Objective  To explore the association between systolic blood pressure variability and in-hospital mortality in patients with sepsis. Methods  This study was a prospective, multicenter, and cohort study. Data were derived from the China Critical Care Sepsis Trial, which was conducted from January 2013 to August 2014. Patients aged ≥18 years with length of stay of intensive care unit （ICU）more than 24 h were included. The patients who were diagnosed  as sepsis for more than 48 h and lack of blood pressure for 2 h or longer were excluded. Systolic blood pressure, diastolic blood pressure, fluid intake and output were collected. The systolic blood pressure coefficient of variation (SBP_cv) was calculated and divided into four groups (Q₁, Q₂, Q₃, Q₄) according to the interquartile of SBP_cv. The multivariable Logistic regression was applied to explore the association between systolic blood pressure variability and in-hospital mortality. Results  A total of  1 356 patients with sepsis were included, with 929 (68.5%) males and 427 (31.5%) females, median age 67.0 years (52.0, 78.0).Among them,  483 (35.6%) patients died during hospitalization. After adjusting for potential confounding factors, for every 10% of SBP_cv increasing, the risk of in-hospital mortality increased 43% (OR=1.43, 95%CI:1.11-1.98). Compared with Q1 group, patients in Q4 group had a 69% increased risk of in-hospital mortality (OR=1.69, 95%CI:1.31-2.25) and a 23% increased risk of 28 d mortality (OR=1.23, 95%CI:1.07-1.84). Conclusion  Higher systolic blood pressure variability was correlated with higher risks of in-hospital mortality and 28 d mortality.

Objective  To investigate the impact of Candida albicans colonization on the mortality, duration of antibiotic therapy, immune and inflammation status in patients with ventilator-associated pneumonia (VAP) caused by multidrug-resistant Pseudomonas aeruginosa. Methods  This prospective multicenter cohort study included patients with VAP caused by multidrug-resistant Pseudomonas aeruginosa (MDR-Pa) admitted to six tertiary teaching hospitals from June 2018 to June 2023. The patients were divided into colonization group and non-colonization group based on the presence of Candida albicans detected in the broncho-alveolar lavage fluid (BALF). The 30-d all-cause mortality, duration of antibiotic therapy, immune and inflammation status were compared between the two groups after VAP diagnosis on the day1, day3, day5, and day7. Results  During the five-year research period, a total of 232 VAP patients caused by MDR-Pa were included from six participating units in the intensive care unit (ICU), with 105 cases in the colonization group and 127 cases in the non-colonization group. The Pseudomonas aeruginosa detected in BALF samples from the non-colonization group showed higher sensitivity to aminoglycosides, cephalosporins, and carbapenems compared to the colonization group (P<0.05). However, both groups showed lower sensitivity to 16 antibiotics compared to China antimicrobial surveillance network (CHINET) 2022 (P<0.05).  Interleukin-17A and (1,3)-β-D glucan levels in the non-colonization group were consistently lower than those in the colonization group at various time points, and other inflammatory markers were more likely to return to normal values (P<0.05). Additionally, the absolute values of T and Th lymphocytes in the non-colonization group recovered to normal levels faster on the day 7 (P<0.05). There was no statistically significant difference in the 30-d all-cause mortality between the two groups (25.7% vs 22.8%, P=0.61), but the non-colonization group had a significantly shorter duration of antibiotic therapy compared to the colonization group ［(11.3±3.1)d vs （14.2±4.7)d, P<0.01］, with a trend towards shorter ICU hospitalization time. Conclusion  The colonization of Candida albicans in the airway does not affect the 30-d all-cause mortality of patients with VAP caused by MDR-Pa. However, it does prolong the inflammatory response and the duration of antibiotic use, as well as delay the recovery of immune function.

Objective  To explore the correlation of simple measurement of inspiratory muscle pressure index from the ventilator (PMIvent) and reference measurement of inspiratory muscle pressure index on experimental condition (PMIref), the relationship between PMIvent and inspiratory effort, and further to determine the clinical feasibility and validity of PMI for assessing inspiratory effort during pressure support ventilation (PSV).  Methods  Adult acute respiratory failure patients undergoing mechanical ventilation were screened daily and enrolled 24 h after switching to PSV mode. Baseline ventilators were set according to the principle of keeping tidal volume/ predicted body weight(VT/PBW) at 6-8 mL/kg and respiratory rate (RR) at 20-30 breaths/min and the decision of the responsible ICU physician. A downward support pressure ( PS )titration was conducted from 20 cmH₂O to 2 cmH₂O. Three end-inspiratory holdings (EIO) and three end-expiratory holdings (EEO) were performed. PMIvent was calculated as the difference between plateau pressure (Pplat) within 2 s after EIO and the airway peak pressure (Ppeak) at EIO. PMIref was calculated as the difference between Pplat at one cardiac cycle after EIO and Ppeak at EIO. Flow, airway pressure (Paw), and esophageal pressure (Pes) signals were displayed continuously and saved. PMIref, PMIvent and esophageal pressure time product per breath (PTPes) were measured. PTPes per minute was calculated as the product of PTPes and RR. The “normal” range of PTPes per minute was defined as 50 to 200 cmH2O·s·min-1. The accuracy of PMIvent compared to PMIref was assessed with a Bland-Altman plot. The correlation between PMI and inspiratory effort was evaluated as the coefficient of determination (R²). The ability of PMI to detect high/low effort was assessed using the area under the receiver operating characteristics curve (ROC AUC). The optimal cut-off values were selected based on the Youden index. Results  The accuracy and precision of PMIvent compared to PMIref showed a low bias (0.18) with smaller 95% limits of agreements (-0.44,0.80). PMIref was significantly related to the PTPes per minute (between-patients R²=0.61, within-patients R²=0.80, respectively). PMIvent was also related to the PTPes per minute (between-patients R²=0.62, within-patients R²=0.81). For a cut-off PTPes<50 cmH₂O·s·min^-1, PMIvent showed an ROC AUC of 0.93 ［0.89,0.96］, and the best threshold was -0.77 cmH₂O. Conclusion  PMIvent can effectively replace PMIref. Like PMIref, PMIvent was significantly related to inspiratory effort and had the potential value to predict low inspiratory effort. 

Objective  To evaluate the influence of vagus nerve stimulation on renal function in septic rats and explore its mechanism. Methods  Forty male SD rats were divided into four groups：sham group, sepsis group, vagus nerve stimulation（VNS）group, and alpha7 nicotinic acetylcholine receptors（α7nAChR）antagonist group（n=10）. Rats in sham injury group only underwent laparotomy to expose the cecum, and then the cecum was returned to the abdominal cavity. Sepsis rat model was constructed by cecal ligation and perforation（CLP）. Rats in VNS group were given electrical stimulation on left cervical vagus nerve for 20 min after CLP. Rats in α7nAChR antagonist group were intraperitoneally injected with 2 mg/kg methyllycaconitine（MLA） at 30 min before CLP. At 24 h after CLP, serum of rats was collected to detect levels of blood urea nitrogen（BUN）, serum creatinine（Scr）, tumor necrosis factor-α（TNF-α）and interleukin-6（IL-6）by biochemical and enzyme-linked immunosorbent assay（ELISA）. The 24 h urine volume of each rat was collected, and the 24 h urine volume per kilogram body weight of each rat was calculated. Urinary neutrophil gelatinase-associated lipocalin（NGAL）and kidney injury molecule-1（KIM-1）were analyzed by ELISA. hematoxylin-eosin (HE) staining and TdT-mediated dUTP nick-end labeling (TUNEL) staining were performed to evaluate renal histopathological changes and tubule cell apoptosis. Results  ① The levels of BUN, Scr, TNF-α and IL-6 of rats in sepsis group were significantly higher than those in sham group and VNS group（P<0.01）. ② The 24 h urine volume per kilogram body weight of rats in sepsis group was significantly lower than that in sham group and VNS group （P<0.01）. ③ The levels of urinary NGAL and KIM-1 in sepsis group were significantly higher than those in sham group and VNS group（P<0.01）. ④ As compared with those of rats in sham group and VNS group, the renal histological damage score and the renal tubule apoptotic cell coun of rats in sepsis group were significantly increased（P<0.01）. ⑤ Scr, BUN, TNF-α, IL-6, urinary NGAL, urinary KIM-1, 24 h urine volume per kilogram, renal histological damage score, and renal tubule cell apoptosis count in sepsis group showed no significant difference from α7nAChR antagonist group（P>0.05）. Conclusion  Electrical stimulation of vagus nerve can significantly alleviate sepsis-induced acute kidney injury in rats，through the activation of α7nAChR dependent cholinergic anti-inflammatory pathway.

Objective  To evaluate the correlation between optic nerve sheath diameter (ONSD) and intracranial pressure (ICP) in patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods  All patients were diagnosed with aSAH and received microsurgery clipping at the Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University from December 1, 2019 to June 1, 2022. The patients received head computed tomography (CT) and subdural ICP monitoring devices were kept to monitor the ICP. The ONSD were measured with CT and ICP was recorded. The agreement among the three observers was evaluated with intraclass correlation coefficient (ICC), and the regression of ONSD and ICP was evaluated with Spearman's correlation coefficient. Results  A total of 184 patients were included, with 282 data of ONSD and ICP recorded. The median ICP was 12 (9, 18) mmHg (1 mmHg=0.133 kPa)， and the median ONSD was 5.59 (5.26, 5.99) mm. The ICC of left and right ONSD measured by three observers was 0.895 (0.872-0.915, P<0.001) and 0.869 (0.841-0.894, P<0.001), respectively. There was a significant positive correlation between ONSD and ICP (r=0.273，95% CI: 0.158-0.381, P<0.001). The area under the receiver operating characteristics curve of ONSD to predict ICP>22 mmHg was 0.753 (95% CI: 0.670-0.836, P<0.001), The cutoff point was 5.61 mm, with 85.2% sensitivity and 55.3% specificity. Conclusion  Measurement of ONSD by CT is repeatable, and it significantly correlates by ICP. 

Objective  To evaluate the effect of prophylactic administration of low-dose dexmedetomidine (DEX) on inflammatory response in elderly patients after hip fracture surgery. Methods  Elderly patients with hip fractures who admitted to the intensive care unit (ICU) after surgery were randomly divided to two groups, labeled “DEX group” or “control group” DEX. DEX group were received a continuous infusion of 0.1 μ g·kg^-1·h^-1 DEX. Control group received 0.025 mL·kg^-1·h^-1 of 0.9% saline intravenously. The serum levels of procalcitonin and interleukin-6 in patients at 0 hours (immediate), 6 hours, 12 hours, and 18 hours after administration were detected. The hemodynamic parameters (heart index, stroke volume index, mean arterial pressure, heart rate) and the occurrence of delirium were recorded. Results  There was no statistically significant difference in the levels of procalcitonin and interleukin-6 between the two groups at each time points (P>0.05).The incidence of delirium in the DEX group was significantly lower than that in the control group (P=0.034). The number of cases of additional use of opioid in the DEX group (P=0.039) and hypertension (P=0.012) were significantly lower than those in the control group. Conclusion  Low dose DEX did not significantly reduce postoperative inflammatory indicators in elderly patients with hip fractures, but it helped to reduce the occurrence of delirium and use of opioid analyesics in patients. Low dose DEX has minimal impact on hemodynamics and may have a circulatory protective effect on patients with postoperative hypertension.

Lung-diaphragmatic protective ventilation aims to limit damage to the lung and diaphragm during mechanical ventilation in critically ill patients. The dynamic monitoring of respiratory drive and inspiratory effort is the focus of the clinical strategies for implementating lung-diaphragm protective ventilation strategies. This paper reviews the existing indicators for dynamic monitoring of respiratory drive and inspiratory effort at the three levels of respiratory muscle, pressure change, and pulmonary ventilation according to the physiological pathway of respiratory drive and discusses their significance, acquisition methods, and thresholds.

Objective  To compare the differences of clinical manifestation between odontogenic sinusitis (ODS) patients with and without sinusitis symptoms. Methods  The clinical data of totally 92 ODS patients’ clinical data were retrospectively collected, who underwent endoscopic sinus surgery in the Department of Otolaryngology, Head and Neck Surgery in Beijing TongRen Hospital, Capital Medical Uniersity, from June 2020 to June 2022. Among them, 77 cases had sinusitis symptoms（SS group）, and 15 cases had no sinusitis symptoms（non-SS group）. The survey items included medical history, symptoms, etiology, endoscopic examination and sinus computed tomography(CT)were compared.Results  Compared with the SS group, the non-SS group has a shorter course of disease ［(4.9 ± 3.4) months vs (10.4 ± 11.0) months, P=0.048)］, and a higher proportion of first consultation in Department of Stomatology (100% vs 24.7%, P=0.035). There was no statistically significant difference in the positive rates of reported toothache and tooth loosening symptoms between the two groups of patients (29.9% vs 53.3%, P=0.133; 18.2% vs 35.3%, P=0.085). The proportion of periodontal endodontic combined lesions (PECL), apical periodontitis (AP), periodontitis (PE), and iatrogenic factor, accounted for the etiology of the two groups of patients, were 53.2% vs 20% (P=0.024); 28.6% vs 33.3% (P=0.76); 11.7% vs 26.7% (P=0.215); and 6.5% vs 20% (P=0.119), respectively. CT of the sinuses showed that the SS group had a higher proportion of involvement in the ostiomeatal complex (OMC), ethmoid sinus, and frontal sinus than non-SS group did, with 83.1% vs 26.7% (P=0.000); 80.5% vs 20% (P=0.000);  and 41.6% vs 0% (P=0.002), based on the evaluation of CT opacification. Conclusions  The multidisciplinary cooperation between Otolaryngology and Stomatology could early identify ODS patients without sinusitis symptoms, diagnose and treat timely dental related diseases, such as PECL, reduce the probability of endoscopic sinus surgery, and improve life quality of  patients. 

Objective  To explore the deposition of fibrin and the expression of genes related to fibrin formation and degradation in nasal mucosa of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and patients with CRSwNP comorbid asthma (CRSwNP+AS). Methods  Immunofluorescence staining was used to evaluate the deposition of fibrin in the nasal mucosa. Real-time fluorescence quantitative polymerse chain reaction (RT-qPCR) was used to detect the expression of genes related to fibrin formation and degradation ［factor ⅩⅢ A chain 1 (F13A1)， plasminogen (PLG)， plasminogen activator tissue type (PLAT)， plasminogen activator urokinase (PLAU) and plasminogen activator inhibitor 1 (PAI-1)］ in nasal mucosa of CRSwNP, CRSwNP+AS and control subjects. The patients received glucocorticoid treatment. Results  Compared with the control group, immunofluorescence staining showed obvious deposition of crosslinked fibrin in the nasal mucosa of patients with CRSwNP, and CRSwNP+AS group had more significant fibrin deposition. Gene expression analysis showed that the expression of F13A1, a gene that promotes fibrin formation, and PAI-1, a gene that inhibits fibrin degradation, were both significantly increased in the CRSwNP and CRSwNP+AS groups. In addition, the expression of F13A1 was significantly higher in CRSwNP+AS group than that in CRSwNP group. The expression of PLAT, which promotes fibrin degradation, was significantly lower in the CRSwNP+AS group than that in the CRSwNP and control groups. PLAU is upregulated in both types of CRSwNP. Glucocorticoid treatment significantly downregulates F13A1 and upregulates the expression of PLAT in patients with CRSwNP+AS. Conclusion  Patients with CRSwNP have excessive fibrin deposition in the nasal mucosa, which may be caused by the dysregulation of genes related to fibrin formation and degradation. Dysregulated F13A1 and PLAT were more significant in CRSwNP+AS. 

Objective  To train C57/6J wild-type mice and Sapap3 gene knockout mice to perform reversal learning induced by olfaction, tactility audition, respectively, and to explore the feasibility of reversal learning paradigm induced by olfaction, tactility audition and the cognitive flexibility of Sapap3 gene knockout mice. Methods  C57/6J wild-type mice and Sapap3 gene knockout mice (8-10 weeks old) were randomly divided into three groups and trained with the head fixed. The correct rate, error rate and learning rate of the licking events at each stage were analyzed to observe the learning ability of the mice under the three reversal learning paradigms. Results  The time required to reach the learning criterion was significantly different between Sapap3 knockout mice and C57/6J wild type mice in the reversal stage of olfactory and auditory reversal learning paradigm. Conclusion  The behavioral paradigm of reversal learning can be used to detect cognitive flexibility, which lays a behavioral foundation for the subsequent research on the diseases and brain regions related to cognitive flexibility.

Objective  To establish an experimental protocol for inducing human macrophages into scar-associated macrophages (SAMs) in vitro. To investigate the mechanism underlying SAMs regulating hepatic stellate cell (HSC) activation. Methods  Published single-cell RNA sequencing (scRNA-Seq) data, which were obtained from human or murine fibrotic liver tissues, were used to study the expression of fibrosis-related genes in SAMs. Phorbol-12-myristate-13-acetate (PMA) and plasminogen (PLG) were used to induce the transformation of human monocyte THP-1 into SAMs. SAM supernatant was collected to culture with LX-2. The expressions of SAM markers, fibrosis-related genes and HSC activation markers were detected by real-time quantitative polymerase chain reaction（RT-qPCR）. Results  scRNA-seq revealed that SAMs were detected in both mouse fibrotic livers or human injured liver. SAMs highly expressed fibrosis-related genes such as SPP1, CTSD. PMA and PLG increased the expressions of SAM markers CD9, TRME2, LGALS3, CD63 in THP-1. Fibrosis-related genes SPP1, CTSD were highly expressed by SAMs. The supernatant of SAMs activated LX-2. Conclusion  SAMs are accumulated in mouse or human liver injury/fibrosis caused by different causes, and represent similar characteristics and functions. PMA and PLG induce the transformation of human monocyte THP-1 into SAMs. SAMs promote the activation of HSCs via SPP1 and CTSD, thus promoting the occurrence and development of liver fibrosis.

Objective  To explore the association between cumulative exposure indicators of serum uric acid to serum creatinine ratio (SUA/Scr) and incident carotid plaque. Methods  This study included 9 228 individuals who met the inclusion and exclusion criteria from the Beijing Health Management Cohort. The cumulative exposure, cumulative exposure burden and high exposure time of SUA/Scr were calculated based on the values of SUA/Scr in three physical examinations in 2010 to 2011 (visit 1), 2012 to 2013 (visit 2), and 2014 to 2015 (visit 3). Carotid plaque was diagnosed by carotid ultrasound, and the follow-up was until December 31, 2021. Logistic regression model was used to analyze the association between SUA/Scr cumulative exposure indicators and carotid plaque occurrence, and sensitivity analysis was performed by excluding the participants with the usage of antihypertensive drugs, or glucose-lowering drugs, or lipid-lowering drugs. Results  The mean age of the study population was (48.89±10.22) years, and 5 846(63.35%) participants were males. The participants were divided into four groups according to the quartiles of SUA/Scr cumulative exposure, namely Q1-Q4 groups. After adjusting for covariates in models, compared with Q1 group, the ORs (95%CIs) of incident carotid plaque in Q2, Q3 and Q4 groups were 1.221 (95%CI：1.066-1.400), 1.255(95%CI： 1.095-1.439) and 1.478 (95%CI：1.287-1.697). Cumulative exposure burden greater than 0 (OR=1.223，95%CI：1.109-1.349) and high exposure time of 6 years (OR=1.332，95%CI：1.171-1.515) were both associated with increased risk of carotid plaque occurrence. Sensitivity analysis excluded participants with the usage of any antihypertensive drugs, glucose-lowering drugs, or lipid-lowering drugs. The results were similar to those in main analysis. Conclusion Cumulative exposure, cumulative exposure burden and high exposure time of SUA/Scr were associated with increased risk of incident carotid plaque. In the primary prevention of carotid plaque, we should focus not only on SUA/Scr value at a single point time, but also on long-term monitoring of SUA/Scr values.

Objective  To establish the fingerprints of the standard decoction of radix Paeoniae Alba, and to identify the active ingredients of radix Paeoniae Alba, in order to provide theoretical basis for the quality control and clinical application of radix Paeoniae Alba. Methods  Ten batches of radix Paeoniae Alba were collected and the standard decoction of radix Paeoniae Alba was prepared; the fingerprints of the standard decoction of radix Paeoniae Alba were established by ultra performance liquid chromatography (UPLC）, and the fingerprints were analyzed by the 2012 version of the Fingerprint Similarity Evaluation System for Traditional Chinese Medicine; and the common peaks were identified by comparing with the control product, and by checking the mass spectral data with the literature. Results  The fingerprints of 10 batches of standard decoction of radix Paeoniae Alba were identified with 22 common peaks, and the peaks were well separated, with the similarity of each sample>0.9. Five common peaks were recognized, which were catechin, albiflora, paeoniflorin,  pyrethrin II, and benzoylpaeoniflorin, respectively. Conclusion  The established fingerprint method has good precision, reproducibility and stability, and can provide a basis for the quality evaluation of radix Paeoniae Alba.

Objective  To construct a bispecific antibody targeting epidermal growth factor receptor（EGFR） and OX40 and evaluate the function for tumor-specific T cell activation. Methods  The gene of anti-OX40/anti-EGFR bispecific antibody was cloned into eukaryotic expression vector, and then the constructed vector were transfected to 293F cells for the bispecific antibody purification. The binding activity of anti-OX40/anti-EGFR bispecific antibody with the cells expressing target proteins  were detected by flow cytometry. To identify the activation of T cells mediated by anti-OX40/anti-EGFR bispecific antibody, the activation of NF-κB signal activation was evaluated by Jurkat-OX40-NF-κB-GFP reporter cells and the activation of primary T cells was detected by interleukin-2（IL-2） and interferon-γ（IFN-γ） secretion of peripheral blood mononuclear cell(PBMC). Results  Anti-OX40/anti-EGFR bispecific antibody was successfully constructed and purified, and its binding ability to HEK293 cells expressing OX40 and EGFR was verified. Jurkat-OX40-NF-κB-GFP reporter cells were activated by the bispecific antibody with the crosslinking of A549 cells. Further, the anti-OX40/anti-EGFR bispecific antibody promoted the secretion of IL-2 and IFN-γ of PBMC. Conclusion  Anti-OX40/anti-EGFR bispecific antibody was successfully constructed which could specifically recognize OX40 and EGFR and activate tumor specific T cells.

Objective  To investigate the effect and mechanism of total glucosides of paeony (TGP) in the treatment of acute lung injury in mice. Methods  Twenty-four female C57 mice were randomly divided into 4 groups： control group, lipopolysaccharide (LPS) model group, TGP group (LPS+TGP), and dexamethasone (DEX) group (LPS+DEX), with 6 mice in each group. Acute lung injury model was established by nasal inhalation of LPS (4 ng/kg) for 5 consecutive days. The LPS+TGP and LPS+DEX groups were given 50 mg·kg^-1·d^-1 TGP and 5 mg·kg^-1·d^-1 DEX by gavage, respectively. The changes in body weight of the mice in each group were observed and recorded. Lung tissue was taken for hematoxylin-eosin (HE) staining to observe lung pathological damage. Flow cytometry was used to detect the changes in the proportions of dendritic cells (DC), neutrophils, and macrophages in peripheral blood, spleen, and lung tissues, as well as the proportions of M1 and M2 macrophages in lung tissues. Enzyme linked immunosorbent assay (ELISA) was used to analyze the levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression levels of IL-1β, IL-6 and tumor necrosis factor-α (TNF-α) in lung tissue. Western blotting was used to detect the nuclear transcription factor-κB p65 (NF-κB p65) and phospho-NF-κB p65 (pNF-κB p65) protein content. Results  TGP and DEX significantly improved the weight loss caused by LPS. HE staining showed that the lung tissue of mice in the LPS group had inflammatory cell infiltration, alveolar septal destruction, and alveolar interstitial thickening, which were mitigated in the LPS+TGP and LPS+DEX groups. The results of flow cytometry of peripheral blood showed that, compared with the LPS group, the proportion of neutrophils in the LPS+TGP and LPS+DEX groups was significantly decreased, while the proportions of DC and macrophages did not change significantly. The results of flow cytometry of spleen tissues showed that, compared with the LPS group, the proportions of neutrophils, DC, and macrophages in the LPS+TGP and LPS+DEX groups were significantly decreased. The results of flow cytometry of lung tissues showed that, compared with the LPS group, the proportion of macrophages in the LPS+TGP and LPS+DEX groups did not change significantly, the proportion of M1 cells decreased significantly, the proportion of M2 macrophages increased, and the proportion of neutrophil is down. ELISA results showed that, compared with the LPS group, the levels of IL-6 and IL-1β in bronchoalveolar lavage fluid were significantly decreased； RT-qPCR results showed that, compared with the LPS group, the expression levels of IL-1β, IL-6 and TNF-α mRNA in lung tissues of the LPS+TGP and LPS+DEX groups were significantly reduced. Western blotting results showed that, the protein expression of NF-κB p65 did not change significantly in the LPS+TGP and LPS+DEX groups compared with the LPS group, and the protein content of pNF-κB p65 was significantly decreased. Conclusion  TGP can improve LPS-induced acute lung injury, which may be related to the reduction of the proportion of peripheral blood neutrophils, lung neutrophils and spleen inflammatory cells, the inhibition of M1 polarization of lung macrophages, the inhibition of NF-κB activation, and the reduction of inflammatory signaling pathway and inflammatory factor release. 

Objective  To analyze differentially expressed proteins in cardiomyocytes after chromatin assembly factor 1 subunit B (CHAF1B) gene knockdown and predict the regulatory network, so as to provide reference for finding the potential therapeutic targets which can promote myocardial cell repair. Methods  Cell transfection and Western blotting methods were used to screen effective small interfering RNA (siRNA). Effective siRNA was used to knock down CHAF1B in human cardiac AC16 cells and then cell viability was detected by cell counting kit-8 method. The total protein was extracted, quantified, reduced, alkylated and then cleaved into peptides by trypsin. The peptides were identified by liquid chromatography with tandem mass spectrometry method. Differentially expressed proteins were identified by searching UniProt protein resource. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction networks (PPI) analysis were conducted. Results  The survival of cardiomyocytes was significantly inhibited after CHAF1B gene knockdown by effective siRNA; the identification results of label-free protein quantitative mass spectrometry showed that there were 69 differentially expressed proteins, of which 50 proteins were significantly up-regulated (fold change≥2，P＜0.05) and 19 were significantly down regulated (fold change≤0.5，P＜0.05). GO analysis showed that these proteins mainly participated in biological processes such as macromolecular composite subunit matrix, cell component biogenesis and assembly, mainly distributed in the cytoplasm, vesicles and other regions, and played molecular functions such as protein binding. KEGG pathway enrichment and PPI analysis showed that the differentially expressed proteins participated in 10 signaling pathways such as proteasome, aminoacyl tRNA biosynthesis, endocytosis, pyrimidine metabolism, and amino acid biosynthesis, etc. The significantly up-regulated proteins such as proteasome subunit alpha type-2 and beta type-7 as well as 26S proteasome regulatory subunit 6B and 10B participated in the proteasome pathway; seryl-tRNA synthetase, glycine-tRNA synthetase, glutamine-tRNA synthetase and lysine-tRNA synthetase mediated aminoacyl tRNA biosynthesis. The significantly down regulated proteins, including actin-related protein 2/3 complex subunit 3 and heat shock 70 000 protein 1-like, participated in endocytosis; ribonucleoside-diphosphate reductase large subunit mediated pyrimidine metabolism. The real time quantitative polymerase chain reaction results confirmed that after transfection with CHAF1B siRNA, the mRNA levels of the gene ARPC3, which synthesized the skeletal related protein 2/3 complex subunit 3, and the key gene QARS1 for aminoacyl tRNA biosynthesis, were significantly reduced in cardiomyocytes. Conclusion  CHAF1B is a key protein for the survival of cardiomyocytes and participates in the regulation of various biological processes in cardiomyocytes. Referring to its regulatory network can help identify intervention steps that promote myocardial cell repair.

Objective  To identify potential diagnostic markers for moderate or severe endometriosis（EM）.Methods  Two publicly available gene expression profiles (GSE51981 and GSE7305 datasets) from human EM and control samples were downloaded from the GEO database. Differentially expressed genes (DEGs) were screened between 48 moderate or severe EM and 71 control samples. The Least absolute shrinkage and selection operator (LASSO) regression model and support vector machine recursive feature elimination (SVM-RFE) analysis were performed to identify candidate biomarkers. The area under the receiver operating characteristic  (AUC)  curve value was obtained and used to evaluate discriminatory ability. The expression level and diagnostic value of the biomarkers in EM were further validated in the GSE7305 dataset. The compositional patterns of the 22 types of immune cell fraction in EM were estimated based on the merged cohorts by using CIBERSORT. Results  A total of 73 DEGs were identified between samples with moderate-to-severe EM and normal controls. These DEGs were significantly enriched in malignant tumors and immune-related pathways. Thirteen candidate gene biomarkers were further screened  by using two machine learning methods, LASSO regression model and SVM-RFE analysis. Among them, the ADAT1 gene showed high diagnostic value for moderate-to-severe EM, which was validated in the validation dataset. Immune infiltration analysis showed that the levels of plasma cells and T cells follicular helper  were significantly higher in moderate-to-severe EM than those in the normal group. The diagnostic marker gene ADAT1 was positively correlated with activated dendritic cells, T cells gamma delta, T cells CD4 memory activated, eosinophils, neutrophils, and B cells naive. In contrast, ADAT1 was negatively correlated with plasma cells, T cells CD8, T cells regulatory and monocytes.Conclusion  ADAT1 may be a diagnostic biomarker for moderate-to-severe EM, providing new insights into the occurrence, progression, and molecular mechanisms of EM.

Objective  To deepen the understanding of acute cerebral infarction with the onset of isolated vertigo. Methods  We retrospectively analyzed the patients with the onset of isolated vertigo that were previously treated in Department of Neurology,  China Civil Aviation General Hospital. They were divided into acute cerebral infarction group(25 cases in the case group) and non-acute cerebral infarction group(25 cases in the control group). The demographic characteristics, risk factors of cerebrovascular disease and imaging characteristics were analyzed. Results  In the case group, the proportions of males and the patients who were over 55 years old were significantly higher than those of control group  (72% vs  44% and 80% vs  52%, respectively, P<0.05 ). The proportions of patients with hypertension and diabetes in the case group were higher than those in the control group(72% vs  56%, 52% vs  40%, respectively), and the proportion of patients with hyperlipidemia was lower than those in the control group (84% vs 96%). There was no significant difference between the two groups(P＞0.05). The proportions of clinical manifestations with nausea, vomiting, hearing loss and nystagmus in the case group were higher than those in the control group (68% vs  56%, 52% vs  40%, 16% vs  4%, and 24% vs  16%, respectively), while the proportion of tinnitus was lower than that in the control group (8% vs 16%). There was no significant difference between the two groups (P >0.05). In the case group, there were 18 cases（72%） of cerebellar infarction, 5 cases（20%） of brainstem infarction, 1 case（4%） of occipital lobe infarction and 1 case（4%） of hippocampus infarction. Conclusion  Among patients with acute cerebral infarction who started with isolated vertigo，Men had a significantly higher risk of acute cerebral infarction than women, and patients over 55 years old had a significantly higher risk than the adult patients under 55 years old. 2.Head magnetic resonance imaging showed most of the infarction sites were in the blood supply area of the vertebrobasilar artery system: located mainly in the cerebellum and brainstem.

Objective  To explore the effect of tumor reduction surgery on the prognosis of upper urinary tract urothelial cancer patients with distant metastasis. Methods  The clinical data of upper urinary tract urothelial cancer patients with distant metastasis were screened in SEER database from January 2010 to December 2015. According to whether tumor reduction surgery was performed or not, the patients were divided into two groups： tumor reduction operation group and non-tumor reduction operation group. Univariate and multivariate Cox proportional hazard regression models were used to analyze the prognostic factors related to the survival of upper urinary tract urothelial cancer patients with distant metastasis. The survival curve was drawn by Kaplan-Meier method to analyze the survival condition of each group. Results  A total of 238 patients were included in this study, 157 patients underwent tumor reduction surgery and 81 patients did not. The overall baseline was relatively stable. Cox univariate analysis showed that tumor reduction surgery, chemotherapy, liver metastasis were independent risk factors for overall survival（ OS）, while tumor reduction surgery and chemotherapy were independent risk factors for cancer special survival（CSS）. Kaplan-Meier curve showed that tumor reduction surgery, chemotherapy and liver metastasis were closely related to OS, while tumor reduction surgery, chemotherapy and liver metastasis were closely related to CSS. Conclusion  For patients with upper urinary tract urothelial carcinoma with distant metastasis, tumor reduction surgery can significantly improve the prognosis. Tumor reduction surgery, chemotherapy, and liver metastasis are independent factors affecting the overall survival outcome. Tumor reduction surgery and chemotherapy are independent factors affecting the cancer special survival outcome.

Objective  Subarachnoid hemorrhage is a severe disease with high mortality and disability rate. The aim of this study is to develop a model to predict the in-hospital mortality of subarachnoid hemorrhage. Methods  Seven hundred and ninty-seven patients with subarachnoid hemorrhage are extracted from 10 hospitals affiliated to Peking University during a 5-year period (2014-2018). A univariate Logistic regression and a multivariate Logistic regression are used to find the predictive factors for subarachnoid hemorrhage. A nomogram was constructed to predict the mortality. Results  Of the included patients, the mortality rate is 7.53%. The predictors are aneurysm, heart disease, brain herniation, intracerebral hematoma, coma, pulmonary infection, respiratory failure and pneumonia (P<0.05). The area under the curve of the nomogram is 0.860 (95%CI：0.809-0.911). Conclusion  An accurate nomogram is developed to predict the in-hospital mortality of patients with subarachnoid hemorrhage. It will help reduce the mortality rates.

Objective  To predict the 7-year risk of hypertension among people who underwent physical examination in functional units in Beijing, and to provide foundation data for prevention of hypertension. Methods  A total of 29 209 people in health management cohort in Beijing in 2020 were selected as research subjects. Based on the information of hypertension incidence, demography, behavior habits and blood index from 2014 to 2020, we use monofactor analysis to choose the risk factors, and establish the risk assessment model for hypertension by Logistic regression, then draw the receiver operating characteristic (ROC) curve to verify the predictive ability of the model. Results  The number of new cases of  hypertension in 7 years were 2 346, the incidence of hypertension was 8.03%; the variables were used to establish a Logistic regression model, and the final model included six variables including parental history of hypertension, body mass index, gender, marriage, exercise intensity and milk drinking frequency. The area under the ROC curve was 0.736. Conclusion  The 7-year risk of hypertension is higher in functional unit population in Beijing, and parental history of hypertension, body mass index (BMI), gender, marriage, exercise intensity and milk drinking frequency are the risk factors for hypertension. Based on this, the risk assessment and prediction model is constructed. 

The severity classification of post-cardiotomy cardiogenic shock is important for developing a rational treatment plan and predicting prognosis. The aim of this article is to explore the definition, etiology, pathophysiology, and general management of post-cardiotomy cardiogenic shock, to provide a review of traditional hemodynamic classification and shock management, and to discuss the current state of research on severity classification and shock management.