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 observe the feasibility of cardiac MR tissue tracking(CMR-TT)technique for quantitatively evaluating myocardial strain of patients with myocardial amyloidosis(CA).Methods Cardiac MRI were collected from 20 patients of immunoglobulin amyloid light-chain CA(AL-CA,group A),20 cases of transthyretin CA(ATTR-CA,group B)and 20 healthy subjects(group C),and myocardial strain parameters were obtained using CMR-TT technique.Left ventricular cardiac function parameters were compared among 3 groups,so were strain parameters of each myocardial segment of left ventricle and global myocardium,including 3D longitudinal strain(LS),3D radial strain(RS)and 3D circumferential strain(CS).Results Compared with those in group C,significant differences of left ventricular cardiac function parameters were found in both group A and B(all P＜0.01),while no statistical difference was found between group A and B(all P＞0.05).Except for apical segment RS(P=0.81),strain parameters in group A and B were both lower than those in group C(all P＜0.01),while no significant difference was detected between group A and B(all P＞0.05).Conclusion CMR-TT technique could be used to quantitatively evaluate left ventricular myocardial strain of CA patients.

Purpose::Ischemia and hypoxia are the main factors limiting limb replantation and transplantation. Static cold storage (SCS), a common preservation method for tissues and organs, can only prolong limb ischemia time to 4 - 6 h. The normothermic machine perfusion (NMP) is a promising method for the preservation of tissues and organs, which can extend the preservation time in vitro by providing continuous oxygen and nutrients. This study aimed to evaluate the difference in the efficacy of the 2 limb preservation methods. Methods::The 6 forelimbs from beagle dogs were divided into 2 groups. In the SCS group ( n = 3), the limbs were preserved in a sterile refrigerator at 4 °C for 24 h, and in the NMP group ( n = 3), the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h, and the solution was changed every 6 h. The effects of limb storage were evaluated by weight gain, perfusate biochemical analysis, enzyme-linked immunosorbent assay, and histological analysis. All statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of variance. The p value of less than 0.05 was considered to indicate statistical significance. Results::In the NMP group, the weight gained percentage was 11.72% ± 4.06%; the hypoxia-inducible factor-1α contents showed no significant changes; the shape of muscle fibers was normal; the gap between muscle fibers slightly increased, showing the intercellular distance of (30.19 ± 2.83) μm; and the vascular α-smooth muscle actin (α-SMA) contents were lower than those in the normal blood vessels. The creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion, decreased after each perfusate change, and remained stable at the end of perfusion showing a peak level of 4097.6 U/L. The lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/L. In the SCS group, the percentage of weight gain was 0.18% ± 0.10%, and the contents of hypoxia-inducible factor-1α increased gradually and reached the maximum level of (164.85 ± 20.75) pg/mL at the end of the experiment. The muscle fibers lost their normal shape and the gap between muscle fibers increased, showing an intercellular distance of (41.66 ± 5.38) μm. The contents of vascular α-SMA were much lower in the SCS group as compared to normal blood vessels.Conclusions::NMP caused lesser muscle damage and contained more vascular α-SMA as compared to SCS. This study demonstrated that NMP of the amputated limb with perfusate solution based on autologous blood could maintain the physiological activities of the limb for at least 24 h.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Arginase 1 deficiency (ARG1-D) is a rare genetic metabolic disorder that leads to progressive spastic paralysis, cognitive impairment, and seizures. Recombinant human arginase 1 (rhArg1) is a potential therapeutic agent for this condition, but its clinical application is limited by low activity and short half-life. In this study, we employed directed evolution to address these issues. A random mutation library of rhArg1 was constructed using error-prone PCR, and high-throughput screening was used to identify mutants with enhanced activity. Site-saturation mutagenesis was also performed to investigate the effects of residues R21 and V182 on enzyme activity. Our findings revealed that under reaction conditions devoid of Mn²⁺, the k_cat values of the mutants V182D, V182S, V182H, and R21N increased by 2.0, 1.9, 1.7, and 1.3 times respectively, compared to rhArg1. The k_cat/K_m values of mutants V182D, V182S, R21D, and R21N were 2.1, 1.7, 1.4, and 1.4 times higher than those of rhArg1, respectively. Additionally, mutants R21D and V182L showed enhanced substrate affinity. Through directed evolution and site-saturation mutagenesis, we successfully obtained rhArg1 mutants with improved activity, thereby enhancing its potential for clinical application.

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 incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.
Humans ; Allergens ; Asian People ; Desensitization, Immunologic/adverse effects* ; Hypersensitivity/epidemiology* ; Retrospective Studies

OBJECTIVE To investigate whether electroacupuncture(EA)ameliorates abnormal trigeminal neuralgia(TN)orofacial pain and anxiety-like behavior by altering synaptic plasticity in the hippocampus CA1.METHODS A mouse infraorbital nerve transection model(pT-ION)of neuropathic pain was established,and EA or sham EA was used to treat ipsilateral acu-puncture points(GV20-Baihui and ST7-Xia-guan).Golgi-Cox staining and transmission elec-tron microscopy(TEM)were administrated to observe the changes of synaptic plasticity in the hippocampus CA1.RESULTS Stable and per-sistent orofacial allodynia and anxiety-like behav-iors induced by pT-ION were related to changes in hippocampal synaptic plasticity.Golgi stain-ings showed a decrease in the density of dendritic spines,especially mushroom-type dendritic spines,in hippocampal CA1 neurons of pT-ION mice.TEM results showed that the density of synapses,membrane thickness of the postsynap-tic density,and length of the synaptic active zone were decreased,whereas the width of the synap-tic cleft was increased in pTION mice.EA attenu-ated pT-ION-induced orofacial allodynia and anx-iety-like behaviors and effectively reversed the abnormal changes in dendritic spines and syn-apse of the hippocampal CA1 region.CONCLU-SION EA modulates synaptic plasticity of hippo-campal CA1 neurons,and reduces abnormal oro-facial pain and anxiety-like behavior,providing evidence for a TN treatment strategy.

Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.
Humans ; Allergens ; Asian People ; Desensitization, Immunologic/adverse effects* ; Hypersensitivity/epidemiology* ; Retrospective Studies

A method based on ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap-tandem mass spectrometry(UHPLC-QTRAP-MS/MS) was developed for the simultaneous determination of 41 bioactive constituents of flavonoids, organic acids, nucleosides, and amino acids in Lysimachiae Herba. The content of multiple bioactive constituents was compared among the samples from different habitats. The chromatographic separation was performed in a Waters XBridge®C_(18) column(4.6 mm×100 mm, 3.5 μm) at 30 ℃. The gradient elution was performed with 0.4% methanol(A)-formic acid water(B) as the mobile phase at a flow rate of 0.8 mL·min~(-1), and the multiple-reaction monitoring(MRM) mode was adopted. According to the content of 41 constituents, hierarchical cluster analysis(HCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and gray relational analysis(GRA) were perfomed to comprehensively evaluate the samples from different habitats. The results showed that the 41 constituents exhibited good linear relationship within the tested concentration ranges, with the correlation coefficients(r) greater than 0.999 4. The method featured good precision, repeatability, and stability with the relative standard deviations(RSDs) less than 5.0%. The average recoveries of the 41 constituents ranged from 98.06% to 101.9%, with the RSDs of 0.62%-4.6%. HCA and OPLS-DA separated 48 batches of Lysimachiae Herba samples from different habitats into three categories: the producing areas in Sichuan and Chongqing, the producing areas in Jiangsu, Zhejiang, and Jiangxi, and the producing areas in Guizhou. The content of 41 constituents varied among the Lysimachiae Herba samples from different habitats. The GRA results revealed that the Lysimachiae Herba sample from Nanchong City, Sichuan Province had the best comprehensive quality. The method developed in this study was accurate and reliable and thus can be used for comprehensive evaluation of Lysimachiae Herba quality and provide basic information for the selection of habitats.
Tandem Mass Spectrometry/methods* ; Multivariate Analysis ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Amino Acids/analysis*