eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Objective:To investigate the clinicopathological characteristics and prognostic factors of different histological subtypes of intrahepatic cholangiocarcinoma (ICC).Methods:The retrospective cohort study was conducted. The clincopathological data of 171 patients with ICC who underwent initial curative resection in Peking University People′s Hospital from January 2015 to December 2023 were collected. There were 94 males and 77 females, aged 60(range, 53-68)years. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were expressed as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi‐square test or Fisher exact probability. The Kaplan‐Meier method was used to draw survival curve and calculate survival rates, and the Log-rank test was used for survival analysis. The COX stepwise regression model was used for univariate and multivariate analyses. Results:(1) Comparison of clinicopathological characteristics of different histological subtypes of ICC. Results of postoperative histopathological examination showed that of the 171 ICC patients, there were 76 cases of large duct type ICC and 95 cases of small duct type ICC. There was a significant difference in cases with concomitant intrahepatic biliary stone between patients with different histological subtypes of ICC ( P<0.05), and there were significant differences in cases with concomitant viral hepatitis, cases with CA19-9 >39 U/mL versus CA19-9 ≤39 U/mL, cases with CA19-9 >1 000 U/mL versus CA19-9 >39-1 000 U/mL, tumor gross morphology, and tumor peri-neural invasion between patients with different histological subtypes of ICC ( χ2=8.906, 18.208, 5.689, 43.886, 6.178, P<0.05). (2) Prognostic analysis of different histological subtypes of ICC. Of the 171 patients, 130 cases were followed up for 22(range, 16-43)months, including 63 cases of large duct type ICC and 67 cases of small duct type ICC. The 5-year overall survival rates of the 63 cases of large duct type ICC and 67 cases of small duct type ICC were 12.60% and 43.70%, respectively, showing a significant difference between them ( χ2=5.799, P<0.05). (3) Analysis of prognostic factors for patients undergoing radical resection of ICC. Results of multivariate analysis showed that tumor perineural invasion and lymph node metastasis were independent risk factors affecting overall survival rates of patients undergoing radical resection of ICC ( hazard ratio=0.447, 0.383, 95% confidence interval as 0.259-0.771, 0.225-0.651, P<0.05). Conclusions:There are differences in both clinicopatholo-gical characteristics and prognosis between patients with large duct type ICC and small duct type ICC. Tumor perineural invasion and lymph node metastasis are independent risk factors affecting overall survival rates of patients undergoing radical resection of ICC.

Objective:To investigate the clinicopathological characteristics and prognostic factors of different histological subtypes of intrahepatic cholangiocarcinoma (ICC).Methods:The retrospective cohort study was conducted. The clincopathological data of 171 patients with ICC who underwent initial curative resection in Peking University People′s Hospital from January 2015 to December 2023 were collected. There were 94 males and 77 females, aged 60(range, 53-68)years. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were expressed as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi‐square test or Fisher exact probability. The Kaplan‐Meier method was used to draw survival curve and calculate survival rates, and the Log-rank test was used for survival analysis. The COX stepwise regression model was used for univariate and multivariate analyses. Results:(1) Comparison of clinicopathological characteristics of different histological subtypes of ICC. Results of postoperative histopathological examination showed that of the 171 ICC patients, there were 76 cases of large duct type ICC and 95 cases of small duct type ICC. There was a significant difference in cases with concomitant intrahepatic biliary stone between patients with different histological subtypes of ICC ( P<0.05), and there were significant differences in cases with concomitant viral hepatitis, cases with CA19-9 >39 U/mL versus CA19-9 ≤39 U/mL, cases with CA19-9 >1 000 U/mL versus CA19-9 >39-1 000 U/mL, tumor gross morphology, and tumor peri-neural invasion between patients with different histological subtypes of ICC ( χ2=8.906, 18.208, 5.689, 43.886, 6.178, P<0.05). (2) Prognostic analysis of different histological subtypes of ICC. Of the 171 patients, 130 cases were followed up for 22(range, 16-43)months, including 63 cases of large duct type ICC and 67 cases of small duct type ICC. The 5-year overall survival rates of the 63 cases of large duct type ICC and 67 cases of small duct type ICC were 12.60% and 43.70%, respectively, showing a significant difference between them ( χ2=5.799, P<0.05). (3) Analysis of prognostic factors for patients undergoing radical resection of ICC. Results of multivariate analysis showed that tumor perineural invasion and lymph node metastasis were independent risk factors affecting overall survival rates of patients undergoing radical resection of ICC ( hazard ratio=0.447, 0.383, 95% confidence interval as 0.259-0.771, 0.225-0.651, P<0.05). Conclusions:There are differences in both clinicopatholo-gical characteristics and prognosis between patients with large duct type ICC and small duct type ICC. Tumor perineural invasion and lymph node metastasis are independent risk factors affecting overall survival rates of patients undergoing radical resection of ICC.

OBJECTIVE: To develop and validate a mechanical power (MP)-oriented nomogram prediction model of weaning failure in mechanically ventilated patients. METHODS: Patients who underwent invasive mechanical ventilation (IMV) for more than 24 hours and were weaned using a T-tube ventilation strategy were collected from the Medical Information Mart for Intensive Care-IV v1.0 (MIMIC-IV v1.0) database. Demographic information and comorbidities, respiratory mechanics parameters 4 hours before the first spontaneous breathing trial (SBT), laboratory parameters preceding the SBT, vital signs and blood gas analysis during SBT, length of intensive care unit (ICU) stay and IMV duration were collected and all eligible patients were enrolled into the model group. Lasso method was used to screen the risk factors affecting weaning outcomes, which were included in the multivariate Logistic regression analysis. R software was used to construct the nomogram prediction model and build the dynamic web page nomogram. The discrimination and accuracy of the nomogram were assessed by receiver operator characteristic curve (ROC curve) and calibration curves, and the clinical validity was assessed by decision curve analysis (DCA). The data of patients undergoing mechanical ventilation hospitalized in ICU of the First People's Hospital of Lianyungang City and the Second People's Hospital of Lianyungang City from November 2021 to October 2022 were prospectively collected to externally validate the model. RESULTS: A total of 3 695 mechanically ventilated patients were included in the model group, and the weaning failure rate was 38.5% (1 421/3 695). Lasso regression analysis finally screened out six variables, including positive end-expiratory pressure (PEEP), MP, dynamic lung compliance (Cdyn), inspired oxygen concentration (FiO₂), length of ICU stay and IMV duration, with coefficients of 0.144, 0.047, -0.032, 0.027, 0.090 and 0.098, respectively. Logistic regression analysis showed that the six variables were all independent risk factors for predicting weaning failure risk [odds ratio (OR) and 95% confidence interval (95%CI) were 1.155 (1.111-1.200), 1.048 (1.031-1.066), 0.968 (0.963-0.974), 1.028 (1.017-1.038), 1.095 (1.076-1.113), and 1.103 (1.070-1.137), all P < 0.01]. The MP-oriented nomogram prediction model of weaning failure in mechanically ventilated patients showed accurate discrimination both in the model group and external validation group, with area under the ROC curve (AUC) and 95%CI of 0.832 (0.819-0.845) and 0.879 (0.833-0.925), respectively. Furthermore, its predictive accuracy was significantly higher than that of individual indicators such as MP, Cdyn, and PEEP. Calibration curves showed good correlation between predicted and observed outcomes. DCA indicated that the nomogram model had high net benefits, and was clinically beneficial. CONCLUSIONS The MP-oriented nomogram prediction model of weaning failure accurately predicts the risk of weaning failure in mechanical ventilation patients and provides valuable information for clinicians making decisions on weaning.
Humans ; Respiration, Artificial/methods* ; Ventilator Weaning/methods* ; Nomograms ; Lung ; Risk Factors

Objective:To analyze the differentially expressed gene (DEG) in rats with sepsis-induced exogenous acute respiratory distress syndrome (ARDS) and explore the early diagnosis and protective mechanism of sepsis-induced ARDS at the transcriptome level.Methods:Twelve 6 to 8 weeks old male Sprague-Dawley (SD) rats were randomly divided into lipopolysaccharide (LPS) induced sepsis-induced ARDS model group (model group, intraperitoneal injection of LPS 15 mg/kg) and control group (intraperitoneal injection of the same volume of normal saline), with 6 rats in each group. RNA was extracted from the left lung tissue of the two groups, and the paired-end sequencing mode of the illumina Hiseq sequencing platform was used for high-throughput sequencing. The DESeq2 software was used to screen DEG with | log 2 (fold change, FC) | ≥ 3 and P < 0.001. Gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on DEG. STRING and CytoScape software were used to construct a protein-protein interaction (PPI) network and screen key genes. The peripheral blood mononuclear cell (PBMC) of 20 septic patients admitted to the emergency and critical care medical department of Lianyungang First People's Hospital from March to November 2021 and 20 age-matched healthy people in the same period were isolated and extracted, and the key genes were verified by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Results:A total of 286 DEG were screened, including 202 up-regulated genes and 84 down-regulated genes. GO enrichment analysis showed that DEG was mainly involved in biological processes such as neutrophil chemotaxis migration, antibacterial humoral response, host immune response, and humoral immune response. KEGG analysis showed that DEG mainly played a biological role through interleukin-17 (IL-17) signaling pathway, tumor necrosis factor (TNF) signaling pathway, and chemokine signaling pathway. In PPI analysis, a total of 262 node proteins were screened, and the interaction relationship was 852 edges. The first 15 key genes were IL-6, TNF, IL-10, IL-1β, chemokine ligand 1 (CXCL1), CXCL10, chemokine receptor 3 (CXCR3), CXCR2, CXCL9, chemokine ligand 7 (CCL7), CXCL11, CCL1, CXCL13, CCL12, and CCL22. Five representative key genes were performed on PBMC of blood samples from septic ARDS patients and healthy controls by RT-qPCR. The results showed that their expression was significantly higher than that in the healthy controls [IL-6 mRNA (2 -ΔΔCt): 2.803±1.081 vs. 0.951±0.359, TNF mRNA (2 -ΔΔCt): 2.376±0.799 vs. 1.150±0.504, CXCL10 mRNA (2 -ΔΔCt): 2.500±0.815 vs. 1.107±0.515, CXCR3 mRNA (2 -ΔΔCt): 1.655±0.628 vs. 0.720±0.388, CCL22 mRNA (2 -ΔΔCt): 1.804±0.878 vs. 1.010±0.850, all P < 0.05], and the trends were consistent with the RNA-Seq results. Conclusion:Biological processes such as chemotactic migration and degranulation of inflammatory cells, cytokine immune response, and signal pathways such as CXCL10/CXCR3 and IL-17 play important roles in the occurrence and development of sepsis-related exogenous ARDS, which would provide new ideas and targets for further study of lung injury mechanisms and clinical prevention and treatment.

Objective:To explore the diagnosis process and treatment experience of severe coronavirus disease 2019 (COVID-19) patients with heparin resistance (HR).Methods:The medical team of the First People's Hospital of Lianyungang admitted 2 severe COVID-19 patients with HR in intensive care unit (ICU) during their support to the designated hospital for the treatment of COVID-19 patients in Lianyungang City in November 2021. The clinical features, laboratory examinations, imaging features, treatment and prognosis of the two patients were analyzed.Results:Both severe COVID-19 patients received mechanical ventilation, 1 patient was treated with extracorporeal membrane oxygenation (ECMO) support. Both patients were complicated with lower extremity deep venous thrombosis and HR phenomenon under routine dose anticoagulant therapy. The maximum daily dose of unfractionated heparin exceeded 35 000 U (up to 43 200 U), the 2 patients failed to meet the standard of anticoagulation treatment, and the course of disease was prolonged. After that, argatroban was given 0.4 μg·kg -1·min -1 combined with anticoagulant therapy, the activated partial thromboplastin time (APTT) of patients undergoing ECMO could be maintained at 55-60 seconds and the activated coagulation time (ACT) of them could be maintained at 180-200 seconds. After ECMO support or later sequential mechanical ventilation, both patients recovered and were discharged, and deep venous thrombosis was also effectively controlled. Conclusion:HR phenomenon often occurs during the treatment of severe COVID-19 patients, the anticoagulation regimen should be adjusted in time, and the anticoagulation effect combined with argatroban is clear.

Objective:To evaluate the clinical efficacy and changes between Dynesys and Posterior lumbar interbody fusion (PLIF) in the treatment of two-level lumbar degenerative disease.Methods:43 consecutive patients with lumbar degenerative disease were treated using the Dynesys or PLIF between June 2010 and June 2012. In all patients, 23patients were implanted Dynesys and other patients for PLIF. The follow-up period was at least 60 months. Used the Visual analogue scale (VAS) and Oswestry disability index (ODI) to evaluate the clinical outcomes. And during the follow-up period, collected the data for the intervertebral height and the range of motion (ROM), for the operation section and the upper adjacent vertebral. MRI and Grading Scale from the University of California at Los Angeles (UCLA) were used to define the change of intervertebral disc signal.Results:The ODI index and VAS score both improved significantly at the final follow-up evaluation ( P<0.05), as compared to the basal line values. And in terms of imaging, there were no significant difference in the vertebral height of the operation section and the upper adjacent vertebral. The range of motion (ROM) for the operative section in the group of PLIF was significantly lower than that in Dynesys group ( P<0.05). And when it comes to the upper adjacent vertebral space, it was higher at the same time ( P<0.05). According to the UCLA Grading Scale, there were 3 cases in the Dynesys group and 11 in the PLIF group had radiological adjacent degeneration, the difference was significant between two groups ( P<0.05). And when it comes to the second intension, there were 3 patients in PLIF groups (TLIF 1; PLIF 2) but only 1 in Dynesys groups. Conclusion:Dynesys and PLIF are both effective for lumbar degenerative disease and show good medium and long-term clinical and radiographic results. But when it comes the risks in developing ASD and the ROM of adjacent segments, Dynesys stabilization can be the better choice.

Objective: To investigate the early clinical efficacy of bone cement modified with mineralized collagen in the treatment of osteoporotic vertebral compression fractures with percutaneous vertebroplasty(PVP). Methods: All 98 cases of sin-gle vertebral osteoporotic compression fracture from June 2017 to August 2018 were studied. Forty-eight cases were treated with bone cement modified with mineralized collagen (modified group) and 50 cases were treated with traditional bone cement (traditional group). The basic clinical information including age, sex and bone mineral density of all patients were analyzed. The injectable time, volume, distribution (bone cement in the vertebra showing a whole mass without interruption or loss is known as type O while bone cement in the vertebra showing two masses with a small amount or none in the middle is known as type H) and leakage of bone cement during operation, visual analogue score(VAS), Oswestry disability index (ODI), height of anterior, middle and posterior columns of injured vertebrae and the incidence of adjacent vertebral fractures were compared between the two groups. Results: There were no significant differences in age, sex, bone mineral density T value and bone ce-ment injection volume between the two groups. VSA score, ODI, anterior and middle column heights were significantly improved on the first day and 6 months after operation (P<0.05), but there was no significant difference between the two groups (P>0.05). In-traoperative cement injectable time was shorter in the traditional group than the modified group,and there was significant different between the two groups (t=3.428, P=0.002). The incidence of adjacent vertebral re-fracture was 12% in the traditional group and 2% in the modified group. There was significant different between the two groups (χ²=7.061, P=0.029). The leakage rate of bone cement was 10% in the traditional group and 6% in the modified group, andthere was significant difference between the two groups (χ²=7.963, P=0.019). The distribution of bone cement (O/H) in the traditional group was 20/30 and that in the modified group was 19/29, and there was significant difference between the two groups (χ²=38.992, P<0.001). Conclusion Modified bone cement has the same clinical effect as traditional bone cement in relieving pain and restoring the height of injured vertebra in the treat-ment of osteoporotic vertebral compression fractures with PVP. However, the injectable time of modified bone cement is longer. The leakage rate and the incidence of re-fracture of adjacent vertebrae are significantly reduced.

Objective To investigate the conventional and functional MRI features of primary central nervous system lymphoma (PCNSL).Methods The conventional MRI,DWI,1H-MRS and PWI data of 21 patients with PCNSL confirmed pathologically were analyzed retrospectively.Results There were 39 lesions in 21 cases.The mean ADC value of the PC-NSL lesions and the contralateral hemisphere normal white matter was (0.78±0.14) × 10 a mm2/s and (0.89 + 0.21) × 10-3 mm2/s,respectively.The difference of ADC value between PCNSL lesions and the contralateral hemisphere normal white matter was statistically significant (t=1.24,P＜0.05).Compared with the normal brain white matter,the PCNSL lesions showed abnormally high Cho/Cr ratio (4.62±2.05 vs 0.83±0.25),high Cho/NAA ratio (6.86±2.36 vs 0.63± 0.34) and low NAA/Cr ratio (0.67±1.73 vs 0.63±.034) on 1H-MRS (all P＜0.05).PCNSL lesions showed relatively low perfusion on PWI.And the cerebral blood volume of PCNSL lesion was lower than that of the surrounding normal brain parenchyma.Conclusion MR DWI,1H-MRS and PWI can reflect the features of PCNSL from different profiles.Combined with routine MRI signs,the accuracy of diagnosis can be further improved.

Objective To investigate the expressions of T cell immunoglobulin and mucin-domain contain-ing moleculesfamily-3(Tim-3)and CD4+ and CD8+ T cells in peripheral blood from patients with coronary heart disease (CHD). Methods 51 CHD patients were divided into two groups:stable angina pectoris group (27 patients)and acute coronary syndromes group(24 patients). Another 25 healthy subjects confirmed by coronary angiography were selected as a control group. Peripheral blood was drawn on admission. Enzyme-linked immunosor-bent assay was used to detect the concentration of Tim-3. Flow cytometry was applied to detect the expressions of CD4+and CD8+. Results As compared with the healthy control group ,the concentration of Tim-3 and the propor-tion of CD8+ in stable angina pectoris group and acute coronary syndrome group were reduced ,and those in acute coronary syndrome group were lower. The differences were statistically significant (P < 0.05). As compared with the healthy control group,the proportion of CD4+ and the ratio of CD4+/CD8+ of stable angina pectoris group and acute coronary syndrome group were increased ,while those in acute coronary syndrome group were higher. The differences were statistically significant(P<0.05). Conclusions At the onset of CHD,the concentration of Tim-3 and the proportion of CD8+ in peripheral blood are reduced ,but the proportion of CD4+ is increased. The more severe the disease,the greater changes the values.