Objective To investigate the therapeutic effects of interleukin 23p19(IL-23p19) monoclonal antibody in the MRL/lpr lupus-like mouse model. Methods A total of 36 female MRL/lpr mice aged 8 weeks were randomly divided into 6 groups: PBS group (blank control), IgG group (isotype IgG), dexamethasone (DEX) group (positive control), and three IL-23p19 monoclonal antibody treatment groups with different dose gradients: low dose (LD, 1 mg/kg), medium dose (MD, 3 mg/kg), and high dose (HD, 10 mg/kg). Drug intervention began at 12 weeks of age via tail vein injection. Urine protein levels were measured using urine protein test strips; serum anti-dsDNA antibody levels were detected by ELISA; serum creatinine and blood urea nitrogen levels were measured using an automatic biochemical analyzer; renal histopathological changes were analyzed by H&E and PAS staining; immunofluorescence was used to assess IgG and C3 immune complex deposition in kidney tissues; flow cytometry was employed to examine the expression of T helper 1(Th1), Th2, Th17, T follicular helper (Tfh), and regulatory T cells(Treg) cell subsets in the spleen; and RT-qPCR was used to detect the expression of related transcription factors in the spleen. Results IL-23p19 monoclonal antibody reduced urine protein levels, alleviated splenomegaly, improved renal function, and decreased anti-dsDNA antibody levels in MRL/lpr mice. It also mitigated glomerulonephritis and reduced renal immune complex deposition. Furthermore, IL-23p19 monoclonal antibody significantly suppressed the proportion of Th1 and Th17 cells while upregulating Treg cell proportion in the spleen. Additionally, it downregulated T-bet and retinoic acid receptor-related orphan receptor γt (RORγt) mRNA levels and upregulated forkhead box P3(FOXP3) mRNA levels in the spleen. Conclusions IL-23p19 monoclonal antibody demonstrates significant therapeutic effects in MRL/lpr mice, likely through modulation of the Th17/Treg cell balance.
Animals ; Female ; Mice, Inbred MRL lpr ; T-Lymphocytes, Regulatory/drug effects* ; Th17 Cells/drug effects* ; Antibodies, Monoclonal/therapeutic use* ; Interleukin-23 Subunit p19/immunology* ; Mice ; Lupus Nephritis/drug therapy* ; Kidney/drug effects* ; Antibodies, Antinuclear/blood*

OBJECTIVE: To investigate the predictive value of oxygenation index (PaO₂/FiO₂) at intensive care unit (ICU) admission on 30-day mortality in patients with sepsis. METHODS: A retrospective study was conducted. Patients with sepsis who were hospitalized in the ICU of the Affiliated Hospital of Jining Medical University from April 2015 to October 2023 were enrolled. The demographic information, comorbidities, sites of infection, vital signs and laboratory test indicators at the time of admission to the ICU, disease severity scores within 24 hours of admission to the ICU, treatment process and prognostic indicators were collected. According to the PaO₂/FiO₂ at ICU admission, patients were divided into Q1 group (PaO₂/FiO₂ of 4.1-16.4 cmHg, 1 cmHg ≈ 1.33 kPa), Q2 group (PaO₂/FiO₂ of 16.5-22.6 cmHg), Q3 group (PaO₂/FiO₂ of 22.7-32.9 cmHg), and Q4 group (PaO₂/FiO₂ of 33.0-94.8 cmHg). Differences in the indicators across the four groups were compared. Multifactorial Cox regression analysis was used to assess the relationship between PaO₂/FiO₂ and 30-day mortality of patients with sepsis. The predictive value of PaO₂/FiO₂, sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) on 30-day prognosis of patients with sepsis was analyzed by receiver operator characteristic curve (ROC curve). RESULTS: A total of 1 711 patients with sepsis were enrolled, including 428 patients in Q1 group, 424 patients in Q2 group, 425 patients in Q3 group, and 434 patients in Q4 group. 622 patients died at 30-day, the overall 30-day mortality was 36.35%. There were statistically significant differences in age, body mass index (BMI), history of smoking, history of alcohol consumption, admission heart rate, respiratory rate, APACHE II score, SOFA score, Glasgow coma score (GCS), site of infection, Combined chronic obstructive pulmonary disease (COPD), blood lactic acid (Lac), prothrombin time (PT), albumin (Alb), total bilirubin (TBil), pH, proportion of mechanical ventilation, duration of mechanical ventilation, proportion of vasoactive medication used, and maximal concentration, length of ICU stay, hospital stay, incidence of acute kidney injury, in-hospital mortality, 30-day mortality among the four groups. Multivariate Cox regression analysis showed that after adjusting for confounding factors, for every 1 cmHg increase in PaO₂/FiO₂ at ICU admission, the 30-day mortality risk decreased by 2% [hazard ratio (HR) = 0.98, 95% confidence interval (95%CI) was 0.98-0.99, P < 0.001]. The 30-day mortality risk in the Q4 group was reduced compared with the Q1 group by 41% (HR = 0.59, 95%CI was 0.46-0.76, P < 0.001). The fitted curve showed that a curvilinear relationship between PaO₂/FiO₂ and 30-day mortality after adjustment for confounders. In the inflection point analysis, for every 1 cmHg increase in PaO₂/FiO₂ at PaO₂/FiO₂ < 28.55 cmHg, the risk of 30-day death in sepsis patients was reduced by 5% (HR = 0.95, 95%CI was 0.94-0.97, P < 0.001); when PaO₂/FiO₂ ≥ 28.55 cmHg, there was no statistically significant association between PaO2/FiO2 and the increase in the risk of 30-day death in sepsis (HR = 1.01, 95%CI was 0.99-1.02, P = 0.512). ROC curve analysis showed that the area under the curve (AUC) for the prediction of 30-day mortality by admission PaO₂/FiO₂ in ICU sepsis patients was 0.650, which was lower than the predictive ability of the SOFA score (AUC = 0.698) and APACHE II score (AUC = 0.723). CONCLUSION In patients with sepsis, PaO₂/FiO₂ at ICU admission is strongly associated with 30-day mortality risk, alerting healthcare professionals to pay attention to patients with low PaO₂/FiO₂ for timely interventions.
Humans ; Sepsis/mortality* ; Intensive Care Units ; Retrospective Studies ; Prognosis ; Hospital Mortality ; Oxygen ; Male ; Predictive Value of Tests ; Female ; Middle Aged ; Aged

Objective:To explore the current situation and influencing factors of quality of life of septic patients in intensive care unit (ICU) after discharge, and to provide theoretical basis for clinical early psychological intervention and continuity of care.Methods:A prospective observational study was conducted. The septic patients who were hospitalized in the department of critical care medicine of the Affiliated Hospital of Jining Medical University and discharged with improvement from January 1 to December 31, 2022 were selected as the research objects. The demographic information, basic diseases, infection site, vital signs at ICU admission, severity scores of the condition within 24 hours after ICU admission, various biochemical indexes, treatment process, and prognostic indexes of all the patients were recorded. All patients were assessed by questionnaire at 3 months of discharge using the 36-item short-form health survey scale (SF-36 scale), the activities of daily living scale (ADL scale), and the Montreal cognitive assessment scale (MoCA scale). Multiple linear regression was used to analyze the factors influencing the quality of life of septic patients after discharge from the hospital.Results:A total of 200 septic patients were discharged with improvement and followed up at 3 months of discharge, of which 150 completed the questionnaire. Of the 150 patients, 57 had sepsis and 93 had septic shock. The total SF-36 scale score of septic patients at 3 months of discharge was 81.4±23.0, and the scores of dimensions were, in descending order, role-emotional (83.4±23.0), mental health (82.9±23.6), bodily pain (82.8±23.3), vitality (81.6±23.2), physical function (81.4±23.5), general health (81.1±23.3), role-physical (79.5±27.0), and social function (78.8±25.2). There was no statistically significant difference in the total SF-36 scale score between the patients with sepsis and septic shock (82.6±22.0 vs. 80.7±23.6, P > 0.05). Incorporating the statistically significant indicators from linear univariate analysis into multiple linear regression analysis, and the results showed that the factors influencing the quality of life of septic patients at 3 months after discharge included ADL scale score at 3 months after discharge [ β= 0.741, 95% confidence interval (95% CI) was 0.606 to 0.791, P < 0.001], length of ICU stay ( β= -0.209, 95% CI was -0.733 to -0.208, P = 0.001), duration of mechanical ventilation ( β= 0.147, 95% CI was 0.122 to 0.978, P = 0.012), total dosage of norepinephrine ( β= -0.111, 95% CI was -0.044 to -0.002, P = 0.028), mean arterial pressure (MAP) at ICU admission ( β= -0.102, 95% CI was -0.203 to -0.007, P = 0.036) and body weight ( β= 0.097, 95% CI was 0.005 to 0.345, P = 0.044). Conclusions:The quality of life of patients with sepsis at 3 months after discharge is at a moderately high level. The influencing factors of the quality of life of patients with sepsis at 3 months after discharge include the ADL scale score at 3 months after discharge, the length of ICU stay, the duration of mechanical ventilation, the total dosage of norepinephrine, MAP at ICU admission and body weight, and healthcare professionals should enhance the treatment and care of the patients during their hospitalization based on the above influencing factors, and pay attention to early psychological intervention and continued care for such patients.

Objective To explore the value of 3D amide proton transfer weighted imaging(APTWI),diffusion weighted imaging(DWI)and the combination for differentiating benign and malignant bone and soft tissue tumors.Methods Non-contrast MRI,APTWI and DWI of pelvis or lower extremity were prospectively acquired in 96 patients with bone and soft tissue tumors.MTRasym and ADC maps were obtained based on APTWI and DWI calculation with an offset of 3.5 ppm,respectively,and the maximum asymmetric magnetization transfer rate(MTRasym)(MTRasymmax),the mean MTRasym(MTRasymmean)and the minimum MTRasym(MTRasymmin),as well as the maximum apparent diffusion coefficient(ADC)(ADCmax),the mean ADC(ADCmean)and the minimum ADC(ADCmin)values were measured.The above parameters were compared between benign and malignant tumors.Then receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of APTWI,DWI and the combination.Results Among 96 patients,there were 41 benign and 55 malignant pelvic or lower limb bone and soft tissue tumors.In benign tumors,MTRasym(3.5 ppm)values,including MTRasymmax.MTRasymmean and MTRasymmin were significantly higher,whereas ADC values including ADCmax,ADCmeanand ADCmin were significantly lower than those in malignant tumors(all P＜0.05).AUC of MTRasymmax and ADCmin for differentiating benign and malignant bone and soft tissue tumors was 0.791 and 0.873,respectively,being not statistically different(P=0.122),but both lower than that of their combination(AUC=0.944,P＜0.001,P=0.041).Conclusion APTWI combined with DWI had high efficacy for differentiating benign and malignant bone and soft tissue tumors.

Objective: To observe whether an Xingnaojing 醒脑静 injection could improve the prognosis of patients, by increasing rifampicin penetration through the blood-brain barrier. Methods: Patients with severe tuberculous meningitis were enrolled in this study. The concentrations of Xingnaojing in cerebrospinal fluid and blood in patients treated with Xingnaojing and control were determined by high performance liquid chromatography. The changes in cerebrospinal fluid and the improvement of clinical symptoms and signs, were evaluated two weeks after admission. The long-term prognosis of the patients in the two groups were evaluated by the Glasgow Outcome Scale (GOS). Results: The concentration of rifampicin in cerebrospinal fluid was significantly higher in the Xingnaojing group (1.77±0.17 μg/mL), than in the control group (1.27±0.16 μg/mL, p<0.05). The difference in concentration of rifampicin in the blood was not significant (P>0.05). The short-term effective rate of the Xingnaojing group was 92.5% (37/40), which was significantly higher than that of the control group (80%, 32/40, p<0.05). After 6 months, 75% (30/40) of the Xingnaojing group had good prognosis according to the GOS score, whereas that of the control group was 50% (20/40) showing significantly better long-term treatment effect of the Xingnaojing group compared to the control group (P<0.05). Conclusion: Xingnaojing injection improved rifampicin penetration into the central nervous system. The increase in rifampicin concentration in cerebrospinal fluid improved outcomes in patients with severe tuberculous meningitis.

Objective:To investigate the correlation between aneurysm wall enhancement (AWE) shown on high-resolution magnetic resonance imaging (HR-MRI) and the risk of intracranial aneurysm rupture risk.Methods:Patients with unruptured intracranial aneurysm admitted to the First Affiliated Hospital of Zhengzhou University from October 2014 to October 2019 were enrolled retrospectively. Three-dimensional digital subtraction angiography was used to measure the morphological parameters of aneurysms. HR-MRI was used to evaluate the enhancement mode. Univariate analysis and multivariate logistic regression analysis were used to determine the independent influencing factors of AWE. The 5-year rupture risk of intracranial aneurysms was assessed based on the PHASES score. Spearman rank correlation analysis was used to determine the correlation between the enhancement mode and the risk of aneurysm rupture. Results:A total of 261 patients and 333 unruptured intracranial saccular aneurysms were included. There were significant differences in the proportion of multiple aneurysms, the size and location of aneurysms between the enhanced group and the non-enhanced group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for confounding factors such as age and gender, multiple aneurysms (odds ratio [ OR] 0.446, 95% confidence interval [ CI] 0.251-0.791; P=0.006), aneurysm size ( OR 1.327, 95% CI 1.218-1.445; P<0.001) and location (anterior cerebral artery/posterior communication artery/posterior circulation: OR 2.058, 95% CI 1.217-3.482; P=0.007) were significantly independently related to AWE. Based on the PHASES score, the 5-year predicted rupture risk of the enhanced group was significantly higher than that of the non-enhanced group (5.2%±6.2% vs. 1.5%±2.0%; P<0.001). Spearman rank correlation analysis showed that there was a significant positive correlation between the extent of aneurysm enhancement and the risk of aneurysm rupture ( r=0.435, P<0.001). Conclusions:AWE shown on HR-MRI is associated with multiple aneurysms, aneurysm size, and location. Application of AWE might predict the risk of rupture of intracranial aneurysms.

Objective: To investigate the levels of serum piR-015151 in patients with brucellosis and evaluate its clinical value in the auxiliary diagnosis of brucellosis. Methods: Serum samples and clinical data from 73 brucellosis patients diagnosed in the Affiliated Hospital of Inner Mongolia Medical University or Zhungeer Qi Center for Disease Control and Prevention and 65 age- and gender-matched healthy controls in the Eastern Theater General Hospital of PLA during 2016 and 2017 were collected. Serum piR-015151 levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic value of serum piR-01515 in brucellosis was evaluated by the receiver operating characteristic (ROC) curve. Results: Serum piR-015151 levels (median \[P25, P75\]) in brucellosis patients (0.216 \[0.069, 0.426\]) were significantly higher than that in healthy controls (0.036 \[0.021, 0.070\], U=834.5,P＜0.01). The area under the ROC curve (AUCROC), sensitivity and specificity of serum piR-015151 in the diagnosis of brucellosis were 0.824 (95% CI: 0.751-0.897), 75.3% and 76.9%, respectively. Conclusion Serum piR-015151 levels in brucellosis patients increase significantly, which may be a potential marker in the auxiliary diagnosis of brucellosis.

Objective To investigate the value of ADC histogram in the differential diagnosis of angiomatous meningioma (AM) and hemangiopericytoma (HPC)and to screen out the best diagnostic parameter.Methods The MRI data of 21 cases with AM and 22 cases with HPC confirmed by surgical pathology were analyzed retrospectively.The ROI were drawn on the maximum cross section of the tumor on ADC maps,and the ADC histogram analysis was performed using the software named Mazda.Then the histogram parameters were statistically analyzed to find out the statistically significant parameters between the two groups,and the ROC curve was drawn to evaluate their diagnostic efficacy.Results ADCvariance ,ADC1th and ADC10th had statistical significances between the two groups (P＝0.030,0.002 and 0.02 1 ). ADC1th had the best diagnostic efficacy among them,with the optimal cut-off value of 0.086×10－3 mm2/s,the AUC was 0.814(P＝0.003),and the sensitivity and specificity were 86.70%and 64.70%,respectively.ADCvariance took the second place,for the AUC was 0.725 (P＝0.030),and the sensitivity and specificity were 7 6.50%and 80.00%,respectively.Conclusion The ADC histogram is of great value in the differential diagnosis of AM and HPC,and the ADC1th is the most effective parameter.

Objective: To recognize the efficacy and safety of paritaprevir/ritonavir-ombitasvir combined with dasabuvir (OBV/PTV/RTV+DSV) in the treatment of genotype 1b chronic hepatitis C. Methods: Patients with genotype 1b chronic hepatitis C who were admitted to the People's Hospital of Henan Province, Huashan Hospital of Shanghai and the Fifth Medical Center of the General Hospital of the People's Liberation Army of China between November 2017 to August 2018 were enlisted. All patients received OBV/PTV/RTV+DSV antiviral therapy. HCV RNA levels were measured at baseline, weeks 1, 2, 3, 4, 8, 12, and 24, then 12 weeks, and 24 weeks after completion of treatment; patients’ comorbidity, concomitant medications, and clinical adverse events were recorded. Results: 108 patients were enrolled in the study, with an average age of 49.1 years, 44 patients were male (40.8%), 96.3% (104/108) were newly diagnosed, and four patients had previous treatment history, of whom three were treated with IFN and one with IFN + DAA. Ninety-eight cases completed 12 weeks treatment and 89 cases were in follow up for 12 weeks, after discontinuation of the drug. Overall, 89 cases (100%) achieved SVR12.One patient treated with PR and DAA had HCV RNA level of 869175 IU/mL at 4 weeks of treatment, which was significantly higher than the baseline HCV RNA level (301776IU/ML), and was judged as failure of treatment; and follow-up was discontinued. Of all enrolled patients, 19 (17.6%) had underlying diseases and 15 (13.9%) had combined medications. During treatment, adverse events (AE) occurred in 11 patients (10.1%). The main adverse events were pruritus and elevated bilirubin. Conclusion Combined antiviral therapy (OBV/PTV/RTV+DSV) of 12 weeks are highly effective with good safety profile in the treatment of Chinese patients with genotype 1b chronic hepatitis C.

Objective To explore the application value of different dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) models in pathological grading of breast invasive ductal carcinoma.Methods Forty-five cases of breast invasive ductal carcinoma confirmed by clinical pathology from June 2016 to October 2017 in Shanxi Provincial People's Hospital were enrolled in this study.Grade 1 and 2 invasive ductal carcinomas were classified into the low-grade group,grade 3 invasive ductal carcinomas was classified as the high-grade group.The whole patients underwent DCE-MRI scans.Volume transport constant (Ktrans) was obtained by using the Extended Tofts Linear model with population arterial input function (AIF).Then,the Reference Region model was used to obtain the reference region model volume transport constant(RRKtrans).The performances of histogram analysis of these two quantitative parameters in pathological grading of breast invasive ductal carcinoma were compared.Results The mean,25 ％,50 ％,75 ％,90 ％ percentiles,kurtosis and skewness of RRKtrans in high grade group were (0.793±0.258)/min,(0.484±0.209)/min,(0.773±0.277)/min,(1.066±0.351)/min,(1.322±0.406)/min,2.647 (1.426,3.679),0.398 (0.297,0.514) respectively,and the corresponding parameters in low grade group were (0.506±0.203)/min,(0.301 ±0.142)/min,(0.487 ±0.211)/min,(0.692±0.281)/min,(0.861±0.323)/min,1.725 (0.779,2.316),0.258 (0.133,0.302) respectively.There were significant differences between the two groups (all P ＜ 0.05).The mean,50 ％,75 ％,90 ％percentiles of Ktrans in high grade groups were (0.099±0.034)/min,(0.110±0.033)/min,(0.132±0.045)/min,(0.140±0.047)/min respectively,and the corresponding parameters in low grade group were (0.067±0.030)/min,(0.082 ±0.067)/min,(0.096 ±0.059)/min,(0.113 ±0.074)/min respectively.There were significant differences between the two groups (all P ＜ 0.05).RRKtrans was superior to Ktrans in distinguishing area under the curve (AUC) of receiver operating characteristic curve (ROC) of high and low grading of breast invasive ductal carcinoma.Conclusion RRKtrans obtained by Reference Region model and Ktrans obtained by Population AIF DCE-MRI have some values in pathological grading of breast invasive ductal carcinoma,but the performance of RRKtrans is superior to Kftrans.