ObjectiveTo prepare curcumin loaded monomethoxyl poly(ethylene glycol)-poly(lactic-co-glycolicacid) (mPEG-PLGA) nanopaticles (CUR-NPs), investigate the effect of curcumin (CUR) and CUR-NPs on reversing corticosteroid resistance induced by cigarette smoke extract (CSE), and compare biological function between CUR and CUR-NPs in macrophages RAW264.7. MethodsmPEG-PLGA nanoparticles loaded with CUR were prepared via emulsion solvent evaporation.In lipopolysaccharide (LPS) stimulated macrophages RAW264.7, budesonide (BUD) was used to treat macrophages RAW264.7.In LPS and CSE stimulated macrophages RAW264.7, BUD (10-10-10-5 mol/L), CUR(10-10-10-5 mol/L), CUR(10-7 mol/L)+BUD(10-9-10-5 mol/L), CUR(10-9-10-5 mol/L)+BUD(10-7 mol/L), and CUR-NPs(10-9-10-5 mol/L)+BUD(10-7 mol/L) were respectively used to treat macrophages RAW264.7 activated.The level of IL-8 in cell culture supernatant was measured by ELISA.In CSE stimulated macrophages RAW264.7, CUR(10-7 and 10-6 mol/L) and CUR-NPs(10-7 and 10-6 mol/L) were used to treat macrophages RAW264.7.The mRNA level of HDAC2 was measured by real-time PCR, the protein level of HDAC2 was measured by Western blot.Cellular uptake of CUR and CUR-NPs in macrophages RAW264.7 was determined by cellular fluorescence intensity observed and detected by laser confocal microscopy imaging. ResultsThe morphology of CUR-NPs was spherical and the mean particle size was (356.4±146.6)nm.Compared with LPS stimulation, co-stimulation of LPS and CSE led to a significant decrease in the maximum inhibitory rate of BUD on IL-8 (P < 0.05) and a significant increase in the 50% inhibitory concentration (IC50) of BUD on IL-8 (P < 0.05).When using LPS+CSE to stimulate, compared with BUD (10-10-10-5 mol/L) group, the maximum inhibitory rate of BUD in CUR (10-7 mol/L)+BUD (10-9-10-5 mol/L) group on IL-8 was significantly higher (P < 0.05) and the IC50 of BUD decreased significantly (P < 0.05).When using LPS+CSE to stimulate, CUR and CUR-NPs in 10-9, 10-8 and 10-7 mol/L concentration, the inhibitory rate of CUR-NPs+BUD (10-7 mol/L) on IL-8 was significantly higher than that of CUR+BUD (10-7 mol/L) (P < 0.05). CSE stimulation induced a significant decrease in the mRNA and protein expression of HDAC2. Compared with CSE group, the mRNA and protein levels of HDAC2 of CUR(10-7 and 10-6 mol/L) group and CUR-NPs(10-7 and 10-6 mol/L) group were significantly higher (P < 0.05).In 10-7 mol/L concentration, the mRNA and protein levels of HDAC2 in CUR-NPs group were significantly higher than those in CUR group.In 10-7 mol/L concentration, cellular uptake of CUR in CUR-NPs was significantly higher than the native CUR. ConclusionsCUR and CUR-NPs can reverse the corticosteroid resistance induced by CSE.CUR-NPs can improve the cellular uptake of CUR.In the case of low concentration, CUR-NPs have more biological activity than CUR.
ObjectiveTo systematically review the clinical efficacy and safety of glucocorticoids, acetaminophen and antimicrobial drugs in the treatment of intrapartum fever in labor analgesia. MethodsThe PubMed, Embase, Cochrane Library, Web of Science, CBM, VIP, and CNKI databases were electronically searched to collect randomized controlled trials (RCTs) of glucocorticoids, acetaminophen, and antimicrobial drugs for intrapartum fever in labor analgesia from inception to June 30, 2023. Two reviewers independently screened the literature, extracted data, and evaluated the risk of bias of the included literature. Meta-analysis was then performed by using RevMan 5.4 software. ResultsA total of 10 RCTs involving 1 337 women were included. Meta-analysis showed that the use of glucocorticoids reduced the incidence of intrapartum fever in women with labor analgesia compared with the control group (OR=0.52, 95%CI 0.33 to 0.82, P<0.01). But there was no statistically significant difference between acetaminophen or antimicrobial drugs and the control group. ConclusionCurrent evidence shows that the use of glucocorticoids can reduce the incidence of intrapartum fever in labor analgesia, but the use of acetaminophen and antimicrobial drugs cannot reduce the incidence of intrapartum fever. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
Objective To evaluate the safety and efficacy of dexamethasone intravitreal implant 0.7 mg (DEX) for treatment of macular edema associated with retinal vein occlusion (RVO). Methods This study was a six-month, randomized, double-masked, sham-controlled, multicenter, phase 3 clinical trial with a 2-month open-label study extension. Patients with branch or central RVO received DEX (n=129) or sham procedure (n=130) in the study eye at baseline; all patients who met re-treatment criteria received DEX at month 6. Efficacy measures included Early Treatment Diabetic Retinopathy Study (ETDRS), best-corrected visual acuity (BCVA), and central retinal thickness (CRT) on optical coherence tomography. Results Time to ≥15-letter BCVA improvement from baseline during the first 6 months (primary endpoint) was earlier with DEX than sham (P＜0.001). At month 2 (peak effect), the percentage of patients with ≥15-letter BCVA improvement from baseline was DEX: 34.9%, sham: 11.5%; mean BCVA change from baseline was DEX: 10.6±10.4 letters, sham: 1.7±12.3 letters; and mean CRT change from baseline was DEX: −407±212 μm, sham: −62±224 μm (all P＜0.001). Outcomes were better with DEX than sham in both branch and central RVO. The most common treatment-emergent adverse event was in-creased intraocular pressure (IOP). Increase sin IOP generally were controlled with topical medication. Mean IOP normalized by month 4, and no patient required incisional glaucoma surgery. Conclusions DEX had a favorable safety profile and provided clinically significant benefit in a Chinese patient population with RVO. Visual and anatomic outcomes were improved with DEX relative to sham for 3 - 4 months after a single implant.
ObjectivesTo assess the efficacy and safety of corticosteroid and antiviral agents for idiopathic facial nerve paralysis (IFNP) by network meta-analysis.MethodsPubMed, EMbase, The Cochrane Library, CBM, CNKI, WangFang Data and VIP databases were electronically searched to collect randomized controlled trials (RCTs) of corticosteroid and antiviral agents for IFNP from inception to January 31th, 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. The meta-analysis was performed by R 3.3.3 and Stata 13.0 software.ResultsA total of 16 RCTs involving 3 061 patients were included. The results of network meta-analysis showed that: for the facial function recovery rates, corticosteroid plus antiviral agents was superior to placebo and antiviral agents alone at 3-month follow-up. Corticosteroid plus antiviral agents was superior to placebo, antiviral agents or corticosteroid alone at 6-month follow-up (if the satisfactory recovery was defined as a House-Brackmann grade class Ⅱ or below). When the follow-up exceeded 6 months, corticosteroid alone was superior to placebo and antiviral agents alone, corticosteroid plus antiviral agents was superior to placebo and antiviral agents alone. All of the differences above were statistically significant. For the sequelae, corticosteroid plus antiviral agents and corticosteroid alone were superior to placebo and antiviral agents alone. Corticosteroid plus antiviral agents was superior to corticosteroid alone. The differences were statistically significant. For the adverse events, there were no significant differences between any other pairwise comparisons of these different interventions.ConclusionConsidering the efficacy and safety, patients with IFNP treated corticosteroid plus antiviral agents are more likely to have a better recovery of facial function and less likely to develop sequelae, followed by corticosteroid alone. More high-quality, large scaled and multicenter RCTs are required to verify the conclusions above, and focus on the treatment of children and patients with severe facial paralysis.
Objective To systematically evaluate the effect and safety of systemic corticosteroids for acute exacerbation of chronic obstructive pulmonary disease (COPD). Methods Databases including PubMed, EMbase, The Cochrane Library (Issue 6, 2015), Wanfang Data, CBM, CNKI were searched to collect randomized controlled trails (RCTs) about systemic corticosteroids for acute exacerbation of COPD from inception to July 2015. The meta-analysis was conducted using RevMan 5.3 software. Results A total of 11 RCTs involving 1298 patients were included. The results of meta-analysis showed that a statistically significant increase in the treatment success rate when using systemic corticosteroids (RR=1.11, 95%CI 1.01-1.21,P=0.02), and a non-significant difference of effect in the subgroup of emergency department and ICU patients (RR=0.98, 95%CI 0.90-1.08,P=0.74;RR=1.19, 95%CI 0.84-1.69,P=0.34). Conclusions Current studies suggest that systemic corticosteroids is beneficial in terms of treatment success rate, but subgroup analysis shows that this benefit is controversial in emergency department and ICU. however, due to the limited quantity of the included studies, the above conclusions still need more high quality research to be verified.
Objective To analyze the risk factors for postoperative cognitive confusion in a surgical intensive care unit. Methods A total of 388 consecutive patients in Surgical Intensive Care Unit of General Hospital of PLA were retrospectively studied. We posed clinical questions according to the patients with older age and large dosage corticosteroid. Using “Postoperative cognitive confusion” and“Intensive Care” as key words, we searched for evidence from MEDLINE (1968-2004). Results We found 3.1% (10/388) of the patients developed postoperative cognitive confusion. Of the 10 postoperative cognitive confusion patients, 9 were over 65 years old. 6.6% (9/136) of the patients (≥ 65 years old) developed postoperative cognitive confusion. While 0.4%(1/252) of the patients (＜65 years old) developed postoperative cognitive confusion. Older age (≥ 65 years old) may induce more postoperative cognitive confusion (P＜0.05). While 7.0% (5/71) of the patients treated by large dose corticosteroids (≥1 000 mg) developed postoperative cognitive confusion. And 1.65% (5/317) of the patients received corticosteroid with large dosage (＜1 000 mg) developed postoperative cognitive confusion. Large dosage corticosteroid (≥1 000 mg) may induce more postoperative cognitive confusion (P＜0.05). Conclusion Older age (≥ 65 years old) and high dose corticosteroid (≥1 000 mg) may be the two main risk factors for postoperative cognitive confusion.
ObjectiveTo explore the effects of corticosteroid on peripheral blood T lymphocyte subsets in patients with coronavirus disease 2019 (COVID-19).MethodsThis was a retrospective study and 376 patients were included in the study. The patients were classified into three type: moderate type (118 patients), severe type (215 patients), critical type (43 patients). Six critical patients died. T lymphocyte subsets were analyzed and compared among these patients. In severe patients, T lymphocyte subsets were compared between no corticosteroid therapy patients (178 patients) and patients who were treated with corticosteroid for 3 to 5 days (37 patients).Results(1) In contrast with those in moderate patients, in severe patients total lymphocytes [(1359.2±597.9)×106 vs. (1703.7±702.4)×106/L, LSD-t=4.786, P<0.001], total T lymphocytes [(949.2±454.0)×106 vs. (1235.5±555.7)×106/L, LSD-t=5.175, P<0.001] and CD8+ T cells [(336.8±189.8)×106 vs. (461.7±242.8)×106/L, LSD-t=5.332, P<0.001] decreased significantly, and CD4+/CD8+ ratio (1.81±0.92 vs. 1.64±0.74, LSD-t=1.574, P=0.116) was increased. In contrast with those in severe patients, in critical patients CD4+/CD8+ ratio (2.23±1.24 vs. 1.81±0.92, LSD-t=2.627, P=0.009) increased and CD8+ T cells [(232.5±159.8)×106/L vs. (336.8±189.8)×106/L, LSD-t=2.867, P=0.004] decreased significantly, total lymphocytes [(1161.1±583.7)×106/L vs. (1359.2±597.9)×106/L, LSD-t=1.772, P=0.077], total T lymphocytes [(790.5±419.3)×106/L vs. (949.2±454.0)×106/L, LSD-t=1.846, P=0.066] also decreased but without significant difference. There was no significant difference between dead and survived critical patients. (2) In severe type, in contrast with no corticosteroid therapy patients, 37 patients were therapy with corticosteroid for 3 to 5 days, and their total T lymphocytes [(770.6±480.3)×106 vs. (986.3±440.7)×106/L, t=2.666, P=0.008] and CD4+/CD8+ ratio (1.30±0.73 vs. 1.91±0.92, t=3.771, P<0.001) were decreased significantly.ConclusionsIn COVID-19 patients, lymphocytes, T lymphocytes and CD8+ T cells are decreased, but CD4+/CD8+ ratio is increased, and these changes are positively related to the severity of the disease. After corticosteroid therapy, the increase of CD4+/CD8+ ratio is relieved, but T lymphocytes are decreased further.
ObjectiveTo evaluate the effect of low-to-moderate doses of corticosteroids on human infections with avian influenza A (H7N9) virus, and explore when to initiate the treatment of corticosteroids and the duration of corticosteroids administration.MethodsThe study collected clinical data of 8 cases with avian influenza A (H7N9) virus infection admitted from January 25, 2017 to May 12, 2017. The final analysis included 5 severe patients who had received adjuvant corticosteroid treatment. The variation curves of WBC, CRP, PCT, CK, HBDH, LDH, temperature, ratio of SpO2/FiO2 were depicted and analyzed. The progress of clinical improvements, deterioration and prognosis were observed and discussed.ResultsThere were 1 female and 4 males in the 5 included patients with a median age of 58.0 years, among them 3 survived. The median time of illness onset to hospitalization and diagnosis confirmed were 4 days and 8 days respectively; the median duration of hospitalization to admission to infective ICU were 3 days. The first course of adjuvant corticosteroid treatment was initiated 11 days (median) after admission with a duration of 4 days (median), during which, the serum levels of HBDH and LDH decreased remarkably except the patient 3, and the oxygenation (SpO2/FiO2) improved except the patient 3. The second course of systemic administration of corticosteroid was given at a median of 26.5 days after admission with a duration of 9 days (median), during which, the patients survived with improved oxygenation (SpO2/FiO2), and weaned from mechanical ventilation.ConclusionsFor patients suffered severe human infection with avian influenza A (H7N9) virus, low-to-moderate doses of corticosteroids may decrease the level of inflammation, regulate the aberrant immune response, improve the oxygenation, make an early unassisted breathing. And corticosteroids treatment can be initiated at the time of disease deterioration, after/at the peak inflammatory response, and within 10-14 days of ARDS. Also, the adjuvant corticosteroids may be administered when oxygenation is dificult to be improved by other ways, or dificult to be liberated from mechanical ventilation, suffering severe septic shock, and refractory fever. And the duration of corticosteroids may be prolonged to 10-14 days, or until the higher level of HBDH and LDH decreased again.
糖皮质激素在甲型H1N1流感中的应用探讨
Objective To formulate an evidence-based treatment for a patient with pulmonary tuberculosis combined with tuberculous meningitis and tuberculous pericarditis. Methods According to the principles of evidencebased clinical practice, we searched The Cochrane Library (Issue 2, 2008), Ovid-Reviews (1991 to 2008), MEDLINE (1950 to 2008), and http://www.guideline.org. to identify the best evidence for treating a patient with pulmonary tuberculosis combined with tuberculous meningitis and tuberculous pericarditis. Results Nine guidelines, 2 systematic reviews, and 11 randomized controlled trials were included. The evidence showed that corticosteroids could help reduce the risk of death and disabling residual neurological deficiencies in patients with tuberculous meningitis. After adjusting for age and gender, the overall death rate of patients with tuberculous pericarditis was significantly reduced by prednisolone (P=0.044), as well as the risk of death from pericarditis (P=0.004). But for patients with pulmonary tuberculosis, there was still a controversy about the use of corticosteroids. Given the evidence, the patient’s clinical conditions, and his preferences, dexamethasone was used for the boy in question. After 7 weeks of treatment, his cerebrospinal fluid returned to normal and pericardial effusion disappeared. Conclusion Corticosteroids should be recommended in HIV-negative people with tuberculous meningitis or/and tuberculous pericarditis. The difference in the effectiveness of various corticosteroids such as dexamethasone, prednisolone, or methylprednisolone and the optimal duration of corticosteroid therapy is still unknown.