Probiotics induce intestinal IgA secretion in weanling mice potentially through promoting intestinal APRIL expression and modulating the gut microbiota composition.

Intestinal infections are strongly associated with infant mortality, and intestinal immunoglobulin A (IgA) is important to protect infants from intestinal infections after weaning. This study aims to screen probiotics that can promote the production of intestinal IgA after weaning and further explore their potential mechanisms of action. In this study, probiotics promoting intestinal IgA production were screened in weanling mouse models. The results showed that oral administration of Bifidobacterium bifidum (B. bifidum) FL228.1 and Bifidobacterium bifidum (B. bifidum) FL276.1 significantly enhanced IgA levels in the small intestine and upregulated the expression of a proliferation-inducing ligand (APRIL) and its upstream regulatory factor toll-like receptor 4 (TLR4). Furthermore, B. bifidum FL228.1 upregulated the relative abundance of Lactobacillus, while B. bifidum FL276.1 increased the relative abundance of Marvinbryantia and decreased Mucispirillum, further elevating intestinal IgA levels. In summary, B. bifidum FL228.1 and B. bifidum FL276.1 can induce IgA production in the intestinal tract of weanling mice by promoting intestinal APRIL expression and mediating changes in the gut microbiota, thus playing a significant role in enhancing local intestinal immunity in infants.

Increased knee torsional misalignment associated with femoral torsion is related to non-contact anterior cruciate ligament injury: a case-control study.

BACKGROUND: Altered axial biomechanics of the knee are recognized as a risk factor for non-contact anterior cruciate ligament (ACL) injury. However, the relationship of knee and segmental torsion to non-contact ACL and combined anterolateral ligament (ALL) injury is unclear. This study aims to determine the relationship of knee and segmental torsion to non-contact ACL injury and to explore their relationship with ALL injuries. METHODS: We divided 122 patients with arthroscopically confirmed non-contact ACL injuries into an ACL injury group (isolated ACL injury, 63 patients) and an ACL + ALL injury group (ACL combined with ALL injury,59 patients). Additionally, 90 normal patients with similar age, gender and body mass index (BMI) were matched as a control group. The tibial tubercle-trochlear groove (TT-TG) distance, distal femoral torsion (DFT), posterior femoral condylar torsion (PFCT) and proximal tibial torsion (PTT) were measured using magnetic resonance imaging (MRI). We assessed the differences between the groups using an independent samples t test and utilized receiver operating characteristic (ROC) curves to determine the cut-off value for the increased risk of ACL injury. RESULTS: In patients with ACL injury, the measurements of the TT-TG (11.8 ± 3.1 mm), DFT (7.7° ± 3.5°) and PFCT (3.6° ± 1.3°) were significantly higher compared to the control group (9.1 ± 2.4 mm, 6.3° ± 2.7° and 2.8° ± 1.3°, respectively; P < 0.05), but the PTT did not differ between the two groups. The TT-TG, DFT and PFCT were not significantly larger in patients combined with ALL injury. ROC curve analysis revealed ACL injury is associated with TT-TG, DFT and PFCT. CONCLUSIONS: Knee torsional alignment is associated with ACL injury, predominantly in the distal femur rather than the proximal tibia. However, its correlation with ALL injury remains unclear. These findings may help identify patients at high risk for non-contact ACL injury and inform the development of targeted prevention and treatment strategies.

Bifidobacterium improves oestrogen-deficiency-induced osteoporosis in mice by modulating intestinal immunity.

Osteoporosis has become one of the major diseases that threaten the health of middle-aged and elderly people, and with the growth of an ageing population, more and more people are affected by osteoporosis these days. In recent years, intestinal flora has been found to affect the host immune system, and an overactive immune system is closely related to bone resorption. Probiotics can effectively improve bone density and strength, reduce bone loss, and improve osteoporosis, but their mechanism of action and relationship with intestinal microbiota are still unclear. In this study, two strains of Bifidobacterium (Bifidobacterium bifidum FL228.1 and Bifidobacterium animalis subsp. Lactis F1-7) that can alleviate intestinal inflammation were screened based on previous experiments. Through the construction of an ovariectomized mouse model, the improvement of osteoporosis by Bifidobacterium was detected, and the influence of Bifidobacterium on intestinal immunity was explored. The results show that Bifidobacterium treatment significantly improved bone mineral density (BMD), bone volume/total volume ratio (BV/TV), and trabecular number (Tb·N), and effectively suppressed bone loss. Furthermore, Bifidobacterium treatment could inhibit the expression of inflammatory cytokines in the gut, alleviate gut inflammation, and thus suppress excessive osteoclast generation. Its mechanism of action includes factors that protect the mucosal barrier, including occludin, ZO-1, claudin-2, and MUC2, and the reduction of pro-inflammatory M1 macrophages. B. bifidum FL228.1 increased the abundance of beneficial bacteria in the colon, including Lactobacillus and Colidextribacter. B. animalis F1-7 increased the abundance of Bifidobacterium and decreased the abundance of Desulfovibrio and Ruminococcus in the colon. These research findings expand our understanding of the gut-bone axis and provide new guidance for the development of probiotic-based therapies for osteoporosis in the future.

A TGF-ß signaling-related lncRNA signature for prediction of glioma prognosis, immune microenvironment, and immunotherapy response.

AIMS: The dysregulation of TGF-ß signaling is a crucial pathophysiological process in tumorigenesis and progression. LncRNAs have diverse biological functions and are significant participants in the regulation of tumor signaling pathways. However, the clinical value of lncRNAs related to TGF-ß signaling in glioma is currently unclear. METHODS: Data on glioma's RNA-seq transcriptome, somatic mutation, DNA methylation data, and clinicopathological information were derived from the CGGA and TCGA databases. A prognostic lncRNA signature was constructed by Cox and LASSO regression analyses. TIMER2.0 database was utilized to deduce immune infiltration characteristics. "ELMER v.2" was used to reconstruct TF-methylation-gene regulatory network. Immunotherapy and chemotherapy response predictions were implemented by the TIDE algorithm and GDSC database, respectively. In vitro and in vivo experiments were conducted to verify the results and clarify the regulatory mechanism of lncRNA. RESULTS: In glioma, a TGF-ß signaling-related 15-lncRNA signature was constructed, including AC010173.1, HOXA-AS2, AC074286.1, AL592424.1, DRAIC, HOXC13-AS, AC007938.1, AC010729.1, AC013472.3, AC093895.1, AC131097.4, AL606970.4, HOXC-AS1, AGAP2-AS1, and AC002456.1. This signature proved to be a reliable prognostic tool, with high risk indicating an unfavorable prognosis and being linked to malignant clinicopathological and genomic mutation traits. Risk levels were associated with different immune infiltration landscapes, where high risk was indicative of high levels of macrophage infiltration. In addition, high risk also suggested better immunotherapy and chemotherapy response. cg05987823 was an important methylation site in glioma progression, and AP-1 transcription factor family participated in the regulation of signature lncRNA expression. AGAP2-AS1 knockdown in in vitro and in vivo experiments inhibited the proliferation, migration, and invasion of glioma cells, as well as the growth of glioma, by downregulating the expression levels of NF-κB and ERK 1/2 in the TGF-ß signaling pathway. CONCLUSIONS: A prognostic lncRNA signature of TGF-ß signaling was established in glioma, which can be used for prognostic judgment, immune infiltration status inference, and immunotherapy response prediction. AGAP2-AS1 plays an important role in glioma progression.

Effects of temperature and charged vacancies on electronic and optical properties of ß-Ga2O3 after radiation damage.

ß-Ga2O3 as an ultra-wide bandgap material is widely used in space missions and nuclear reactor environments. It is well established that the physical properties of ß-Ga2O3 would be affected by radiation damage and temperature in such application scenarios. Defects are inevitably created in ß-Ga2O3 upon irradiation and their dynamic evolution is positively correlated with the thermal motion of atoms as temperature increases. This work utilizes first-principles calculations to investigate how temperature influences the electronic and optical properties of ß-Ga2O3 after radiation damage. It finds that the effect of p-type defects caused by Ga vacancies on optical absorption diminishes as temperature increases. The high temperature amplifies the effect of oxygen vacancies to ß-Ga2O3, however, making n-type defects more pronounced and accompanied by an increase in the absorption peak in the visible band. The self-compensation effect varies when ß-Ga2O3 contains both Ga vacancies and O vacancies at different temperatures. Moreover, in the case of Ga3- (O2+) vacancies, the main characters of p(n)-type defects caused by uncharged Ga0 (O0) vacancies disappear. This work aims to understand the evolution of physical properties of ß-Ga2O3 under irradiation especially at high temperatures, and help analyze the damage mechanism in ß-Ga2O3-based devices.

P-coumaric acid ameliorates Aß25-35-induced brain damage in mice by modulating gut microbiota and serum metabolites.

Alzheimer's disease (AD) is a progressive neurodegenerative disease for which there is a lack of effective therapeutic drugs. There is great potential for natural products to be used in the development of anti-AD drugs. P-coumaric acid (PCA), a small molecule phenolic acid widely distributed in the plant kingdom, has pharmacological effects such as neuroprotection, but its anti-AD mechanism has not been fully elucidated. In the current study, we investigated the mechanism of PCA intervention in the Aß25-35-induced AD model using gut microbiomics and serum metabolomics combined with in vitro and in vivo pharmacological experiments. PCA was found to ameliorate cognitive dysfunction and neuronal cell damage in Aß25-35-injected mice as measured by behavioral, pathological and biochemical indicators. 16S rDNA sequencing and serum metabolomics showed that PCA reduced the abundance of pro-inflammatory-associated microbiota (morganella, holdemanella, fusicatenibacter and serratia) in the gut, which were closely associated with metabolites of the glucose metabolism, arachidonic acid metabolism, tyrosine metabolism and phospholipid metabolism pathways in serum. Next, in vivo and in vitro pharmacological investigations revealed that PCA regulated Aß25-35-induced disruption of glucose metabolism through activation of PI3K/AKT/Glut1 signaling. Additionally, PCA ameliorated Aß25-35-induced neuroinflammation by inhibiting nuclear translocation of NF-κB and by modulating upstream MAPK signaling. In conclusion, PCA ameliorated cognitive deficits in Aß25-35-induced AD mice by regulating glucose metabolism and neuroinflammation, and the mechanism is related not only to restoring homeostasis of gut microbiota and serum metabolites, but also to PI3K/AKT/Glut1 and MAPK/NF-κB signaling.

[Effect of aqueous extract of Corni Fructus on Aß_(25-35)-induced brain injury and neuroinflammation in mice with Alzheimer's disease].

The purpose of this study was to investigate the effect of aqueous extract of Corni Fructus on ß-amyloid protein 25-35(Aß_(25-35))-induced brain injury and neuroinflammation in Alzheimer's disease(AD) mice to provide an experimental basis for the treatment of AD by aqueous extract of Corni Fructus. Sixty C57BL/6J male mice were randomly divided into a sham group, a model group, a positive control group(huperizine A, 0.2 mg·kg~(-1)), a low-dose aqueous extract of Corni Fructus group(1.3 g·kg~(-1)), a medium-dose aqueous extract of Corni Fructus group(2.6 g·kg~(-1)), and a high-dose aqueous extract of Corni Fructus group(5.2 g·kg~(-1)). The AD model was induced by lateral ventricular injection of Aß_(25-35) in mice except for those in the sham group, and AD model mice were treated with corresponding drugs by gavage for 24 days. The behavioral test was performed one week before animal dissection. Hematoxylin-eosin(HE) staining was performed to observe the morphology of neurons in the hippocampal region. Flow cytometry was used to detect the apoptosis level of primary hippocampal cells in mice. ELISA kits were used to detect the levels of ß-amyloid protein 1-42(Aß_(1-42)) and phosphorylated microtubule-associated protein Tau(p-Tau) in mouse brain tissues. Immunofluorescence and Western blot were used to detect the expression of related proteins in mouse brain tissues. MTT assay was used to detect the effect of compounds in aqueous extract of Corni Fructus on Aß_(25-35)-induced N9 cell injury. Molecular docking was employed to analyze the interactions of caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol with ß-amyloid precursor protein(APP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). Aqueous extract of Corni Fructus could improve the learning and memory abilities of Aß_(25-35)-induced mice by increasing the duration of the autonomous activity, the rate of autonomous alternation, the preference coefficient, and the discrimination coefficient, and reduce Aß_(25-35)-induced brain injury and neuroinflammation in mice by increasing the expression levels of interleukin-10(IL-10) and B-cell lymphoma-2(Bcl-2) in brain tissues, decreasing the expression levels of Aß_(1-42), p-Tau, IL-6, TNF-α, cysteine aspartate-specific protease 3(caspase-3), cysteine aspartate-specific protease 9(caspase-9), and Bcl-2-associated X protein(Bax), and decreasing the number of activated glial cells in brain tissues. The results of cell experiments showed that esculetin and(+)-lyoniresinol could improve Aß_(25-35)-induced N9 cell injury. Molecular docking results showed that caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol had good binding affinity with APP and weak binding affinity with IL-6 and TNF-α. Aqueous extract of Corni Fructus could ameliorate cognitive dysfunction and brain damage in Aß_(25-35)-induced mice by reducing the number of apoptotic cells and activated glial cells in the brain and decreasing the expression level of inflammatory factors. Caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol may be the material basis for the anti-AD effect of aqueous extract of Corni Fructus.

Biomarker Discovery for Early Diagnosis of Papillary Thyroid Carcinoma Using High-Throughput Enhanced Quantitative Plasma Proteomics.

The incidence of thyroid cancer (TC) has been increasing over the last 50 years worldwide. A higher rate of overdiagnosis in indolent thyroid lesions has resulted in unnecessary treatment. An accurate detection of TC at an early stage is highly demanded. We aim to develop an enhanced isobaric labeling-based high-throughput plasma quantitative proteomics to identify biomarkers in a discovery cohort. Selected candidates were tested by enzyme-linked immunosorbent assay (ELISA) in the training cohort and validation cohort. In total, 1063 proteins were quantified, and 129 proteins were differentially expressed between patients and healthy subjects. Serum levels of ISG15 and PLXNB2 were significantly elevated in patients with papillary thyroid cancer (PTC) or thyroid adenoma, compared to healthy subjects (p < 0.001) and patients with nodular goiter (p < 0.001). Receiver operating characteristic (ROC) analysis of combined markers (ISG15 and PLXNB2) significantly distinguished PTC from healthy control (HC) subjects. Similar differentiations were also found between thyroid adenoma and HC subjects. Notably, this combined marker could distinguish stage-I PTC from HC subjects (area under the curve (AUC) = 0.872). Our results revealed that ISG15 and PLXNB2 are independent diagnostic biomarkers for PTC and thyroid adenoma, showing a promising value for the early detection of PTC.

Efficacy and safety of methylphenidate and ginseng in cancer-related fatigue: a network meta-analysis of randomized controlled trials.

Background: Incidence of cancer-related fatigue (CRF), which can persist 5 to 10 years, is nearly 85% in cancer patients. It severely affects the quality of life and is strongly associated with poor prognosis. As clinical trial data on CRF treated with methylphenidate and ginseng, two potential medicines, has been accumulating, an updated meta-analysis was performed to evaluate and compare the efficacy and safety of the two medicines in CRF. Methods: Randomized controlled trials that investigated methylphenidate or ginseng in the treatment of CRF were identified through a literature search. The primary outcome was CRF relief. Standardized mean difference (SMD) was used to analyze the effect. Results: Eight studies on methylphenidate were included and the pooled SMD was 0.18 [95% confidence interval (95% CI): -0.00 to 0.35, P=0.05]. Five studies on ginseng were included and the SMD was 0.32 (95% CI: 0.17-0.46, P<0.0001). Results of network meta-analysis showed that the order was ginseng, methylphenidate, placebo from high efficacy to low and ginseng was significantly better than methylphenidate (SMD =0.23, 95% CI: 0.01-0.45). Incidences of insomnia and nausea caused by ginseng were significantly lower than those caused by methylphenidate (P<0.05). Conclusions: Both methylphenidate and ginseng can significantly ameliorate CRF. Ginseng may be superior to methylphenidate because ginseng may be more effective and might cause less adverse events. Head-to-head trials with fixed protocol are warranted to identify the optimal medical strategy.

ETS2 alleviates acute-on-chronic liver failure by suppressing excessive inflammation.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a syndrome with high short-term mortality. The mechanism of the transcription factor ETS2 in ACLF remains unclear. This study aimed to clarify the molecular basis of ETS2 in ACLF pathogenesis. Peripheral blood mononuclear cells from patients with HBV-ACLF (n = 50) were subjected to RNA sequencing. Transcriptome analysis showed that ETS2 expression was significantly higher in ACLF patients than in patients with chronic liver diseases and healthy subjects (all p < 0.001). Area-under-ROC analysis of ETS2 demonstrated high values for the prediction of 28-/90-day mortality in ACLF patients (0.908/0.773). Significantly upregulated signatures of the innate immune response (monocytes/neutrophils/inflammation-related pathways) were observed in ACLF patients with high ETS2 expression. Myeloid-specific ETS2 deficiency in liver failure mice resulted in deterioration of biofunctions and increased expression of pro-inflammatory cytokines (IL-6/IL-1ß/TNF-α). Knockout of ETS2 in macrophages confirmed the downregulation of IL-6 and IL-1ß caused by both HMGB1 and lipopolysaccharide, and an NF-κB inhibitor reversed the suppressive effect of ETS2. ETS2 is a potential prognostic biomarker of ACLF patients that alleviates liver failure by downregulating the HMGB1-/lipopolysaccharide-triggered inflammatory response and may serve as a therapeutic target for ACLF.

Orthotopic Transplantation of Functional Bioengineered Livers in Rats.

Functional bioengineered livers (FBLs) are promising alternatives to orthotopic liver transplantation. However, orthotopic transplantation of FBLs has not yet been reported. This study aimed to perform the orthotopic transplantation of FBLs in rats subjected to complete hepatectomy. FBLs were developed using rat whole decellularized liver scaffolds (DLSs) with human umbilical vein endothelial cells implanted via the portal vein, and human bone marrow mesenchymal stem cells (hBMSCs) and mouse hepatocyte cell line implanted via the bile duct. FBLs were evaluated in terms of endothelial barrier function, biosynthesis, and metabolism and orthotopically transplanted into rats to determine the survival benefit. The FBLs with well-organized vascular structures exhibited endothelial barrier function, with reduced blood cell leakage. The implanted hBMSCs and hepatocyte cell line were well aligned in the parenchyma of the FBLs. The high levels of urea, albumin, and glycogen in the FBLs indicated biosynthesis and metabolism. Orthotopic transplantation of FBLs achieved a survival time of 81.38 ± 4.263 min in rats (n = 8) subjected to complete hepatectomy, whereas control animals (n = 4) died within 30 min (p < 0.001). After transplantation, CD90-positive hBMSCs and the albumin-positive hepatocyte cell line were scattered throughout the parenchyma, and blood cells were limited within the vascular lumen of the FBLs. In contrast, the parenchyma and vessels were filled with blood cells in the control grafts. Thus, orthotopic transplantation of whole DLS-based FBLs can effectively prolong the survival of rats subjected to complete hepatectomy. In summary, this work was the first to perform the orthotopic transplantation of FBLs, with limited survival benefits, which still has important value for the advancement of bioengineered livers.

Transcriptomics confirm the establishment of a liver-immune dual-humanized mouse model after transplantation of a single type of human bone marrow mesenchymal stem cell.

BACKGROUND AND AIMS: Human bone marrow mesenchymal stem cells (hBMSCs) are important for developing a dual-humanized mouse model to clarify disease pathogenesis. We aimed to elucidate the characteristics of hBMSC transdifferentiation into liver and immune cells. METHODS: A single type of hBMSCs was transplanted into immunodeficient Fah-/- Rag2-/- IL-2Rγc-/- SCID (FRGS) mice with fulminant hepatic failure (FHF). Liver transcriptional data from the hBMSC-transplanted mice were analysed to identify transdifferentiation with traces of liver and immune chimerism. RESULTS: Mice with FHF were rescued by implanted hBMSCs. Human albumin/leukocyte antigen (HLA) and CD45/HLA double-positive hepatocytes and immune cells were observed in the rescued mice during the initial 3 days. The transcriptomics analysis of liver tissues from dual-humanized mice identified two transdifferentiation phases (cellular proliferation at 1-5 days and cellular differentiation/maturation at 5-14 days) and ten cell lineages transdifferentiated from hBMSCs: human hepatocytes, cholangiocytes, stellate cells, myofibroblasts, endothelial cells and immune cells (T/B/NK/NKT/Kupffer cells). Two biological processes, hepatic metabolism and liver regeneration, were characterized in the first phase, and two additional biological processes, immune cell growth and extracellular matrix (ECM) regulation, were observed in the second phase. Immunohistochemistry verified that the ten hBMSC-derived liver and immune cells were present in the livers of dual-humanized mice. CONCLUSIONS: A syngeneic liver-immune dual-humanized mouse model was developed by transplanting a single type of hBMSC. Four biological processes linked to the transdifferentiation and biological functions of ten human liver and immune cell lineages were identified, which may help to elucidate the molecular basis of this dual-humanized mouse model for further clarifying disease pathogenesis.

Contributions of key countries, enterprises, and refineries to greenhouse gas emissions in global oil refining, 2000-2021.

The refining industry is the third-largest source of global greenhouse gas (GHG) emissions from stationary sources, so it is at the forefront of the energy transition and net zero pathways. The dynamics of contributors in this sector such as crucial countries, leading enterprises, and key emission processes are vital to identifying key GHG emitters and supporting targeted emission reduction, yet they are still poorly understood. Here, we established a global sub-refinery GHG emission dataset in a long time series based on life cycle method. Globally, cumulative GHG emissions from refineries reached approximately 34.1 gigatons (Gt) in the period 2000-2021 with an average annual increasing rate of 0.7%, dominated by the United States, EU27&UK, and China. In 2021, the top 20 countries with the largest GHG emissions of oil refining accounted for 83.9% of global emissions from refineries, compared with 79.5% in 2000. Moreover, over the past two decades, 53.9-57.0% of total GHG emissions came from the top 20 oil refining enterprises with the largest GHG emissions in 12 of these 20 countries. Retiring or installing mitigation technologies in the top 20% of refineries with the largest GHG emissions and refineries with GHG emissions of more than 0.1 Gt will reduce the level of GHG emissions by 38.0%-100.0% in these enterprises. Specifically, low-carbon technologies installed on furnaces and boilers as well as steam methane reforming will enable substantial GHG mitigation of more than 54.0% at the refining unit level. Therefore, our results suggest that policies targeting a relatively small number of super-emission contributors could significantly reduce GHG emissions from global oil refining.

Modified Nuss procedure for the treatment of pectus excavatum: Experience of 259 patients.

BACKGROUND: Pectus excavatum is not rare in China. Many treatments for this disease have proved to have many shortcomings. Nuss procedure has been a ground-breaking technology, but it also has some disadvantages. Hence, this study was conducted to review our experience in the use of modified Nuss procedure in our hospital. METHODS: Data from 259 patients suffered from pectus excavatum between August 2020 and August 2021 who were treated with modified Nuss procedure was analyzed retrospectively. RESULT: Age was from 3 to 37 years. The average was 15.54 years. The male was 213 cases and the female was 46 cases. The time patients or their family members found pectus excavatum varied. 10 cases had been repaired previously when patients were admitted in our hospital. The clinical symptoms also varied. Each case had an improvement in Haller index. The average of the postoperative hospitalization was 3.97 days. Most cases were inserted 1 bar. Complication rate was also very low. All patients or their parents or their guardians were satisfied with the appearance of the chest wall after operation. There was no death in the whole observation period. CONCLUSION: From our experience, this modified Nuss procedure have obtained optimistic outcomes with more minimal invasion and low complication rate. This surgical method may be applied to many other hospitals in the future.

Impacts of ezetimibe on risks of various types of cancers: a meta-analysis and systematic review.

BACKGROUND: Ezetimibe is a widely used medication to reduce the plasma cholesterol level, particularly low-density lipoprotein level. However, its impact on cancer remains controversial. Here, its impacts on risks of various types of cancers were meta-analyzed. METHODS: PubMed and Cochrane Library electronic databases were searched and randomized controlled trials with followed up for at least 24 weeks were selected and included. The experimental group was defined as those patients treated with ezetimibe alone or with other medications, and the control group was defined as those who received a placebo or the matched medication. The number of new cancer cases or cancer-related deaths was extracted. Statistical analysis was performed using Review Manager (version 5.3). RESULTS: Nine trials enrolling 35 222 patients were included in the analyses. Compared with the control group, ezetimibe increased the number of new intestine cancer patients [relative risk (RR), 1.30; 95% confidence interval (CI), 1.02-1.67; P = 0.03] and had a trend to increase the number of new breast cancer patients (RR, 1.39; 95% CI, 0.98-1.98; P = 0.07). There was no significant difference in new hepatobiliary cancer, prostate cancer, skin cancer or cancer of other sites. Ezetimibe did not significantly increase the risk of new cancer in total (RR, 1.03; 95% CI, 0.96-1.11; P = 0.38), cancer-related death (RR, 1.11; 95% CI, 0.98-1.26; P = 0.10) or cancer events (RR, 1.04; 95% CI, 0.97-1.12; P = 0.30). In terms of lipid-lowering effect, ezetimibe significantly reduced total cholesterol and low-density lipoprotein cholesterol, increased high-density lipoprotein cholesterol. CONCLUSION: Ezetimibe may increase the risk of intestine cancer and has a trend of increasing the risk of breast cancer. There is no evidence to support that it increases or decreases the risk of other types.

Bifidobacterium animalis sup F1-7 Acts as an Effective Activator to Regulate Immune Response Via Casepase-3 and Bak of FAS/CD95 Pathway.

Intestinal microecology was closely related to immune regulation, but the related mechanism was still unclear. This study aimed to reveal how microorganisms improved immune response via casepase-3 and Bak of FAS/CD95 pathway. Bifidobacterium animalis F1-7 inhibited the melanoma B16-F10 cells in vitro effectively; had a potent anticancer effect of lung cancer mice; effectively improved the spleen immune index and CD3+ (75.8%) and CD8+ (19.8%) expression level; strengthened the phagocytosis of macrophages; inhibited the overexpression of inflammatory factors IL-6 (319.10 ± 2.46 pg/mL), IL-8 (383.05 ± 9.87 pg/mL), and TNF-α (2003.40 ± 11.42 pg/mL); and promoted the expression of anti-inflammatory factor IL-10 (406.00 ± 3.59 pg/mL). This process was achieved by promoting caspase-8/3 and BH3-interacting domain death agonist (Bid), Bak genes, and protein expression. This study confirmed the B. animalis F1-7 could act as an effective activator to regulate immune response by promoting the expression of caspase-8/3, Bid and Bak genes, and proteins and by activating the FAS/CD95 pathway. Our study provided a data support for the application of potentially beneficial microorganisms of B. animalis F1-7 as an effective activator to improve immunity.

Efficacy of ginseng oral administration and ginseng injections on cancer-related fatigue: A meta-analysis.

BACKGROUND: Up to 90% of patients who are under the active treatment suffer from cancer-related fatigue (CRF). CRF can persist about 10 years after diagnosis and/or treatment. Accumulating reports support that ginseng and ginseng injections are both potential drugs for the treatment of CRF but few studies put them together for analysis. METHODS: Two reviewers independently extracted data in 3 databases (PubMed, Cochrane Library and China National Knowledge Infrastructure) from their inception to May 24, 2021. The primary outcome was the effect of ginseng in alleviating CRF. The secondary outcome was ginseng in alleviating emotional or cognitive fatigue. Standardized mean difference (SMD) was employed. RESULTS: Twelve studies were included to evaluate efficacy of ginseng oral administration and ginseng injections on CRF. The pooled SMD was 0.40 (95% confidence Interval [95% CI] [0.29-0.51], P < .00001). Six studies were included to evaluate efficacy of ginseng oral administration on CRF and the SMD was 0.29 (95% CI [0.15-0.42], P < .0001). The order was 2000 mg/d, 3000 mg/d, 1000 mg/d and placebo from high efficacy to low. Ten studies were included to evaluate efficacy of ginseng injections on CRF and the SMD was 0.74 (95% CI [0.59-0.90], P < .00001). Emotional fatigue was reported in 4 studies, ginseng oral administration in 2 and ginseng injections in 2. The pooled SMD was 0.12 (95% CI [-0.04 to 0.29], P = .15). Cognitive fatigue was reported in 4 studies focusing on ginseng injections and the SMD was 0.72 (95% CI [0.48-0.96], P < .00001). CONCLUSION: Ginseng can improve CRF. Intravenous injection might be better than oral administration. Ginseng injections may alleviate cognitive fatigue. No evidence was found to support that ginseng could alleviate emotional fatigue.

Analysis of the Risk Factors for Elevated D-Dimer Level After Breast Cancer Surgery: A Multicenter Study Based on Nursing Follow-Up Data.

D-dimer level is often used to assess the severity of trauma as well as the risk of thrombosis. This study investigated the risk factors for high postoperative D-dimer level. This study included a total of 2706 patients undergoing breast cancer surgery to examine the associations between various clinicopathological factors and variation in D-dimer levels. After adjusting for other factors, T stage, neoadjuvant chemotherapy, blood loss, surgery type, diabetes, and elevated leukocyte and neutrophil counts were found to be significant risk factors for D-dimer variation. This study identified several factors associated with elevated D-dimer levels and consequent thrombosis after breast cancer surgery, which may aid in the development of more precise preventive measures and interventions as well as serve as a reference for future research.

Bifidobacterium bifidum relieved DSS-induced colitis in mice potentially by activating the aryl hydrocarbon receptor.

Inflammatory bowel disease (IBD) characterized by relapsed intestinal inflammation and barrier function disruption is still a great therapeutic challenge. This study aimed to screen probiotics that have the potential to help alleviate IBD and further elucidate their mechanism of action. Caco-2 cell differentiated monolayers and RAW264.7 cells stimulated by lipopolysaccharide (LPS) were used for probiotic screening in vitro, and then the efficacies of the obtained six bacterial strains were evaluated in mice with dextran sulfate sodium (DSS)-induced colitis. The results showed that all of the strains at varying degrees could increase the transepithelial electrical resistance (TEER) value, decrease the influx of FITC-dextran in Caco-2 cell monolayers and attenuate the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in LPS-stimulated RAW264.7 cells. In vivo experiments indicated that Bifidobacterium bifidum FL-276.1 (FL-276.1) and Bifidobacterium bifidum FL-228.1 (FL-228.1) showed the best efficacies to ameliorate body weight loss, colon shortening, and intestinal barrier disruption. Accordingly, in FL-276.1 and FL-228.1 groups, the genes of zonula occludens-1 (ZO-1), claudin-4, occludin and mucin 2 (Muc2) in mouse colonic tissues were significantly upregulated, while TNF-α, IL-1ß and IL-6 were downregulated. Further results showed that strains FL-276.1 and FL-228.1 could activate the aryl hydrocarbon receptor (AhR) in the intestine. Our study showed that the two Bifidobacterium bifidum strains, FL-276.1 and FL-228.1, ameliorated DSS-induced colitis by enhancing the intestinal barrier and anti-inflammation potentially via the AhR pathway.

Pre-Emptive Antifibrinolysis: Its Role and Efficacy in Hip Fracture Patients Undergoing Total Hip Arthroplasty.

BACKGROUND: We aimed to determine the efficacy of pre-emptive antifibrinolysis with tranexamic acid (TXA) in decreasing hidden blood loss (HBL) in the elderly hip fracture patients. METHODS: Ninety-six elderly hip fracture patients receiving hip arthroplasty were randomized to receive 100 mL of normal saline (group A) or 1.5 g of TXA (group B) intravenously q12 hours from postadmission day 1 (PAD1) to the day before surgery. Both groups were treated with 1.5 g of TXA q12 hours from postoperative day 1 (POD1) to POD3. HBL was calculated by formulas and recorded as the primary outcome. RESULTS: In overall analyses, no difference was found in HBL, while the decline of hemoglobin (ΔHb), allogeneic blood transfusion (ABT) rate, fibrinogen degradation product (FDP-on PAD2, PAD3, POD1, and POD2), and d-dimer (D-D-on PAD2, PAD3, and POD1) were lower in group B. In subgroup analyses for patients receiving intervention within 72 hours of injury, group B had lower postoperative HBL, ΔHb, ABT rate, FDP, and D-D levels (on PAD2, PAD3, POD1, and POD2). For patients receiving intervention over 72 hours after injury, no difference was detected in perioperative HBL, ΔHb, and ABT rate between the 2 groups. The FDP and D-D levels were lower in group B on PAD2 and PAD3. No difference was found in coagulation parameters, wound complications, venous thromboembolism rate, and 90-day mortality in all analyses. CONCLUSION: Early administration (within 72 hours of injury) of multidose of TXA is effective in reducing perioperative HBL in elderly hip fracture patients. Delayed use (over 72 hours after injury) of TXA was not beneficial.