Acid Neutralization by Composite Lysine Nanoparticles for Spinal Cord Injury Recovery through Mitigating Mitochondrial Dysfunction.

After spinal cord injury (SCI), significant alterations in the tissue microenvironment lead to mitochondrial dysfunction, inducing apoptosis and inhibiting the remodeling of neural circuits, thereby impeding recovery. Although previous studies have demonstrated a marked decrease in pH at the injury site, creating an acidic microenvironment, the impact of improving this acidic microenvironment on SCI recovery has not been investigated. This study prepared a lysine@hollow mesoporous silica nanoparticle/gelatin methacrylate (GelMA) (L@H/G) composite hydrogel. The L@H/G composite hydrogel was demonstrated to release lysine and efficiently improve the acidic microenvironment slowly. Significantly, the composite hydrogel reduced cell apoptosis, promoted nerve regeneration, inhibited glial scar formation, and ultimately enhanced motor function recovery in mice with SCI. Mechanistically, the L@H/G hydrogel improved the mitochondrial tricarboxylic acid (TCA) cycle and fatty acid metabolism, restoring energy supply and facilitating mitochondrial function recovery. To the best of our knowledge, this is the first report confirming that improving the acidic microenvironment could promote SCI repair, providing a potential therapeutic strategy for SCI.

An effective insulin infusion protocol for severe traumatic brain injury patients: A retrospective observational study.

PURPOSE: Severe traumatic brain injury (sTBI) patients often experience stress hyperglycaemia, which can lead to negative outcomes. This study aims to introduce an effective insulin infusion protocol specifically designed for sTBI patients. METHODS: Data was collected from all sTBI patients during two periods: 1 October 2019 to 30 April 2020, and 1 June 2020 to 31 December 2020. In May 2020, a new insulin infusion protocol was implemented. Blood glucose management, infection, coagulation, and prognosis were compared in these two periods. RESULT: 195 patients were included, with 106 using the new protocol. The proportion of hyperglycaemia decreased from 40.04% to 26.91% (P<0.05), and the proportion of on-target blood glucose levels increased from 35.69% to 38.98% (P<0.05). Average blood glucose levels decreased from 9.98±2.79mmol/L to 8.96±2.82mmol/L (P<0.05). There was no substantial increase in hypoglycaemia, which remained controlled below 1%. The new protocol positively influenced glucose concentration and dispersion trends. There were no significant differences in catheter-related infections, antibiotic use, mechanical ventilation (MV) duration, length of stay in ICU, Glasgow Outcome Scale (GOS), or mortality. However, the conventional protocol group had a higher coagulation tendency (R-value of thromboelastography 4.80±1.35min vs. 5.52±1.87min, P<0.05), with no difference in deep vein thrombosis (DVT) incidence. CONCLUSION: Our findings suggest that a customized insulin infusion process for sTBI patients can effectively manage blood glucose. While there is no significant improvement in infection control or prognosis, it may have a positive impact on coagulation without affecting the occurrence of DVT.

Application of the PDCA Cycle for Managing Hyperglycemia in Critically Ill Patients.

INTRODUCTION: Stress hyperglycemia is a common symptom in critically ill patients, and is not only a marker indicating the severity of illness but is also related to worsening outcomes. Managing stress hyperglycemia without increasing the likelihood of hypoglycemia is one of the most pressing challenges to be urgently addressed in clinics. The Plan-Do-Check-Act (PDCA) cycle management has been put forward in various surgical management scenarios, and has proven to be effective in the diagnosis and treatment of different diseases. It possesses dynamic characteristics and can be updated according to the results of glycemic control and feedback. This study focused on the use of PDCA to manage glucose levels in critically ill patients. METHODS: Based on the glucose level of 1003 critically ill patients admitted to the emergency intensive care unit (EICU) from 1 October 2019 to 31 December 2020, we collected and matched the prevalence of hyperglycemia, hypoglycemia, and glucose variability on a quarterly basis. According to the PDCA management method, we analyzed the possible causes, supervised the implementation of measures, summarized the feedback on improvements, and then proposed new improvement measures for implementation in the next quarter. RESULTS: Three measures were proposed and applied to enhance the management of hyperglycemia: (I) Updating and formulating three editions of the insulin infusion protocol and increasing the initial and maintenance doses of insulin on a case-by-case basis; (II) reducing the use of parenteral nutrition and ensuring that enteral nutrition is consumed at a uniform and slow rate; and (III) forming a training method during the COVID-19 pandemic and improving implementation of the insulin infusion protocol. Following PDCA management, the prevalence of hyperglycemia fell from 43.18% to 32.61%, the incidence of hypoglycemia was below 1.00%, and there was no significant fluctuation in blood glucose variability. CONCLUSION: The PDCA method is helpful in developing a superior insulin infusion protocol for critically ill patients and lowering the prevalence of hyperglycemia in critically ill patients.

Application of the PDCA Cycle for Managing Hyperglycemia in Critically Ill Patients.

Introduction: Stress hyperglycemia is a common symptom in critically ill patients, and is not only a marker indicating the severity of illness but is also related to worsening outcomes. Managing stress hyperglycemia without increasing the likelihood of hypoglycemia is one of the most pressing challenges to be urgently addressed in clinics. The Plan-Do-Check-Act (PDCA) cycle management has been put forward in various surgical management scenarios, and has proven to be effective in the diagnosis and treatment of different diseases. It possesses dynamic characteristics and can be updated according to the results of glycemic control and feedback. This study focused on the use of PDCA to manage glucose levels in critically ill patients. Methods: Based on the glucose level of 1003 critically ill patients admitted to the emergency intensive care unit (EICU) from 1 October 2019 to 31 December 2020, we collected and matched the prevalence of hyperglycemia, hypoglycemia, and glucose variability on a quarterly basis. According to the PDCA management method, we analyzed the possible causes, supervised the implementation of measures, summarized the feedback on improvements, and then proposed new improvement measures for implementation in the next quarter. Results: Three measures were proposed and applied to enhance the management of hyperglycemia: (I) Updating and formulating three editions of the insulin infusion protocol and increasing the initial and maintenance doses of insulin on a case-by-case basis; (II) reducing the use of parenteral nutrition and ensuring that enteral nutrition is consumed at a uniform and slow rate; and (III) forming a training method during the COVID-19 pandemic and improving implementation of the insulin infusion protocol. Following PDCA management, the prevalence of hyperglycemia fell from 43.18% to 32.61%, the incidence of hypoglycemia was below 1.00%, and there was no significant fluctuation in blood glucose variability. Conclusion: The PDCA method is helpful in developing a superior insulin infusion protocol for critically ill patients and lowering the prevalence of hyperglycemia in critically ill patients.

Minocycline improves the functional recovery after traumatic brain injury via inhibition of aquaporin-4.

Traumatic brain injury (TBI) is one of the main concerns worldwide as there is still no comprehensive therapeutic intervention. Astrocytic water channel aquaporin-4 (AQP-4) system is closely related to the brain edema, water transport at blood-brain barrier (BBB) and astrocyte function in the central nervous system (CNS). Minocycline, a broad-spectrum semisynthetic tetracycline antibiotic, has shown anti-inflammation, anti-apoptotic, vascular protection and neuroprotective effects on TBI models. Here, we tried to further explore the underlying mechanism of minocycline treatment for TBI, especially the relationship of minocycline and AQP4 during TBI treatment. In present study, we observed that minocycline efficaciously reduces the elevation of AQP4 in TBI mice. Furthermore, minocycline significantly reduced neuronal apoptosis, ameliorated brain edema and BBB disruption after TBI. In addition, the expressions of tight junction protein and astrocyte morphology alteration were optimized by minocycline administration. Similar results were found after treating with TGN-020 (an inhibitor of AQP4) in TBI mice. Moreover, these effects were reversed by cyanamide (CYA) treatment, which notably upregulated AQP4 expression level in vivo. In primary cultured astrocytes, small-interfering RNA (siRNA) AQP4 treatment prevented glutamate-induced astrocyte swelling. To sum up, our study suggests that minocycline improves the functional recovery of TBI through reducing AQP4 level to optimize BBB integrity and astrocyte function, and highlights that the AQP4 may be an important therapeutic target during minocycline treating for TBI.

Clinical and radiographic characteristics, management and short-term outcomes of patients with COVID-19 in Wenzhou, China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging viral disease. Here, we report the clinical features, management, and short-term outcomes of COVID-19 patients in Wenzhou, China, an area outside Wuhan. METHODS: Patients admitted to the Infectious Diseases Department of Ruian People's Hospital in Wenzhou, from January 21 to February 7, 2020, were recruited. Medical data on epidemiological history, demographics, clinical characteristics, laboratory tests, chest computerized tomography (CT) examination, treatment, and short-term outcomes were retrospectively reviewed. Blood biochemistry and routine tests were examined using standard methods and automatic machines. CT examination was performed several times during hospitalization as necessary. RESULTS: A total of 67 confirmed COVID-19 cases were diagnosed; 64 (95.4%) were common cases and three (4.5%) were severe cases. The most common symptoms at admission were fever (86.6%), cough (77.6%), productive cough (52.2%), chest distress (17.9%), and sore throat (11.9%), followed by diarrhea (7.4%), headache (7.4%), shortness of breath (6.0%), dizziness (4.5%), muscular soreness (4.5%), and running nose (4.5%). Thirty patients (47.8%) had increased C-reactive protein levels. The CT radiographs at admission showed abnormal findings in 54 (80.6%) patients. The patients were treated mainly by oxygen therapy and antiviral drugs. By March 3, 2020, all 67 patients completely recovered and had negative nucleic acid tests. The patients were discharged from the hospital and transferred to a medical observation isolation center for further observation. CONCLUSION: Cases of COVID-19 in Wenzhou are milder and have a better prognosis, compared to those in Wuhan. Timely and appropriate screening, diagnosis, and treatment are the key to achieve good outcomes.

Diagnosis of severe scrub typhus infection by next-generation sequencing:a case report.

BACKGROUND: Scrub typhus is an acute febrile illness, which was caused by Orientia tsutsugamushi and transmitted through the bite of chiggers. The diagnosis of scrub typhus could be missed diagnosis due to the absence of the pathognomonic eschar. CASE PRESENTATION: A 76-year-old man was hospitalized with fever and kidney injury and was diagnosed of hemorrhagic fever with renal syndrome first. However, the situation of the illness deteriorated into refractory septic shock and multiple organ dysfunction rapidly,although the treatment of anti-sepsis was used in 3rd-5th day. Orientia tsutsugamushi was determined to be the causative pathogen by Next-generation sequencing of his plasma sample in 6th day. Then, the patient was treated with doxycycline and azithromycin and recovered quickly. CONCLUSIONS: Next-generation sequencing was a new diagnostic technology and could identify scrub typhus in accurately and fast without the pathognomonic eschar.

The effects of an enteral nutrition feeding protocol on critically ill patients: A prospective multi-center, before-after study.

PURPOSE: The aim of this study was to explore the effects of an enteral nutrition (EN) feeding protocol in critically ill patients. METHODS: This was a prospective multi-center before-after study. We compared energy related and prognostic indicators between the control group (pre-implementation stage) and intervention group (post-implementation stage). The primary endpoint was the percentage of patients receiving EN within 7 days after ICU admission. RESULTS: 209 patients in the control group and 230 patients in the intervention group were enrolled. The implementation of the EN protocol increased the percentage of target energy reached from day 3 to day 7, and the difference between two groups reached statistical significance in day 6 (P = .01) and day 7 (P = .002). But it had no effects on proportion of patient receiving EN (P = .65) and start time of EN (P = .90). The protocol application might be associated with better hospital survival (89.1% vs 82.8%, P = .055) and reduce the incidence of EN related adverse (P = .004). There was no difference in ICU length of stay, duration of mechanical ventilation and ICU cost. CONCLUSION: The implementation of the enteral feeding protocol is associated with improved energy intake and a decreased incidence of enteral nutrition related adverse events for critically ill patients, but it had no statistically beneficial effects on reducing the hospital mortality rate. Trial registration ClinicalTrials.gov, NCT02976155. Registered November 29, 2016- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02976155.

Determination of serum neutrophil gelatinase-associated lipocalin as a prognostic biomarker of acute spontaneous intracerebral hemorrhage.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is currently known as an acute phase protein and implicated in acute brain injury. Herein, we sought to gauge serum NGAL level in patients after acute (<24 h) spontaneous intracerebral hemorrhage (ICH) and to investigate its relation to neurological outcome. METHODS: Serum NGAL levels were measured in 106 patients and 106 controls. National Institutes of Health Stroke Scale (NIHSS) score, Glasgow coma scale (GCS) score, ICH score and hematoma volume were recorded for assessing hemorrhagic severity. An unfavorable outcome was defined as modified Rankin Scale >2 at 90 days. RESULTS: As opposed to the controls, the patients had significantly raised serum NGAL levels. Correlations were observed between NGAL levels and serum C-reactive protein levels, blood glucose levels, GCS score, NIHSS score, ICH score and ICH volume. Multivariate analysis identified serum NGAL as a predictor for unfavorable outcome at 90 days. It also showed high prognostic ability under receiver operating characteristic curve. CONCLUSIONS: Enhanced NGAL level is revealed after acute spontaneous ICH, in association with inflammatory degree and hemorrhagic severity, and intimately correlated with a worse prognosis.

Retrospective analysis of nosocomial infections in the intensive care unit of a tertiary hospital in China during 2003 and 2007.

BACKGROUND: Nosocomial infections are a major threat to patients in the intensive care unit (ICU). Limited data exist on the epidemiology of ICU-acquired infections in China. This retrospective study was carried out to determine the current status of nosocomial infection in China. METHODS: A retrospective review of nosocomial infections in the ICU of a tertiary hospital in East China between 2003 and 2007 was performed. Nosocomial infections were defined according to the definitions of Centers for Disease Control and Prevention. The overall patient nosocomial infection rate, the incidence density rate of nosocomial infections, the excess length of stay, and distribution of nosocomial infection sites were determined. Then, pathogen and antimicrobial susceptibility profiles were further investigated. RESULTS: Among 1980 patients admitted over the period of time, the overall patient nosocomial infection rate was 26.8% or 51.0 per 1000 patient days., Lower respiratory tract infections (LRTI) accounted for most of the infections (68.4%), followed by urinary tract infections (UTI, 15.9%), bloodstream (BSI, 5.9%), and gastrointestinal tract (GI, 2.5%) infections. There was no significant change in LRTI, UTI and BSI infection rates during the 5 years. However, GI rate was significantly decreased from 5.5% in 2003 to 0.4% in 2007. In addition, A. baumannii, C. albicans and S. epidermidis were the most frequent pathogens isolated in patients with LRTIs, UTIs and BSIs, respectively. The rates of isolates resistant to commonly used antibiotics ranged from 24.0% to 93.1%. CONCLUSION: There was a high and relatively stable rate of nosocomial infections in the ICU of a tertiary hospital in China through year 2003-2007, with some differences in the distribution of the infection sites, and pathogen and antibiotic susceptibility profiles from those reported from the Western countries. Guidelines for surveillance and prevention of nosocomial infections must be implemented in order to reduce the rate.