Short- and Long-Term Effects of Different Antibiotics on the Gut Microbiota and Cytokines Level in Mice.

Background: Antibiotics are the first line of treatment for infectious diseases. However, their overuse can increase the spread of drug-resistant bacteria. The present study analyzed the impact of different types of antibiotics on the gut microbiome and cytokines level of mice. Methods: A total of five groups of 8-week-old male BALB/c mice (n = 35) were treated with piperacillin-tazobactam (TZP), ceftriaxone (CRO), tigecycline (TGC), levofloxacin (LEV) or normal saline (Ctrl), respectively, for up to 4 weeks. Fecal samples were analyzed by bacterial 16S rRNA gene sequencing for bacterial identification. Blood samples were used for the determination of 23 serum cytokines using multiplex immunoassay. Results: Exposure to antibiotics was shown to affect the normal weight gain of mice. Significant changes in gut composition caused by TZP, CRO and TGC treatment included the decreased abundance of Bacteroidetes (p < 0.01), Muribaculaceae (p < 0.01) and Lachnospiraceae (p < 0.01), and the increased abundance of Proteobacteria (p < 0.05), Enterobacteriaceae (including Klebsiella and Enterobacter) (p < 0.01) and Enterococcaceae (including Enterococcus) (p < 0.01). After 4-week treatment, the TZP, CRO and LEV groups had significantly lower concentrations of several serum cytokines. Correlation analysis of the top 30 bacterial genera and cytokines showed that Enterococcus and Klebsiella were strongly positively correlated with tumor necrosis factor-α (TNF-α), interleukins (IL) IL-12p70 and IL-1ß. Desulfovibrio, Candidatus Saccharimonas, norank_f__norank_o__Clostridia_UCG-014, Lactobacillus, and Roseburia were strongly negatively correlated with these cytokines. Conclusion: This study demonstrates the effects of various antibiotics on the intestinal microflora and immune status of mice. Compared with TZP, CRO and TGC, LEV had minimal impact on the gut microbiota. In addition to TGC, long-term TZP, CRO and LEV intervention can lead to a decrease in serum cytokine levels, which may depend on the intestinal microflora, antibiotic used and the duration of treatment.

Status and influencing factors of disease uncertainty among family caregivers of patients with moderate and severe craniocerebral injury: a quantitative and qualitative study.

BACKGROUND: Disease uncertainty widely exists among family caregivers of patients with moderate and severe craniocerebral injury. This negative emotional reaction will reduce the ability of family caregivers to make decisions during the critical stage of the patient, causing serious effects on the rescue and prognosis of patients with moderate and severe craniocerebral injury. Therefore, this article aims to understand the state of the uncertainty of the disease of family caregivers of patients with moderate and severe craniocerebral injury in China, to analyze the influencing factors, and to explore the specific resource of the uncertainty of the disease combined with qualitative study. The outcomes will provide a theoretical basis for formulating an accurate clinical nursing intervention strategy. METHODS: This study was conducted in the neurosurgery ward. A total of 214 family caregivers were evaluated using five previously validated scales: (i) Mishel Uncertainty in Illness Scale for family member, (ii) Simplified Coping Style Questionnaire, (iii) Social Support Rating Scale, and (iv) Self-Rating Anxiety Scale, (v) Zarit Caregiver Burden Interview. Kolmogorov-Smirnov was used to test the normality of the data distribution. The potential determinants of disease uncertainty were evaluated using the univariate statistical analysis. A multivariate linear regression model was adopted to assess the predictors of disease uncertainty in family caregivers of patients with moderate and severe craniocerebral injury. Objective sampling method was used to conduct semi-structured interviews with 17 family caregivers of patients with moderate and severe craniocerebral injury, and Colaizzi 7-step analysis method was used to analyze and summarize the interview data. RESULTS: The evaluated participants exhibited critically high levels of perceived uncertainty. The results of multiple linear regression showed that the influencing factors of family caregivers' disease uncertainty were anxiety, number of other caregivers, GOS, negative coping style, and caregiver burden. The qualitative research focuses on two main topics: the sources of disease uncertainty among family caregivers of patients with moderate and severe craniocerebral injury and experience to cope with the situation. CONCLUSION: The main cause of disease uncertainty of family caregivers of patients with moderate and severe craniocerebral injury is that patients' disease progression and prognosis as well as caregivers' own pressure of responsibility and negative mental status. Furthermore, caregivers' own pressure of responsibility and negative mental status are not clear. Therefore, helping family caregivers adopt positive coping approaches, guiding them to actively seek support from family and society, improving their nursing skills, and understanding of disease progression and prognosis all play an important role in alleviating the uncertainty of the disease.

Effects of Staged Nursing Care on Neuroendoscopic Transsphenoidal Pituitary Adenoma Resection and Postoperative Complications.

Objective: The purpose of this study was to determine whether staged nursing had an impact on the outcome of neuroendoscopic transsphenoidal pituitary tumor resection and postoperative complications. Methods: As research participants, we chose 88 individuals with pituitary adenomas who were treated at our institution between February 2020 and November 2021; all patients received endoscopic transsphenoidal pituitary adenoma excision. The patients were randomly divided into two groups: the routine group (n = 44) and the stage group (n = 44). Patients in the routine group received care according to the routine nursing mode, and patients in the stage group received care according to the stage nursing mode. The staged nursing interventions included preoperative, intraoperative, and postoperative nursing. Postoperative recovery-related indicators such as the self-rating anxiety scale (SAS) and a self-rating depression scale (SDS), contentment, comfort, and postoperative complications were compared between the two groups. Results: The postoperative recovery-related indexes of patients in the stage group were significantly lower than those in the routine group (P < 0.05); the SAS and SDS scores in the stage group after treatment were significantly lower than those in the routine group (P < 0.05); patients in the stage group were significantly more satisfied with their treatment after treatment than those in the routine group (P < 0.05); patients in the stage group were significantly more comfortable after treatment than those in the routine group (P < 0.05); a significantly lower incidence of postoperative complications was observed in the stage group compared to the routine group (P < 0.05). Conclusion: Patients with neuroendoscopic transsphenoidal pituitary tumor excision benefit greatly from staged nursing. The nursing approach may successfully assure the procedure's smooth completion, boost patients' postoperative recovery, and reduce patients' worry, despair, and other unpleasant feelings. The nursing approach may successfully increase clinical satisfaction and comfort of patients by minimizing the likelihood of postoperative problems, and it is well-suited for practical use.

Interleukin-6 and granulocyte colony-stimulating factor as predictors of the prognosis of influenza-associated pneumonia.

BACKGROUND: Pneumonia is a common complication of influenza and closely related to mortality in influenza patients. The present study examines cytokines as predictors of the prognosis of influenza-associated pneumonia. METHODS: This study included 101 inpatients with influenza (64 pneumonia and 37 non-pneumonia patients). 48 cytokines were detected in the serum samples of the patients and the clinical characteristics were analyzed. The correlation between them was analyzed to identify predictive biomarkers for the prognosis of influenza-associated pneumonia. RESULTS: Seventeen patients had poor prognosis and developed pneumonia. Among patients with influenza-associated pneumonia, the levels of 8 cytokines were significantly higher in those who had a poor prognosis: interleukin-6 (IL-6), interferon-γ (IFN-γ), granulocyte colony-stimulating factor (G-CSF), monocyte colony-stimulating factor (M-CSF), monocyte chemoattractant protein-1 (MCP-1), monocyte chemoattractant protein-3, Interleukin-2 receptor subunit alpha and Hepatocyte growth factor. Correlation analysis showed that the IL-6, G-CSF, M-CSF, IFN-γ, and MCP-1 levels had positive correlations with the severity of pneumonia. IL-6 and G-CSF showed a strong and positive correlation with poor prognosis in influenza-associated pneumonia patients. The combined effect of the two cytokines resulted in the largest area (0.926) under the receiver-operating characteristic curve. CONCLUSION: The results indicate that the probability of poor prognosis in influenza patients with pneumonia is significantly increased. IL-6, G-CSF, M-CSF, IFN-γ, and MCP-1 levels had a positive correlation with the severity of pneumonia. Importantly, IL-6 and G-CSF were identified as significant predictors of the severity of influenza-associated pneumonia.

Postoperative complications and quality of life in patients with pituitary adenoma.

BACKGROUND: Pituitary adenomas (PAs) are tumors that arise from the cells of the anterior pituitary gland. PAs are the most common tumors to occur in the sella area and the third most common intracranial neoplasm in surgery. Due to developments such as microscopy and neuroendoscopy, the curative effect of PA surgery continues to improve. However, postoperative complications may still occur. PA surgery can result in iatrogenic trauma, which is a primary cause of cerebrospinal fluid (CSF) rhinorrhea. PA surgery can affect the posterior pituitary gland, causing decreased antidiuretic hormone secretion and increased urine output, which can lead to hyponatremia. The nasal cavity and sphenoid sinuses may also be damaged during PA surgery, causing the sphenoethmoidal recess to be blocked. This increases the risk of infection. The purpose of this study was to analyze quality of life in PA patients post-resection, and to provide references for the development of early targeted risk assessment programs and intervention measures. METHODS: We selected patients who underwent neuroendoscopic transnasal PA resection at the Affiliated Hospital of Nantong University between January 2017 and October 2019. These patients' hospital records were retrospectively obtained, including details of any postoperative complications. The patients were followed up by telephone 12 weeks following discharge, and we used the EuroQol 5 Dimensions (EQ-5D) health scale to assess the patients' quality of life. RESULTS: At follow-up 3 months after discharge, 68 people (41.72%) had experienced at least one common complication, including 7 cases of infection (4.29%), 56 cases of hypopituitarism (34.36%), 18 cases of CSF rhinorrhea (11.04%), 28 cases of diabetes insipidus (17.18%), and 25 cases of hyponatremia (15.34%). Patients that experienced complications reported having more serious problems on the dimensions of the EQ-5D descriptive system (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) than patients without complications. The scores of patients with complications on the EQ-5D visual analog scale (EQ-VAS) were lower than that of patients without complications. CONCLUSIONS: Postoperative complications are negatively associated with quality of life in PA patients. Actively preventing common complications could therefore improve these patients' quality of life and reduce their burden of disease.

Effects of p38 MAPK signaling pathway on cognitive function and recovery of neuronal function after hypoxic-ischemic brain injury in newborn rats.

To explore the effects of p38 MAPK signaling pathway on cognitive function and recovery of neuronal function after hypoxic-ischemic brain injury (HIBI) in newborn rats. Seventy-two healthy SPF grade SD newborn rats were randomly and equally divided into Normal group (healthy rats) and Sham group (rats underwent sham operation), Model group (HIBI model rats), p38 MAPK Inhibitor group (HIBI model rats treated with p38 MAPK inhibitor) and p38 MAPK Activator group (HIBI model rats treated with p38 MAPK activator). On postnatal day 28, Morris water maze, tail suspension test and inclined plane test were conducted on rats in each group. Twenty-four hours after modeling, the expression of p-p38 MAPK protein and apoptosis related genes in rat hippocampal tissues was detected by TUNEL staining, qRT-PCR and Western blot. Compared with Normal group, escape latency and inclined plane test time were prolonged, the number of passing through the platform and tail suspension time were reduced (all P < 0.05); Bax and Caspase-3 mRNA and protein expression levels and p-p38 MAPK protein level were increased, Bcl-2 mRNA level was decreased, and neuronal apoptosis proportion was increased in Model group (all P < 0.05). Compared with Model group, the above indicators showed reversed and enhanced trends in p38 MAPK Inhibitor and p38 MAPK Activator groups, respectively (all P < 0.05). Inhibition of p38 MAPK signaling pathway can effectively improve the learning and memory ability and motor function of newborn rats with HIBI, and reduce neuronal apoptosis in the hippocampal tissues, thereby promoting neuronal recovery.

Acetal-linked paclitaxel prodrug micellar nanoparticles as a versatile and potent platform for cancer therapy.

Endosomal pH-activatable paclitaxel (PTX) prodrug micellar nanoparticles were designed and prepared by conjugating PTX onto water-soluble poly(ethylene glycol)-b-poly(acrylic acid) (PEG-PAA) block copolymers via an acid-labile acetal bond to the PAA block and investigated for potent growth inhibition of human cancer cells in vitro. PTX was readily conjugated to PEG-PAA with high drug contents of 21.6, 27.0, and 42.8 wt % (denoted as PTX prodrugs 1, 2, and 3, respectively) using ethyl glycol vinyl ether (EGVE) as a linker. The resulting PTX conjugates had defined molecular weights and self-assembled in phosphate buffer (PB, pH 7.4, 10 mM) into monodisperse micellar nanoparticles with average sizes of 158.3-180.3 nm depending on PTX contents. The in vitro release studies showed that drug release from PTX prodrug nanoparticles was highly pH-dependent, in which ca. 86.9%, 66.4% and 29.0% of PTX was released from PTX prodrug 3 at 37 °C in 48 h at pH 5.0, 6.0, and pH 7.4, respectively. MTT assays showed that these pH-sensitive PTX prodrug nanoparticles exhibited high antitumor effect to KB and HeLa cells (IC(50) = 0.18 and 0.9 µg PTX equiv/mL, respectively) as well as PTX-resistant A549 cells. Notably, folate-decorated PTX prodrug micellar nanoparticles based on PTX prodrug 3 and 20 wt % folate-poly(ethylene glycol)-b-poly(D,L-lactide) (FA-PEG-PLA) displayed apparent targetability to folate receptor-overexpressing KB cells with IC(50) over 12 times lower than nontargeting PTX prodrug 3 under otherwise the same conditions. Furthermore, PTX prodrug nanoparticles could also load doxorubicin (DOX) to simultaneously release PTX and DOX under mildly acidic pH. These acetal-linked PTX prodrug micellar nanoparticles have appeared as a highly versatile and potent platform for cancer therapy.