rate in patients with diffuse large B-cell lymphoma.

BACKGROUND: Although many patients receive good prognoses with standard therapy, 30-50% of diffuse large B-cell lymphoma (DLBCL) cases may relapse after treatment. Statistical or computational intelligent models are powerful tools for assessing prognoses; however, many cannot generate accurate risk (probability) estimates. Thus, probability calibration-based versions of traditional machine learning algorithms are developed in this paper to predict the risk of relapse in patients with DLBCL. METHODS: Five machine learning algorithms were assessed, namely, naïve Bayes (NB), logistic regression (LR), random forest (RF), support vector machine (SVM) and feedforward neural network (FFNN), and three methods were used to develop probability calibration-based versions of each of the above algorithms, namely, Platt scaling (Platt), isotonic regression (IsoReg) and shape-restricted polynomial regression (RPR). Performance comparisons were based on the average results of the stratified hold-out test, which was repeated 500 times. We used the AUC to evaluate the discrimination ability (i.e., classification ability) of the model and assessed the model calibration (i.e., risk prediction accuracy) using the H-L goodness-of-fit test, ECE, MCE and BS. RESULTS: Sex, stage, IPI, KPS, GCB, CD10 and rituximab were significant factors predicting the 3-year recurrence rate of patients with DLBCL. For the 5 uncalibrated algorithms, the LR (ECE = 8.517, MCE = 20.100, BS = 0.188) and FFNN (ECE = 8.238, MCE = 20.150, BS = 0.184) models were well-calibrated. The errors of the initial risk estimate of the NB (ECE = 15.711, MCE = 34.350, BS = 0.212), RF (ECE = 12.740, MCE = 27.200, BS = 0.201) and SVM (ECE = 9.872, MCE = 23.800, BS = 0.194) models were large. With probability calibration, the biased NB, RF and SVM models were well-corrected. The calibration errors of the LR and FFNN models were not further improved regardless of the probability calibration method. Among the 3 calibration methods, RPR achieved the best calibration for both the RF and SVM models. The power of IsoReg was not obvious for the NB, RF or SVM models. CONCLUSIONS: Although these algorithms all have good classification ability, several cannot generate accurate risk estimates. Probability calibration is an effective method of improving the accuracy of these poorly calibrated algorithms. Our risk model of DLBCL demonstrates good discrimination and calibration ability and has the potential to help clinicians make optimal therapeutic decisions to achieve precision medicine.

Adverse Events Associated With Anti-IL-23 Agents: Clinical Evidence and Possible Mechanisms.

Background: Anti-interleukin (IL)-23 agents are widely used for autoimmune disease treatment; however, the safety and risks of specific symptoms have not been systematically assessed. Objectives: The aim of this study was to summarize the characteristics and mechanisms of occurrence of five immunological and non-immunological adverse events caused by different anti-IL-23 agents. Methods: The Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched for eligible randomized clinical trials published from inception through May 1, 2020. Randomized clinical trials that reported at least one type of adverse event after treatment were included, regardless of sex, age, ethnicity, and diagnosis. Two investigators independently screened and extracted the characteristics of the studies, participants, drugs, and adverse event types. The Cochrane Handbook was used to assess the methodological quality of the included randomized clinical trials. Heterogeneity was assessed using the I2 statistic. Meta-regression was applied to determine the sources of heterogeneity, and subgroup analysis was used to identify the factors contributing to adverse events. Results: Forty-eight studies were included in the meta-analysis, comprising 25,624 patients treated with anti-IL-23 agents. Serious immunological or non-immunological adverse events were rare. Anti-IL-12/23-p40 agents appeared to cause adverse events more easily than anti-IL-23-p19 agents. The incidence of cancer did not appear to be related to anti-IL-23 agent treatment, and long-term medication could lead to mental diseases. The prevention of complications should be carefully monitored when administered for over approximately 40 weeks to avoid further adverse reactions, and the incidence of infection was the highest among general immunological adverse events. Conclusions: The application of anti-IL-23 agents induced a series of immunological and non-immunological adverse events, but these agents tend to be well-tolerated with good safety profiles.