Sepsis is a systemic inflammatory response caused by severe infection or trauma, and is one of the common causes of acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). Sepsis-acute lung injury(SALI) is a critical clinical condition with high morbidity and mortality. Its pathogenesis is complex and not yet fully understood, and there is currently a lack of targeted and effective treatment options. Pyroptosis, a novel form of programmed cell death, plays a key role in the pathological process of SALI by activating inflammasomes and releasing inflammatory factors, making it a potential therapeutic target. In recent years, the role of traditional Chinese medicine(TCM) in regulating signaling pathways related to pyroptosis through multi-components and multi-targets has attracted increasing attention. TCM may intervene in pyroptosis by inhibiting the activation of NLRP3 inflammasomes and regulating the expression of Caspase family proteins, thus alleviating inflammatory damage in lung tissues. This paper systematically reviews the molecular regulatory network of pyroptosis in SALI and explores the potential mechanisms and research progress on TCM intervention in cellular pyroptosis. The aim is to provide new ideas and theoretical support for basic research and clinical treatment strategies of TCM in SALI.
Pyroptosis/drug effects* ; Humans ; Sepsis/genetics* ; Acute Lung Injury/physiopathology* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Inflammasomes/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics*

Objective to compare the application value of MELD score,AIMS65 score and platelet-albumin-bilirubin index(PALBI)in the prediction of 28 d death in patients with cirrhosis combined with acute upper gastrointestinal hemorrhage(AUGIB)with a view to providing a reference basis for clinical screening of the most appropriate prognostic prediction score.Methods 378 patients with cirrhosis AUGIB treated in the Department of Critical Care Medicine of the First Affiliated Hospital of Harbin Medical University from January 2020 to December 2023 were retrospectively included,and were categorized into 60(15.9％)in the death group and 318(84.1％)in the survival group based on 28 d survival.Clinical data of all cirrhotic AUGIB patients were retrospectively collected through an online medical record system,and MELD score,AIMS65 score and PALBI score were calculated.The effects of MELD score,AIMS65 score,and PALBI score on death in cirrhotic AUGIB patients were analyzed using binary logistic regression,and finally,the efficacy of these three scores in predicting death in cirrhotic AUGIB patients was assessed using ROC curves.Results Univariate analysis showed that the proportion of diabetes mellitus and hepatic encephalopathy,as well as the prothrombin time,erythrocyte distribution width,C-reactive protein,MELD score,AIMS65 score,and PALBI score were increased and albumin was decreased in the death group compared with the survival group,and the difference was statistically significant(P＜0.05).The results of multifactorial logistic regression analysis showed that after correcting for confounders such as diabetes mellitus,proportion of hepatic encephalopathy,and prothrombin time,the MELD score(OR=1.621,95％CI:1.185-2.217),AIMS65 score(OR=1.914,95％CI:1.361-2.690),PALBI score(OR=1.984,95％CI:1.410-2.791)were independent risk factors for death in patients with cirrhosis AUGIB.The ROC curves showed that the AUCs of MELD score,AIMS65 score,and PALBI score for predicting death at 28 d of cirrhosis were 0.685(95％CI:0.614-0.756),0.828(95％CI:0.771-0.885),0.860(95％CI:0.808-0.913).Conclusion MELD score,AIMS65 score,and PALBI score were all independent risk factors for death in cirrhotic AUGIB patients and suggestive of prognostic risk,with AIMS65 score and PALBI score having the highest predictive value.

Objective To investigate the characteristics of hemodynamic changes in superior mesenteric artery(SMA)of patients with acute suppurative appendicitis(ASA)to facilitate the diagnosis of ASA.Methods Ninety-three ASA patients diagnosed by ultrasound and confirmed by pathology in some hospital from January 2015 to December 2022 were enrolled into an ASA group,and 88 soldiers without abnormalities in the annual physical examination at the hospital in 2021 were divided into a control group,and the two groups were compared in terms of SMA hemodynamic indexes including peak systolic velocity(PSV),end diastolic velocity(EDV),resistance index(RI)and systolic/diastolic ratio(S/D).The statistically significant data of the above indexes were selected to draw the ROC curve and obtain the cut-off values.SPSS 22.0 software was used for statistical analysis.Results The PSV was(212±69)cm/s in the ASA group and(118±26)cm/s in the control group,with statistically significant differences(P＜0.05),and the two groups had the differences in EDV,RI,and S/D not statistically significant(P＞0.05).The ROC curve was plotted based on the PSV data,and a cutoff value of 238 cm/s was obtained with an AUC of 0.714.Conclusion Ultrasound examination of SMA hemodynamic changes in suspected ASA patients facilitates a definitive diagnosis and is of guidance for clinical treatment.[Chinese Medical Equipment Journal,2023,44(10):64-67]

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

Taking the Chinese city of Xiamen as an example, simulation and quantitative analysis were performed on the transmissions of the Coronavirus Disease 2019 (COVID-19) and the influence of intervention combinations to assist policymakers in the preparation of targeted response measures. A machine learning model was built to estimate the effectiveness of interventions and simulate transmission in different scenarios. The comparison was conducted between simulated and real cases in Xiamen. A web interface with adjustable parameters, including choice of intervention measures, intervention weights, vaccination, and viral variants, was designed for users to run the simulation. The total case number was set as the outcome. The cumulative number was 4,614,641 without restrictions and 78 under the strictest intervention set. Simulation with the parameters closest to the real situation of the Xiamen outbreak was performed to verify the accuracy and reliability of the model. The simulation model generated a duration of 52 days before the daily cases dropped to zero and the final cumulative case number of 200, which were 25 more days and 36 fewer cases than the real situation, respectively. Targeted interventions could benefit the prevention and control of COVID-19 outbreak while safeguarding public health and mitigating impacts on people's livelihood.
COVID-19/prevention & control* ; China/epidemiology* ; Humans ; Machine Learning ; Pandemics/prevention & control* ; Policy ; Reproducibility of Results ; SARS-CoV-2

Bombesin receptor subtype-3(BRS-3) is an orphan receptor in the bombesin receptor family. Its signal transduction mechanism and biological function have attracted much attention. Seeking the ligand for BRS-3 is of great significance for exploring its function. Considering the fact that the activation of BRS-3 receptor can induce the change in intracellular Ca~(2+) concentration, the fluo-rometric imaging plate reader(FLIPR) was utilized for ligand screening at the cellular level. Among more than 400 monomeric compounds isolated from Chinese herbs, yuanhunine from Corydalis Rhizoma and sophoraisoflavanone A and licoriphenone from Glycyrrhizae Radix et Rhizoma antagonized BRS-3 to varying degrees. It was confirmed in HEK293 cells expressing BRS-3 that yuanhunine, sophoraisoflavanone A, and licoriphenone inhibited the calcium current response after the activation of BRS-3 by [D-Phe~6,β-Ala~(11),Phe~(13),Nle~(14)]bombesin-(6-14) in a dose-dependent manner with the IC_(50) values being 8.58, 4.10, and 2.04 μmol·L~(-1), respectively. Further study indicated that yuanhunine and sophoraisoflavanone A exhibited good selectivity for BRS-3. In this study, it was found for the first time that monomers derived from Chinese herbs had antagonistic activity against orphan receptor BRS-3, which has provided a tool for further study of BRS-3 and also the potential lead compounds for new drug discovery. At the same time, it provides reference for the research and development of innovative drugs based on the active ingredients of Chinese herbs.
Drugs, Chinese Herbal/chemistry* ; HEK293 Cells ; Humans ; Ligands ; Receptors, Bombesin

Objective:To explore the value of metagenomics next generation sequencing of cerebrospinal fluid in the diagnosis test of the pathogen of neurobrucellosis.Methods:Medical records of neurobrucellosis patients who were admitted to Xuanwu Hospital, Capital Medical University from May 2017 to February 2021 were reviewed. Seven patients who underwent cerebrospinal fluid metagenomics next generation sequencing were enrolled. Their clinical characteristics, cerebrospinal fluid results, serological and pathogenic results were analyzed.Results:Among the seven neurobrucellosis patients, including five males and two females, the age was from 21 to 49 [38 (24, 47)] years. Three patients had a history of exposure to cattle and sheep. The duration from onset to diagnosis was 2 to 30 [12 (5, 18)] months. The main neurological manifestations were headache for seven patients, loss of hearing for three patients, paralysis for four patients and urinary and fecal dysfunction for four patients. The blood tests showed that the rose bengal test was positive in three of seven patients, Brucella serum agglutination test was positive in four of six patients, and the blood culture was negative in four patients. The cerebrospinal fluid tests showed that rose bengal test was positive in one of five patients, Brucella serum agglutination test was positive in two of four patients, and the cerebrospinal fluid culture was positive in two of five patients. Cerebrospinal fluid metagenomics next generation sequencing was positive for Brucella in five patients.Conclusions:Comparing with the cerebrospinal fluid Brucella serum agglutination test and cerebrospinal fluid culture, cerebrospinal fluid metagenomics next generation sequencing is sensitive to the diagnosis of neurobrucellosis. It is recommended to perform cerebrospinal fluid metagenomics next generation sequencing in patients with clinically suspected neurobrucellosis or central nervous system infections of which the pathogen cannot be confirmed.

OBJECTIVE: To examine the association between family socioeconomic status (SES) and body mass index (BMI) z-score of children and adolescents, and the mediating effect of milk intake in this association. METHODS: In the study, 2 496 students and their parents were selected from 16 schools (4 urban middle schools, 4 rural middle schools, 4 urban primary schools, and 4 rural primary schools) using a stratified cluster sampling method. The frequency and amount of weekly milk intake from the 7-day Food Records reported by the students were extracted. The parents' education and household income were the indicators of family SES. The mediating effect of milk intake between family SES and BMI z-score of children and adolescents were tested using the PROCESS add-on SPSS software. RESULTS: Parents' education level and household income were positively correlated with BMI z-score of children and adolescents (P=0.001 and 0.038, respectively). The overall average daily intake of milk was (0.92±0.84) servings, and the frequency was (4.43±2.70) days per week. The students of primary school, in urban areas, with higher parents' education level, with higher household income, and being non-obese were likely to have higher frequency and amount of milk intake. Milk intake was one of the mediating factors in the relationship between family SES and BMI z-score of children and adolescents. Specifically, the mediating effect of the frequency of milk intake accounted for -6.57% and -10.21% of the total effects of the association between the parents' education and the household income with BMI z-score of children and adolescents, respectively. The mediating effect of the daily intake of milk accounted for -3.63% and -5.86% of the total effects of the association between the parents' education and the household income with BMI z-score of children and adolescents, respectively. CONCLUSION The milk intake of Chinese children and adolescents still needs to be improved. High family SES was found to contribute to high BMI z-score, mediated by the milk intake which was the protective factors of BMI z-score. Further research is needed to study other dietary or physical exercise behaviors that mediate the relationship between family SES and BMI z-score of children and adolescents in order to adopt more targeted interventions.
Adolescent ; Animals ; Body Mass Index ; Child ; Cross-Sectional Studies ; Diet ; Humans ; Milk ; Schools ; Social Class

BACKGROUND: Sleep disorders are common but under-researched symptoms in patients with multiple system atrophy (MSA). We investigated the frequency and factors associated with sleep-related symptoms in patients with MSA and the impact of sleep disturbances on disease severity. METHODS: This cross-sectional study involved 165 patients with MSA. Three sleep-related symptoms, namely Parkinson's disease (PD)-related sleep problems (PD-SP), excessive daytime sleepiness (EDS), and rapid eye movement sleep behavior disorder (RBD), were evaluated using the PD Sleep Scale-2 (PDSS-2), Epworth Sleepiness Scale (ESS), and RBD Screening Questionnaire (RBDSQ), respectively. Disease severity was evaluated using the Unified MSA Rating Scale (UMSARS). RESULTS: The frequency of PD-SP (PDSS-2 score of ≥18), EDS (ESS score of ≥10), and RBD (RBDSQ score of ≥5) in patients with MSA was 18.8%, 27.3%, and 49.7%, respectively. The frequency of coexistence of all three sleep-related symptoms was 7.3%. Compared with the cerebellar subtype of MSA (MSA-C), the parkinsonism subtype of MSA (MSA-P) was associated with a higher frequency of PD-SP and EDS, but not of RBD. Binary logistic regression revealed that the MSA-P subtype, a higher total UMSARS score, and anxiety were associated with PD-SP; that male sex, a higher total UMSARS score, the MSA-P subtype, and fatigue were associated with EDS; and that male sex, a higher total UMSARS score, and autonomic onset were associated with RBD in patients with MSA. Stepwise linear regression showed that the number of sleep-related symptoms (PD-SP, EDS, and RBD), disease duration, depression, fatigue, and total Montreal Cognitive Assessment score were predictors of disease severity in patients with MSA. CONCLUSIONS Sleep-related disorders were associated with both MSA subtypes and the severity of disease in patients with MSA, indicating that sleep disorders may reflect the distribution and degree of dopaminergic/non-dopaminergic neuron degeneration in MSA.
Cross-Sectional Studies ; Humans ; Male ; Multiple System Atrophy ; REM Sleep Behavior Disorder ; Severity of Illness Index ; Sleep