Characteristic Fingerprint Spectrum of α-Synuclein Mutants on Terahertz Time-Domain Spectroscopy.

OBJECTIVE: Alpha-Synuclein (α-Syn), a presynaptic neuronal protein encoded by the SNCA gene, is involved in the pathogenesis of Parkinson's disease. Point mutations and multiplications of the α-Syn (A30P and A53T) are correlated with early-onset Parkinson's disease characterized by rapid progression and poor prognosis. Currently, the clinical identification of SNCA variants, especially disease-related A30P and A53T mutants, remains challenging and also time-consuming. This study has aimed to develop a novel label-free detection method for distinguishing the SNCA mutants using transmission terahertz (THz) time-domain spectroscopy. METHODS: The protein was spin-coated onto the quartz to form a thin film, which was measured using THz time-domain spectroscopy. The spectral characteristics of THz broadband pulse waves of α-Syn protein variants (SNCA wild type [WT], A30P, and A53T) at different frequencies were analyzed via Fourier transform. RESULTS: The amplitude A intensity (AWT, AA30P, and AA53T) and peak occurrence time in THz-TDS sensitively distinguished the three protein variants. The phase φ difference in THz frequency domain followed the trend of φWT>φA30P>φA53T. There was a significant difference in THz frequency amplitude A' corresponding to the frequency ranging from 0.4 THz to 0.66 THz (A'A53T>A'A30P>A'WT). At a frequency of 0.4-0.6 THz, the transmission T of THz waves distinguished three variants (TA53T>TA30P>TWT), while there was no difference in the transmission T at 0.66 THz. CONCLUSION: The SNCA wild-type protein and two mutant variants (A30P and A53T) had distinct characteristic fingerprint spectra on THz time-domain spectroscopy. This novel label-free detection method has great potential for the differential diagnosis of Parkinson's disease subtypes.

A generalizable and easy-to-use COVID-19 stratification model for the next pandemic via immune-phenotyping and machine learning.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has affected billions of people worldwide, and the lessons learned need to be concluded to get better prepared for the next pandemic. Early identification of high-risk patients is important for appropriate treatment and distribution of medical resources. A generalizable and easy-to-use COVID-19 severity stratification model is vital and may provide references for clinicians. Methods: Three COVID-19 cohorts (one discovery cohort and two validation cohorts) were included. Longitudinal peripheral blood mononuclear cells were collected from the discovery cohort (n = 39, mild = 15, critical = 24). The immune characteristics of COVID-19 and critical COVID-19 were analyzed by comparison with those of healthy volunteers (n = 16) and patients with mild COVID-19 using mass cytometry by time of flight (CyTOF). Subsequently, machine learning models were developed based on immune signatures and the most valuable laboratory parameters that performed well in distinguishing mild from critical cases. Finally, single-cell RNA sequencing data from a published study (n = 43) and electronic health records from a prospective cohort study (n = 840) were used to verify the role of crucial clinical laboratory and immune signature parameters in the stratification of COVID-19 severity. Results: Patients with COVID-19 were determined with disturbed glucose and tryptophan metabolism in two major innate immune clusters. Critical patients were further characterized by significant depletion of classical dendritic cells (cDCs), regulatory T cells (Tregs), and CD4+ central memory T cells (Tcm), along with increased systemic interleukin-6 (IL-6), interleukin-12 (IL-12), and lactate dehydrogenase (LDH). The machine learning models based on the level of cDCs and LDH showed great potential for predicting critical cases. The model performances in severity stratification were validated in two cohorts (AUC = 0.77 and 0.88, respectively) infected with different strains in different periods. The reference limits of cDCs and LDH as biomarkers for predicting critical COVID-19 were 1.2% and 270.5 U/L, respectively. Conclusion: Overall, we developed and validated a generalizable and easy-to-use COVID-19 severity stratification model using machine learning algorithms. The level of cDCs and LDH will assist clinicians in making quick decisions during future pandemics.

[Meta analysis of the predictive efficacy of various derived indicators of sequential organ failure assessment in outcomes of patients with sepsis].

OBJECTIVE: To systematically review and evaluate the predictive efficacy of various derived indicators of sequential organ failure assessment (SOFA) in mortality rate of sepsis patients. METHODS: Literature on sepsis and SOFA scores were searched in PubMed, Embase and Cochrane Library. The retrieval time will be set to the time of database-building to February, 2023. The main outcome measures included 28-day mortality, 30-day mortality, in-hospital mortality, intensive care unit (ICU) mortality and long-term mortality. Literature screening, data extraction and quality evaluation were carried out independently by 2 researchers. Data were analyzed by Revman 5.3.5, Meta-disc and Stata software. Deek funnel plots were used to assess publication bias in the included studies. RESULTS: A total of 40 articles including 51 trials were included. Of these, 32 were in English and 8 in Chinese, 17 were in prospective trials and 34 were in retrospective trials, 38 were in initial SOFA-related trials and 9 were in the change of SOFA score (ΔSOFA)-related studies, a total of 59 962 patients were enrolled. (1) The area under the receiver operator characteristic curve (AUC) of initial SOFA and ΔSOFA for predicting outcome in sepsis was 0.773 and 0.787 (Z = 0.115, P > 0.05), respectively. There was no significant difference between the two indexes in predicting the outcome of patients with sepsis. (2) In subgroup analysis, due to limitations in the number of literature articles, the 28-day mortality rate and 30-day mortality rate were merged for discussion. The predictive power of ΔSOFA for 28-day or 30-day mortality was significantly higher than that of initial SOFA (AUC was 0.854, 0.787, Z = 2.603, P ≤ 0.01). (3) There were few studies on ΔSOFA in predicting in-hospital mortality, ICU mortality and long-term mortality of sepsis patients. The AUC of the initial SOFA for predicting the study endpoints described above was: ICU mortality (0.814) > 28-day or 30-day mortality (0.787) > in-hospital mortality (0.697) > long-term mortality (0.646). (4) Initial SOFA and ΔSOFA in patients with sepsis of non-Han original had good predictive performance and there was no significant difference between them (AUC was 0.766, 0.811, respectively). However, the pooled sensitivity of ΔSOFA was higher (92%). (5) In prospective studies, initial SOFA was better at predicting outcomes in patients with sepsis (AUC was 0.804, pooled sensitivity 64%). The sensitivity of ΔSOFA indicators in predicting the outcome of sepsis patients was significantly higher than the initial SOFA (78% vs. 64%). The funnel plot showed that there was no significant publication bias in the included literature. CONCLUSIONS: ΔSOFA has a relatively high diagnostic efficacy in predicting short-term (28-day or 30-day) mortality in patients with sepsis.

SAH and SAM/SAH ratio associate with acute kidney injury in critically ill patients: A case-control study.

BACKGROUND: Acute kidney injury (AKI) is a serious clinical emergency with an acute onset, rapid progression and poor prognosis, which has high morbidity and mortality in hospitalized patients. DNA methylation plays an important role in the occurrence and progression of kidney disease, and aberrant methylation and certain altered methylation-related metabolites have been reported in AKI patients. However, the specific alterations of methylation-related metabolites in the AKI patients were not investigated clearly. METHOD: In this study, 61 AKI and 61 matched non-AKI inpatients were recruited after propensity score matching the age and hypertension. And 11 methylation-related metabolites in the plasma and urine of the two groups were quantified by using UHPLC-MS/MS method. RESULTS: Certain methylation-relate intermediates were up-regulated in the plasma (choline, trimethylamine N-oxide (TMAO), trimethyl lysine (TML), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH)) and down-regulated in the urine of AKI inpatients (choline, betaine, TMAO, dimethylglycine (DMG), SAM and taurine). The correlation analysis revealed a relatively strong correlation between plasma SAH, SAM/SAH ratio and renal function index (serum creatinine (SCr) and estimated glomerular filtration rate (eGFR), r = 0.523-0.616), and the correlation of urinary intermediates with renal function index was weaker than that in the plasma. Furthermore, receiver operating characteristic (ROC) analysis showed that plasma SAH and urinary SAM/SAH ratio represented the best distinguishing efficiency with AUC 0.844 and 0.794, respectively. Moreover, the findings of binary regression analysis demonstrated plasma choline, TMAO, TML, SAM and SAH were the risk markers of AKI (up-regulation in plasma, OR > 1), urinary choline, betaine, TMAO, DMG and SAM were protective markers of AKI (down-regulation in urine, OR < 1), and SAM/SAH ratio was a protective marker in plasma and urine (down-regulation in both two biofluids, OR = 0.510, 0.383-0.678 in plasma, OR = 0.904, 0.854-0.968 in urine), indicating the increased risk of AKI when combined with the alteration of plasma and urinary levels. CONCLUSION: The comprehensive analysis of plasma and urine samples from AKI inpatients offers a more extensive assessment of methylated metabolic alterations, suggesting a close relationship between AKI stress and altered methylation ability. The plasma level of SAH and SAM/SAH ratio and urinary SAM/SAH ratio both showed a strong correlation with renal function (SCr and eGFR) and good accuracy for distinguishing AKI in the two biomatrices, which exhibited promising prospects in predicting renal function decline and providing further information for the pathogenesis of AKI.

Voluntary Respiration Control: Signature Analysis by EEG.

The perception of voluntary respiratory consciousness is quite important in some situations, such as respiratory assistance and respiratory rehabilitation training, and the key signatures about voluntary respiration control may lie in the neural signals from brain manifested as electroencephalography (EEG). The present work aims to explore whether there exists correlation between voluntary respiration and scalp EEG. Evoke voluntary respiration of different intensities, while collecting EEG and respiration signal synchronously. Data from 11 participants were analyzed. Spectrum characteristics at low-frequency band were studied. Computation of EEG-respiration phase lock value (PLV) and EEG sample entropy were conducted as well. When breathing voluntarily, the 0-2 Hz band EEG power is significantly enhanced in frontal and right-parietal area. The distance between main peaks belonging to the two signals in 0-2 Hz spectrum graph tends to get smaller, while EEG-respiration PLV increases in frontal area. Besides, the sample entropy of EEG shows a trend of decreasing during voluntary respiration in both areas. There's a strong correlation between voluntary respiration and scalp EEG. Significance: The discoveries will provide guidelines for developing a voluntary respiratory consciousness identifying method and make it possible to monitor people's intention of respiration by noninvasive BCI.

Inflammatory biomarkers and delirium: a Mendelian randomization study.

Background: The association between inflammatory biomarkers and individual delirium symptoms remains controversial in observational studies. We investigated the relationship between inflammatory biomarkers and the risk of developing delirium. Methods: A bidirectional two-sample Mendelian randomization (MR) was performed. Genetic instruments associated with peripheral tumor necrosis factor-a (TNF-a) C-reactive protein (CRP), interleukin (IL)-1α, IL-1ß, IL-2, IL-8, IL-6, soluble IL-6 receptor alpha (sIL-6Rα), and soluble gp130 were identified in three different large summary genome-wide association studies (GWAS) conducted in the European population. Summary-level statistics for delirium not induced by alcohol and other psychoactive substances were obtained from the FinnGen consortium (2,612 cases and 325,306 controls). The estimated causal effects were performed using instruments' variants at the genome-wide significant level (P < 5e-8 and P < 5e-6), applying a linkage disequilibrium clumping approach with a threshold of r2 < 0.001 for each of the exposures. Reverse causation was also performed. The inverse-variance weighted method (IVW), MR-Egger method, weighted median method, MR-Egger regression, and MR Pleiotropy RESidual Sum were used for MR analyses. Results: At the genome-wide significant level (P < 5e-8, r2 < 0.001), genetically predicted sIL-6Rα was significantly associated with a decreased risk of delirium with less than three single-nucleotide polymorphisms (SNPs) in all three GWAS data sources (ORWaldratio = 0.89, 95% CI: 0.79-0.96, PWaldratio = 0.0016; ORIVW = 0.88, 95% CI: 0.79-0.97, PIVW = 0.008; ORIVW = 0.88, 95% CI: 0.80-0.96, PIVW = 0.004). The causal relationship between sIL-6Rα and delirium became non-significant when a more liberal threshold of P of < 5e-6 was applied (all PIVW > 0.05). At the two genome-wide significance levels (P < 5e-8 and P < 5e-6), we found no evidence for the causal effects of peripheral TNF-α, CRP, IL-1α, IL-1ß, IL-2, IL-6, IL-8, and soluble gp130 on delirium (all P > 0.05). The MR-Egger intercept and MR-PRESSO results indicated that no SNP had possible pleiotropy (all P > 0.05). Regarding the reverse, no evidence for an effect of delirium on these inflammatory biomarkers could be found (all P > 0.05). Conclusion: The results of this MR analysis did not support that peripheral TNF-α, CRP, IL-1α, IL-1ß, IL-2, IL-6, sIL-6Rα, soluble gp130, and IL-8 were causally associated with delirium. More research is needed to explore the role of inflammatory factors in the pathogenesis of delirium.

T cell receptor ß repertoires in patients with COVID-19 reveal disease severity signatures.

Background: The immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial in maintaining a delicate balance between protective effects and harmful pathological reactions that drive the progression of coronavirus disease 2019 (COVID-19). T cells play a significant role in adaptive antiviral immune responses, making it valuable to investigate the heterogeneity and diversity of SARS-CoV-2-specific T cell responses in COVID-19 patients with varying disease severity. Methods: In this study, we employed high-throughput T cell receptor (TCR) ß repertoire sequencing to analyze TCR profiles in the peripheral blood of 192 patients with COVID-19, including those with moderate, severe, or critical symptoms, and compared them with 81 healthy controls. We specifically focused on SARS-CoV-2-associated TCR clonotypes. Results: We observed a decrease in the diversity of TCR clonotypes in COVID-19 patients compared to healthy controls. However, the overall abundance of dominant clones increased with disease severity. Additionally, we identified significant differences in the genomic rearrangement of variable (V), joining (J), and VJ pairings between the patient groups. Furthermore, the SARS-CoV-2-associated TCRs we identified enabled accurate differentiation between COVID-19 patients and healthy controls (AUC > 0.98) and distinguished those with moderate symptoms from those with more severe forms of the disease (AUC > 0.8). These findings suggest that TCR repertoires can serve as informative biomarkers for monitoring COVID-19 progression. Conclusions: Our study provides valuable insights into TCR repertoire signatures that can be utilized to assess host immunity to COVID-19. These findings have important implications for the use of TCR ß repertoires in monitoring disease development and indicating disease severity.

[Incidence of maternal sepsis in ICUs of hospitals in Beijing: a multicenter cohort study].

OBJECTIVE: To investigate the epidemiological data of maternal sepsis in intensive care unit (ICU), analyze the common causes, outcomes of maternal sepsis, and the risk factors of multi-drug resistant (MDR) bacteria. METHODS: A retrospective cohort study. Maternal sepsis cases admitted to ICUs of Peking University Third Hospital, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, and Beijing Friendship Hospital Affiliated to Capital Medical University from January 2008 to September 2022 were enrolled. The following data were recorded: demographic characteristics, sequential organ failure assessment (SOFA) during infection, infection time, infection sites, invasive intervention measures before infection, microbial culture results, blood routine test during infection, body temperature, and clinical outcomes caused by infection. According to the time of sepsis occurrence, the patients were divided into pre-ICU sepsis group and ICU sepsis group, and the causes of sepsis in the two groups were analyzed. According to whether MDR occurred, the patients were divided into MDR group and non-MDR group, and clinical outcomes were analyzed. Multivariate Logistic regression was used to analyze the risk factors of MDR bacteria infection in obstetrics with sepsis. RESULTS: 160 patients were enrolled, among which 104 cases of sepsis happened before ICU and 56 cases of sepsis happened during ICU, 53 cases were with MDR bacteria and 107 cases were without MDR bacteria. The median age of the patients was 30.5 (28.0, 34.0) years old, the median temperature was 38.8 (38.2, 39.5) centigrade, and the median white blood cell count (WBC) was 17.2 (13.2, 21.3)×109/L, the median SOFA score was 5.0 (3.0, 8.0), and 130 cases (81.2%) were referred from other hospitals. The main infection sites were uterine cavity in 64 cases (40.0%), lung in 48 cases (30.0%), abdominal and pelvic cavity in 30 cases (18.8%), urinary system in 27 cases (16.9%). Sepsis led to hysterectomy in 6 cases (3.8%), stillbirth in 8 cases (5.0%), and neonatal death in 2 cases (1.3%). The main surgical intervention measures were cesarean section (44 cases, accounting for 27.5%), followed by exploratory laparotomy (19 cases, 11.9%). The median length of ICU stay was 5.0 (3.0, 10.0) days, and the median hospital length was 14.0 (10.0, 20.8) days. Intrauterine infection was the primary cause of sepsis happened during ICU, accounting for 50.0% (28/56), of which postpartum hemorrhage accounted for 85.7% (24/28). The proportion of diabetes [28.3% (15/53) vs. 14.0% (15/107)], intrauterine operation [41.5% (22/53) vs. 23.4% (25/107)], intrauterine infection [50.9% (27/53) vs. 34.6% (37/107)] and bacteremia [18.9% (10/53) vs. 2.8% (3/107)] in the MDR group were significantly higher than those in the non-MDR group (all P < 0.05). Multivariate Logistic regression analysis showed that diabetes [odds ratio (OR) = 2.348, 95% confidence interval (95%CI) was 1.006-5.480, P = 0.048] and intrauterine operation (OR = 2.541, 95%CI was 1.137-5.678, P = 0.023) were independent risk factors for MDR bacterial infection in obstetrics with sepsis. CONCLUSIONS: Intrauterine infection is the common cause of maternal sepsis in ICU, and postpartum hemorrhage is the common cause of secondary intrauterine infection in ICU. MDR bacteria can lead to serious clinical outcomes. Diabetes and intrauterine operation are independent risk factors for MDR bacteria' infection.

Therapeutic Efficacy of Human Mesenchymal Stem Cells With Different Delivery Route and Dosages in Rat Models of Spinal Cord Injury.

Recent studies have shown that the use of mesenchymal stem/stromal cells (MSCs) may be a promising strategy for treating spinal cord injury (SCI). This study aimed to explore the effectiveness of human umbilical cord-derived MSCs (hUC-MSCs) with different administration routes and dosages on SCI rats. Following T10-spinal cord contusion in Sprague-Dawley rats (N = 60), three different dosages of hUC-MSCs were intrathecally injected into rats (SCI-ITH) after 24 h. Intravenous injection of hUC-MSCs (SCI-i.v.) and methylprednisolone reagent (SCI-PC) were used as positive controls (N = 10/group). A SCI control group without treatment and a sham operation group were injected with Multiple Electrolyte Injection solution. The locomotor function was assessed by Basso Beattie Bresnahan (BBB) rating score, magnetic resonance imaging (MRI), histopathology, and immunofluorescence. ELISA was conducted to further analyze the nerve injury and inflammation in the rat SCI model. Following SCI, BBB scores were significantly lower in the SCI groups compared with the sham operation group, but all the treated groups showed the recovery of hind-limb motor function, and rats receiving the high-dose intrathecal injection of hUC-MSCs (SCI-ITH-H) showed improved outcomes compared with rats in hUC-MSCs i.v. and positive control groups. Magnetic resonance imaging revealed significant edema and spinal cord lesion in the SCI groups, and significant recovery was observed in the medium and high-dose hUC-MSCs ITH groups. Histopathological staining showed that the necrotic area in spinal cord tissue was significantly reduced in the hUC-MSCs ITH-H group, and the immunofluorescence staining confirmed the neuroprotection effect of hUC-MSCs infused on SCI rats. The increase of inflammatory cytokines was repressed in hUC-MSCs ITH-H group. Our results confirmed that hUC-MSC administered via intrathecal injection has dose-dependent neuroprotection effect in SCI rats.

Features of gut microbiota in patients with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a psychological disorder, which is characterized by the misunderstanding of body image, food restriction, and low body weight. An increasing number of studies have reported that the pathophysiological mechanism of AN might be associated with the dysbiosis of gut microbiota. The purpose of our study was to explore the features of gut microbiota in patients with AN, hoping to provide valuable information on its pathogenesis and treatment. METHODS: In this cross-sectional study, from August 2020 to June 2021, patients with AN who were admitted into Peking University Third Hospital and Peking University Sixth Hospital ( n   =  30) were recruited as the AN group, and healthy controls (HC) were recruited from a middle school and a university in Beijing ( n   =  30). Demographic data, Hamilton Depression Scale (HAMD) scores of the two groups, and length of stay of the AN group were recorded. Microbial diversity analysis of gut microbiota in stool samples from the two groups was analyzed by 16S ribosomal RNA (rRNA) gene sequencing. RESULTS: The weight (AN vs. HC, [39.31 ±â€Š7.90] kg vs. [56.47 ±â€Š8.88] kg, P  < 0.001) and body mass index (BMI, AN vs. HC, [14.92 ±â€Š2.54] kg/m 2vs. [20.89 ±â€Š2.14] kg/m 2 , P  < 0.001) of patients with AN were statistically significantly lower than those of HC, and HAMD scores in AN group were statistically significantly higher than those of HC. For alpha diversity, there were no statistically significant differences between the two groups; for beta diversity, the two groups differed obviously regarding community composition. Compared to HC, the proportion of Lachnospiraceae in patients with AN was statistically significantly higher (AN vs. HC, 40.50% vs. 31.21%, Z  = -1.981, P  = 0.048), while that of Ruminococcaceae was lower (AN vs. HC, 12.17% vs. 19.15%, Z  = -2.728, P  = 0.007); the proportion of Faecalibacterium (AN vs. HC, 3.97% vs. 9.40%, Z  = -3.638, P  < 0.001) and Subdoligranulum (AN vs. HC, 4.60% vs. 7.02%, Z  = -2.369, P  = 0.018) were statistically significantly lower, while that of Eubacterium_hallii_group was significantly higher (AN vs. HC, 7.63% vs. 3.43%, Z  = -2.115, P  = 0.035). Linear discriminant effect (LEfSe) analysis (LDA score >3.5) showed that o_Lachnospirales, f_Lachnospiraceae, and g_Eubacterium_hallii_group (o, f and g represents order, family and genus respectively) were enriched in patients with AN. Microbial function of nutrient transport and metabolism in AN group were more abundant ( P  > 0.05). In AN group, weight and BMI were significantly negatively correlated with the abundance of Bacteroidota and Bacteroides , while positively correlated with Subdoligranulum . BMI was significantly positively correlated with Firmicutes; HAMD scores were significantly negatively correlated with Faecalibacterium. CONCLUSIONS: The composition of gut microbiota in patients with AN was different from that of healthy people. Clinical indicators have correlations with the abundance of gut microbiota in patients with AN.

Severe Thrombocytopenia Caused by Vancomycin in the Intensive Care Unit: A Case Report.

Thrombocytopenia can cause substantial morbidity and mortality in critically ill patients. There are multiple etiology factors and various mechanisms associated with thrombocytopenia, of which drug-induced thrombocytopenia (DITP) deserves attention. Herein, we describe a case of severe thrombocytopenia during intensive care unit (ICU) hospitalization that was likely to be associated with vancomycin. By revealing the process of identifying this case of DITP and reviewing relevant clinical studies, a risk alert of vancomycin-related severe hematotoxicity should be considered.

Rapid and Accurate Detection of SARS Coronavirus 2 by Nanopore Amplicon Sequencing.

Objective: We aimed to evaluate the performance of nanopore amplicon sequencing detection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in clinical samples. Method: We carried out a single-center, prospective cohort study in a Wuhan hospital and collected a total of 86 clinical samples, including 54 pharyngeal swabs, 31 sputum samples, and 1 fecal sample, from 86 patients with coronavirus disease 2019 (COVID-19) from Feb 20 to May 15, 2020. We performed parallel detection with nanopore-based genome amplification and sequencing (NAS) on the Oxford Nanopore Technologies (ONT) minION platform and routine reverse transcription quantitative polymerase chain reaction (RT-qPCR). In addition, 27 negative control samples were detected using the two methods. The sensitivity and specificity of NAS were evaluated and compared with those of RT-qPCR. Results: The viral read number and reference genome coverage were both significantly different between the two groups of samples, and the latter was a better indicator for SARS-CoV-2 detection. Based on the reference genome coverage, NAS revealed both high sensitivity (96.5%) and specificity (100%) compared with RT-qPCR (80.2 and 96.3%, respectively), although the samples had been stored for half a year before the detection. The total time cost was less than 15 h, which was acceptable compared with that of RT-qPCR (∼2.5 h). In addition, the reference genome coverage of the viral reads was in line with the cycle threshold value of RT-qPCR, indicating that this number could also be used as an indicator of the viral load in a sample. The viral load in sputum might be related to the severity of the infection, particularly in patients within 4 weeks after onset of clinical manifestations, which could be used to evaluate the infection. Conclusion: Our results showed the high sensitivity and specificity of the NAS method for SARS-CoV-2 detection compared with RT-qPCR. The sequencing results were also used as an indicator of the viral load to display the viral dynamics during infection. This study proved the wide application prospect of nanopore sequencing detection for SARS-CoV-2 and may more knowledge about the clinical characteristics of COVID-19.

Soft Exoskeleton Mimics Human Cough for Assisting the Expectoration Capability of SCI Patients.

This paper describes the design of a bionic soft exoskeleton and demonstrates its feasibility for assisting the expectoration function rehabilitation of patients with spinal cord injury (SCI). METHODS: A human-robot coupling respiratory mechanic model is established to mimic human cough, and a synergic inspire-expire assistance strategy is proposed to maximize the peak expiratory flow (PEF), the key metric for promoting cough intensity. The negative pressure module of the exoskeleton is a soft "iron lung" using layer-jamming actuation. It assists inspiration by increasing insufflation to mimic diaphragm and intercostal muscle contraction. The positive pressure module exploits soft origami actuators for assistive expiration; it pressures human abdomen and bionically "pushes" the diaphragm upward. RESULTS: The maximum increase in PEF ratios for mannequins, healthy participants, and patients with SCI with robotic assistance were 57.67%, 278.10%, and 124.47%, respectively. The soft exoskeleton assisted one tetraplegic SCI patient to cough up phlegm successfully. CONCLUSION: The experimental results suggest that the proposed soft exoskeleton is promising for assisting the expectoration ability of SCI patients in everyday life scenarios. SIGNIFICANCE: The proposed soft exoskeleton is promising for advancing the application field of rehabilitation exoskeletons from motor functions to respiratory functions.

Are Proton Pump Inhibitors More Effective Than Histamine-2-Receptor Antagonists for Stress Ulcer Prophylaxis in Critically Ill Patients? A Systematic Review and Meta-Analysis of Cohort Studies.

BACKGROUND: Histamine-2-receptor antagonists (H2RAs) have been largely replaced by proton pump inhibitors (PPIs) for stress ulcer prophylaxis (SUP) despite the inconclusive evidence concerning comparative effectiveness. OBJECTIVE: To compare the effectiveness of PPIs and H2RAs on SUP in real-world setting. METHODS: PubMed, Embase, and the Cochrane Library were searched from inception to September 19, 2021. We included cohort studies comparing PPIs with H2RAs in critically ill adult patients and explicitly reporting the outcome of gastrointestinal (GI) bleeding or mortality. Newcastle-Ottawa Scale was used to assess potential risk of bias. We conducted a random-effects meta-analysis and only the studies with adjusted effect estimates were pooled. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assess the overall quality of the evidence. RESULTS: Thirteen cohort studies (N = 145 149) were eligible and 11 of them available for full texts were of low to moderate risk of bias. Meta-analysis of adjusted effect estimates indicated that PPIs were associated with a significantly higher risk of GI bleeding, compared with H2RAs (8 studies, odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.30-3.01, low certainty). Post hoc pooling analysis also suggested that PPIs were associated with a slightly higher risk of mortality in comparison with H2RAs (7 studies, OR = 1.27, 95% CI = 1.13-1.42, low certainty). CONCLUSION AND RELEVANCE: The systematic review of cohort studies showed that PPIs were associated with higher risks of GI bleeding and mortality, although the certainty of evidence was low. Overall, we suggest not excluding H2RAs for SUP, while further studies are essential for elucidating the risk stratification, optimal regimen, and specific duration.

Non-contact screening system based for COVID-19 on XGBoost and logistic regression.

BACKGROUND: The coronavirus disease (COVID-19) effected a global health crisis in 2019, 2020, and beyond. Currently, methods such as temperature detection, clinical manifestations, and nucleic acid testing are used to comprehensively determine whether patients are infected with the severe acute respiratory syndrome coronavirus 2. However, during the peak period of COVID-19 outbreaks and in underdeveloped regions, medical staff and high-tech detection equipment were limited, resulting in the continued spread of the disease. Thus, a more portable, cost-effective, and automated auxiliary screening method is necessary. OBJECTIVE: We aim to apply a machine learning algorithm and non-contact monitoring system to automatically screen potential COVID-19 patients. METHODS: We used impulse-radio ultra-wideband radar to detect respiration, heart rate, body movement, sleep quality, and various other physiological indicators. We collected 140 radar monitoring data from 23 COVID-19 patients in Wuhan Tongji Hospital and compared them with 144 radar monitoring data from healthy controls. Then, the XGBoost and logistic regression (XGBoost + LR) algorithms were used to classify the data according to patients and healthy subjects. RESULTS: The XGBoost + LR algorithm demonstrated excellent discrimination (precision = 92.5%, recall rate = 96.8%, AUC = 98.0%), outperforming other single machine learning algorithms. Furthermore, the SHAP value indicates that the number of apneas during REM, mean heart rate, and some sleep parameters are important features for classification. CONCLUSION: The XGBoost + LR-based screening system can accurately predict COVID-19 patients and can be applied in hotels, nursing homes, wards, and other crowded locations to effectively help medical staff.

Bone Tumor Suppression in Rabbits by Hyperthermia below the Clinical Safety Limit Using Aligned Magnetic Bone Cement.

Demonstrating highly efficient alternating current (AC) magnetic field heating of nanoparticles in physiological environments under clinically safe field parameters has remained a great challenge, hindering clinical applications of magnetic hyperthermia. In this work, exceptionally high loss power of magnetic bone cement under the clinical safety limit of AC field parameters, incorporating direct current field-aligned soft magnetic Zn0.3 Fe2.7 O4 nanoparticles with low concentration, is reported. Under an AC field of 4 kA m-1 at 430 kHz, the aligned bone cement with 0.2 wt% nanoparticles achieves a temperature increase of 30 °C in 180 s. This amounts to a specific loss power value of 327 W gmetal-1 and an intrinsic loss power of 47 nHm2 kg-1 , which is enhanced by 50-fold compared to randomly oriented samples. The high-performance magnetic bone cement allows for the demonstration of effective hyperthermia suppression of tumor growth in the bone marrow cavity of New Zealand White Rabbits subjected to rapid cooling due to blood circulation, and significant enhancement of survival rate.

[Clinical characteristics of critically ill pregnant women with different admission methods to intensive care unit: data analysis from 2006 to 2019 in the university hospital].

OBJECTIVE: To compare the clinical characteristics of critically ill pregnant women admitted to the intensive care unit (ICU) with different admission methods, in order to make more effective and rational use of ICU resources. METHODS: A retrospective study was conducted. The clinical data of critically ill pregnant women admitted to ICU of Peking University Third Hospital from January 2006 to July 2019 were analyzed. According to the admission mode to ICU, the pregnant women were divided into emergency admission group (transferred to ICU on the same day or the next day due to critical illness) and planned admission group (transferred to ICU 2 days after admitting in obstetric ward). The clinical characteristics of ICU critical pregnant women, such as the incidence, causes of admission, severity of the disease, main treatment measures, mortality, and medical expenses were collected, and a comparative analysis between the two groups was performed. RESULTS: During the nearly 14 years, a total of 576 critical pregnant women in ICU were enrolled, accounting for 0.8% (576/71 790) of the total number of obstetric inpatients and 4.6% (576/12 412) of the total number of ICU inpatients. Seven maternal deaths accounted for 1.2% of all critically pregnant women transferred to ICU, and the overall mortality of pregnant women was 10/100 thousand. Of the 576 critically pregnant women, there were 327 patients (56.8%) in the emergency admission group and 249 patients (43.2%) in the planned admission group. Compared with the planned admission group, the proportion of elective cesarean section in the emergency admission group was significantly lower (17.7% vs. 94.0%, P < 0.01), and the proportion of emergency cesarean section was significantly higher (65.1% vs. 2.4%, P < 0.01), the acute physiology and chronic health evaluation (APACHE II, APACHE III) scores, simplified acute physiology score II (SAPS II) and Marshall score were significantly higher [APACHE II score: 6.0 (4.0, 9.8) vs. 4.0 (3.0, 7.0), APACHE III score: 14.0 (11.0, 20.3) vs. 12.0 (9.0, 16.0), SAPS II score: 8 (0, 12) vs. 3 (0, 8), Marshall score: 2 (1, 4) vs. 1 (1, 3), all P < 0.01]. The length of ICU stay in the emergency admission group was significantly longer than that in the planned admission group [days: 2 (1, 5) vs. 2 (1, 3), P < 0.01], and the total length of hospital stay was significantly shorter [days: 9 (7, 13) vs. 13 (10, 18), P < 0.01]. Both in the emergency admission group and the planned admission group, obstetric factors were the main reason for admission, 60.9% (199/327) and 70.3% (175/249), respectively. The proportion of postpartum hemorrhage was the highest [35.2% (115/327) and 57.0% (142/249)], followed by preeclampsia/eclampsia [7.0% (23/327) and 7.6% (19/249)]. Only 7 of the 19 critically pregnant women with puerperal infection were planned admission. All 21 patients with acute fatty liver of pregnancy (AFLP) during pregnancy were emergency admission. Among the emergency and planned admission patients, 73 patients (22.3%) and 42 patients (16.9%) required mechanical ventilation (duration of mechanical ventilation > 24 hours), 99 patients (30.3%) and 35 patients (14.1%) needed vasoactive agents, 67 patients (20.5%) and 20 patients (8.0%) received hemodynamic monitoring, and 123 patients (37.6%) and 154 patients (61.8%) were given anticoagulation therapy, respectively. In terms of severity score of critical pregnant women, there were significant differences in APACHE II, APACHE III, SAPS II and Marshall scores of pregnant women with different diseases. Among them, the APACHE III, SAPS II and Marshall scores of AFLP were the highest [21.0 (15.0, 32.5), 12.0 (6.0, 16.5) and 6.0 (3.5, 8.0), respectively]. The APACHE II and APACHE III scores of postpartum hemorrhage were the lowest [4.0 (3.0, 7.0), 12.0 (10.0, 16.0)]. The SAPS II score of pneumonia was the lowest [2.0 (0, 14.0)]. The Marshall score for puerperal infection was the lowest [1.0 (0, 3.0)]. In terms of the total medical expenses, the cost in the emergency admission group was significantly lower than that in the planned admission group [10 thousand Yuan: 3.1 (2.0, 4.7) vs. 4.1 (2.9, 5.8), P < 0.05]. CONCLUSIONS: Compared with the critically ill pregnant women who planned to be admitted to ICU, the patients emergency admitted to ICU were more complicated and urgent, and the severity of the condition was scored higher. At present, the severity scoring system commonly used in ICU can only partly evaluate the severity of critically ill pregnant women, therefore, it is necessary to design the specific severity scoring system for critically ill pregnant women to effectively and rationally use the precious ICU resources.

Dose Optimization of Vancomycin for Critically Ill Patients Undergoing CVVH: A Prospective Population PK/PD Analysis.

The optimal dose of vancomycin in critically ill patients receiving continuous venovenous hemofiltration (CVVH) remains unclear. The objective of this study was to identify factors that significantly affect pharmacokinetic profiles and to further investigate the optimal dosage regimens for critically ill patients undergoing CVVH based on population pharmacokinetics and pharmacodynamic analysis. A prospective population pharmacokinetic analysis was performed at the surgical intensive care unit in a level A tertiary hospital. We included 11 critically ill patients undergoing CVVH and receiving intravenous vancomycin. Serial blood samples were collected from each patient, with a total of 131 vancomycin concentrations analyzed. Nonlinear mixed effects models were developed using NONMEM software. Monte Carlo Simulation was used to optimize vancomycin dosage regimens. A two-compartment model with first-order elimination was sufficient to characterize vancomycin pharmacokinetics for CVVH patients. The population typical vancomycin clearance (CL) was 1.15 L/h and the central volume of distribution was 16.9 L. CL was significantly correlated with ultrafiltration rate (UFR) and albumin level. For patients with normal albumin and UFR between 20 and 35 mL/kg/h, the recommended dosage regimen was 10 mg/kg qd. When UFR was between 35 and 40 mL/kg/h, the recommended dosage regimen was 5 mg/kg q8h. For patients with hypoalbuminemia and UFR between 20 and 25 mL/kg/h, the recommended dosage regimen was 5 mg/kg q8h. When UFR was between 25 and 40 mL/kg/h, the recommended dosage regimen was 10 mg/kg q12h. We recommend clinicians choosing the optimal initial vancomycin dosage regimens for critically ill patients undergoing CVVH based on these two covariates.

Shock in China 2018 (SIC-study): a cross-sectional survey.

BACKGROUND: Shock is a critical illness that seriously threatens the lives of patients. This study explains the epidemiology of shock, mortality of shock, and identify factors that related to hospital death. METHODS: This is a multi-centre cross-sectional survey, which included 1,064 tertiary hospitals in 31 provinces, municipalities, and autonomous regions across China mainland. Totally 289,428 patients who diagnosed with shock based on the ICD-10 abstracted from the Hospital Quality Monitoring System (HQMS) in 2018, a national database administrated by National Health Commission of the PRC. RESULTS: Patients diagnosed with shock were screened and classified according to the type of shock. Regression analysis was used to identify factors that related to death. A total of 79,668,156 medical records were included in HQMS in 2018, from which a total of 289,428 records with shock were identified. Hypovolemic shock occurred in 128,436 cases (44.38%), septic shock occurred in 121,543 cases (41.99%), cardiogenic shock occurred in 44,597 cases (15.41), and obstructive shock occurred in 3,168 cases (1.09%). Of these, 8,147 cases (2.81%) had mixed shock, which means had two or more types of shock. For all the shock cases, the top three frequent concomitant diseases recorded were circulatory system diseases (55.22%), digestive system diseases (53.64%), and respiratory system diseases (53.31%). Of the four types of shock, cases with cardiogenic shock had the highest in-hospital mortality (31.6%), followed by those with obstructive shock (25.2%), septic shock (22.9%), and hypovolemic shock (15.5%). Interestingly, the combination of shock and malignant tumors is one of the major factors that related to hospital deaths. CONCLUSIONS: Shock is a serious disease with a high fatality rate and huge clinical costs. According to this epidemiological survey of shock in China 2018, we should clarify the factors related to the hospital death in shock cases.

Disseminated intravascular coagulation associated organ failure in obstetric patients admitted to intensive care units: a multicenter study in China.

We aimed to determine disseminated intravascular coagulation (DIC)-associated organ failure and underlying diseases based on data from three ICU wards in tertiary hospitals in China from 2008 to 2016. The diagnosis of DIC was confirmed by an International Society of Thrombosis and Hemostasis score greater than or equal to 5. The maternal outcomes included the changes in organ function 24 h after ICU admission. The durations of hospital stay and ICU stay were recorded as secondary outcomes. Among 297 ICU admissions (median Sequential Organ Failure Assessment score, 4) for obstetric diseases, there were 87 DIC cases, with an estimated DIC incidence of 87 per 87,580 deliveries. Postpartum hemorrhage was the leading disease associated with DIC (71, 81.6%), followed by hypertensive disorders (27, 31.0%), sepsis (15, 17.2%), acute fatty liver of pregnancy (11, 12.6%) and amniotic fluid embolism (10, 11.5%). Compared with patients without DIC, those with DIC had higher rates of multiple organ dysfunction syndrome/death (27.6% vs 4.8%, p = 0.000), organ failure (36.8% vs 24.3%, p = 0.029), among which organ failure included acute renal failure (32.2% vs 10.0%, p = 0.000), respiratory failure (16.1% vs 8.6%, p = 0.057), disturbance of consciousness (12.6% vs 2.4%, p = 0.000) and DIC group also had higher rates of massive transfusion (52.9% vs 21.9%, p = 0.000), hysterectomy (32.2% vs 15.7%, p = 0.001), longer ICU (4 days vs 2 days, p = 0.000) and hospital stays (14 days vs 11 days, p = 0.005). DIC and amniotic fluid embolism were independent risk factors for organ failure in patients admitted to the ICU. Postpartum hemorrhage was the leading cause of DIC associated organ failure in obstetrics admitted to the ICU. The control of obstetric bleeding in a timely manner may improve obstetric prognoses.