Objective:This study aimed to explore the performance of renal resistive index (RRI), semiquantitative power Doppler ultrasound (PDU) score, and renal venous Doppler waveform (RVDW) pattern in predicting 28-day renal dysfunction in critically ill patients and establish nomogram model.Methods:This was a prospective, observational study. Critically ill patients admitted to the emergency intensive care unit (ICU) of Cangzhou Central Hospital from January 2018 to October 2022 were included. Patients underwent renal ultrasound examination to obtain RRI, PDU score and RVDW pattern within 24 h after ICU admission. The following clinical variables were collected during the renal ultrasound examination session, including heart rate, mean arterial pressure, type and dose of vasoactive drugs, oxygen therapy parameters, and average urine volume per hour derived from a period of 6 h prior to the ultrasound examination. The data on duration of AKI and mortality were recorded on the 28th day of follow-up. Patients were divided into 28-day normal renal function group and 28-day renal dysfunction group according to 28-day renal dysfunction. 28-days of renal dysfunction was defined as failure to achieve renal function recovery within 28 days of ICU admission. The difference of each index between the two groups was compared. Associated factors for 28-day renal dysfunction were determined by univariate and multivariate COX regression analyses. A nomogram was developed based on the independently factors associated with 28-day renal dysfunction. Survival receiver operator characteristic (ROC) curves were plotted to assess diagnostic performance in predicting 28-day renal dysfunction. Delong’s test was used to compare area under the curves (AUC) between each predictor.Results:187 patients were enrolled for the final analysis: 97 with no AKI, 48 with AKI stage 1, 24 with AKI stage 2, and 18 with AKI stage 3 upon enrollment. At 28-day follow up, 16 patients had renal dysfunction and 2 required continuous renal replacement therapy (CRRT). The multivariate COX regression showed that RVDW and SCr upon enrollment were the independent risk predictors. Nomogram based on RVDW and SCr upon enrollment showed the best performance in predicting 14-day renal dysfunction (AUC = 0.918, 95% CI:0.871-0.964, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05). Nomogram also showed the best performance in predicting 28-day renal dysfunction (AUC = 0.924, 95% CI:0.865-0.983, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05) except for SCr upon enrollment. The optimal cutoff for nomogram in predicting 28-day renal dysfunction was ≤89.5 (sensitivity, 81.2%; specificity, 90.6%; Youden index, 0.719). Kaplan-Meier analysis showed that the median duration of renal dysfunction in the groups with total nomogram score >85.9 and ≤85.9 was 0 and 22 days (HR=0.220, 95% CI:0.129-0.376, P<0.001). Conclusions:SCr and RVDW pattern within 24 h from ICU admission were independent factors associated with 28-day renal dysfunction in critically ill patients. The value of the nomogram model based on these two factors in predicting 28-day renal dysfunction is superior to each single intrarenal Doppler spectrum indicator and clinical indicator.

OBJECTIVE To investigate the protective effects and potential mechanism of penehyclidine hydrochloride （PHC） on myocardial ischemia-reperfusion （I/R） injury in mice through the macrophage migration inhibitory factor （MIF）/adenosine monophosphate-activated protein kinase （AMPK） signaling pathways. METHODS Male C57BL/6 mice were randomly divided into sham operation group， I/R group， I/R+PHC group （PHC 20 μg/kg）， I/R+ISO-1 group （MIF inhibitor 35 mg/kg）， I/R+ PHC+ISO-1 group （with the same dosage as each single drug group）， with 8 mice in each group. Except for the sham operation group， the myocardial I/R injury model was prepared by coronary artery ligation. Thirty minutes before ligation， mice in each drug group were injected with 1 mL of the corresponding drug solution through the tail vein. After 120 min of reperfusion， the levels of cardiac function indexes [heart rate， stroke volume， ejection fraction， cardiac output， left ventricular posterior wall thickness in systole （LVPWs）， left ventricular posterior wall thickness in diastole （LVPWd）]， serum inflammatory factors [interleukin-6 （IL- 6）， IL-10， tumor necrosis factor-α （TNF-α）] in mice were detected in each group； the pathological changes and ultrastructure of myocardial tissue were observed， and the protein expressions of B cell lymphoma-2 （Bcl-2）， phosphorylated AMPKα （p-AMPKα） and MIF in myocardial tissue were detected. RESULTS Compared with the sham operation group， the myocardial cells in the I/R group were loosely arranged， with severe infiltration of inflammatory cells and obvious mitochondrial damage. Serum levels of IL-6 and TNF-α and protein expression of p-AMPKα in myocardial tissue were significantly increased or upregulated， while heart rate， stroke volume， ejection fraction， cardiac output， LVPWd and serum level of IL-10 were significantly decreased （P＜0.05）. Compared with the I/R group， the myocardial tissue lesions in the I/R+PHC group were alleviated； serum levels of IL-6 and TNF-α were decreased significantly， while heart rate， stroke volume， ejection fraction， cardiac output， LVPWs， LVPWd， serum level of IL-10， and protein expressions of Bcl-2， p- AMPKα and MIF in myocardial tissue were significantly increased or upregulated （P＜0.05）. However， myocardial tissue lesions of mice in the I/R+ISO-1 group worsened， with most quantitative indicators significantly deteriorating （P＜0.05）； MIF inhibitor could generally reverse the protective effect of PHC on I/R mice （P＜0.05）. CONCLUSIONS PHC can improve cardiac function， reduce myocardial inflammation， and restore the ultrastructure of myocardial tissue in I/R mice. These effects may be related to the activation of the MIF/AMPK signaling pathway.

Objective To investigate the effect of ursodeoxycholic acid(UDCA)on the symptoms after severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in patients with primary biliary cholangitis(PBC)and their family member.Methods A questionnaire survey was conducted to collect related information from 171 PBC patients who attended The First Affiliated Hospital of Air Force Medical University before March 22,2023 and 128 family members,including demographic information,comorbidities,UDCA administration,SARS-CoV-2 infection,vaccination,symptoms,therapeutic medication,and the changes in liver disease-related symptoms.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups.Results The median age was 51 years in the PBC patients and 49 years in the family members,with no significant difference between the two groups(P>0.05).Compared with the family member group,the PBC group had significantly lower body mass index(22.2±2.4 kg/m2 vs 23.3±2.9 kg/m2,P<0.001)and proportion of male individuals(10%vs 55%,P<0.001).All PBC patients received UDCA at a dose of 13—15 mg/kg,and SARS-CoV-2 infection rate was 100%in both groups.The family members had a significantly higher SARS-CoV-2 vaccination rate than the PBC patients(91%vs 57%,P<0.001).Compared with the family members,the PBC patients had significantly milder symptoms of sneezing,nasal obstruction,chest pain,and abnormal taste(P<0.05).Compared with the family members,the PBC patients had significantly lower rates of use of compound cold medicine(11%vs 20%,P<0.05)and Lianhua Qingwen capsules(12%vs 21%,P<0.05).For the PBC patients after SARS-CoV-2 infection,the liver disease-related symptoms such as fatigue,abdominal distension,dry mouth and dry eyes,pruritus,and yellow skin were aggravated by 37%,2%,27%,10%,and 3%,respectively.Conclusion Compared with the immediate family members of PBC patients who do not take UDCA,the PBC patients receiving UDCA do not show a reduction in SARS-CoV-2 infection rate,but UDCA may have a certain effect on alleviating infection-related symptoms in such patients.PBC patients may still experience the aggravation of liver disease-related symptoms after SARS-CoV-2 infection,and the long-term effect on PBC patients after SARS-CoV-2 infection should be taken seriously in clinical practice.

Objective:To investigate the mechanism of benzyl isothiocyanate(BITC) in the treatment of anaplastic thyroid cancer(ATC).Methods:Using network pharmacological analysis, key targets of BITC and ATC were screened, followed by GO and KEGG enrichment analysis. In order to validate the findings, AutoDock software was used to dock BITC and ATC key targets. BITC was applied to two ATC cell lines(8505C and CAL-62). Flow cytometry was used to analyze cell apoptosis. Autophagy inhibitors hydroxychloroquine sulfate(HCQ) and 3-methyladenine(3MA) were used in combination with BITC. Real-time quantitative PCR was conducted to detect the gene level of LC3B, while Western blotting was utilized to examine the expression of NF-κB, LC3B Ⅱ, Beclin-1, and Bcl-2. In animal experiments, a mouse tumor model was constructed using CAL-62 cells, treated with intraperitoneal injections of BITC(100 mg/kg) and normal saline respectively, administered every other day for a total of 21 days. Immunoblotting of tumor tissue was performed to detect the expression of LC3B Ⅱ, Bcl-2, Beclin-1, and NF-κB.Results:A total of 10 key targets with binding energies≤-4.0 kcal/mol were identified. KEGG analysis showed that these genes are mainly involved in NF-κB signaling pathway and apoptosis. BITC inhibited ATC cells with IC50 values of 27.56 μmol/L for 8505C and 28.30 μmol/L for CAL-62. The expression levels of NF-κB, Beclin-1, and Bcl-2 decreased, while LC3B Ⅱ and LC3B gene expression increased. Combining 3MA with BITC enhanced cell inhibition LC3B Ⅱ expression. HCQ increased LC3B Ⅱ expression without enhancing cell and viability inhibition. In the mouse tumor model, compared to the control group, the treatment group had higher LC3B Ⅱ and lower Bcl-2, Beclin-1, and NF-κB levels.Conclusion:BITC could inhibit the growth of ATC cells in vitro and in vivo, disrupt the autophagy degradation, and inhibit the NF-κB pathway.

Objective:To explore the predictive value of bedside ultrasound monitoring of optic nerve sheath diameter (ONSD) for short-term neurological prognosis in critically ill patients without primary brain injury.Methods:An observational prospective study was conducted to enroll critically ill patients without primary brain injury admitted to the emergency intensive care unit (ICU) of Cangzhou Central Hospital from January 2021 to April 2022. The exclusion criteria were as follows: age < 18, combined ocular and optic nerve pathology or injuries, impaired consciousness due to prior neuropathy, primary brain injury, ICU stay < 3 days, death or loss of follow-up within 28 days. Bedside ultrasound measurements of ONSD were performed within 24 hours of ICU admission and on day 3 of ICU admission. The consciousness status was assessed daily during ICU hospitalization. If the Glasgow Coma Scale (GCS) is 15 and the confusion assessment method intensive care unit (CAM-ICU) is negative, the consciousness status will be defined as nonconsciousness disorder. While if the GCS score is less than 15 or the CAM-ICU is positive, the consciousness status will be defined as consciousness disorder. According to the status of consciousness at 28 days, patients were divided into a nonconscious disorder group and a conscious disorder group, and the difference in each index was compared between the two groups. Univariate and multivariate Cox regression were used to analyze the factors influencing 28-day neurological function prognosis, and a Kaplan?Meier survival curve was plotted to analyze the relationship between ONSD and 28-day neurological function prognosis.Results:Sixty-one critically ill patients without primary brain injury (48 in the nonconscious disorder group and 13 in the conscious disorder group) were recruited. Compared to patients in the unconscious disorder group, those in the conscious disorder group had lower GCS upon ICU admission [7(4, 8) vs. 8(6, 14), P<0.05], longer length of mechanical ventilation (MV) [28(15, 28) days vs. 10(4, 14) days, P<0.001], and longer length of ICU stay [28(28, 28) days vs. 12(7, 20) days, P<0.001]. Patients in the conscious disorder group had a higher ONSD within 24 hours of ICU admission [(5.75±0.53) mm vs. (5.45±0.60) mm, P=0.114] and a higher ONSD 3 days after ICU admission [(5.54±0.64) mm vs. (5.22±0.65) mm, P=0.124] than patients in the unconscious disorder group, but the differences were not statistically significant. Multivariate Cox regression analysis showed that use of MV, GCS upon ICU admission and ONSD on day 3 of ICU admission were independent risk factors. Kaplan?Meier survival analysis showed that patients with an ONSD < 5.30 mm on day 3 had a better 28-day neurological prognosis. Moreover, among the patients with ONSD within 24 hours ≥5.30 mm, the patients with ONSD decreased to < 5.30 mm on day 3 had significantly better 28-day neurological prognosis than those with ONSD ≥ 5.30 mm on day 3 ( P=0.042). Conclusions:ONSD within 24 hours of ICU admission, especially ONSD levels and changes in ONSD on day 3, had predictive value for the short-term neurological prognosis of critically ill patients without primary brain injury.

Objective To investigate the relationship between disease courses and severity and monocyte subsets distribution and surface CD31 intensity in patients of hemorrhagic fever with renal syndrome (HFRS). Methods Peripheral blood samples from 29 HFRS patients and 13 normal controls were collected. The dynamic changes of classical monocyte subsets (CD14⁺⁺CD16^-), intermediated monocyte subsets (CD14⁺⁺CD16⁺) and non-classical monocyte subsets (CD14⁺CD16⁺⁺) and the mean fluorescent intensity (MFI) of CD31 on monocyte subsets were detected by multiple-immunofluorescent staining and flow cytometry. Results In acute phase of HFRS, the ratio of classical monocyte subsets to total monocytes was dramatically decreased compared to convalescent phase and normal control. It was still much lower in convalescent phase compared to normal controls. The ratio of classical monocyte subsets to total monocytes were decreased in HFRS patients compared to that in normal control, whereas there was no difference between severe/critical groups and mild/moderate groups. On the contrary, the ratio of intermediate monocyte subsets to total monocytes in acute phase of HFRS was significantly increased compared to convalescent phase and normal control. The ratio of intermediate monocyte subsets to total monocytes were increased in HFRS patients compared to that in normal control, whereas no difference was found between severe/critical groups and mild/moderate groups. Phases or severity groups had no difference in ratio of non-classical monocyte subsets to total monocytes. Additionally, the ratio of classical monocyte subsets had a tendency to decline and that of intermediate monocyte subsets showed an increase both to total monocytes between the acute and convalescent phases in 11 HFRS patients with paired-samples. Moreover, in acute phase of HFRS, the mean fluorescent intensity (MFI) of CD31 on three monocyte subsets all decreased, specifically classical monocyte subsets showed the highest MFI of CD31 while the normal control reported the highest MFI of CD31 in non-classical monocyte subsets. In convalescent phase, the MFI of CD31 on classical and intermediated monocyte subsets were both lower than that of normal control, while MFI of CD31 was still significantly lower than normal control on non-classical monocyte subsets. Finally, MFI of CD31 on classical and intermediated monocyte subsets in severe/critical group were both lower than those in mild/moderate group, showing no statistical difference in MFI of CD31 on non-classical monocyte subset across groups of different disease severity. Conclusion The ratio of classical and intermediated monocyte subsets to total monocytes are correlated with the course of HFRS, and so are the surface intensity of CD31 on these monocyte subsets with the disease course and severity. The surface intensity of CD31 on non-classical monocyte subsets, however, is correlated only with the course of the disease. Together, the underlying mechanisms for the observed changes in monocyte subsets in HFRS patients should be further investigated.
Humans ; Monocytes ; Lipopolysaccharide Receptors ; Hemorrhagic Fever with Renal Syndrome ; Receptors, IgG ; Disease Progression

Objective:To investigate the practicality and safety of performing a radical prostatectomy(RP)shortly after the diagnosis of prostate cancer using a combination of prostate targeted biopsy and intraoperative frozen section.Methods:Prospective enrollment was conducted for patients suspected of having prostate cancer based on abnormal prostate specific antigen(PSA)levels.The inclusion criteria for the study were as follows: patients aged 80 years or younger with an ECOG score of 1 or lower.Prior to biopsy, patients underwent both prostate magnetic resonance imaging(MRI)and prostate specific membrane antigen positron emission tomography/computed tomography(PSMA PET/CT)to determine the likelihood of prostate cancer with clinical stages within T 2-3aN 0M 0.In order to be included in the study, patients must agree to receive RP after their prostate cancer diagnosis has been confirmed by biopsy.All enrolled patients underwent a targeted prostate biopsy, consisting of 1-2 cores.These specimens were then examined through frozen section analysis.For patients diagnosed with prostate cancer through intraoperative frozen section pathology, RP was immediately performed.In this study, transperineal prostate targeted+ systematic biopsy was utilized for patients with undiagnosed prostate cancer.Additionally, routine pathological examination of specimens was conducted.The study analyzed the baseline data, surgical conditions, pathological results, and follow-up information of patients in a descriptive manner. Results:Seven patients, ranging in age from 54 to 77 years with a mean age of 66.7 years, were enrolled in the study.Their mean PSA level was 12.668 μg/L, ranging from 4.359 to 22.195 μg/L.Of these patients, 4 had a PI-RADS score of 4 and 3 had a score of 5.The maximum diameter of the index lesion was 1.3 cm, ranging from 0.5 to 2.2 cm.PSMA PET/CT scores were 4 in 1 case and 5 in 6 cases.The index lesions detected by PSMA PET/CT were consistent with those detected by MRI, and the maximum standardized uptake value(SUVmax)was 15.7, ranging from 5.3 to 39.4.Prostate cancer was diagnosed through targeted biopsy and intraoperative frozen section pathology.Four cases had a Gleason score of 3+ 3=6, while one case had a Gleason score of 3+ 4=7, another had a score of 4+ 3=7, and the last had a score of 4+ 4=8.All patients underwent RP treatment immediately after the prostate cancer diagnosis.Only one patient had slight adhesion at the apex of the prostate, while the other six patients were evaluated by surgeons as having no obvious adhesion at the apex.All surgeries were completed successfully, with a mean operation time of 149.7(ranging from 108 to 255)minutes.After RP, whole mount pathology results indicated that all cases were prostate adenocarcinoma, with a Gleason score of 3+ 4=7 in four cases and 4+ 3=7 in three cases.The pathological stages were pT2 in three cases and pT3a in four cases, with five cases having negative surgical margins and two cases with positive surgical margins.During the study, all patients were monitored for a period of 5.4 months(ranging from 3 to 7 months)and no complications of Clavien Dino≥Ⅰ were observed.PSA levels were measured at 6 weeks and 3 months after surgery, with readings of 0.020 μg/L(ranging from 0 to 0.079 μg/L)and 0.016 μg/L(ranging from 0 to 0.087 μg/L), respectively.No hormonal therapy or radiotherapy was administered during this time.Four patients were able to recover from urinary continence.Conclusions:Based on a combination of MRI and PSMA PET/CT, it is both safe and feasible to promptly perform RP following the diagnosis of prostate cancer through targeted biopsy for index lesions, along with intraoperative frozen section.

Group 2 innate lymphoid cells (ILC2s) are novel innate immune cells. Similar to T cells, ILC2s can secrete Th2 cytokines and initiate and maintain type 2 immune responses, which are also named as cross-border immune cells between innate immunity and adaptive immunity. In recent years, infectious diseases caused by pathogenic viruses have become a global healthcare challenge with the outbreaks of Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS) and novel coronavirus disease 2019 (COVID-19). As a member of the innate lymphocyte family, ILC2s are involved in the development of group 2 inflammatory diseases and can activate immune activity, playing an essential role in the repair of tissue damage and in the body’s defense, which also can participate in the immune response and play an important role in viral immunity when a virus attacks on the body. This study reviews the defensive role of ILC2s in viral infections, providing a theoretical basis for elaborating the role of ILC2s in viral infectious diseases.

Hepatocyte growth factor (HGF) is a mesenchymal-derived growth factor, which is widely used in the basic and clinical research of pediatric multi-system due to various biological functions.As a protective factor for lung tissues, HGF has significant biological effects on enhancing lung tissue development, stimulating DNA production of lung epithelial cells, repairing lung microvascular endothelial cells, inhibiting apoptosis induced by lung injury, and delaying pulmonary fibrosis.HGF is closely related to the occurrence and development of respiratory diseases in children.This study aims to review the physiological characteristics of HGF and the mechanism in children′s respiratory diseases.

Objective:To explore the application value of automated machine learning (autoML) model in predicting the risk of preeclampsia in the first trimester.Methods:From January 2017 to October 2020, 2 180 singleton pregnant women who were registered in Jinan Second Maternal and Child Health Hospital and underwent pregnancy examination at 12 weeks of gestation were selected. The pregnant women were divided into preeclampsia group (103 cases) and control group (2 077 cases) according to the occurrence of preeclampsia. The differences in clinical data and hematological indexes in the two groups were compared, and the correlation between each index and the risk of preeclampsia was analyzed too. All the pregnant women were randomly divided into training set and test set according to the ratio of 7∶3, and the autogluon autoML algorithm was used to build a variety of machine learning models, and training and cross-validation were performed in the training set to compare the accuracy of the different models. The importance of each index in the autoML model was analyzed, and the autoML model and the logistic regression model were used to predict the risk of preeclampsia in pregnant women in the test set respectively, and the receiver operating characteristic (ROC) curve was used to evaluate the prediction performance of the autoML and the logistic regression model.Results:The age, pre-pregnancy body mass index, body mass index at 12 weeks of gestation, waist circumference at 12 weeks of gestation, proportion of drinking history, high-sensitivity C-reactive protein (hs-CRP), triglyceride, low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), platelet distribution width (PDW), mean platelet volume, thyroid stimulating hormone (TSH) and β-human chorionic gonadotropin were all significantly higher than those in the control group (all P<0.05), and the free tri-iodothyronine (free T3), free thyroxine (free T4), placental growth factor (PIGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and pregnancy-associated plasma protein-A (PAPP-A) were all significantly lower than those in the control group (all P<0.05). Correlation analysis showed that the correlation between pre-pregnancy body mass index, body mass index at 12 weeks gestation, waist circumference at 12 weeks gestation, hs-CRP, triacylglycerol, AST, TSH, free T3, free T4, β-HCG, PIGF, sFlt-1, PAPP-A and preeclampsia risk were obviously higher; but the correlation between each index were lower. A total of 18 models in 8 categories were constructed with the autoML model algorithm, and the neural network _L2 based on FastAI had the highest accuracy in the training set (0.963) and the validation set (0.971). The TSH, LDL-C, PDW, waist circumference at 12 weeks of gestation, sFlt-1, AST were more important in the model, while the free T4, total cholesterol, pregnancy times, drinking history, parity and family history of hypertension were less important indicators. The area under the ROC curve of the autoML model for predicting the risk of preeclampsia in the first trimester was significantly higher than that of the logistic regression model (0.984 vs 0.765, P=0.002), while there was no statistical difference in the prediction accuracy of the two prediction models in the training set ( P>0.05). The prediction accuracy and sensitivity of the autoML model in the test set were both significantly higher than those of the logistic regression model (99.54% vs 98.32%, 93.75% vs 75.00%, both P<0.05). Conclusions:Factors such as TSH, LDL-C, PDW, waist circumference, sFlt-1 and AST in the first trimester of pregnancy have a certain correlation with the risk of preeclampsia. The autoML model based on the indicators of the first trimester has a high predictive value for the risk of preeclampsia.