Effects of different doses of remimazolam on hemodynamics during general anesthesia in patients with septic shock.

OBJECTIVE: The stability of hemodynamics plays a vital role in the process of anesthesia induction for patients with septic shock. As a new-type benzodiazepine, remimazolam has numerous advantages, including rapid induction, rapid recovery, stable hemodynamics, and mild respiratory depression. Nevertheless, reports about the effects of remimazolam on hemodynamics in patients with septic shock are still limited. The study aimed to evaluate the effects that different doses of remimazolam have on hemodynamics in inducing general anesthesia in patients with septic shock. PATIENTS AND METHODS: Admitted to the intensive care unit of our hospital from January 2023 to June 2023, 75 patients with septic shock caused by acute appendicitis-induced sepsis were selected as observation subjects. They were randomly assigned to receive low-dose [0.2 mg/(kg·h)], medium-dose [0.3 mg/(kg·h)], and high-dose [0.4 mg/(kg·h)] remimazolam by using a random number table, with 25 patients in each group. Their intraoperative conditions were recorded, including operation duration, intraoperative hemorrhage volume, intraoperative transfusion volume, and decannulation time. Hemodynamic parameters, including mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), and stoke volume index (SVI) were collected at seven-time points (T0: before induction; T1: before intubation; T2: after intubation; T3: the start of operation; T4: 15 min after operation; T5: 30 min after operation; T6: the end of operation). We also compared hepatic and renal function indexes, including blood urea nitrogen (BUN), serum creatinine (sCr), procalcitonin (PCT), white blood cells (WBC), tumor necrosis factor-α2 (TNF-α2), and Interleukin-6 (IL-6), of the three groups of patients before operation and 1, 3, 5, 7 days after operation. In addition, the incidence of adverse reactions in the three groups was recorded and compared. RESULTS: During remimazolam induction, the number of patients with intraoperative need for rescue remimazolam in the medium-dose and high-dose groups was significantly lower than in the low-dose group (p < 0.05). In terms of hemodynamic indexes, MAP in the high-dose group at T2 was lower than that at T0 (p < 0.05), and MAP at T2 was significantly lower in the high-dose group than that in the medium-dose group (p < 0.05). Furthermore, MAP at T4 in the medium-dose and high-dose groups declined compared with the low-dose group (p < 0.05). There were no significant differences in HR, CI, and SVI at different time points among the three groups (p > 0.05), but levels of HR and SVI decreased and CI increased after anesthesia compared with those before operation. Additionally, in comparison with the levels before operation, levels of sCR, BUN, PCT, WBC, TNF-α, and IL-6 were higher on postoperative days 1, 3 (p < 0.05) and lower on postoperative day 7 (p < 0.05). After the operation, both levels of BUN and sCR in the medium-dose and high-dose groups were lower than those in the low-dose group (p < 0.05). CONCLUSIONS: Remimazolam is safe and effective for inducing general anesthesia in patients with septic shock. Low, medium, and high doses of remimazolam can maintain a stable hemodynamic state, and the recovery of hepatic and renal function is certain to depend on the dose.

Circ_NCKAP1 promotes skin basal cell carcinoma progression by sponging the miR-148b-5p/HSP90 axis.

OBJECTIVE: Skin basal cell carcinoma (BCC) is the most common malignant skin tumor. Recent studies demonstrated that circular RNAs (circRNAs) are implicated in tumorigenesis and may represent potential therapeutic targets. The aim of the present study was to explore the expression profiles of circRNAs and their role in skin BCC. MATERIALS AND METHODS: Three pairs of skin BCC tissues and adjacent tissues were used to perform a circRNA microarray for screening of circRNA expression profiles. Circ_NCKAP1 was selected as a target circRNA by RT-qPCR verification and bioinformatics analysis. The effect of circ_NCKAP1 knockdown on cell proliferation and apoptosis was assessed using CCK8 and Annexin V-FITC/PI assays, and its regulation over the miR-148b-5p/HSP90 axis was assessed by dual-luciferase reporter assay. RESULTS: Circ_NCKAP1 was found to be significantly upregulated in skin BCC tissues (p<0.05). In vitro loss-of-function assays demonstrated that circ_NCKAP1 knockdown markedly inhibited cell proliferation and promoted cell apoptosis (p<0.05). Moreover, Dual-Luciferase reporter assay identified that circ_NCKAP1 could bind to miR-148b-5p directly, and HSP90 was targeted by miR-148b-5p. CONCLUSIONS: Circ_NCKAP1 can promote skin BCC progression by sponging the miR-148b-5p/HSP90 axis, and circ_NCKAP1 may be a potential target for skin BCC therapy.

Maintenance of cellular annexin A1 level is essential for PI3K/AKT/mTOR-mediated proliferation of pancreatic beta cells.

Annexin A1 (AnxA1, also known as lipocortin-1), is a calcium-dependent phospholipid binding protein with diverse functions. Previous studies have indicated that AnxA1 is associated with age-related ß-cell dysfunction and aging, which lead to decreased ß-cell proliferation capacity. However, it has been uncertain whether AnxA1 affects the proliferation of pancreatic beta (ß) cells. In the present study, we reduced AnxA1 expression in the MIN6 islet ß-cell line using small interfering RNA (AnxA1-siRNA), then measured cell cycle distribution and cellular proliferation. We also measured the expression levels of cell cycle-related proteins such as cyclin D1, cyclin E, and cyclin-dependent kinase 2 (CDK2) by Western blot analysis. We investigated the phosphatidylinositol 3-kinase (PI3K)/ serine/threonine protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway to explore the potential mechanism underlying the observed effects. Knockdown of AnxA1 expression using siRNA reduced the rates of MIN6 cell proliferation. The proportions of cells in S and G2/M phases also decreased upon inhibition of AnxA1. Moreover, AnxA1 protein expression in MIN6 cells was positively related to the protein levels of cyclin D1, cyclin E, and CDK2. Activation of the PI3K/Akt/mTOR signaling pathway by AnxA1 may be involved in the signaling cascade to regulate cell proliferation. This study identified a positive correlation between AnxA1 protein and pancreatic ß-cell proliferation. AnxA1 protein expression might affect the proliferation of MIN6 cells via regulation of cyclin D1, cyclin E, and CDK2 proteins, as well as the PI3K/Akt/mTOR signaling pathway.

A comparative meta-analysis of the efficacy of statin-ezetimibe co-therapy versus statin monotherapy in reducing cardiovascular and cerebrovascular adverse events in patients with type 2 diabetes mellitus.

OBJECTIVE: This study evaluates the efficacy of statin-ezetimibe co-therapy compared to statin monotherapy in reducing cardiovascular and/or cerebrovascular disease (CVD) prevalence in diabetes and non-diabetes patients. PATIENTS AND METHODS: Literature search was conducted in electronic databases and study selection was based on pre-determined eligibility criteria. Random-effects metanalyses were performed to examine the risk of CVD incidence between statin-ezetimibe co-therapy and statin monotherapy and subgroups were performed to examine the significance of differences between diabetic and non-diabetic individuals. A pooled analysis of hazard ratios of statin-ezetimibe combination versus statin monotherapy in the prevalence of CVD reported by the individual studies was also performed. RESULTS: 8 studies (136893 individuals; 80790 diabetics, 85555 non-diabetics; age 63.5 years [95% confidence interval (CI) 61.2, 65.8]; 61.5% [95% CI 55.2, 67.8] males) were included. Follow-up duration was 45 months [95% CI 27.5, 62.5]. Risk of CVD prevalence was significantly less with ezetimibe-statin than with statin alone in both diabetes (RR 0.69 [95% CI 0.67, 0.73]; p<0.00001) and in non-diabetes (RR 0.68 [95% CI 0.52, 0.90]; p=0.006) subjects (subgroup difference: chi2=0.00; p=0.97). Risk of prevalence of stroke was significantly less with ezetimibe-statin than with statin monotherapy in diabetes (RR 0.74 [95% CI 0.56, 0.98]; p=0.03) but non-significantly less in non-diabetes patients (RR 0.74 [95% CI 0.39, 1.41]; p=0.39) and this sub-group difference was also not statistically significant (chi2=0.00; p=0.99). CONCLUSIONS: Statin-ezetimibe co-therapy is found more efficacious than statin monotherapy in reducing the incidence of CVD with no significant difference between diabetic and non-diabetic individuals.

Presence of pldA and exoU in mucoid Pseudomonas aeruginosa is associated with high risk of exacerbations in non-cystic fibrosis bronchiectasis patients.

OBJECTIVES: To explore the association between the virulence genes exoU and pldA in isolated mucoid Pseudomonas aeruginosa and the clinical outcomes of patients with non-cystic fibrosis (CF) bronchiectasis. METHODS: A prospective observational cohort study was performed in the Shanghai Pulmonary Hospital from October 2012 to January 2015. We consecutively enrolled all non-CF bronchiectasis patients with mucoid P. aeruginosa isolates obtained from bronchoalveolar lavage fluid or sputum. The exposure variable was the presence of virulence gene, exoU or pldA, in the strains. The primary outcome was exacerbation of bronchiectasis. Logistic regression analysis was performed to evaluate the association between virulence genes and exacerbation. RESULTS: The final analysis included 147 patients (mean (SD) age, 57.86 (11.43) years, 101 female subjects) with median (interquartile range) follow-up of 18 (13-26) months. The following factors were relative to exacerbations: body mass index ≤18.5 kg/m2 (odds ratio (OR) = 5.05; 95% confidence interval (CI), 1.37-18.57), length of stay ≥8 days (OR = 2.65; 95% CI, 1.14-6.19) and positive for either virulence gene (OR = 6.80; 95% CI, 1.47-31.37). The gene-positive group had more exacerbations per year (mean 2.37, SD 2.10, n = 33 vs. mean 0.79, SD 0.83, n = 114) and a higher proportion of patients with exacerbation (31/33, 93.94% vs. 74/114, 64.91%). The proportion of patients being exoU or pldA positive increased as the exacerbation frequency of bronchiectasis increased. CONCLUSIONS: The virulence genes exoU and pldA in mucoid P. aeruginosa are significant risk factors for exacerbations in patients with non-CF bronchiectasis.

[Clinical significance of syndecan-1 and syndecan-2 expression in gallbladder squamous cell/adenosquamous carcinoma and adenocarcinoma].

Objective: To investigate the expression of syndecan-1 and syndecan-2 and their clinicopathological significance in patients with gallbladder squamous cell (SC)/adenosquamous carcinoma (ASC) and adenocarcinoma (AC). Methods: A total of 126 patients with SC/ASC (n=46) and AC (n=80) were included in this study. The expression levels of syndecan-1 and syndecan-2 were detected by Envison™ immunohistochemistry assay. The clinical and prognostic significance of syndecan-1 and syndecan-2 were analyzed. Results: In the 46 SC/ASC samples, syndecan-1 and syndecan-2 were positively expressed in 29 (63.0%) and 28 (60.9%) tumor tissues, respectively. (Positive expression was defined based on the staining in the component of squamous cell carcinoma. That is to say, the tissue which adenocarcinoma part was positively stained, but squamous cell carcinoma part was negatively stained is also regarded as negative.) In the 80 AC samples, 47 (58.8%) cases showed syndecan-1 positive expression, and 51 (63.8%) showed syndecan-2 positive expression. There was no significant difference in the positive rates of syndecan-1 and syndecan-2 between SC/ASC and AC groups (P>0.05 for all). The levels of syndecan-1 and syndecan-2 were associated with tumor size, TNM staging, lymph node metastasis, invasion of adjacent tissue, and surgical procedures in SC/ASC patients (P<0.05 for all). However, their expression was associated with tumor differentiation, tumor size, TNM staging, lymph node metastasis, invasion of adjacent tissue, and surgical procedures in AC patients (P<0.05 for all). The Kaplan-Meier survival analysis of SC/ASC and AC patients revealed that the average survival time for patients with positive syndecan-1 and syndecan-2 expression was significantly shorter than that of those with negative expression (P<0.01 for all). Cox multivariate analysis indicated that syndecan-1 and syndecan-2 expression were independent unfavorable prognostic factors for SC/ASC and AC patients (P<0.05 for all). Conclusion: The syndecan-1 and syndecan-2 expression are associated with the tumor progression and poor prognosis in patients with gallbladder SC/ASC and AC.

Assessment of obestatin and arginine vasopressin (AVP) levels in acute renal failure and acute heart failure.

OBJECTIVE: We conducted this study to assess the clinical application of obestatin and arginine vasopressin (AVP) levels in cases of acute renal failure (ARF) and acute heart failure (AHF). PATIENTS AND METHODS: 30 cases of ARF, 30 cases of AHF, 30 cases of ARF complicated with AHF, and 30 cases of healthy subjects (control group) were successively selected. An ELISA test was conducted to detect levels of obestatin and AVP. Routine biochemistry testing was applied to detect the levels of serum creatinine and calculate the glomerular filtration rate (GFR). Electrochemiluminescence double antibody sandwich fluorescence immune testing was applied to detect NT-proBNP and color Doppler ultrasound diagnostic apparatus was applied to detect renal arterial resistive index (RI) and left ventricular ejection fraction (LVEF). The 30-day mortality was documented. RESULTS: Compared to other groups, the group of patients suffering from ARF complicated with AHF had significantly higher levels of obestatin and AVP, and significantly higher levels of serum creatinine, NT-proBNP and RI; however, their GFR and LVEF levels were the lowest. Differences were statistically significant (p < 0.05). Levels of obestatin and AVP are positively correlated with serum creatinine, NT-proBNP and RI levels, but negatively correlated with GFR and LVEF levels. The mortality rate of the group suffering from ARF complicated with AHF was markedly increased (p = 0.035). The obestatin and AVP levels of the death group were significantly higher than that of the survival group. However, the comparison among levels of serum creatinine, GFR, NT-proBNP, RI and LVEF revealed no statistical significance (p > 0.05). CONCLUSIONS: Obestatin and AVP levels were closely related to the severity of ARF and AHF and survival prognosis, which could be a sensitive indicator for diagnoses and prognoses.

Adsorption dynamics and rate assessment of volatile organic compounds in active carbon.

In this paper, an investigation was presented about terahertz time-domain spectroscopy (THz-TDS) as a novel tool for the characterization of the dynamic adsorption rate of volatile organic compounds, including isooctane, ethanol, and butyl acetate, in the pores of active carbon. The THz-TDS peak intensity (EP) was extracted and corresponded to the measurement time frames. By analyzing EP with time, the entire process could be divided into three physical parts including volatilization, adsorption and stabilization so that the adsorption dynamics could be clearly identified. In addition, based on the pseudo-second-order kinetic model and the relationship between EP and time in the adsorption process, a mathematical model was built in terms of the adsorbed rate parameter and the THz parameter. Consequently, the adsorption rate of isooctane, ethanol, and butyl acetate could be assessed by the THz measurement, indicating that THz spectroscopy could be used as a promising selection tool to monitor the adsorption dynamics and evaluate adsorption efficiency in the recovery of pollutants.

Corticosteroids for the treatment of human infection with influenza virus: a systematic review and meta-analysis.

Administration of corticosteroids to patients affected by influenza virus, especially pandemic avian influenza virus, although relatively common, remains controversial. A systematic review and meta-analysis was performed to assess the impact of corticosteroid treatment on outcomes of patients with influenza virus infection. The PubMed, EMBASE, Web of Science and Cochrane Library databases were searched up to February, 2015. Studies comparing corticosteroid treatment with no corticosteroid treatment in patients with influenza virus infection were included. The primary outcomes assessed were the association of mortality and nosocomial infection with corticosteroid treatment. Two authors independently extracted the data. ORs and weighted mean differences (WMDs) were used to describe dichotomous data and continuous data, respectively. Nineteen studies with 4916 patients were included in this meta-analysis. The results showed that corticosteroid treatment was significantly associated with mortality (OR 1.98, 95% CI 1.62-2.43, p < 0.00001) and nosocomial infection (OR 3.16, 95% CI 2.09-4.78, p < 0.00001). The durations of mechanical ventilation (WMD 3.82, 95% CI 1.49-6.15, p 0.001) and intensive-care unit stay (WMD 4.78, 95% CI 2.27-7.29, p 0.0002) were both markedly longer in the corticosteroid treatment group than in the control group. These findings suggest that routine steroid use may not be ideal for influenza virus infection. However, these results are derived from observational studies, with some important biases. They should be examined in future sufficiently powered randomized trials.

[Plasma level and effects of thromboxane A2 and 6-keto-PGF1 alpha in patients with acute obstructive suppurative cholangitis].

The changes of the plasma thromboxane B2 (TXB2) and 6-keto-PGF1 alpha, the stable metabolites of TXA2 and PGI2, respectively and their effects on platelet counts, platelet aggregation and hypotension were studied in patients with AOSC. The results showed that the plasma TXB2, 6-keto-PGF1 alpha and 6-keto-PGF1 alpha/TXB2 ratios in these patients were markedly increased, however, the platelet counts markedly decreased and platelet aggregation inhibited significantly. After operation, they recovered to normal gradually. There were negative correlation between TXB2 with platelet count and 6-keto-PGF1 alpha with platelet aggregation, as well as both TXB2 and 6-keto-PGF1 alpha with blood pressure. TXA2 was an important factor which lead to platelet decrement and take part in the pathological course of disseminated intravascular coagulation (DIC) and multiple organ failure (MOF), but PGI2 might play an important role in improving microcirculation and preventing DIC and MOF through the inhibition of platelet aggregation.