Whole-protein enteral nutrition formula supplementation reduces Escherichia and improves intestinal barrier function in HIV-infected immunological nonresponders.

People living with human immunodeficiency virus (PLWH) have persistent malnutrition, intestinal barrier dysfunction, and gut microbial imbalance. The interplay between gut microbiota and nutrients is involved in the immune reconstitution of PLWH. To evaluate the effects of whole-protein enteral nutrition formula supplementation on T-cell levels, intestinal barrier function, nutritional status, and gut microbiota composition in human immunodeficiency virus (HIV)-infected immunological nonresponders (INRs) who failed to normalize CD4+ T-cell counts, with a number <350 cells/µL, a pilot study was carried out in 13 HIV-infected INRs undergoing antiretroviral therapy who received a 3-month phase supplementation of 200 mL/200 kcal/45 g whole-protein enteral nutrition formula once daily. Our primary endpoint was increased CD4+ T-cell counts. Secondary outcome parameters were changes in intestinal barrier function, nutritional status, and gut microbiota composition. We showed that CD4+ T-cell counts of HIV-infected INRs increased significantly after the 3-month supplementation. Dietary supplementation for 3 months improved the intestinal barrier function and nutritional status of HIV-infected INRs. Furthermore, the enteral nutrition formula significantly decreased the relative abundance of Escherichia at the genus level and increased the alpha diversity of gut microbiota in HIV-infected INRs. The findings demonstrated that the whole-protein enteral nutrition formula aids in reducing Escherichia and improving intestinal barrier function in HIV-infected INRs. This study provides insight into the role of nutrients in the improvement of immune reconstitution in HIV-infected INRs. This study is registered in the Chinese Clinical Trial Registry (Document No. ChiCTR2000037839; http://www.chictr.org.cn/index.aspx).

Effect of intraoperative remimazolam on postoperative sleep quality in elderly patients after total joint arthroplasty: a randomized control trial.

PURPOSE: To investigate the effect of intraoperative remimazolam sedation on postoperative sleep quality in elderly patients after total joint arthroplasty. METHODS: Between May 15, 2021 and March 26, 2022, 108 elderly patients (age ≥ 65 years) who received total joint arthroplasty under neuraxial anesthesia were randomized into remimazolam group (a loading dose of 0.025-0.1 mg/kg and followed by an infusion rate of 0.1-1.0 mg/kg/h till end of surgery) or routine group (sedation was given on patient's requirement by dexmedetomidine 0.2-0.7 µg/kg/h). Primary outcome was the subjective sleep quality at surgery night which was evaluated by Richards Campbell Sleep Questionnaire (RCSQ). Secondary outcomes included RCSQ scores at postoperative first and second nights and numeric rating scale pain intensity within first 3 days after surgery. RESULTS: RCSQ score at surgery night was 59 (28, 75) in remimazolam group which was comparable with 53 (28, 67) in routine group (median difference 6, 95% CI - 6 to 16, P = 0.315). After adjustment of confounders, preoperative high Pittsburg sleep quality index was associated worse RCSQ score (P = 0.032), but not remimazolam (P = 0.754). RCSQ score at postoperative first night [69 (56, 85) vs. 70 (54, 80), P = 0.472] and second night [80 (68, 87) vs. 76 (64, 84), P = 0.066] were equivalent between two groups. Safety outcomes were comparable between the two groups. CONCLUSIONS: Intraoperative remimazolam did not significantly improve postoperative sleep quality in elderly patients undergoing total joint arthroplasty. But it is proved to be effective and safe for moderate sedation in these patients. CLINICAL TRIAL NUMBER AND REGISTRY URL: ChiCTR2000041286 ( www.chictr.org.cn ).

Bacterial communities during composting cultivation of oyster mushroom Pleurotus floridanus using broken eggs as the nitrogen source and study of agronomic and nutritional properties.

Introduction: Broken eggs are a byproduct of the poultry industry and a potential nitrogen source for mushroom cultivation. However, its feasibility needs to be evaluated experimentally. Methods: In this study, a series of different addition amounts (0, 1.8, 3.6, 5.3 and 8.5%, w/w) of broken egg mixture (BEM) were applied in the composting cultivation process of oyster mushroom. The physicochemical properties and bacterial communities of composting substrate, and agronomic and nutritional properties of fruiting bodies were determined. Results and discussion: The results showed that the BEM addition significantly (P < 0.05) increased the total nitrogen content in the composted substrate, and the contents of crude protein, total amino acids and essential amino acids of mushrooms. The P3 treatment (initial C/N of 26:1) showed the highest biological efficiency (BE) of 100.19% and a low contamination rate (CR) of 7.00%, while the higher dosage of BEM (P4 and P5) led to a sharp decrease in BE and a sharp increase in CR. High throughput sequencing revealed that the addition of BEM significantly (P < 0.05) changed the bacterial communities in the substrate at the beginning of composting. Streptococcus and Lactococcus were predominant bacterial genera in BEM treatments at the beginning stage of composting, while Acinetobacter became predominant at the ending stage. The co-occurrence network analysis showed that the P3 treatment demonstrated a much more complex bacterial community. The structural equation model analysis indicated that the addition of BEM affected the bacterial communities and nitrogen metabolism during composting, which further affected agronomic and nutritional properties of oyster mushrooms. An appropriate amount of BEM combined with composting processes can significantly improve the yield and quality of oyster mushroom, providing a new way for efficient utilization of BEM.

Applications of dynamic visual acuity test in clinical ophthalmology.

Dynamic visual acuity test (DVAT) plays a key role in the assessment of vestibular function, the visual function of athletes, as well as various ocular diseases. As the visual pathways conducting dynamic and static signals are different, DVATs may have potential advantages over the traditional visual acuity tests commonly used, such as static visual acuity, contrast sensitivity, and static perimetry. Here, we provide a review of commonly applied DVATs and their several uses in clinical ophthalmology. These data indicate that the DVAT has its unique clinical significance in the evaluation of several ocular disorders.

Association between CD4+ T cell counts and gut microbiota and serum cytokines levels in HIV-infected immunological non-responders.

BACKGROUND: CD4+ T cell counts in certain human immunodeficiency virus (HIV)-infected patients called immunological non-responders (INRs) could not return to a normal level even with sustained antiretroviral therapy (ART) because of persistent immune activation, which is associated with pro-inflammatory cytokines production and an altered intestinal microbiome profile. Changes in gut bacterial composition have been linked to low CD4+ T cell counts in HIV-infected individuals. However, the association between CD4+ T cell counts and gut microbiota community composition and cytokines levels in INRs (CD4+ T cell counts < 500 cells/µL) from Yunnan Province, China, has not been previously investigated. METHODS: To address this issue, we carried out a cross-sectional study of 34 HIV-infected INRs. The patients were divided into CD4 count > 200 cells/µL group and CD4 count < 200 cells/µL group. The gut microbiota composition of each subject was analyzed by 16S rRNA gene sequencing. We also compared CD8+ T cell counts, pro-inflammatory cytokines levels, and nutritional status between the two groups. RESULTS: Compared to INRs with CD4 count > 200 cells/µL, those with CD4 count < 200 cells/µL had a lower CD4/CD8 ratio, lower nutritional status and higher serum levels of tumor necrosis factor (TNF)-α, interferon-γ-inducible protein (IP)-10 and interleukin (IL)-1α. Ruminococcaceae was less abundant in the CD4 count < 200 cells/µL group than in the CD4 count > 200 cells/µL group, and difference in alpha diversity was observed between the two groups. Moreover, CD4+ T cell counts were negatively associated with TNF-α and IL-1α levels and positively associated with the relative abundance of Ruminococcaceae. CONCLUSIONS: Our study demonstrated that lower CD4+ T cell counts in INRs are associated with a reduced abundance of Ruminococcaceae in the gut and elevated serum pro-inflammatory cytokines levels. Thus, interventions targeting gut microbiota to increase CD4+ T cell counts are a potential strategy for promoting immune reconstitution in HIV-infected INRs.

Clinicopathological significance of epidermal growth factor receptor expression in papillary thyroid carcinoma: a meta-analysis.

INTRODUCTION: This study aimed to determine the relationship between the expression of epidermal growth factor receptor (EGFR) and pathological indicators in papillary thyroid carcinoma (PTC). EVIDENCE ACQUISITION: PubMed, Embase, Web of Science, MEDLINE, and Cochrane Library databases were searched for relevant clinical trials. The odds ratio (OR) and 95% confidence interval (CI) showed the effect magnitude of the expression of EGFR, age, gender, tumor size, lymph node metastasis (LNM), extrathyroid extension(ETE), and TNM(Tumor, Lymph node, Metastasis) stage. Stata 12.0 was used for statistical analysis of data. EVIDENCE SYNTHESIS: A total of 845 cases of PTC were included through the retrieval of 8 studies performed abroad. EGFR significantly correlated with extrathyroid extension (OR = 3.25; 95% CI: 1.25-8.43; Z = 2.42; P = 0.015), LNM (OR = 8.40; 95% CI: 5.44-12.97; Z = 9.61; P = 0.000), and TNM stage (OR = 2.30, 95% CI: 1.51-3.51; Z = 3.87; P= 0.000). EGFR had no correlation with age (OR =1.13; 95% CI: 0.83-1.53; Z = 0.77; P = 0.44], gender (OR = 0.93; 95% CI: 0.66-1.33; Z = 0.38; P = 0.70), and tumor size (OR = 1.68; 95% CI: 1.06-2.68; Z = 2.19; P = 0.03). Sensitivity analysis demonstrated that the studies by Cui Tang and Alfred King Yin Lam in LNM impacted the pooled OR. After removing these two studies, relatively stable results between the expression of EGFR and LNM were obtained. CONCLUSIONS: The results in the expression of EGFR is frequent and cancer-specific event in PTC. Besides, the expression of EGFR was involved in the progression and metastasis of PTC.

Pre-Digested Protein Enteral Nutritional Supplementation Enhances Recovery of CD4+ T Cells and Repair of Intestinal Barrier in HIV-Infected Immunological Non-Responders.

AIDS patients with immune non-response are prone to malnutrition, intestinal barrier damage, thus aggravating chronic immune activation and inflammation. However, nutritional interventions targeting malnutrition may be beneficial to restore immune function, improve clinical outcomes, and reduce mortality remains largely unclear. This work aimed to evaluate the efficacy of a nutritional supplement in HIV-infected immune non-responders (INRs). The subjects received oral supplementation of a pre-digested protein nutrition formula for three months. We show that the CD4+ T and CD8+ T cell counts were significantly increased after supplementation of the pre-digested enteral nutritional supplement. Among all pro-inflammatory cytokines in the serum, only IL-1ß level was significantly decreased, while TNF-ß was significantly increased (P < 0.05). The levels of intestinal mucosal damage markers, diamine oxidase (DAO), D-lactic acid (D-lactate), and lipopolysaccharide (LPS), decreased significantly (P < 0.05) after the nutritional intervention. Moreover, at month 3 after the intervention, the body weight, body mass index, albumin, and hemoglobin of all subjects were significantly increased (P < 0.05). The correlation analysis demonstrated a significantly negative correlation of CD4+ T cell count with levels of DAO (r = -0.343, P = 0.004), D-lactate (r = -0.250, P = 0.037), respectively, and a significantly positive correlation of IL-1ß level with levels of DAO (r = 0.445, P < 0.001), D-lactate (r = 0.523, P < 0.001), and LPS (r = 0.622, P < 0.001). We conclude that the pre-digested enteral nutrition supplement is effective for HIV-infected INRs.

Interleukin-1ß Protection Against Experimental Sepsis in Mice.

The inflammatory response involving interleukin-1ß (IL-1ß) has been thought to play an important role in the development of late-phase sepsis. However, in this study, we wanted to explore the possibility of using IL-1ß to improve the prognosis of sepsis by triggering local differentiation of bone marrow cells (BMCs) into regulatory dendritic cells (DCs) in vivo, thereby reversing the immune paralysis in late-phase sepsis. Sepsis mouse models were induced by cecal ligation and puncture (CLP) and lethal Escherichia coli O18 infection. Mice were injected intraperitoneally with IL-1ß after CLP and after the lethal infection. Septic BMCs and liver immune cells were isolated at 0, 3, 6, 9, and 14 days post-CLP. BMCs and liver cells isolated from septic mice treated with IL-1ß were adoptively transferred into CLP mice. GFP+-C57BL/6 parabiosis models were established. Serum IL-1ß levels were determined by enzyme-linked immunosorbent assay (ELISA) kit, and the number, ratio, and phenotype of immune cells were observed by flow cytometry. IL-1ß treatment improved the survival of sepsis and increased the numbers of BMCs and liver immune cells in septic mice. Moreover, IL-1ß stimulation increased the number and the percentage of CD11c-CD45RBhigh DCs in septic BM and liver. Adoptive transfer of septic BMCs, liver immune cells, and CD11c-CD45RBhigh DCs treated with IL-1ß into CLP mice attenuated sepsis. IL-1ß triggered the redistribution of CD11c-CD45RBhigh DCs as well as BMCs in parabiosis models. IL-1ß protects against sepsis by stimulating local proliferation and differentiation of BMCs into CD11c-CD45RBhigh DCs at immune organs and non-immune organs.

Regulation of Gut Microbiota on Immune Reconstitution in Patients With Acquired Immunodeficiency Syndrome.

Human immunodeficiency virus type 1 (HIV-1) infection of CD4+ T cells in the gut plays an insidious role in acquired immunodeficiency syndrome (AIDS) pathogenesis. Host immune function is closely related to gut microbiota. Changes in the gut microbiota cause a different immune response. Previous studies revealed that HIV-1 infection caused changes in gut microbiota, which induced immune deficiency. HIV-1 infection results in an abnormal composition and function of the gut microbiota, which may disrupt the intestinal epithelial barrier and microbial translocation, leading to long-term immune activation, including inflammation and metabolic disorders. At the same time, an abnormal gut microbiota also hinders the effect of antiviral therapy and affects the immune reconstruction of patients. However, studies on the impact of the gut microbiota on immune reconstitution in patients with HIV/AIDS are still limited. In this review, we focus on changes in the gut microbiota caused by HIV infection, as well as the impact and regulation of the gut microbiota on immune function and immune reconstitution, while we also discuss the potential impact of probiotics/prebiotics and fecal microbiota transplantation (FMT) on immune reconstitution.

High Mobility Group Protein 1 Reverses Immune System Paralysis in Late-Phase Sepsis.

High mobility group protein 1 (HMGB1) is considered to be the primary inflammatory factor triggering immune paralysis in late-phase sepsis. In this study, however, we wanted to explore the possibility of using HMGB1 to boost local differentiation of bone marrow cells (BMCs) into regulatory dendritic cells (DCs) in vivo, thereby inducing immune reversal in late-phase sepsis and improving the prognosis. For this purpose, sepsis was induced by cecal ligation and puncture (CLP). Mice were injected intraperitoneally with HMGB1 (10, 50, or 250 µg/kg of body weight) 7 days before CLP. BMCs and liver immune cells were isolated at 0, 3, 5, and 7 days post-CLP. Mice were intranasally infected with Pseudomonas aeruginosa 3 days post-CLP as a secondary pneumonia infection model. BMCs and liver cells isolated from septic mice pretreated with HMGB1 were adoptively transferred into CLP mice. GFP+-C57BL/6 and C3H/HeN-C3H/HeJ parabiosis models were established. We found that HMGB1 pretreatment improved the survival of sepsis and increased the numbers of BMCs and liver immune cells in CLP mice. Furthermore, HMGB1 stimulation improved survival in the secondary pneumonia infection model. HMGB1 increased the number as well as the percentage of CD11c- CD45RBhigh DCs in septic BM and liver. Adoptive transfer of septic cells pretreated with HMGB1 into CLP mice attenuated sepsis. HMGB1 enhanced the redistribution of CD11c- CD45RBhigh DCs through TLR4 signaling in parabiosis models. We conclude that HMGB1 triggers immune reversal through the mobilization, redistribution, and local immune differentiation of BMCs, thereby compensating for impaired immunity and leading to sufficient bacterial eradication.

Polysaccharides from Bupleurum Induce Immune Reversal in Late Sepsis.

BACKGROUND: Bupleurum chinense, a well-known Traditional Chinese Medicine, has been used for thousands of years in China. In this study, we would suggest that Bupleurum polysaccharides (BPS) could improve the prognosis of sepsis through its impact on redistribution of BMCs, which triggers immune reversal in late sepsis. METHODS: BALB/c mice were divided into five groups: sham burn group, burn plus P aeruginosa group, burn plus P aeruginosa with BPS (40 mg/kg, 100 mg/kg, and 250 mg/kg) treatment group, and they were sacrificed at post-burn day (PBD) 0, 3, 5, and 7. BMCs, liver cells, and dendritic cells (DCs) were harvested. Flow cytometry was used to determine the change of phenotypes of DCs and isolate these cells. Cytometric beads array was utilized to analyze the level of inflammatory factors. Cell therapy of BMCs, liver cells, and DCs was administrated to explore the protective role of regional organ immunity. RESULTS: BPS could decrease the lethality of burn sepsis in a dose-dependent fashion and increase both the percentage of CD11cCD45RB DCs in bone marrow (BM) and liver and the number of BMCs and liver cells significantly. Cell therapy of BMCs, liver cells, and CD11cCD45RB DCs at PBD7 could protect septic mice from sepsis. CONCLUSION: BPS has shown its potential in promoting the prognosis of post-burn sepsis through its effect on immune redistribution of BMCs, especially via differentiation of CD11cCD45RB DC cells in BM and nonimmune organs to induce immune reversal in late sepsis.

Differentiation of isolated human umbilical cord mesenchymal stem cells into neural stem cells.

AIM: To investigate whether umbilical cord human mesenchymal stem cell (UC-MSC) was able to differentiate into neural stem cell and neuron in vitro. METHODS: The umbilical cords were obtained from pregnant women with their written consent and the approval of the Clinic Ethnics Committee. UC-MSC were isolated by adherent culture in the medium contains 20% fetal bovine serum (FBS), then they were maintained in the medium contain 10% FBS and induced to neural cells in neural differentiation medium. We investigated whether UC-MSC was able to differentiate into neural stem cell and neuron in vitro by using flow cytometry, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence (IF) analyzes. RESULTS: A substantial number of UC-MSC was harvested using the tissue explants adherent method at about 2wk. Flow cytometric study revealed that these cells expressed common markers of MSCs, such as CD105 (SH2), CD73 (SH3) and CD90. After induction of differentiation of neural stem cells, the cells began to form clusters; RT-PCR and IF showed that the neuron specific enolase (NSE) and neurogenic differentiation 1-positive cells reached 87.3%±14.7% and 72.6%±11.8%, respectively. Cells showed neuronal cell differentiation after induced, including neuron-like protrusions, plump cell body, obviously and stronger refraction. RT-PCR and IF analysis showed that microtubule-associated protein 2 (MAP2) and nuclear factor-M-positive cells reached 43.1%±10.3% and 69.4%±19.5%, respectively. CONCLUSION: Human umbilical cord derived MSCs can be cultured and proliferated in vitro and differentiate into neural stem cells, which may be a valuable source for cell therapy of neurodegenerative eye diseases.

Visual function and vision-related quality of life after vitrectomy for idiopathic macular hole: a 12mo follow-up study.

AIM: To investigate the visual function and the relationship with vision-related quality of life (VRQOL) after macular hole repair surgery. METHODS: Prospective case series. Thirty-six consecutive eyes in 36 patients who underwent pars plana vitrectomy (PPV) and internal limiting membrane (ILM) peeling were included. The 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was answered by the participants before and 3 and 12mo after operation. Follow-up visits examinations included best-corrected visual acuity (BCVA), clinical examination, and central macular thickness (CMT) measured by optical coherence tomography (OCT). RESULTS: Macular-hole closure was achieved in 35 of 36 eyes (97.2%). At baseline and months 3 and 12, the logMAR BCVAs (mean±SD) were 1.15±0.47, 0.68±0.53 (P<0.0001 versus baseline), and 0.55±0.49 (P<0.001 versus baseline, P =0.273 versus month 3), respectively; the CMTs (µm) were 330±81, 244±62 (P<0.001 versus baseline), and 225±58 (P<0.001 versus baseline, P=0.222 versus month 3), respectively; the median preoperative VFQ-25 composite score of 73.50 (63.92-81.13) increased postoperatively to 85.50 (80.04-89.63) at 3mo (P<0.001) and 86.73(82.50-89.63) at 12mo (P<0.001) respectively. The improved BCVA was correlated with improvements in five subscales (r=-0.605 to -0.336, P<0.001 to P=0.046) at 12mo. CONCLUSION: PPV with ILM peeling improved anatomic outcome, visual function, and VRQOL. The improved BCVA was an important factor related to the improved VRQOL.

Propofol injection combined with bone marrow mesenchymal stem cell transplantation better improves electrophysiological function in the hindlimb of rats with spinal cord injury than monotherapy.

The repair effects of bone marrow mesenchymal stem cell transplantation on nervous system damage are not satisfactory. Propofol has been shown to protect against spinal cord injury. Therefore, this study sought to explore the therapeutic effects of their combination on spinal cord injury. Rat models of spinal cord injury were established using the weight drop method. Rats were subjected to bone marrow mesenchymal stem cell transplantation via tail vein injection and/or propofol injection via tail vein using an infusion pump. Four weeks after cell transplantation and/or propofol treatment, the cavity within the spinal cord was reduced. The numbers of PKH-26-positive cells and horseradish peroxidase-positive nerve fibers apparently increased in the spinal cord. Latencies of somatosensory evoked potentials and motor evoked potentials in the hindlimb were noticeably shortened, amplitude was increased and hindlimb motor function was obviously improved. Moreover, the combined effects were better than cell transplantation or propofol injection alone. The above data suggest that the combination of propofol injection and bone marrow mesenchymal stem cell transplantation can effectively improve hindlimb electrophysiological function, promote the recovery of motor funtion, and play a neuroprotective role in spinal cord injury in rats.

A comparative study on the transplantation of different concentrations of human umbilical mesenchymal cells into diabetic rats.

AIM: To observe the effects of intravitreal injections of different concentrations of human umbilical mesenchymal stem cells on retinopathy in rats with diabetes mellitus. METHODS: Healthy and adult male Sprague-Dawley (SD) rats were randomly assigned to a normal control group (group A), a diabetic retinopathy (DR) blank control group (group B), a high-concentration transplantation group (group C), a low-concentration transplantation group (group D) and a placebo transplantation group (group E). The expression of nerve growth factor (NGF) protein in the retinal layers was detected by immunohistochemical staining at 2, 4, 6 and 8wk. RESULTS: The expression of NGF was positive in group A and most positive in the retinal ganglion cell layer. In groups B and E, the expression of NGF was positive 2wk after transplantation and showed an increase in all layers. However, the level of expression had decreased in all layers at 4wk and was significantly reduced at 8wk. In groups C and D, the expression of NGF had increased at 2wk and continued to increase up to 8wk. The level of expression in group C was much higher than that in group D. CONCLUSION: DR can be improved by intravitreal injection of human umbilical mesenchymal stem cells. High concentrations of human umbilical mesenchymal stem cells confer a better protective effect on DR than low concentrations.