Liberation from Mechanical Ventilation in Critically Ill Patients: Korean Society of Critical Care Medicine Clinical Practice Guidelines.

BACKGROUND: Successful liberation from mechanical ventilation is one of the most crucial processes in critical care because it is the first step by which a respiratory failure patient begins to transition out of the intensive care unit and return to their own life. Therefore, when devising appropriate strategies for removing mechanical ventilation, it is essential to consider not only the individual experiences of healthcare professionals, but also scientific and systematic approaches. Recently, numerous studies have investigated methods and tools for identifying when mechanically ventilated patients are ready to breathe on their own. The Korean Society of Critical Care Medicine therefore provides these recommendations to clinicians about liberation from the ventilator. METHOD: Meta-analyses and comprehensive syntheses were used to thoroughly review, compile, and summarize the complete body of relevant evidence. All studies were meticulously assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method, and the outcomes were presented succinctly as evidence profiles. Those evidence syntheses were discussed by a multidisciplinary committee of experts in mechanical ventilation, who then developed and approved recommendations. RESULT: Recommendations for nine population, intervention, comparator, outcome (PICO) questions about ventilator liberation are presented in this document. This guideline includes seven conditional recommendations, one expert consensus recommendation, and one conditional deferred recommendation. CONCLUSIONS: We developed these clinical guidelines for mechanical ventilation liberation to provide meaningful recommendations. These guidelines reflect the best treatment for patients seeking liberation from mechanical ventilation.

Establishment and Validation of a Risk Prediction Model for Non-Invasive Ventilation Failure After Birth in Premature Infants with Gestational Age < 32 Weeks.

OBJECTIVES: This study was performed to construct and validate a risk prediction model for non-invasive ventilation (NIV) failure after birth in premature infants with gestational age < 32 weeks. METHODS: The data were derived from the multicenter retrospective study program - Jiangsu Provincial Neonatal Respiratory Failure Collaboration Network from Jan 2019 to Dec 2021. The subjects finally included were preterm infants using NIV after birth with gestational age less than 32 weeks and admission age within 72 h. After screening by inclusion and exclusion criteria, 1436 babies were subsequently recruited in the study, including 1235 infants in the successful NIV group and 201 infants in the failed NIV group. RESULTS: (1) Gestational age, 5 min Apgar, Max FiO2 during NIV, and FiO2 fluctuation value during NIV were selected by univariate and multivariate analysis. (2) The area under the curve of the prediction model was 0.807 (95% CI: 0.767-0.847) in the training set and 0.825 (95% CI: 0.766-0.883) in the test set. The calibration curve showed good agreement between the predicted probability and the actual observed probability (Mean absolute error = 0.008 for the training set; Mean absolute error = 0.012 for the test set). Decision curve analysis showed good clinical validity of the risk model in the training and test cohorts. CONCLUSION: This model performed well on dimensions of discrimination, calibration, and clinical validity. This model can serve as a useful tool for neonatologists to predict whether premature infants will experience NIV failure after birth.

Impact of Respiratory Phase during Pleural Puncture on Complications in CT-Guided Percutaneous Lung Biopsy.

Purpose: This study investigated whether the respiratory phase during pleural puncture in CT-guided percutaneous transthoracic needle biopsy (PTNB) affects complications. Materials and Methods: We conducted a retrospective review of 477 lung biopsy CT scans performed during free breathing. The respiratory phases during pleural puncture were determined based on the table position of the targeted nodule using CT scans obtained during free breathing. We compared the rates of complications among the inspiratory, mid-, and expiratory respiratory phases. Logistic regression analysis was performed to control confounding factors associated with pneumothorax. Results: Among the 477 procedures, pleural puncture was performed during the expiratory phase in 227 (47.6%), during the mid-phase in 108 (22.6%), and during the inspiratory phase in 142 (29.8%). The incidence of pneumothorax was significantly lower in the expiratory puncture group (40/227, 17.6%; p = 0.035) and significantly higher in the mid-phase puncture group (31/108, 28.7%; p = 0.048). After controlling for confounding factors, expiratory-phase puncture was found to be an independent protective factor against pneumothorax (odds ratio = 0.571; 95% confidence interval = 0.360-0.906; p = 0.017). Conclusion: Our findings suggest that pleural puncture during the expiratory phase may reduce the risk of pneumothorax during image guided PTNB.

Intubation at Birth Is Associated with Death after Pulmonary Hemorrhage in Very Low Birth Weight Infants.

OBJECTIVE: This retrospective cohort study was performed to clarify the association between intubation in the delivery room and the mortality after pulmonary hemorrhage in very low birth weight infants (VLBWIs) during hospitalization. METHODS: The study participants were screened from the VLBWIs admitted to the neonatal intensive care unit (NICU) of the Children's Hospital Affiliated to Nanjing Medical University from 31 July 2019 to 31 July 2022. The newborns who ultimately were included were those infants who survived until pulmonary hemorrhage was diagnosed. These subjects were divided into the intubation-at-birth group (n = 29) and the non-intubation-at-birth group (n = 35), retrospectively. RESULTS: Univariate analysis found that the intubation group had a higher mortality and shorter hospital stay than the non-intubation group (p < 0.05) (for mortality: 25/29 (86.21%) in intubation group versus 14/35 (40.00%) in non-intubation group). By multivariate analysis, the result further showed that intubation in the delivery room was related to shorter survival time and higher risk of death (adjusted hazard ratio: 2.341, 95% confidence interval: 1.094-5.009). CONCLUSIONS: Intubation at birth suggested a higher mortality in the VLBWIs when pulmonary hemorrhage occurred in the NICU.

Respiratory pathogen and clinical features of hospitalized patients in acute exacerbation of chronic obstructive pulmonary disease after COVID 19 pandemic.

Respiratory infections are common causes of acute exacerbation of chronic obstructive lung disease (AECOPD). We explored whether the pathogens causing AECOPD and clinical features changed from before to after the coronavirus disease 2019 (COVID-19) outbreak. We reviewed the medical records of patients hospitalized with AECOPD at four university hospitals between January 2017 and December 2018 and between January 2021 and December. We evaluated 1180 patients with AECOPD for whom medication histories were available. After the outbreak, the number of patients hospitalized with AECOPD was almost 44% lower compared with before the outbreak. Patients hospitalized with AECOPD after the outbreak were younger (75 vs. 77 years, p = 0.003) and more often stayed at home (96.6% vs. 88.6%, p < 0.001) than patients of AECOPD before the outbreak. Hospital stay was longer after the outbreak than before the outbreak (10 vs. 8 days. p < 0.001). After the COVID-19 outbreak, the identification rates of S. pneumoniae (15.3 vs. 6.2%, p < 0.001) and Hemophilus influenzae (6.4 vs. 2.4%, p = 0.002) decreased, whereas the identification rates of P. aeruginosa (9.4 vs. 13.7%, p = 0.023), Klebsiella pneumoniae (5.3 vs. 9.8%, p = 0.004), and methicillin-resistant Staphylococcus aureus (1.0 vs. 2.8%, p = 0.023) increased. After the outbreak, the identification rate of influenza A decreased (10.4 vs. 1.0%, p = 0.023). After the outbreak, the number of patients hospitalized with AECOPD was lower and the identification rates of community-transmitted pathogens tended to decrease, whereas the rates of pathogens capable of chronic colonization tended to increase. During the period of large-scale viral outbreaks that require quarantine, patients with AECOPD might be given more consideration for treatment against strains that can colonize chronic respiratory disease rather than community acquired pathogens.

Appendectomy and the Risk of Parkinson's Disease: A Korean Nationwide Study.

BACKGROUND: The vermiform appendix is considered a potential reservoir for the abnormal α-synuclein aggregate in Parkinson's disease (PD). Previous epidemiologic evidence on the association between appendectomy and PD risk remains inconclusive, especially outside the Western world. OBJECTIVES: To investigate the association between appendectomy and PD risk in Korea. METHODS: Among 703,831 eligible adult subjects in the National Health Insurance Service sample cohort, we identified 16,122 patients who underwent appendectomy. The rest formed the control group. PD risk was assessed using time-dependent Cox regression analyses. RESULTS: The appendectomy group did not have altered risk of PD compared with the control group in either unadjusted [hazard ratio (HR) 1.32, 95% confidence interval (CI) 0.97-1.80, P = 0.08] or adjusted model (HR 1.42, CI 0.88-2.30, P = 0.15). No further statistical difference appeared when stratified by sex. CONCLUSIONS: Appendectomy is not associated with altered risk of PD in the Korean population.

Clinical and Genetic Characteristics Associated With Survival Outcome in Late-Onset Huntington's Disease in South Korea.

BACKGROUND AND PURPOSE: The onset of Huntington's disease (HD) usually occurs before the age of 50 years, and the median survival time from onset is 15 years. We investigated survival in patients with late-onset HD (LoHD) (age at onset ≥60 years) and the associations of the number of mutant CAG repeats and age at onset (AAO) with survival in patients with HD. METHODS: Patients with genetically confirmed HD at six referral centers in South Korea between 2000 and 2020 were analyzed retrospectively. Baseline demographic, clinical, and genetic characteristics and the survival status as at December 2020 were collected. RESULTS: Eighty-seven patients were included, comprising 26 with LoHD (AAO=68.77±5.91 years, mean±standard deviation; 40.54±1.53 mutant CAG repeats) and 61 with common-onset HD (CoHD) (AAO=44.12±8.61 years, 44.72±4.27 mutant CAG repeats). The ages at death were 77.78±7.46 and 53.72±10.86 years in patients with LoHD and CoHD, respectively (p<0.001). The estimated survival time was 15.21±2.49 years for all HD patients, and 10.74±1.95 and 16.15±2.82 years in patients with LoHD and CoHD, respectively. More mutant CAG repeats and higher AAO were associated with shorter survival (hazard ratio [HR]=1.05, 95% confidence interval [CI]=1.01-1.09, p=0.019; and HR=1.17, 95% CI=1.03-1.31, p=0.013; respectively) for all HD patients. The LoHD group showed no significant factors associated with survival after disease onset, whereas the number of mutant CAG repeats had a significant effect (HR=1.12, 95% CI=1.01-1.23, p=0.034) in the CoHD group. CONCLUSIONS: Survival after disease onset was shorter in patients with LoHD than in those with CoHD. More mutant CAG repeats and higher AAO were associated with shorter survival in patients with HD.

The application value of metagenomic next-generation sequencing technology in the diagnosis and treatment of neonatal infectious meningitis - a single center retrospective case-control study.

OBJECTIVE: This retrospective study was conducted to investigate the application value of metagenomics next generation sequencing (mNGS) technology in the diagnosis and treatment of neonatal infectious meningitis. METHODS: From 1 January 2020 to 31 December 2022, 73 newborns suspected of infectious meningitis were hospitalized. After screening by inclusion and exclusion criteria, 69 newborns were subsequently included in the study, containing 27 cases with positive mNGS result and 42 cases with negative mNGS result. Furthermore, according to the diagnosis of meningitis, mNGS positive group and mNGS negative group were further divided into infectious meningitis with mNGS (+) group (n = 27) and infectious meningitis with mNGS (-) group (n = 26), respectively. RESULTS: (1) Compared with cerebrospinal fluid (CSF) culture, mNGS has better diagnostic value [positive predictive value (PPV) = 100.00% (27/27), negative predictive value (NPV) = 38.10% (16/42), agreement rate = 62.32% (43/69), area under the curve (AUC) = 0.750, 95% confidence interval (CI): 0.636-0.864]. (2) There were significant differences in the onset age, age at first CSF test, CSF leukocyte count, CSF glucose, positive rate of CSF culture, blood leukocyte count, procalcitonin (PCT), C-reaction protein (CRP), age at first mNGS test and adjusting anti-infective medication in the comparison between infectious meningitis with mNGS (+) group and infectious meningitis with mNGS (-) group (p < 0.05). (3) mNGS could help improve the cure rate [crude odds ratio (OR) = 3.393, 95%CI: 1.072-10.737; adjusted OR = 15.580, 95%CI: 2.114-114.798]. CONCLUSION: Compared with classic meningitis detection methods, mNGS has better PPV, NPV, agreement rate, and AUC. mNGS could help improve the cure rate.

Clinical feasibility of post-contrast accelerated 3D T1-Sampling Perfection with Application-optimized Contrasts using different flip angle Evolutions (SPACE) with iterative denoising for intracranial enhancing lesions: a retrospective study.

BACKGROUND: Post-contrast T1-Sampling Perfection with Application-optimized Contrasts using different flip angle Evolutions (SPACE) is the preferred 3D T1 spin-echo sequence for evaluating brain metastases, regardless of the prolonged scan time. PURPOSE: To evaluate the application of accelerated post-contrast T1-SPACE with iterative denoising (ID) for intracranial enhancing lesions in oncologic patients. MATERIAL AND METHODS: For evaluation of intracranial lesions, 108 patients underwent standard and accelerated T1-SPACE during the same imaging session. Two neuroradiologists evaluated the overall image quality, artifacts, degree of enhancement, mean contrast-to-noise ratiolesion/parenchyma, and number of enhancing lesions for standard and accelerated T1-SPACE without ID. RESULTS: Although there was a significant difference in the overall image quality and mean contrast-to-noise ratiolesion/parenchyma between standard and accelerated T1-SPACE without ID and accelerated SPACE with and without ID, there was no significant difference between standard and accelerated T1-SPACE with ID. Accelerated T1-SPACE showed more artifacts than standard T1-SPACE; however, accelerated T1-SPACE with ID showed significantly fewer artifacts than accelerated T1-SPACE without ID. Accelerated T1-SPACE without ID showed a significantly lower number of enhancing lesions than standard- and accelerated T1-SPACE with ID; however, there was no significant difference between standard and accelerated T1-SPACE with ID, regardless of lesion size. CONCLUSION: Although accelerated T1-SPACE markedly decreased the scan time, it showed lower overall image quality and lesion detectability than the standard T1-SPACE. Application of ID to accelerated T1-SPACE resulted in comparable overall image quality and detection of enhancing lesions in brain parenchyma as standard T1-SPACE. Accelerated T1-SPACE with ID may be a promising replacement for standard T1-SPACE.

Deep learning-based image reconstruction for the multi-arterial phase images: improvement of the image quality to assess the small hypervascular hepatic tumor on gadoxetic acid-enhanced liver MRI.

PURPOSE: To evaluated the impact of a deep learning (DL)-based image reconstruction on multi-arterial-phase magnetic resonance imaging (MA-MRI) for small hypervascular hepatic masses in patients who underwent gadoxetic acid-enhanced liver MRI. METHODS: We retrospectively enrolled 55 adult patients (aged ≥ 18 years) with small hepatic hypervascular mass (≤ 3 cm) between December 2022 and February 2023. All patients underwent MA-MRI, subsequently reconstructed with a DL-based application. Qualitative assessment with Linkert scale including motion artifact (MA), liver edge (LE), hepatic vessel clarity (HVC) and image quality (IQ) was performed. Quantitative image analysis including signal to noise ratio (SNR), contrast to noise ratio (CNR) and noise was performed. RESULTS: On both arterial phases (APs), all qualitative parameters were significantly improved after DL-based image reconstruction. (LE on 1st AP, 1.22 vs 1.61; LE on 2nd AP, 1.21 vs 1.65; HVC on 1st AP, 1.24 vs 1.39; HVC on 2nd AP, 1.24 vs 1.44; IQ on 1st AP, 1.17 vs 1.45; IQ on 2nd AP, 1.17 vs 1.47, all p values < 0.05). The SNR, CNR and noise were significantly improved after DL-based image reconstruction. (SNR on AP1, 279.08 vs 176.14; SNR on AP2, 334.34 vs 199.24; CNR on AP1, 106.09 vs 64.14; CNR on AP2, 129.66 vs 73.73; noise on AP1, 1.51 vs 2.33; noise on AP2, 1.45 vs 2.28, all p values < 0.05). CONCLUSIONS: Gadoxetic acid-enhanced MA-MRI with DL-based image reconstruction improved the qualitative and quantitative parameters. Despite the short acquisition time, high-quality MA-MRI is now achievable.

Liberation from mechanical ventilation in critically ill patients: Korean Society of Critical Care Medicine Clinical Practice Guidelines.

BACKGROUND: Successful liberation from mechanical ventilation is one of the most crucial processes in critical care because it is the first step by which a respiratory failure patient begins to transition out of the intensive care unit and return to their own life. Therefore, when devising appropriate strategies for removing mechanical ventilation, it is essential to consider not only the individual experiences of healthcare professionals, but also scientific and systematic approaches. Recently, numerous studies have investigated methods and tools for identifying when mechanically ventilated patients are ready to breathe on their own. The Korean Society of Critical Care Medicine therefore provides these recommendations to clinicians about liberation from the ventilator. METHODS: Meta-analyses and comprehensive syntheses were used to thoroughly review, compile, and summarize the complete body of relevant evidence. All studies were meticulously assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method, and the outcomes were presented succinctly as evidence profiles. Those evidence syntheses were discussed by a multidisciplinary committee of experts in mechanical ventilation, who then developed and approved recommendations. RESULTS: Recommendations for nine PICO (population, intervention, comparator, and outcome) questions about ventilator liberation are presented in this document. This guideline includes seven conditional recommendations, one expert consensus recommendation, and one conditional deferred recommendation. CONCLUSIONS: We developed these clinical guidelines for mechanical ventilation liberation to provide meaningful recommendations. These guidelines reflect the best treatment for patients seeking liberation from mechanical ventilation.

Association between mechanical power and intensive care unit mortality in Korean patients under pressure-controlled ventilation.

BACKGROUND: Mechanical power (MP) has been reported to be associated with clinical outcomes. Because the original MP equation is derived from paralyzed patients under volume-controlled ventilation, its application in practice could be limited in patients receiving pressure-controlled ventilation (PCV). Recently, a simplified equation for patients under PCV was developed. We investigated the association between MP and intensive care unit (ICU) mortality. METHODS: We conducted a retrospective analysis of Korean data from the Fourth International Study of Mechanical Ventilation. We extracted data of patients under PCV on day 1 and calculated MP using the following simplified equation: MPPCV = 0.098 ∙ respiratory rate ∙ tidal volume ∙ (ΔPinsp + positive end-expiratory pressure), where ΔPinsp is the change in airway pressure during inspiration. Patients were divided into survivors and non-survivors and then compared. Multivariable logistic regression was performed to determine association between MPPCV and ICU mortality. The interaction of MPPCV and use of neuromuscular blocking agent (NMBA) was also analyzed. RESULTS: A total of 125 patients was eligible for final analysis, of whom 38 died in the ICU. MPPCV was higher in non-survivors (17.6 vs. 26.3 J/min, P<0.001). In logistic regression analysis, only MPPCV was significantly associated with ICU mortality (odds ratio, 1.090; 95% confidence interval, 1.029-1.155; P=0.003). There was no significant effect of the interaction between MPPCV and use of NMBA on ICU mortality (P=0.579). CONCLUSIONS: MPPCV is associated with ICU mortality in patients mechanically ventilated with PCV mode, regardless of NMBA use.

Increasing incidence of Parkinson's disease in patients with epilepsy: A Nationwide cohort study.

BACKGROUND: Although epilepsy is an uncommon comorbidity of Parkinson's disease (PD), the exact incidence of PD among the patients with epilepsy is not clarified yet. OBJECTIVES: We aimed to estimate the incidence of PD in patients with epilepsy and explore the association between epilepsy and PD. METHODS: Epilepsy patients enrolled in the National Health Insurance Service Health Screening Cohort (NHIS-HealS) (2002-2013) between 2003 and 2007 were set up as the experimental group. The major outcome was the occurrence of PD. Non-epilepsy patients were obtained through Propensity Score Matching of 'greedy nearest neighbor' algorithm in 1:1 ratio. The Cox Proportional Hazards model was used to calculate PD incidence and hazard ratio (HR). RESULTS: A total of 10,510 patients were finally included in the study, which contained 5255 patients in epilepsy and non-epilepsy groups, respectively. During the follow-up period, 85 patients with Parkinson's disease among 5255 patients with epilepsy and 57 patients with Parkinson's disease among 5255 patients without epilepsy occurred. The 10,000 Person-Year (PY), representing the number of PD patients per 10,000 per year, was 21.38 in the epilepsy group and 11.18 in the non-epilepsy group. When all variables were adjusted, it was found that the epilepsy group had a 2.19 times significantly higher risk of developing Parkinson's disease than the control group (The adjusted HR: 2.19 (95% CI, 1.55-3.12)). CONCLUSION: This study indicates an increased risk of PD in patients with epilepsy. However, further research is needed to prove an exact causal relationship between these two brain disorders.

Tuberculous Pericarditis Mimicking a Malignant Pericardial Tumor: A Case Report.

Tuberculous pericarditis is an extrapulmonary manifestation of tuberculosis that is most commonly associated with pericardial thickening, effusion, and calcification. We present a case of tuberculous pericarditis mimicking a malignant pericardial tumor in a 77-year-old male. CT revealed an irregular and nodular pericardial thickening. MRI revealed high signal intensity on T1-weighted fat-suppressed images and peripheral rim enhancement after gadolinium administration. MRI can be helpful in determining the differential diagnoses in cases of tuberculous pericarditis with nonspecific imaging findings.

Present and Future of AI-IoT-Based Healthcare Services for Senior Citizens in Local Communities: A Review of a South Korean Government Digital Healthcare Initiatives.

South Korea is promoting digital healthcare services in the public sector. One notable initiative is the "artificial intelligence and the internet of things (AI-IoT)-based healthcare project for senior citizens", which was implemented by the Korea Health Promotion Institute (KHPI). This project utilized an IoT-based digital healthcare service that integrates information technology and screen-based AI speaker functions. Services through this project are intended for senior citizens aged 65 years (or older) who face challenges in visiting public healthcare institutions owing to limitations on outdoor activities, especially in the post-coronavirus 2019 era. This article shares the recent outcomes of this project and outlines the mid-to-long-term development strategies for this style of South Korean digital healthcare initiatives.

Design and performance evaluation of a firefighting protective suit with an incorporated liquid-cooled system.

A liquid-cooled garment with active cooling function can make up for deficiency of the human thermoregulatory system and passive thermal insulation of the firefighting protective suit. Fabrics treated at different inlet temperatures and pipeline intervals were applied in multilayered liquid-cooled fabric assemblies (LCFAs). The heat absorbed by the skin and the second-degree burn time were evaluated by the stored energy test under low heat radiation. Results indicated that the thermal protective performance of the LCFAs was significantly improved, with the second-degree burn time increasing more than 50% on average. There was a strong negative correlation between the thermal protective performance and cooling effect under different pipeline intervals, while the negative correlation was weak for different inlet temperatures. The results gained from this study may provide valuable insight for design of the inlet temperature and pipeline interval of a liquid-cooled system in the firefighting protective suit.

Caregiver Burden of Patients With Huntington's Disease in South Korea.

OBJECTIVE: This is the first prospective cohort study of Huntington's disease (HD) in Korea. This study aimed to investigate the caregiver burden in relation to the characteristics of patients and caregivers. METHODS: From August 2020 to February 2022, we enrolled patients with HD from 13 university hospitals in Korea. We used the 12-item Zarit Burden Interview (ZBI-12) to evaluate the caregiver burden. We evaluated the clinical associations of the ZBI-12 scores by linear regression analysis and investigated the differences between the low- and high-burden groups. RESULTS: Sixty-five patients with HD and 45 caregivers were enrolled in this cohort study. The average age at onset of motor symptoms was 49.3 ± 12.3 years, with an average cytosine-adenine-guanine (CAG)n of 42.9 ± 4.0 (38-65). The median ZBI-12 score among our caregivers was 17.6 ± 14.2. A higher caregiver burden was associated with a more severe Shoulson-Fahn stage (p = 0.038) of the patients. A higher ZBI-12 score was also associated with lower independence scale (B = -0.154, p = 0.006) and functional capacity (B = -1.082, p = 0.002) scores of patients. The caregiving duration was longer in the high- than in the low-burden group. Caregivers' demographics, blood relation, and marital and social status did not affect the burden significantly. CONCLUSION: HD patients' neurological status exerts an enormous impact on the caregiver burden regardless of the demographic or social status of the caregiver. This study emphasizes the need to establish an optimal support system for families dealing with HD in Korea. A future longitudinal analysis could help us understand how disease progression aggravates the caregiver burden throughout the entire disease course.

Protective mechanism of rhubarb decoction against inflammatory damage of brain tissue in rats with mild hepatic encephalopathy： A study based on the PI3K/AKT/mTOR signaling pathway / 临床肝胆病杂志

ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.

Protective effect of the mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt extract on respiratory disorders.

Air pollutants, such as particulate matter (PM) and diesel exhaust particles (DEP), are associated with respiratory diseases. Therefore, preventive and therapeutic strategies against PM-and DEP (PM10D)-induced respiratory diseases are needed. Herein, we evaluate the protective effects of a mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt (LJH) extract against airway inflammation associated with exposure to PM10D. To determine the anti-inflammatory effects of the LJH extract, reactive oxygen species (ROS) production and the expression of inflammatory pathways were determined in PM10-induced MH-S cells. For the respiratory protective effects, BALB/c mice were exposed to PM10D via intranasal injection, and a mixture of L. plantarum KC3 and LJH extract was administered orally for 12 days. LJH extract inhibited ROS production and the phosphorylation of downstream factors of NF-κB in PM10-stimulated MH-S cells. The mixture of L. plantarum KC3 and LJH repressed the infiltration of neutrophils, reduced the immune cells number, and suppressed the proinflammatory mediators and cyclooxygenase (COX)-2 expressions in PM10D-induced airway inflammation with reduced phosphorylation of downstream factors of NF-κB. In addition, these effects were not observed in an alveolar macrophage depleted PM10D-induced mouse model using clodronate liposomes. The extract mixture also regulated gut microbiota in feces and upregulated the mRNA expression of Foxp3, transforming growth factor (TGF)-ß1, and interleukin (IL)-10 in the colon. The L. plantarum KC3 and LJH extract mixture may inhibit alveolar macrophage- and neutrophil-mediated inflammatory responses and regulate gut microbiota and immune response in PM10D-induced airway inflammation, suggesting it is a potential remedy to prevent and cure airway inflammation and respiratory disorders.