Inhibitory effects of high-dose methylprednisolone on bacterial translocation from gut and endotoxin release following acute spinal cord injury-induced paraplegia in rats

BACKGROUND： Previous studies have shown that autonomic dysfunction results in gastrointestinal motility disorders and ultimately results in bacterial translocation following acute spinal cord injury （SCI）. Intensive methylprednisolone dosing improves neurological recovery in SCI patients. However, it remains uncertain whether high-dose methylprednisolone inhibits bacterial translocation and endotoxin release following acute SCI. OBJECTIVE： To investigate the inhibitory effect of methylprednisolone on bacterial translocation and endotoxin release from the gut in paraplegic rats. DESIGN, TIME AND SETTING： The randomized, controlled study was performed at the Orthopedic Lab, First Affiliated Hospital, Nanchang University, China, from April to December 2008. MATERIALS： Methylprednisolone （Pfizer, USA）, automatic microbial identification instrument ATB Expression and reagent ID 32 system （BioMerieux, France）, Limulus test kit （ACC, USA）, and optical microscope （Olympus, Japan） were used in this study. METHODS： A paraplegia model was established following SCI in 48 Wistar rats, aged 7 weeks. The rats were equally and randomly assigned to saline and methylprednisolone groups. Immediately post-injury, the methylprednisolone group was administered 30 mg/kg methylprednisolone via caudal intravenous infusion, followed by a 23-hour infusion of 5.4 mg/kg per hour. The saline group received an equal volume of saline as placebo. MAIN OUTCOME MEASURES： At 24 hours, 72 hours, and 1 week after SCI, blood samples were collected for bacterial cultures, and bacteria and endotoxin were identified using ATB Expression and Limulus test kits. In addition, mesenteric lymph node, spleen, and liver samples were collected for bacterial cultures. Histological examinations of mesenteric lymph node, spleen, liver, jejunum, and ileum were performed 1 week post-injury. Locomotor function in the hind limb was evaluated using the Basso, Beattie, and Bresnahan score at pre-injury time point, as well as 24 hours, 72 hours, and 1 week post-injury. RESULTS： Endotoxemia and bacterial growth were identified at 24 hours post-injury in both groups. However, plasma endotoxin levels were significantly decreased in the methylprednisolone group compared with the saline group at 72 hours and 1 week post-injury （P 〈 0.05）. Translocated bacteria mainly comprised Bacillus coli, Enterobacter cloacae, Escherichia coli, Proteus vulgaris, and Enterococcus faecalis following SCI combined with paraplegia. Histological changes were not as severe in the methylprednisolone group compared with the saline group 1 week after injury. Basso, Beattie, and Bresnahan scores were significantly better in the methylprednisolone group compared with the saline group 1 week after injury （P 〈 0.05）. CONCLUSION： High-dose methylprednisolone inhibited bacterial translocation from the gut and endotoxin release in rats with SCI.

Intravenous immunoglobulin accompanied with high-dose methylprednisolone therapy for 17 children with anti-N-methyl-D-aspartate receptor encephalitis:Clinic and nursing

Objective:An increasing number of pediatric patients are being diagnosed with anti-N-methyl-Daspartate receptor(NMDAR)encephalitis,whose treatment requires immunotherapy through nursing interventions.This study aimed to analyze the clinical features and long-term prognosis of pediatric anti-NMDAR encephalitis and to gather nursing experiences of immunotherapy.Methods:Seventeen children diagnosed with anti-NMDAR encephalitis were admitted to the pediatric department.They were subjected to a therapy of intravenous immunoglobulin(IVIG)accompanied with high-dose methylprednisolone(HDMP).Multidisciplinary cooperation and intensive care were used to manage them.The effects of nursing intervention and therapy were repeatedly assessed and analyzed throughout the course of treatment and recovery.Results:None of the patients manifested adverse drug reaction(ADR)during IVIG administration.At the first administration of HDMP,ADRs were promptly and efficiently treated in four patients(24%;i.e.,one case each of hyperglycosemia,hypertension,aggravated symptoms,and gastrointestinal bleed).Two patients underwent rehabilitation,and six patients received hyperbaric oxygenation during hospitalization.Nine patients with indwelling gastric tubes experienced four times of unplanned extubation.Hospital stay ranged from 11 days to 59 days,with the mean duration of 26 days.Discharge evaluation revealed that 16 patients who scored 0e2 on the modified Rankin scale presented obvious remission,and one patient who had a mRS score of 4 exhibited less improvement.The mRS scores of hospitalization,discharge,and six-month follow-up displayed statistically significant differences.Conclusions:Nursing interventions of immunotherapy ensures the security of IVIG administration.Multidisciplinary cooperation promotes remission.Our findings can serve as reference for healthcare teams.

Effects of high-dose glucose-insulin-potassium on acute coronary syndrome patients receiving reperfusion therapy:a meta-analysis

BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs).RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio [RR] 0.57,95% confidence interval [95% CI]:0.35 to 0.94,P=0.03) and the risk of heart failure(RR 0.48,95% CI:0.25 to 0.95,P=0.04) and improved the left ventricular ejection fraction(LVEF)(mean difference [MD] 2.12,95% CI:0.40 to 3.92,P=0.02) at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95% CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95% CI:1.74 to 47.29,P=0.009) and hypoglycemia(RR 6.50,95% CI:1.28 to 33.01,P=0.02) but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD) activity but not glutathione peroxidase(GSH-Px) or catalase(CAT) activity.CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering eflcacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.

Therapeutic efficacy of methylprednisolone sodium succinate via diverse administration routes for mid-to high-frequency sudden sensorineural hearing loss

BACKGROUND Sudden sensorineural hearing loss(SSNHL),characterized by a rapid and unexplained loss of hearing,particularly at moderate to high frequencies,presents a significant clinical challenge.The therapeutic use of methylprednisolone sodium succinate(MPSS)via different administration routes,in combination with conventional medications,remains a topic of interest.AIM To compare the therapeutic efficacy of MPSS administered via different routes in combination with conventional drugs for the treatment of mid-to high-frequency SSNHL.METHODS The medical records of 109 patients with mid-to high-frequency SSNHL were analyzed.The patients were divided into three groups based on the route of administration:Group A[intratympanic(IT)injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection],Group B(intravenous injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection),and Group C(single IT injection of MPSS).The intervention effects were compared and analyzed.RESULTS The posttreatment auditory thresholds in Group A(21.23±3.34)were significantly lower than those in Groups B(28.52±3.36)and C(30.23±4.21;P<0.05).Group A also exhibited a significantly greater speech recognition rate(92.23±5.34)than Groups B and C.The disappearance time of tinnitus,time to hearing recovery,and disappearance time of vertigo in Group A were significantly shorter than those in Groups B and C(P<0.05).The total effective rate in Group A(97.56%)was significantly greater than that in Groups B and C(77.14%and 78.79%,χ^(2)=7.898,P=0.019).Moreover,the incidence of adverse reactions in Groups A and C was significantly lower than that in Group B(4.88%,3.03%vs 2.57%,χ^(2)=11.443,P=0.003),and the recurrence rate in Group A was significantly lower than that in Groups B and C(2.44%vs 20.00%vs 21.21%,χ^(2)=7.120,P=0.028).CONCLUSION IT injection of MPSS combined with conventional treatment demonstrates superior efficacy and safety compared to systemic administration via intravenous infusion and a single IT injection of MPSS.This approach effectively improves patients'hearing and reduces the risk of disease recurrence.

Influence of ganglioside combined with methylprednisolone sodium succinate on efficacy and neurological function in patients with acute myelitis

BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.

Using Pharmacokinetic Modeling and Electronic Health Record Data to Predict Clinical and Safety Outcomes after Methylprednisolone Exposure during Cardiopulmonary Bypass in Neonates

Background:Infants undergoing cardiac surgery with cardiopulmonary bypass(CPB)frequently receive intraoperative methylprednisolone(MP)to suppress CPB-related inflammation;however,the optimal dosing strategy and efficacy of MP remain unclear.Methods:We retrospectively analyzed all infants under 90 days-old who received intra-operative MP for cardiac surgery with CPB from 2014–2017 at our institution.We combined real-world dosing data from the electronic health record(EHR)and two previously developed population pharmacokinetic/pharmacodynamic models to simulate peak concentration(Cmax)and area under the concentration-time curve for 24 h(AUC24)for MP and the inflammatory cytokines interleukin-6(IL-6)and interleukin-10(IL-10).We evaluated the relationships between post-operative,safety,and other clinical outcomes obtained from the EHR with each predicted exposure using non-parametric tests.Results:A total of 142 infants with median post-natal age 8(interquartile range[IQR]:5,37)days received a total dose of 30(19,49)mg/kg of MP.Twelve(8%)died,37(26%)met the composite post-operative outcome,114(80%)met the composite safety outcome,and 23(16%)had a major complication.Predicted median Cmax and AUC24 IL-6 exposure was significantly higher for infants meeting the composite post-operative outcome and those with major complications.Predicted median Cmax and AUC24 MP exposure was significantly higher for infants requiring insulin.No exposure was associated with death or other safety outcomes.Conclusions:Pro-inflammatory IL-6,but not MP exposure,was associated with post-operative organ dysfunction,suggesting current MP dosing may not adequately suppress IL-6 or increase IL-10 to impact clinical outcomes.Prospective study will be required to define the optimal exposure-efficacy and exposure-safety profiles in these infants.

The Effect of Dexamethasone versus Methylprednisolone in the Treatment of COVID-19 Patients in Jordan

Background: Previous studies focused on the treatment effect of steroids versus no steroids in treating severe COVID-19 patients, a few studies evaluated outcomes for treating those patients with either dexamethasone or methylprednisolone. Currently, we evaluate the difference in mortality associated with treating COVID-19 patients with dexamethasone versus methylprednisolone. Methods: With a retrospective multicenter study, records were reviewed for the admitted patients with severe COVID-19 during the peak of the severe COVID-19 pandemic. All admitted patients on dexamethasone or methylprednisolone were included. Patients were analyzed as all populations and propensity scores matched patients. Propensity scores were calculated for several confounders by the generalized linear model, and a “greedy” near-neighbor matching algorithm was used. Continuous variables with nonnormal distribution were analyzed by Wilcoxon signed rank test. Chi-squared and Fischer exact test analyzed categorical variables. P-values were adjusted by the Bonferroni method for both data cohorts. Body mass index was in categories. Radiological findings were divided into five categories. The outcomes: mortality, the need for home oxygen therapy, recovery, and residual symptoms on discharge were analyzed by an independent two-sample test for equality of proportions (with Yates correction), and logistic regression analysis. Results: Among the 1128 reviewed records, patients on dexamethasone or methylprednisolone were 1071, and the propensity score-matched patients were 784: dexamethasone 393 and methylprednisolone 391. There was no significant difference in the characteristics of patients between the two steroids (p-value and adjusted p-value > 0.05) for most variables. PSM adjusted a few discrepant variables before analysis. The outcome of the unmatched patients demonstrated dexamethasone benefit in the need for home oxygen therapy ( 0.05). However, matched patients demonstrated significantly lower mortality associated with dexamethasone treatment (difference -2.68%, 95%CI, -1.0, -0.004, p = 0.03, and OR 1.7, p = 0.017), and no difference for the other outcomes, including the need for home oxygen therapy (p-value > 0.05). Conclusion: Dexamethasone treatment caused significantly less mortality than methylprednisolone in treating our COVID-19 patients, but no significant difference in recovery, the need for home oxygen therapy, and residual symptoms on discharge.

Severe inflammatory disorder in trisomy 8 without myelodysplastic syndrome and response to methylprednisolone:A case report

BACKGROUND Patients with trisomy 8 consistently present with myeloid neoplasms and/or auto-inflammatory syndrome.A possible link between myelodysplastic syndromes(MDS)with trisomy 8(+8-MDS)and inflammatory disorders is well recognized,several cases having been reported.However,inflammatory disorders in patients without MDS have been largely overlooked.Generally,Behçet's disease is the most common type in+8-MDS.However,inflammatory disorders with pulmonary involvement are less frequent,and no effective treatment has been established.CASE SUMMARY A 27-year-old man with recurrent fever,fatigue for>2 mo,and unconsciousness for 1 day was admitted to our emergency department with a provisional diagnosis of severe pneumonia.Vancomycin and imipenem were administered and sputum collected for metagenomic next-generation sequencing.Epstein–Barr virus and Mycobacterium kansasii were detected.Additionally,chromosomal analysis showed duplications on chromosome 8.Two days later,repeat metagenomic next-generation sequencing was performed with blood culture.Cordyceps portugal,M.kansasii,and Candida portugal were detected,and duplications on chromosome 8 confirmed.Suspecting hematological disease,we aspirated a bone marrow sample from the iliac spine,examination of which showed evidence of infection.We added fluconazole as further antibiotic therapy.Seven days later,the patient’s condition had not improved,prompting addition of methylprednisolone as an anti-inflammatory agent.Fortunately,this treatment was effective and the patient eventually recovered.CONCLUSION Severe inflammatory disorders with pulmonary involvement can occur in patients with trisomy 8.Methylprednisolone may be an effective treatment.

Neuroprotection of Erythropoietin and Methylprednisolone against Spinal Cord Ischemia-Reperfusion Injury

Recent research based on various animal models has shown the neuroprotective effects of erythropoietin （EPO）. However, few studies have examined such effects of EPO in the clinic. In this study we enrolled patients with spinal cord ischemia-reperfusion （I-R） injury to investigate the clinical application of EPO and methylprednisolone （MP） for the neuroprotection against spinal cord I-R injury. Retrospective analysis of 63 cases of spinal cord I-R injury was performed. The Frankel neurological performance scale was used to evaluate the neurological function after spinal cord injury （SCI）, including 12 cases of scale B, 30 cases of scale C, and 21 cases of scale D. These cases were divided into 2 groups： group A （27 cases） got treatment with both EPO and MP; group B （36 cases） got treatment with MP only. The neurological function of patients after treatment was evaluated by American Spinal Cord Injury Association （ASIA） index score, and activity of daily living （ADL） of the patients was also recorded. All patients got follow-up and the follow-up period ranged from 24 to 39 months （mean 26 months）. There was no significance difference in neurological function between groups A and B before the treatment （P〉0.05）. However, the neurological function and ADL scores were significantly improved 1 week, 1 year or 2 years after the treatment compared to those before the treatment （P〈0.05）, and the improvement was more significant in group A than in group B （P〈0.05）. It is suggested that the clinical application of EPO and MP provides the neuroprotection against spinal cord I-R injury.

Methylprednisolone promotes recovery of neurological function after spinal cord injury： association with Wnt/β-catenin signaling pathway activation

Some studies have indicated that the Wnt/β-catenin signaling pathway is activated following spinal cord injury, and expression levels of specific proteins, including low-density lipoprotein receptor related protein-6 phosphorylation, β-catenin, and glycogen synthase kinase-3β, are significantly altered. We hypothesized that methylprednisolone treatment contributes to functional recovery after spinal cord injury by inhibiting apoptosis and activating the Wnt/β-catenin signaling pathway. In the current study, 30 mg/kg methylprednisolone was injected into rats with spinal cord injury immediately post-injury and at 1 and 2 days post-injury. Basso, Beattie, and Bresnahan scores showed that methylprednisolone treatment significantly promoted locomotor functional recovery between 2 and 6 weeks post-injury. The number of surviving motor neurons increased, whereas the lesion size significantly decreased following methylprednisolone treatment at 7 days post-injury. Additionally, caspase-3, caspase-9, and Bax protein expression levels and the number of apoptotic cells were reduced at 3 and 7 days post-injury, while Bcl-2 levels at 7 days post-injury were higher in methylprednisolone-treated rats compared with saline-treated rats. At 3 and 7 days post-injury, methylprednisolone up-regulated expression and activation of the Wnt/β-catenin signaling pathway, including low-density lipoprotein receptor related protein-6 phosphorylation, β-catenin, and glycogen synthase kinase-3β phosphorylation. These results indicate that methylprednisolone-induced neuroprotection may correlate with activation of the Wnt/β-catenin signaling pathway.

High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding:A meta-analysis

AIM:To evaluate the efficacy of high-dose proton pump inhibitors(PPIs)vs low-dose PPIs for patients with upper gastrointestinal bleeding.METHODS:PubMed,Embase,the Cochrane Library,and Web of Science were searched to identify relevant randomized controlled trials(RCTs).Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis.The primary endpoint was rebleeding;secondary endpoints were patient numbers that needed surgery,and mortality.The meta-analysis was performed with a fixed effects model or random effects model.RESULTS:Nine eligible RCTs including 1342 patients were retrieved.The results showed that high-dose intravenous PPI was not superior to low-dose intra-venous PPI in reducing rebleeding[odds ratio(OR)= 1.091,95%confidential interval(CI):0.777-1.532],need for surgery(OR=1.522,95%CI:0.643-3.605) and mortality(OR=1.022,95%CI:0.476-2.196).Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients(OR=0.831,95%CI,0.467-1.480)and European patients(OR=1.263,95%CI:0.827-1.929).CONCLUSION:Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.

Methylprednisolone inhibits activated CD4^+ T cell survival promoted by toll-like receptor ligands

BACKGROUND: Methylprednisolone (MP) can affect the survival of CD4(+) T lymphocytes and plays an important role in adaptive immune responses; however, its mechanism of action is not clear. Recent studies have shown that toll-like receptors (TLRs) on CD4(+) T cells can directly modulate adaptive immune responses by affecting the survival and proliferation of activated CD4(+) T cells. This study aimed to investigate the relationship between MP, TLRs and activated CD4(+) T cells. METHODS: We separated and purified CD4(+) T cells from mice, activated them in vitro, and co-cultured them with TLR ligands, MP or inhibitors of nuclear factor-kappa B (NF-kappa B) and activator protein 1 (AP-1). We then assessed CD4(+) T cell survival and proliferation and the expression of NF-kappa B and AP-1. RESULTS: Activated CD4(+) T cells showed increased TLR-3 and TLR-9 mRNA expression, but polyinosinic-polycytidylic acid (poly I:C) and MP had no effect on the expression of these mRNAs. Still, poly I:C and CpG oligodeoxynucleotides (CpG DNA) increased the survival of activated CD4(+) T cells, whereas MP reduced the survival of activated CD4(+) T cells and could inhibit the survival effects of poly I:C and CpG DNA. The NF-kappa B essential modifier-binding domain (NBD) inhibited the survival of activated CD4(+) T cells induced by poly I:C and CpG DNA, but the AP-1 inhibitor crucumin did not have the same effect. The increased expression of NF-kappa B induced by poly I:C and CpG DNA in activated CD4(+) T cells could be inhibited by MP, but the same was not true for the increased expression of AP-1 induced by poly I:C and CpG DNA. Finally, the proliferation of activated CD4(+) T cells was not affected by poly I:C or MP. CONCLUSION: The survival of activated CD4(+) T cells is promoted by TLR ligands, but this effect is inhibited by MP.

Methotrexate combined with methylprednisolone for the recovery of motor function and differential gene expression in rats with spinal cord injury

Methylprednisolone is a commonly used drug for the treatment of spinal cord injury, but high doses of methylprednisolone can increase the incidence of infectious diseases. Methotrexate has anti-inflammatory activity and immunosuppressive effects, and can reduce in- flammation after spinal cord injury. To analyze gene expression changes and the molecular mechanism of methotrexate combined with methylprednisolone in the treatment of spinal cord injury, a rat model of spinal cord contusion was prepared using the PinPointTM preci- sion cortical impactor technique. Rats were injected with methylprednisolone 30 mg/kg 30 minutes after injury, and then subcutaneously injected with 0.3 mg/kg methotrexate 1 day after injury, once a day, for 2 weeks. TreadScan gait analysis found that at 4 and 8 weeks after injury, methotrexate combined with methylprednisolone significantly improved hind limb swing time, stride time, minimum longitudinal deviation, instant speed, footprint area and regularity index. Solexa high-throughput sequencing was used to analyze differential gene ex- pression. Compared with methylprednisolone alone, differential expression of 316 genes was detected in injured spinal cord treated with methotrexate and methylprednisolone. The 275 up-regulated genes were mainly related to nerve recovery, anti-oxidative, anti-inflammatory and anti-apoptotic functions, while 41 down-regulated genes were mainly related to proinflammatory and pro-apoptotic functions. These results indicate that methotrexate combined with methylprednisolone exhibited better effects on inhibiting the activity of inflammatory cytokines and enhancing antioxidant and anti-apoptotic effects and thereby produced stronger neuroprotective effects than methotrexate alone. The 316 differentially expressed genes play an important role in the above processes.

Methylprednisolone inhibits Nogo-A protein expression after acute spinal cord injury

Oligodendrocyte-produced Nogo-A has been shown to inhibit axonal regeneration. Methylprednisolone plays an effective role in treating spinal cord injury, but the effect of methylprednisolone on Nogo-A in the injured spinal cord remains unknown. The present study established a rat model of acute spinal cord injury by the weight-drop method. Results showed that after injury, the motor behavior ability of rats was reduced and necrotic injury appeared in spinal cord tissues, which was accompanied by increased Nogo-A expression in these tissues. After intravenous injection of high-dose methylprednisolone, although the pathology of spinal cord tissue remained unchanged, Nogo-A expression was reduced, but the level was still higher than normal. These findings implicate that methylprednisolone could inhibit Nogo-A expression, which could be a mechanism by which early high dose methylprednisolone infusion helps preserve spinal cord function after spinal cord injury.

Predictors of post-treatment stenosis in cervical esophageal cancer undergoing high-dose radiotherapy

AIM To evaluate toxicity and treatment outcome of highdose radiotherapy(RT) for cervical esophageal cancer(CEC).METHODS We reviewed a total of 62 consecutive patients who received definitive RT for stage Ⅰ to Ⅲ cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local(occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed.RESULTS Grade 1, 2, and 3 esophagitis occurred in 19(30.6%), 39(62.9%), and 4 patients(6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients(25.8%) developed post-RT stenosis, of which 7 cases(43.8%) were malignant. Four patients(6.5%) developed tracheoesophageal fistula(TEF), of which 3(75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4(P = 0.001), complete circumference involvement(P < 0.0001), stenosis at diagnosis(P = 0.024), and endoscopic complete response(P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis(P = 0.003). A higher dose(≥ 60 Gy) was not associated with occurrence of postRT stenosis or TEF. With a median follow-up of 24.3(range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival(OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement(P = 0.023), stenosis at diagnosis(P < 0.0001), and occurrence of post-RT stenosis or TEF(P < 0.001) in univariate analysis, while stenosis at diagnosis(P = 0.004) and occurrence of post-RT stenosis or TEF(P = 0.023) were significant in multivariate analysis. CONCLUSION Chemoradiation for CEC was well tolerated, and a higher dose was not associated with stenosis. Patients with complete circumferential involvement require close follow-up.

Methylprednisolone and tetrandrine in combination with direct current electrical field for treating acute spinal cord injury

BACKGROUND： The direct current electrical field can effectively promote the regeneration of the spinal cord; moreover, methylprednisolone （MP） can relieve secondary edema after spinal cord injury. Tetrandrine （Tet） is an effective component of hanfangji and can protect the effect of spinal cord and axis-cylinder. Whether direct current electrical field combining with MP or Tet has synergic or strengthening effect on treating complete spinal cord injury or not should be studied further. OBJECTIVE：To study the effect of direct current electrical field assisted by MP and Tet on treating spinal cord injury. DESIGN： Randomized controlled animal study. SETTING： People＇s Hospital of Hainan Province. MATERIALS： A total of 45 healthy hybrid dogs, of both genders, weighing 10 - 12 kg, aged 1.5 - 2 years, were provided by Animal Center of Hainan Province. Somatosensory evoked potential meter （DANTEC Company）, IBAS-2.0 imaging analysis meter （Germany）, and self-made electronic stimulator. METHODS： The experiment was carried out in Hainan People＇s Hospital from May 2001 to June 2004. All experimental dogs were randomly divided into 4 groups： control group （n =9）, electrostimulating group （n =12）, MP ＋ electrostimulating group （n =12） and Tet ＋ electrostimulating group （n =12）. ① After anesthesia, Allen WD method was used to induce complete spinal cord injury. The metal bar, which was 10 cm in height fell freely and vertically hit the spinal cord to provide a complete spinal cord injury. Dogs in control group and electrostimulating group were implanted electrical stimulators 6 hours after spinal cord injury （no electricity in control group）; dogs in MP ＋ electrostimulating group were injected 30 mg/kg MP for 15 minutes at 2 hours after spinal cord injury and electrical stimulators implanted at 6 hours after injury; dogs in Tet ＋ electrostimulating group were intravenously injected with 7.5 mg/kg Tet at 2 hours after spinal cord injury and electrical stimulators implanted at 6 hours after injury; and then, 7.5 mg/kg Tet injected at days 2 and 3 after injury. ② Specimens were taken from control group from three dogs of every month; from the injured segments of spinal cords at 1 month, 2 months and 3 months; and from electrostimulating group, MP ＋ electrostimulating group and Tet ＋ electrostimulating group of 4 dogs for histological examinations. ③Detection of neurological function： Neurological function was evaluated with the functional 10 grading system. The scores ranged from 0 to 10 （0： complete paraplegia; 10： normality）. ④Detection of cortical somatosensory evoked potential （CSEP）： According to the scheme formulated by the International Electroencephalographical Association, the patterns of the fundamental waves were P1 - N1 - P1 waves. The latency of the P1 wave and the amplitude of P1 -N1 waves were mainly observed individually at 1, 2 and 3 months after the injury. ⑤Histological detection： All spinal cord specimens of the injuried segment were harvested at 1, 2 and 3 months after injury. They were stained with hematoxylin and Nissl staining methods, and then were observed under an optical microscope, and the neurons were counted. The sectional areas of the neurons and the density of the Nissl bodies were measured by a system image pattern analysis （IBAS-2.0, Germany）. MAIN OUTCOME MEASURES： The neurological function, cortical somatosensory evoked potential, neuronal amount, sectional area of neurons and Nissl body density at 1 to 3 months after injury. RESULTS： All 45 experimental dogs were involved in the final analysis. ① Detection of neurological function： One month later, the dogs in MP ＋ electrostimulating group could walk, but the dogs in electrostimulating group and Tet ＋ electrostimulating group could stand. Two months after injury, the dogs in MP ＋ electrostimulating group almost recovered to normal, but the dogs in electrostimulating group could walk and those in Tet ＋ electrostimulating group could run. Those in control group had no parent recovery.②Detection of P1 latency and P1 - N1 amplitude： Changes of P1 latency in control group were long and P1 -N1 amplitude was very low at 1 month later. Compared to electrostimulating group, MP ＋ electrostimulating group and Tet ＋ electrostimulating group, there were significant differences （P 〈 0.05）. P1 latency was manifestly shortened and amplitude were raised in electrostimulating group, MP ＋ electrostimulating group and Tet ＋ electrostimulating group. Those in MP ＋ electrostimulating group and Tet ＋ electrostimulating group were superior to those in electrostimulating group and there were significant differences （P 〈 0.05）. ③Sectional areas of neurons and Nissl body density： At 1 - 3 months after injury, sectional areas of neurons were larger in electrostimulating group [（170.14 ±7.45）, （209.60 ±14.80）, （312.47±12.63） μm^2], MP ＋ electrostimulating group [（282.18±15.25）, （418.18±16.27）, （515.25±15.10） μm^2] and Tet ＋ electrostimulating group [（231.81±7.38）, （322.67±8.45）, （386.82±10.42） μm^2] control group[（98.12±4.93）, （113.50±6.74）, （122.59±8.03） μm^2, P 〈 0.05]; especially, sectional area was the largest in MP ＋ electrostimulating group. At 1 - 3 months after injury, Nissl body density was more in electrostimulating group （ 170.14 ±7.45, 209.60 ± 14.80, 312.47 ± 12.63 ）, MP ＋ electrostimulating group （282.18±15.25, 418.18±16.27, 515.25±15.10） and Tet ＋ electrostimulating group （231.81±7.38, 322.67±8.45, 386.82±10.42） than control group （98.12±4.93, 113.50±6.74, 122.59±8.03, P 〈 0.05）; especially, Nissl body density was the most in MP ＋ electrostimulating group. CONCLUSION： The direct current electrical field can effectively promote spinal cord regeneration. The combination of direct current electrical field with large dose MP or Tet has synergistic effects for treating spinal cord injury. The curative effects of direct current electrical field with large dose MP are much better than those with Tet.

Methylprednisolone exerts neuroprotective effects by regulating autophagy and apoptosis

Methylprednisolone markedly reduces autophagy and apoptosis after secondary spinal cord injury. Here, we investigated whether pretreatment of cells with methylprednisolone would protect neuron-like cells from subsequent oxidative damage via suppression of autophagy and apoptosis. Cultured N2 a cells were pretreated with 10 μM methylprednisolone for 30 minutes, then exposed to 100 μM H2O2 for 24 hours. Inverted phase contrast microscope images, MTT assay, flow cytometry and western blot results showed that, compared to cells exposed to 100 μM H2O2 alone, cells pretreated with methylprednisolone had a significantly lower percentage of apoptotic cells, maintained a healthy morphology, and showed downregulation of autophagic protein light chain 3B and Beclin-1 protein expression. These findings indicate that methylprednisolone exerted neuroprotective effects against oxidative damage by suppressing autophagy and apoptosis.

Preliminary study of therapeutic effects of panax notoginside and methylprednisolone on pulmonary fibrosis in rats

Objective: To study the therapeutic effects of panax notoginside (PN) and methylprednisolone (MP) on pulmonary fibrosis in rats. Methods: Bleomycin was introduced into the bronchial tree of 75 Wistar male rats through a tracheal incision to establish a rat model of pulmonary fibrosis (PF). The rats were equally divided into 3 groups: PF group, PN treated group and MP treated group. Five rats of each group were killed 1, 3, 7, 14 and 28 d after the administration of bleomycin and the specimens of lung tissue and plasma were collected for the determination of content of collagen Ⅰ and Ⅲ with immunohistochemical method and the level of MIP-1α and MCP-1 with ELIZA. Results: The severity of PF, the content of collagen Ⅰ and Ⅲ and the level of MIP-1α and MCP-1 were significantly decreased in PN and MP treated groups than in PF group (P<0.05). Conclusion: PN and MP are effective to control the development of PF induced with bleomycin in rats.

Methylprednisolone accelerate chest computed tomography absorption in COVID-19:A three-centered retrospective case control study from China

BACKGROUND Based on the results of some large randomized controlled trials(RCTs)confirmed the efficacy of corticosteroids in coronavirus disease 2019(COVID-19),corticosteroids have been included in World Health Organization guidelines,but remain controversial.AIM To investigate the ef
cacy and safety of low-to-moderate dose(30 to 40 mg/d)short-term methylprednisolone for COVID-19 patients.METHODS The clinical data of 70 patients diagnosed with COVID-19 who received antiviral therapy with Arbidol for 7-10 d before admission but had no obvious absorption on chest computed tomography(CT)imaging were retrospectively analyzed.Arbidol(as the control group)and methylprednisolone(as the corticosteroid group)were given respectively after admission.After treatment,chest CT was reexamined to evaluate the absorption of pulmonary lesions.Additionally,we evaluated and compared the lymphocyte count,erythrocyte sedimentation rate(ESR),interleukin-6(IL-6),serum ferritin,lactate dehydrogenase(LDH),creatine kinase-MB(CK-MB),hypersensitive C-reactive protein(hs-CRP)and D-dimer levels,and also analyzed the incidence of toxic and side effects.RESULTS All patients in the corticosteroid group had varying degrees of CT absorption,which was significantly better than that in the control group(CT obvious absorption rate:89.47%vs 12.5%,P<0.05).The average daily dose and course of methylprednisolone in the patients with significant improvement on chest CT was(38.55±13.17)mg and(6.44±1.86)d respectively.During the treatment,the lymphocyte count,ESR,IL-6,serum ferritin,LDH,CK-MB,hs-CRP and D-dimer levels all improved gradually,indicating that both Arbidol and methylprednisolone therapy were contributed to improving the condition of COVID-19 patients.The corticosteroid regimen did not prolong the clearance time of severe acute respiratory syndrome coronavirus 2.There were no severe adverse reactions such as gastrointestinal bleeding,secondary severe infection,hypertension,diabetic ketoacidosis,mental disorders or electrolyte disorders during the whole corticosteroid treatment process.CONCLUSION Low-to-moderate dose short-term methylprednisolone can accelerate the chest CT imaging absorption of COVID-19 so as to improve symptoms and alleviate the condition in a short term,reduce the hospital stay,meanwhile avoid severe COVID-19 phases.The protocol has been proven to be effective and safe in clinical use.