A rescue diet raises the plasma calcium concentration and ameliorates rheumatoid arthritis in mice: Role of CaSR-mediated inhibition of osteoclastogenesis.

Calcium modulates bone cell recruitment, differentiation, and function by binding to the calcium-sensing receptor (CaSR). However, the function of CaSR induced by high extracellular calcium (Ca2+ e ) in the regulation of osteoclast formation in rheumatoid arthritis (RA) remains unknown. Here, we used TNFα-transgenic (TNFTG ) RA mice and their wildtype (WT) littermates fed a normal or a rescue diet (high calcium, high phosphorus, and high lactose diet, termed rescue diet) to compare their joint bone phenotypes. In comparison to TNFTG mice fed the normal diet, articular bone volume and cartilage area are increased, whereas inflamed area, eroded surface, TRAP+ surface, and osteoclast-related genes expression are decreased in TNFTG mice fed the rescue diet. Besides, TNFTG mice fed the rescue diet were found to exhibit more CaSR+ area and less NFATc1+ /TRAP+ area. Furthermore, at normal Ca2+ e concentrations, osteoclast precursors (OCPs) from TNFTG mice formed more osteoclasts than OCPs from WT mice, but the number of osteoclasts gradually decreased when the Ca2+ e concentration increased. Meanwhile, the expression of CaSR increased responding to a high level of Ca2+ e , whereas the expression of NF-κB/NFATc1 signaling molecules decreased. At last, the knockdown of CaSR blocked the inhibition of osteoclast differentiation attributed to high Ca2+ e . Taken together, our findings indicate that high Ca2+ e inhibits osteoclast differentiation in RA mice partially through the CaSR/NF-κB/NFATc1 pathway.

Factors associated with urinary retention after vaginal delivery under intraspinal anesthesia: a path analysis model.

INTRODUCTION AND HYPOTHESIS: Women who have intraspinal anesthesia for delivery are more likely to experience postpartum urinary retention (PUR), which, if not recognized and treated promptly, can result in long-term urinary dysfunction. Many factors influencing PUR have been proposed, but no study has been conducted to investigate the relationship between them. This study is aimed at determining the influencing factors of PUR and to explore the relationship between them. METHODS: A prospective, cross-sectional survey using self-made questionnaires was conducted among 372 puerperae in a Grade A hospital in Guangzhou, China, from April to September 2022. SPSS25.0 and AMOS24.0 were used for data analysis, and a path analysis model was established to determine the relationship between the influencing factors. RESULTS: The incidence of PUR was 49.85%. Residence, the level of postpartum pain, and the change of postnatal urination position had a direct effect on PUR. Episiotomy and analgesic duration have both direct and indirect effects on PUR. Forceps delivery, perineal edema and oxytocin had an indirect effect on PUR. Variables could influence the occurrence of PUR by mediating the analgesic duration, episiotomy, postpartum pain level, and postnatal urination position changes. CONCLUSIONS: This study provides an empirical model to illustrate the relationship between PUR and related factors in women who delivered under intraspinal anesthesia. In future management, more attention should be paid to women who live in cities, have higher levels of postpartum pain, longer analgesic duration, higher grade of perineal edema, and received episiotomy, forceps delivery, and oxytocin during labor.

3-Year outcomes after left atrial appendage closure in patients with nonvalvular atrial fibrillation: cardiomyopathy related with increased death and stroke rate.

INTRODUCTION: Left atrial appendage closure (LAAC) is a novel treatment for stroke prevention in high-risk patients with non-valvular atrial fibrillation (NVAF). However, the long-term outcomes after LAAC in Chinese NVAF patients are still lacking. METHODS: This was a single-center, bidirectional, nonrandomized registered study. Patients who underwent LAAC implantation from May 2014 to April 2021 in a large Chinese center were enrolled. The primary endpoint was combined all-cause death and stroke. RESULTS: From May 2014 to April 2021, a total of 673 NVAF patients were enrolled. The overall successful implantation rate was 97.62% (657 of 673). The rate of perioperative adverse events was 1.19% (8 of 673), including 3 cardiac tamponades, 2 ischemic strokes, one device-related thrombus (DRT) and 2 device dislocations. 604 (92.24%) patients completed the follow-up, the median follow-up period was 36.9 months (IQR 24.8-56.5 months). 16 stroke events occurred in 15 patients (one patient suffered from both hemorrhagic and ischemic strokes). 13 patients (2.15%) had ischemic stroke, and the fatal rate was 0.33% (2 of 604). 3 patients (0.15%) suffered from hemorrhagic stroke, and the fatal rate was 0.17% (1 of 604). The overall stroke rate was 0.74% per-year. The combined death and stroke rate was 1.93% per-year. In the multivariate Cox regression analysis, age ≥ 75 (hazard ratio 2.264, 95% CI 1.074-4.772, P = 0.032) and ventricular cardiomyopathy (hazard ratio 2.738, 95% CI 1.060-7.071, P = 0.037) were independent predictors of combined mortality and stroke. CONCLUSION: The overall successful implantation rate of LAAC was 97.62% and the rate of perioperative adverse events was 1.19% in this study, and the stroke rate was 0.74% per year during the long-term follow-up. Age ≥ 75 years and ventricular cardiomyopathy were independent predictors of the primary endpoint. Trial registration This study was retrospectively registered.

Safety and efficacy of gene therapy with onasemnogene abeparvovec in the treatment of spinal muscular atrophy: A systematic review and meta-analysis.

Spinal muscular atrophy (SMA) is an autosomal recessive hereditary disease which leads to progressive muscle weakness and atrophy. Our systematic review and meta-analysis aims to explore the efficacy and safety of onasemnogene abeparvovec in SMA patients. We searched PubMed, EMBASE, Web of Science and Cochrane through April 2022. Ten reports enrolling 250 SMA patients were included. CHOP INTEND and motor-milestone significant improvements were detected at both short- and long-term follow-up. Common adverse events included pyrexia, vomiting, thrombocytopenia and elevated aminotransferases. Thrombocytopenia (79.3%, 95%CI: 65.8~90.5) and elevated aminotransferases (71.7%, 95%CI: 62.5~80.1) were more common in SMA patients aged older than 8 months. Despite the paucity of randomized control trial data and low quality of evidence to establish the safety and efficacy of onasemnogene abeparvovec in the treatment of SMA, the data suggest that it is a valuable option for patients with this condition.

Native and Engineered Probiotics: Promising Agents against Related Systemic and Intestinal Diseases.

Intestinal homeostasis is a dynamic balance involving the interaction between the host intestinal mucosa, immune barrier, intestinal microecology, nutrients, and metabolites. Once homeostasis is out of balance, it will increase the risk of intestinal diseases and is also closely associated with some systemic diseases. Probiotics (Escherichia coli Nissle 1917, Akkermansia muciniphila, Clostridium butyricum, lactic acid bacteria and Bifidobacterium spp.), maintaining the gut homeostasis through direct interaction with the intestine, can also exist as a specific agent to prevent, alleviate, or cure intestinal-related diseases. With genetic engineering technology advancing, probiotics can also show targeted therapeutic properties. The aims of this review are to summarize the roles of potential native and engineered probiotics in oncology, inflammatory bowel disease, and obesity, discussing the therapeutic applications of these probiotics.

Affibody-conjugated 5-fluorouracil prodrug system preferentially targets and inhibits HER2-expressing cancer cells.

Overexpression of HER2 is associated with cancer phenotypes, such as proliferation, survival, metastasis and angiogenesis, and has been validated as a therapeutic target. However, only a portion of patients benefited from anti-HER2 treatments, and many would develop resistance. A more effective HER2 targeted therapeutics is needed. Here, we adopted a prodrug system that uses 5-fluorocytosine (5-FC) and a HER2-targeting scaffold protein, ZHER2:2891, fused with yeast cytosine deaminase (Fcy) to target HER2-overexpressing cancer cells and to convert 5-FC to a significantly more toxic chemotherapeutic, 5-fluorouracil (5-FU). We cloned the coding gene of ZHER2:2891 and fused with those of ABD (albumin-binding domain) and Fcy. The purified ZHER2:2891-ABD-Fcy fusion protein specifically binds to HER2 with a Kd value of 1.6 nM ZHER2:2891-ABD-Fcy binds to MDA-MB-468, SKOV-3, BT474, and MC38-HER2 cells, which overexpress HER2, whereas with a lower affinity to HER2 non-expresser, MC38. Correspondingly, the viability of HER2-expressing cells was suppressed by relative low concentrations of ZHER2:2891-ABD-Fcy in the presence of 5-FC, and the IC50 values of ZHER2:2891-ABD-Fcy for HER2 high-expresser cells were approximately 10-1000 fold lower than those of non-HER2-targeting Fcy, and ABD-Fcy. This novel prodrug system, ZHER2:2891-ABD-Fcy/5-FC, might become a promising addition to the existing class of therapeutics specifically target HER2-expressing cancers.

Effect of VEGFC on lymph flow and inflammation-induced alveolar bone loss.

The lymphatic system plays a crucial role in the maintenance of tissue fluid homeostasis and the immunological response to inflammation. The effects of lymphatic drainage dysfunction on periodontitis have not been well studied. Here we show that lymphatic vessel endothelial receptor 1 (LYVE1)+ /podoplanin (PDPN)+ lymphatic vessels (LVs) are increased in the periodontal tissues, with accumulation close to the alveolar bone surface, in two murine periodontitis models: rheumatoid arthritis (RA)-associated periodontitis and ligature-induced periodontitis. Further, PDPN+ /alpha-smooth muscle actin (αSMA)- lymphatic capillaries are increased, whereas PDPN+ /αSMA+ collecting LVs are decreased significantly in the inflamed periodontal tissues. Both mouse models of periodontitis have delayed lymph flow in periodontal tissues, increased TRAP-positive osteoclasts, and significant alveolar bone loss. Importantly, the local administration of adeno-associated virus for vascular endothelial growth factor C, the major growth factor that promotes lymphangiogenesis, increases the area and number of PDPN+ /αSMA+ collecting LVs, promotes local lymphatic drainage, and reduces alveolar bone loss in both models of periodontitis. Lastly, LYVE1+ /αSMA- lymphatic capillaries are increased, whereas LYVE1+ /αSMA+ collecting LVs are decreased significantly in gingival tissues of patients with chronic periodontitis compared with those of clinically healthy controls. Thus, our findings reveal an important role of local lymphatic drainage in periodontal inflammation-mediated alveolar bone loss. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Short-term non-vitamin K antagonist oral anticoagulants vs. warfarin in preventing device-related thrombosis after left atrial appendage closure.

Up to now we have had few evidences on the Non-vitamin K Antagonist Oral Anticoagulants (NOACs)' efficacy and safety in preventing device-related thrombosis (DRT) after percutaneous left atrial appendage closure (LAAC). After LAAC implantation, short-term anticoagulation (NOACs or warfarin) was prescribed. Baseline clinical characteristics, procedural parameters and postoperative follow up data were collected and compared between the two groups. From May 2014 to June 2018, 361 consecutive patients underwent LAAC implantation in our center. 170 patients received warfarin for 45 days at least after LAAC implantation, who were compared with 170 age-matched patients on NOACs. The basic clinical characteristics, as well as procedural parameters were comparable between the two groups, while the NOACs group had higher average CHA2DS2-VASc score (3.3  ±  1.6 vs. 2.9  ±  1.5, P = 0.022*). At 45 days follow up, 289 (86.5%) patients received transoesophageal echocardiography (TEE), and the overall incidence of DRT was 2.4%. The DRT rate was not significantly different between the NOACs and warfarin groups (2.7% vs. 2.1%, P > 0.05), while the NOACs group showed lower all bleeding rate (1.2% vs. 9.0%, P < 0.01). The rates of ischemic stroke as well as major bleeding were comparable between the two groups. Except for 7 DRTs and 1 major peri-device leakage (> 5 mm), anticoagulation was terminated in all other patients. During the follow-up thereafter (mean 868 days), the rates of all-cause death, ischemic stroke and bleeding were comparable between the two groups. Short-term NOACs after LAAC appear to be as effective as warfarin in preventing DRT, with lower bleeding rate.

The effect of probiotic supplementation during pregnancy on the interaction network of vaginal microbiome.

AIM: To evaluate the effect of probiotic supplementation on the vaginal microbiome and provide the effective evidences for clinical management of pregnant women. METHODS: A total of 28 healthy pregnant women at 32 weeks of gestation were enrolled. The women were divided randomly to the probiotic group where they were prescribed with 2 g combined probiotics daily (13 cases) during the third trimester of pregnancy or to the control group (15 cases) on a voluntary basis. Their vaginal samples were taken for analyzing microbiome with the 16S rDNA amplicon sequencing of V4 region. RESULTS: There was no significant difference on the clinical characteristics between the probiotic and control groups. The complexity of vaginal microbial network increased from 32 weeks of gestation to antepartum. Lactobacillus was the dominant microbiota. The probiotic supplementation had no obvious influence on the structure of the vaginal microbiome, whereas the relationships of some pivotal vaginal microbiota at the genus level changed in the probiotic group. CONCLUSION: The vaginal microbiome varied during the third trimester of pregnancy. The features of the vaginal microbiota after probiotic supplementation had shifted and the interaction network had the tendency to be loose. The probiotic supplementation may be useful in regulating the interaction network of vaginal microbiome.

Effects of an orally supplemented probiotic on the autophagy protein LC3 and Beclin1 in placentas undergoing spontaneous delivery during normal pregnancy.

BACKGROUND: Probiotic supplementation has been shown to be beneficial and is now widely promoted as an auxiliary medicine for maternal health, but the underlying mechanism is still unclear. Thus, this study aimed to explore the effects of probiotic supplementation on the placental autophagy-related proteins LC3 and Beclin1. METHOD: A population-based cohort of specimens was collected under sterile conditions from 37 healthy nulliparous pregnant women who underwent systemic examination and delivered at the First Affiliated Hospital of Jinan University (Guangzhou, China). At 32 weeks of gestation, the pregnant women in the probiotic group were orally supplemented with golden bifid, and the pregnant women in the control group received no probiotic. Pregnant women with pregnancy-associated complications were excluded in the follow-up period, and 25 pregnant women undergoing spontaneous delivery were enrolled. The placental tissue specimens were collected at term. Western blotting was used to detect the protein expression, and qRT-PCR was used to detect the mRNA expression of the placental autophagy-related proteins LC3 and Beclin1. RESULTS: ①There was no significant difference in the expression levels of either LC3 or Beclin1 protein between the two groups (P > 0.05). ②Probiotic supplementation induced a modest but not significant decrease in the content of LC3-mRNA with a significant decrease in the content of Beclin1-mRNA (P < 0.05). CONCLUSION: Our study indicates that probiotic supplementation may reduce Beclin1-mRNA levels.

Evaluation of Femoral Head Perfusion by Contrast-Enhanced Ultrasound in a Rabbit Model of Steroid-Induced Osteonecrosis.

OBJECTIVES: To study the technical feasibility of contrast-enhanced ultrasound (CEUS) in evaluating femoral head perfusion in a rabbit model of steroid-induced femoral head osteonecrosis. METHODS: Twenty rabbits were divided randomly into a control group (n = 8) and an experimental group (n = 12). Rabbits in the experimental group were induced by lipopolysaccharide and methylprednisolone to build a model of steroid-induced femoral head osteonecrosis. Contrast-enhanced ultrasound examinations were performed at 3 and 5 weeks after induction. Then, pathologic examinations and microvessel density (MVD) calculations were performed on the excised rabbit femoral heads. RESULTS: The MVD of the experimental group decreased significantly 3 and 5 weeks after induction compared with that of the control group. According to the CEUS examination results, significant differences existed in the ascending slope, descending slope, mean transit time, and time to peak between the groups at 5 weeks (P < .05). A correlation analysis showed that the descending slope had a certain correlation with the MVD (correlation coefficient, 0.376). A receiver operating characteristic curve was used to analyze the capacity of the CEUS parameters to predict the occurrence of osteonecrosis. The areas under the curve for the ascending slope and descending slope were 0.758 and 0.760, respectively (P < .05). CONCLUSIONS: Contrast-enhanced ultrasound can visualize the microcirculation in steroid-induced osteonecrosis of the femoral head in rabbits and may be a useful imaging method for the early monitoring and prediction of femoral head osteonecrosis.

Distribution and correlates of plasma folate, vitamin B12, and homocysteine in a sample of low-income minority children aged 6 months to 9 years in the U.S.

Background: Precision nutrition emphasizes tailoring dietary requirements across populations and life stages. Optimal folate and vitamin B12 levels are important for normal growth and development, but data are lacking for low-income minority U.S. children during early life periods. This study aimed to describe folate, vitamin B12, homocysteine (Hcy) levels, and influencing factors to address the gaps. Methods: Blood samples from children aged 6 months to 9 years and mothers 48-72 hours postpartum in the Boston Birth Cohort (BBC) were tested for folate, vitamin B12, and Hcy. Maternal and child characteristics, sociodemographic factors, and feeding status were obtained from a standard maternal questionnaire interview at the enrollment and follow-up, and medical records. The distribution of children's folate, vitamin B12, and Hcy were described and factors influencing these biomarkers were analyzed. Results: A wide distribution of folate, vitamin B12, and Hcy levels was observed in this sample, with longitudinal trends consistent with National Health and Nutrition Examination Survey (NHANES) data. Multivariate analysis showed that very preterm birth correlated with higher folate levels (adjusted ß 4.236; 95% CI: 1.218, 7.253; p=0.006). Children aged 1-2 years and 3-8 years had lower folate levels compared to those <1 year (adjusted ß -10.191 and -7.499 respectively; p<0.001). Vitamin B12 levels were higher in Black children (adjusted fold change 1.139; 95% CI: 1.052, 1.233; p=0.001) and those children whose mothers' B12 levels were at the highest quartile (Q4) (adjusted fold change 1.229; 95% CI: 1.094, 1.380; p=0.001). Delayed solid food introduction (> 6 months) correlated with lower children's B12 levels (adjusted fold change 0.888; 95% CI: 0.809, 0.975; p=0.013). Hcy levels were lower in Black children (adjusted fold change 0.962; 95% CI: 0.932, 0.993; p=0.018), higher in children with maternal Hcy levels in Q4 (adjusted fold change 1.081; 95% CI: 1.03, 1.135; p=0.002) and in children aged 3-8 years (adjusted fold change 1.084; 95% CI: 1.040, 1.131; p< 0.001). Conclusions: This study revealed wide variations in plasma folate, vitamin B12, and Hcy levels among low-income minority U.S. children and identified race, maternal levels, child's age, prematurity, and timing of solid food introduction as significant correlates.

A sustained decrease in the systolic/diastolic ratio may be a sign of severe adverse events in the umbilical cord: a report of eight cases.

A high systolic/diastolic (S/D) ratio of umbilical cord blood is a manifestation of intrauterine hypoxia. However, the clinical significance of a persistently decreased S/D ratio of umbilical cord blood has not been reported. We report eight cases of a persistently decreased S/D ratio of umbilical cord blood, with two cases of umbilical thrombus, five cases of excessive torsion, and one case of a true cord knot. Fetuses with a persistently decreased S/D ratio of umbilical cord blood may be at risk, and it may be an important indication of umbilical cord lesions.

Phenotypic and genotypic characterization of NPRL3-related epilepsy: Two case reports and literature review.

Nitrogen permease regulator-like 3 (NPRL3) has been reported to play a role in seizure onset. The principal manifestation of NPRL3-related epilepsy is a range of epilepsy-associated syndromes, such as familial focal epilepsy with variable foci (FFEVF), sleep-related hypermotor epilepsy (SHE), and temporal lobe epilepsy (TLE). The association between phenotype and genotype of NPRL3 mutations remains inadequately described. This study aimed to explore the phenotypic and genotypic spectra of NPRL3-related epilepsy. We reported two novel NPRL3 variants in two unrelated epilepsy cases, including a nonsense (c.1174C > T, p.Gln392*) and a missense variant (c.1322C > T, p.Thr441Met). Following a review of the literature, a total of 116 cases of NPRL3-related epilepsy were assessed, mostly with nonsense and frameshift mutations. Our findings suggest that patients harboring various NPRL3 variants exhibit variable clinical manifestations. In addition, it may be worthwhile to consider the existence of NPRL3 mutations in epilepsy patients with a family history. This study provides useful information for the treatment and prognosis by expanding the phenotypic and genotypic spectrum of NPRL3-related epilepsy. PLAIN LANGUAGE SUMMARY: This study expands the phenotypic and genotypic spectra of NPRL3-related epilepsy by reporting two cases with different novel variants. Following a review of the literature, it was observed that patients harboring various NPRL3 variants exhibited a variability of clinical manifestations. Also, patients carrying nonsense mutations are frequently prone to drug resistance and other severe comorbidities such as developmental delay, but more cases need to be collected to confirm these findings.

Synergy of de-walled Ganoderma Lucidum spore powder (GLSP) on targeted therapy in advanced non-squamous non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutant: protocol for a randomized, double-blind, placebo-controlled study.

BACKGROUND: Osimertinib is regarded as a promising third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced non-squamous non-small cell lung cancer (NSCLC) patients who developed T790M. However the adverse effects, primarily fatigue, remain an overwhelming deficiency of Osimertinib, hindering it from achieving adequate clinical efficacy for such NSCLC. Ganoderma lucidum has been used for thousands of years in China to combat fatigue, while Ganoderma Lucidum spores powder (GLSP) is the main active ingredient. The aim of this study is to investigate whether GLSP is sufficiently effective and safe in improving fatigue and synergizing with Osimertinib in non-squamous NSCLC patients with EGFR mutant. METHOD/DESIGN: A total of 140 participants will be randomly assigned to receive either de-walled GSLP or placebo for a duration of 56 days. The primary outcome measure is the fatigue score associated with EGFR-TKI adverse reactions at week 8, evaluated by the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30). Secondary outcomes include evaluation of treatment effectiveness, assessment of quality of life (QoL), and exploration of immune indicators and gut microbiota relationships. Following enrollment, visits are scheduled biweekly until week 12. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2300072786. Registrated on June 25, 2023.

Renal function modifies the association between hemoconcentration and outcomes in hospitalized heart failure patients.

Evidence-based management of decongestion is lacking in hospitalized heart failure (HHF) patients, especially in patients with impaired renal function. Hemoconcentration is an objective measure of decongestion that portends a favorable prognosis and guides management in HHF patients with preserved renal function. We aim to investigate whether it remains a prognosticator in patients with renal impairment, and to refine the identification of subpopulations who will benefit from hemoconcentration-guided therapy. HHF patients admitted to Heart Failure Center of Fuwai Hospital were consecutively included from December 2006 to June 2018. Patient characteristics were depicted. Relationships between in-hospital hemoconcentration, worsening renal function (WRF), and one-year all-cause mortality were investigated in the total population and compared between renal function groups using survival analysis and cubic splines, with a special focus on renal function-based interactions. The association was further validated in sensitivity analyses. Clinically relevant cut-offs and subpopulations were identified by subpopulation treatment effect pattern plots (STEPP) and subgroup analysis. 3661 participants (30.4% with impaired renal function) were included. Hemoconcentration, reflected by an in-hospital increase in hemoglobin, hematocrit, or a relative reduction in estimated plasma volume from baseline to discharge, was predictive of decreased one-year mortality in the total cohort despite its correlation with higher WRF incidence. The prognostic value of hemoconcentration differed in patients with impaired and preserved renal function. Hemoconcentration was related to a favorable prognosis in patients with preserved renal function (HR, 0.69; 95% CI, 0.53-0.90; P = 0.007), especially in young male patients with New York Heart Association functional class III-IV, reduced ejection fraction, and baseline eGFR > 75 mL/min/1.73m2. Contrarily, impaired renal function patients experienced a higher incidence of WRF, and hemoconcentration was no longer related to outcome (HR, 0.90; 95% CI, 0.64-1.26; P = 0.545), with findings consistent in all clinically relevant subgroups. In HHF patients, the prognostic value of hemoconcentration differs by renal function, and the clinical utility of hemoconcentration is contingent on preserved renal function.

Selection of Fermentation Supernatant from Probiotic Strains Exhibiting Intestinal Epithelial Barrier Protective Ability and Evaluation of Their Effects on Colitis Mouse and Weaned Piglet Models.

The intestinal epithelial barrier can prevent the invasion of pathogenic microorganisms and food antigens to maintain a consistent intestinal homeostasis. However, an imbalance in this barrier can result in various diseases, such as inflammatory bowel disease, malnutrition, and metabolic disease. Thus, the aim of this study was to select probiotic strains with epithelial barrier-enhancing ability in cell-based model and further investigate them for their improving effects on colitis mouse and weaned piglet models. The results showed that selected specific cell-free fermentation supernatants (CFSs) from Ligilactobacillus salivarius P1, Lactobacillus gasseri P12, and Limosilactobacillus reuteri G7 promoted intestinal epithelial cell growth and proliferation, strengthening the intestinal barrier in an intestinal epithelial cell line Caco-2 model. Further, the administration of CFSs of L. salivarius P1, L. gasseri P12, and L. reuteri G7 were found to ameliorate DSS-induced colitis in mice. Additionally, spray-dried powders of CFS from the three strains were examined in a weaned piglet model, only CFS powder of L. reuteri G7 could ameliorate the feed/gain ratio and serum levels of D-lactate and endotoxin. In conclusion, a new potential probiotic strain, L. reuteri G7, was selected and showed ameliorating effects in both colitis mouse and weaned piglet models.

Association of point-of-care testing for sST2 with clinical outcomes in patients hospitalized with heart failure.

AIMS: This study aimed to investigate the association of soluble suppression of tumorigenicity-2 (sST2) measured by point-of-care testing assay with clinical outcomes in patients hospitalized with heart failure after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). METHODS: A total of 1726 consecutive patients hospitalized with heart failure from July 2015 to December 2021 were enrolled. Baseline serum sST2 concentrations were measured by immunofluorescence assay. Primary endpoint event was the composite of all-cause death, heart transplantation, or left ventricular assist device. RESULTS: During the median follow-up duration of 682 days, 434 patients (25.1%) suffered from primary endpoint events. Baseline sST2 remained an independent predictor of the primary endpoint event in patients hospitalized with heart failure after adjusting for other predictors including NT-proBNP and hs-cTnT [per log (unit) increase, adjusted hazard ratio (HR) (95% confidence interval) (CI): 1.20 (1.09, 1.32), P < 0.001]. And baseline sST2 had a better prognostic value for patients with chronic decompensated heart failure [per log (unit) increase, adjusted HR (95% CI): 1.19 (1.07, 1.31)] than for those with acute new onset heart failure [per log (unit) increase, adjusted HR (95% CI): 1.28 (0.94, 1.75), P value for interaction <0.001], as well as a better prognostic value for patients with New York Heart Association (NYHA) functional class I-II [per log (unit) increase, adjusted HR (95% CI): 1.67 (1.11, 2.52)] than for those with NYHA functional class III-IV [per log (unit) increase, adjusted HR (95% CI): 1.18 (1.07, 1.31), P value for interaction <0.001]. Baseline sST2 was also a good predictor of the primary endpoint event in patients hospitalized with heart failure at 1 month, 3 months, 1 year and 2 years (area under the curve: 0.789, 0.775, 0.736 and 0.733, respectively), and the best cut-off values were 27.2 ng/ml, 27.1 ng/ml, 27.1 ng/ml and 25.1 ng/ml, respectively. Furthermore, baseline sST2 could provide additional prognostic value when added to baseline NT-proBNP and hs-cTnT (all P values <0.05). According to the category of elevated biomarkers (including NT-proBNP, hs-cTnT, and sST2), patients with three elevated biomarkers had a higher risk of the primary endpoint event compared with those with one or two elevated biomarkers (all P values <0.05). CONCLUSIONS: Baseline sST2 remained an independent predictor of adverse events after adjusting for other predictors including NT-proBNP and hs-cTnT, particularly in patients with chronic decompensated heart failure and NYHA functional class I-II. And in the basis of baseline NT-proBNP and hs-cTnT, adding baseline sST2 could provide additional prognostic value for patients hospitalized with heart failure.

A secure 2G-RFID-Sys mechanism for applying to the medical emergency system.

In the Medical Emergency System, any moment of delay in an emergency such as ambulance dispatch, ambulance diversion and clinical handover communication can significantly reduce a patient's chance of survival. Without the disadvantage of centralized management, a new type of RFID application named 2G-RFID-Sys will be more efficient. It is suitable for the tagged ambulance dispatch management in a huge range. In this article, the prototype of 2G-RFID-Sys and the responsibility of each participant are refined. We take an example of applying the 2G-RFID-Sys to the Medical Emergency System, the traffic condition of the ambulance will be able to ensure.

Percutaneous left atrial appendage closure in patients with hypertrophic cardiomyopathy and persistent atrial fibrillation: 3-year-followed case series.

Hypertrophic cardiomyopathy (HCM) patients with atrial fibrillation (AF) are at high risk for stroke. Left atrial appendage closure (LAAC) is a promising alternative for stroke prevention in AF patients. We aimed to review the clinical outcomes of patients with AF and HCM at our center. We reviewed 673 patients who underwent LAAC implantation from 2014 to 2021 in a tertiary center, of whom 15 had HCM. AF Patients with HCM were compared with sex and age matched controls who also underwent LAAC. From 2014 to 2021, 673 AF patients received LAAC in a single center, of whom, 15 patients had HCM. LAAC devices were successfully implanted in 14 HCM patients and 59 patients in the control group. During the follow-up period (median 1151 days range: 132-2457 days), 2 HCM patient had ischemic strokes. There were another 2 HCM patients who had sudden cardiac death (SCD). Compared with the control, HCM patients had higher cumulative rate of combined death and stroke (26.67% vs 3.33%, P = .024). In our initial clinical experience, the cumulative stroke and death rate of the HCM patients was significantly higher than that of the non-HCM patients.