Characteristic fingerprint spectrum of α-synuclein mutants on terahertz time-domain spectroscopy.

α-Synuclein, a presynaptic neuronal protein encoded by the SNCA gene, is involved in the pathogenesis of Parkinson's disease. Point mutations and multiplications of α-synuclein (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 aimed to develop a novel label-free detection method for distinguishing the SNCA mutants using transmission terahertz (THz) time-domain spectroscopy. 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-synuclein protein variants (SNCA wild type, A30P, and A53T) at different frequencies were analyzed via Fourier transform. The amplitude A intensity (AWT, AA30P, and AA53T) and peak occurrence time in THz time-domain spectroscopy 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 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), whereas there was no difference in the transmission T at 0.66 THz. 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.

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.

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.

Good abdominal drainage fluid penetration and pharmacokinetics analysis of vancomycin for severe acute pancreatitis: A case report.

WHAT IS KNOWN AND OBJECTIVE: The antibiotic concentration in abdominal drainage fluid is very important for the treatment of patients with severe acute pancreatitis (SAP). Previous studies show that quinolones and carbapenems have high abdominal tissue levels, whereas aminoglycosides fail to penetrate into abdominal tissue in sufficient concentrations. However, there are limited data with respect to vancomycin. This case aims to investigate the penetration of vancomycin to abdominal drainage fluid in a 44-year-old SAP patient. CASE SUMMARY: We report a case of a 44-year-old female with SAP, on treatment of vancomycin. The time courses of vancomycin concentration in plasma and abdominal drainage fluid of the patient were described. Simultaneous measurement of abdominal drainage fluid and serum concentrations demonstrated that vancomycin can rapidly penetrate into abdominal tissue in acceptable amounts. WHAT IS NEW AND CONCLUSION: This case demonstrated that it took about 30 minutes for vancomycin to get from plasma to abdominal drainage fluid and about 76% of vancomycin could move into abdominal drainage fluid for SAP patients.

Prominent coagulation disorder is closely related to inflammatory response and could be as a prognostic indicator for ICU patients with COVID-19.

The new outbreak of Coronavirus Disease 2019 (COVID-19) has emerged as a serious global public health concern. A more in-depth study of blood coagulation abnormality is needed. We retrospectively analyzed 147 consecutive patients with COVID-19 who were admitted to three ICUs in Wuhan from February 9th, 2020 to March 20th, 2020. The baseline coagulation and other characteristics were studied. Our results showed that the prolonged PT, FDP, DD were positively correlated with the levels of neutrophils, ferritin, LDH, total bilirubin, multi-inflammation cytokines, and negatively correlated with the lymphocytes level (p < 0.01). The level of ATIII was significantly negatively correlated with the levels of neutrophils, ferritin, LDH, total bilirubin, IL2R, IL6 and IL8 (p < 0.05). The patients in the ARDS group had a more prominent abnormality in PT, FDP, DD and ATIII, while the patients in the AKI group had more prolonged PT, more severe FDP and DD level, more inferior ATIII and Fib level than those in the non-AKI group (p < 0.01). The value of PT, DD and FDP were positively correlated with the classical APACHE II, SOFA and qSOFA scores, while the ATIII was negatively correlated with them (p < 0.001). The high levels of PT, FDP and DD were correlated with in-hospital mortality (p < 0.001). In conclusion, blood coagulation disorder was prominent in ICU patients with COVID-19 and was correlated with multi-inflammation factors. The abnormality of blood coagulation parameters could be an adverse prognostic indicator for ICU patients with COVID-19.

EBT: a statistic test identifying moderate size of significant features with balanced power and precision for genome-wide rate comparisons.

MOTIVATION: In genome-wide rate comparison studies, there is a big challenge for effective identification of an appropriate number of significant features objectively, since traditional statistical comparisons without multi-testing correction can generate a large number of false positives while multi-testing correction tremendously decreases the statistic power. RESULTS: In this study, we proposed a new exact test based on the translation of rate comparison to two binomial distributions. With modeling and real datasets, the exact binomial test (EBT) showed an advantage in balancing the statistical precision and power, by providing an appropriate size of significant features for further studies. Both correlation analysis and bootstrapping tests demonstrated that EBT is as robust as the typical rate-comparison methods, e.g. χ 2 test, Fisher's exact test and Binomial test. Performance comparison among machine learning models with features identified by different statistical tests further demonstrated the advantage of EBT. The new test was also applied to analyze the genome-wide somatic gene mutation rate difference between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), two main lung cancer subtypes and a list of new markers were identified that could be lineage-specifically associated with carcinogenesis of LUAD and LUSC, respectively. Interestingly, three cilia genes were found selectively with high mutation rates in LUSC, possibly implying the importance of cilia dysfunction in the carcinogenesis. AVAILABILITY AND IMPLEMENTATION: An R package implementing EBT could be downloaded from the website freely: http://www.szu-bioinf.org/EBT . CONTACT: wangyj@szu.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

[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.

Extracorporeal closed-loop respiratory regulation for patients with respiratory difficulty using a soft bionic robot.

OBJECTIVE: Respiratory regulation is critical for patients with respiratory dysfunction. Clinically used ventilators can lead to long-term dependence and injury. Extracorporeal assistance approaches such as iron-lung devices provide a noninvasive alternative, however, artificial actuator counterparts have not achieved marvelous biomimetic ventilation as human respiratory muscles. Here, we propose a bionic soft exoskeleton robot that can achieve extracorporeal closed-loop respiratory regulation by emulating natural human breath. METHODS: For inspiration, a soft vacuum chamber is actuated to produce negative thoracic pressure and thus expand lung volume by pulling the rib cage up and outward through use of external negative pressure. For expiration, a soft origami array under positive pressure pushes the abdominal muscles inward and the diaphragm upward. To achieve in vitro measurement of respiratory profile, we describe a wireless respiratory monitoring device to measure respiratory profiles with high accuracy, validated by quantitative comparisons with spirometer as gold-standard reference. By constructing a human-robot coupled respiratory mechanical model, a model-based proportional controller is designed for continuous tracking of the target respiratory profile. RESULTS: In experiments with ten healthy participants and ten patients with respiratory difficulty, the robot can adjust its assistive forces in real time and drive human-robot coupling respiratory system to track the target profile. CONCLUSION: The biomimetic robot can achieve extracorporeal closed-loop respiratory regulation for a diverse population. SIGNIFICANCE: The soft robot has important potential to assist respiration for people with respiratory difficulty, whether in a hospital or a home setting.

Detection of In Vivo-like Cells by a Biosensor Chip Based on Metamaterials in Terahertz Regime.

Early diagnosis of diseases, especially cancer, is critical for effective treatment. The unique properties of terahertz technology have attracted attention in this field. However, current terahertz bio-detection methods face challenges due to differences between the test environment and the actual in vivo conditions. In this study, a novel method is proposed for detecting in vivo-like cells using a biosensor chip composed of metamaterials and a cavity. The cavity has a thickness of ~50 µm. The structure can protect cells from damage and provides a liquid environment like an in vivo state. Through simulation analysis, the metamaterials sensor exhibits a theoretical sensitivity of 0.287 THz/RIU (Refractive Index Unit) with a 50 µm thick analyte. The detection method is experimentally validated using the apoptosis of glioma cells and various cell types. The biosensor investigates the apoptosis of glioma cells under the impact of temozolomide, and the trend of the results was consistent with the Cell Counting Kit-8 method. Furthermore, at a concentration of ~5200 cells/cm2, the experimental results demonstrate that the sensor can distinguish between neurons and glioma cells with a resonance frequency difference of approximately 30 GHz. This research has significant potential for detecting glioma cells and offers an alternative approach to in vivo-like cell detection.

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.

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.

Lipidome is a valuable tool for the severity prediction of coronavirus disease 2019.

Objective: To describe the lipid metabolic profile of different patients with coronavirus disease 2019 (COVID-19) and contribute new evidence on the progression and severity prediction of COVID-19. Methods: This case-control study was conducted in Peking University Third Hospital, China. The laboratory-confirmed COVID-19 patients aged ≥18 years old and diagnosed as pneumonia from December 2022 to January 2023 were included. Serum lipids were detected. The discrimination ability was calculated with the area under the curve (AUC). A random forest (RF) model was conducted to determine the significance of different lipids. Results: Totally, 44 COVID-19 patients were enrolled with 16 mild and 28 severe patients. The top 5 super classes were triacylglycerols (TAG, 55.9%), phosphatidylethanolamines (PE, 10.9%), phosphatidylcholines (PC, 6.8%), diacylglycerols (DAG, 5.9%) and free fatty acids (FFA, 3.6%) among the 778 detected lipids from the serum of COVID-19 patients. Certain lipids, especially lysophosphatidylcholines (LPCs), turned to have significant correlations with certain immune/cytokine indexes. Reduced level of LPC 20:0 was observed in severe patients particularly in acute stage. The AUC of LPC 20:0 reached 0.940 in discriminating mild and severe patients and 0.807 in discriminating acute and recovery stages in the severe patients. The results of RF models also suggested the significance of LPCs in predicting the severity and progression of COVID-19. Conclusion: Lipids probably have the potential to differentiate and forecast the severity, progression, and clinical outcomes of COVID-19 patients, with implications for immune/inflammatory responses. LPC 20:0 might be a potential target in predicting the progression and outcome and the treatment of COVID-19.

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.

[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.

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.

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.

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.

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.

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.

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.