BACKGROUND:Gold nanoparticles are of great significance in the development of multifunctional transdermal drug delivery systems.Smaller gold nanoparticles can penetrate the dermis through the intercellular pathway,but are limited to their easy agglomeration and colloidal morphology,which makes it difficult to exert effects on low delivery efficiency. OBJECTIVE:To develop an ultrasound-optimized hydrogel delivery system by combining phase change nanodroplets with bio-adhesive hydrogel for percutaneous delivery of gold nanoparticles. METHODS:The ultrasound-responsive nanodroplets loaded with gold nanoparticles were prepared by the emulsion solvent evaporation method and loaded into the polydopamine-modified methylacryloyl gelatin hydrogel to prepare a composite hydrogel scaffold.The structure and chemical composition of the ultrasound-responsive nanogold carrier were characterized.The microstructure,porosity,permeability,rheology,in vitro hemostasis,and antibacterial properties of the composite hydrogel were characterized.The cell compatibility of the hydrogel scaffold was evaluated by live/dead staining,and the optimization effects of low-intensity pulsed ultrasound on the permeability,porosity,and mechanical properties of hydrogel were evaluated. RESULTS AND CONCLUSION:(1)Transmission electron microscopy and ultraviolet-visible spectroscopy proved the successful construction of nanogold carriers.The particle size and potential results demonstrated that the synthesized nanoscaled ultrasonic responsive carrier had good stability.(2)Live/dead cell staining proved that the prepared composite hydrogel scaffold had certain biocompatibility.(3)Scanning electron microscopy exhibited that the prepared composite hydrogel scaffold had a porous network structure,and numerous pores of about 2 μm appeared inside the macropores after the addition of nanodroplets and ultrasonic irradiation.The permeability experiment displayed that low-intensity pulsed ultrasound could optimize the porosity and permeability of hydrogel materials.The hemostatic performance of the composite hydrogel scaffold was better than that of the hemostatic sponge and polydopamine@methylacrylylated gelatin hydrogel scaffold.Under the irradiation of low-intensity pulsed ultrasound,the composite hydrogel scaffolds had good antioxidant effects and antibacterial properties.(4)Thermal imaging results manifested that gold nanoparticles were encapsulated in ultrasound-responsive nanobubbles,and more uniform dispersion could be obtained under ultrasonic excitation.(5)The results of the mechanical property test demonstrated that the storage modulus of the hydrogel increased before and after loading gold nanoparticles-nanodroplets,which showed stronger mechanical properties.The elongation at break was 122%,and the ductility was better than that without gold nanoparticles-nanodroplets(P<0.05).(6)These findings indicate that the composite hydrogel scaffold has good biocompatibility,antibacterial property,oxidation resistance,and hemostatic effect.

Objective:To improve the aqueous solubility, biocompatibility, fluorescence, and sonosensitivity of curcumin, this study aims to transform curcumin into curcumin-derived carbon dots (Cur-CDs) to enhance the efficacy of sonodynamic therapy (SDT) of atherosclerosis (AS).Methods:Cur-CDs were synthesized via a hydrothermal method. The morphology was characterized by transmission electron microscopy, while Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy were applied to analyze the chemical composition and surface functional groups. Optical properties were examined by UV-visible spectrophotometry and fluorescence spectroscopy. Cell proliferation and viability assay and a hemolysis experiment were performed to assess biocompatibility. The sonosensitivity of Cur-CDs was determined by the measurement of reactive oxygen species (ROS) produced by Cur-CDs.To verify the effect of Cur-CDs-mediated SDT on macrophage phenotype, the M1 and M2 macrophage marker genes were detected via real-time fluorescence quantitative polymerase chain reaction. The ability of Cur-CDs in plaque detection was assessed through in vivo fluorescence imaging and ex vivo aortic fluorescence imaging. Atherosclerotic plaque mice were divided into five groups: control group, curcumin group, Cur-CDs group, curcumin + low-intensity pulsed ultrasound (LIPUS) group, and Cur-CDs+ LPIUS group. Aortic Oil red O staining and blood lipid level measurements were conducted to evaluate the therapeutic efficacy of SDT on the plaques.Results:Cur-CDs exhibited a spherical morphology and a distinct lattice structure with the diameter of (1.87±0.35)nm. The aqueous solubility of Cur-CDs was about 10 5 times that of curcumin because of their abundant oxygen-containing hydrophilic functional groups.Cur-CDs at concentrations up to 500 mg/L had no significant impact on cell proliferation and viability, with a negligible hemolysis rate of <1%, indicating good biocompatibility of Cur-CDs. Cur-CDs exhibited a stable and excellent fluorescence with the maximum excitation and emission wavelengths of 420 nm and 530 nm, respectively. Cur-CDs had the potential to be used for plaque fluorescence imaging, with the fluorescence intensity at the plaque being significantly greater than that of curcumin( P<0.01). It was observed that Cur-CDs activated by LIPUS were capable of producing ROS, including 1O 2, ·OH, and ·O 2-, with the total amount of ROS exceeding that of curcumin( P<0.05). Cur-CDs-mediated SDT facilitated the transformation of macrophage phenotype from M1 to M2, with a more pronounced effect than that observed with curcumin-mediated SDT. Oil red O staining revealed the most significant reduction in plaque area and lipid content in the Cur-CDs+ LIPUS group, which was about three times greater than that in the curcumin+ LIPUS group, confirming the excellent efficacy of Cur-CDs-mediated SDT on plaques. Conclusions:The successfully prepared Cur-CDs exhibit superior aqueous solubility, biocompatibility, fluorescence, and sonosensitivity than curcumin, contributing to the significant improvement in sonodynamic efficacy on plaques.

Objective:To comprehensively evaluate the effectiveness of preventive measures for acute kidney injury (AKI) in children and identify the effective strategies.Methods:Databases were systematically searched including CNKI, Wanfang, VIP, China Biology Medicine National Knowledge Infrastructure, PubMed, Embase, Cochrane Library databases, and the reference lists of relevant papers for randomized controlled trials on preventing pediatric AKI up to December 2023. Literature screening was conducted based on the inclusion and exclusion criteria, followed by data extraction and quality assessment of included studies. Traditional and network meta-analyses were performed, along with trial sequential analysis (TSA).Results:A total of 21 studies involving 3 483 children were included. Traditional and network meta-analysis showed that dexmedetomidine was effective in preventing AKI in children undergoing cardiac surgery or cardiac angiography ( OR=0.26, 0.27; 95% CI 0.11-0.64, 0.13-0.58). Remote ischemic preconditioning (RIPC) was effective in preventing AKI in children after cardiac surgery ( OR=0.43, 0.44; 95% CI 0.24-0.79, 0.23-0.83). Traditional and network meta-analysis specific to children with sepsis or septic shock showed that balanced solution was effective in preventing pediatric AKI ( OR=0.58, 0.52; 95% CI 0.42-0.79, 0.37-0.73). TSA indicated that the total sample sizes of dexmedetomidine (348 cases) and RIPC (666 cases) both reached the required information size (320 and 534 cases); additionally, the Z-curve for balanced solution (cumulative Z=3.38) crossed the TSA monitoring boundary ( Z=3.29). Conclusion:Dexmedetomidine reduces the risk of AKI in children undergoing cardiac surgery or cardiac angiography, RIPC decreases the risk of AKI in children after cardiac surgery, and balanced solution lowers the risk of AKI in children with sepsis or septic shock.

Objective:To demonstrate the type of CEBPA gene mutations among patients with acute myeloid leukemia (AML), clinical characteristics, and prognostic effect on patient outcomes.Methods:Demographic data, clinical features, laboratory characteristics, and data about treatment and follow-up of 57 patients with CEBPA mutated AML diagnosed at Peking Union Medical College Hospital between April 2016 and November 2022 were collected and analyzed.Results:In total, 57 patients with CEBPA mutation accounted for 16.1% of all the 353 patients with AML, among which 28 patients had CEBPA-bZIPinf and 29 had CEBPA-other. Compared with the CEBPA-other group, the CEBPA-bZIPinf group was younger (54 vs 64 years, P=0.010), de novo AML was more common ( P=0.001), and the level of bone marrow blast was higher (68.0% vs 36.3%, P=0.001). Moreover, 24 patients from the CEBPA-bZIPinf group and 19 from the CEBPA-other group received chemotherapy. The one-course complete remission (CR) rate of the CEBPA-bZIPinf group was significantly higher than that of the CEBPA-other (87.5% vs 47.4%, P=0.010) and CEBPA-wt (87.5% vs 50.3%, P=0.002) groups. After a median follow-up of 11 months, the median OS of the CEBPA-bZIPinf group was significantly longer than that of the CEBPA-wt group (not reached vs 22.1 months, P=0.012) . Conclusion:CEBPA-bZIPinf mutated AML is a unique clinical entity, with a younger age of diagnosis, better response to chemotherapy, and better prognosis.

The research shows that personality assessment can be achieved by regression model based on electroencephalogram (EEG). Most of existing researches use event-related potential or power spectral density for personality assessment, which can only represent the brain information of a single region. But some research shows that human cognition is more dependent on the interaction of brain regions. In addition, due to the distribution difference of EEG features among subjects, the trained regression model can not get accurate results of cross subject personality assessment. In order to solve the problem, this research proposes a personality assessment method based on EEG functional connectivity and domain adaption. This research collected EEG data from 45 normal people under different emotional pictures (positive, negative and neutral). Firstly, the coherence of 59 channels in 5 frequency bands was taken as the original feature set. Then the feature-based domain adaptation was used to map the feature to a new feature space. It can reduce the distribution difference between training and test set in the new feature space, so as to reduce the distribution difference between subjects. Finally, the support vector regression model was trained and tested based on the transformed feature set by leave-one-out cross-validation. What's more, this paper compared the methods used in previous researches. The results showed that the method proposed in this paper improved the performance of regression model and obtained better personality assessment results. This research provides a new method for personality assessment.
Algorithms ; Brain ; Electroencephalography/methods* ; Emotions ; Humans ; Personality Assessment

Objective:To investigate the clinical and laboratory characteristics of systemic sclerosis (SSc) patients at different age of onset.Methods:Data of SSc patients with onset age ≥18 years old who were registered in the Peking Union Medical College Hospital and Chinese Rheumatism Data Center from August 2008 to June 2020 were included. Patients were divided into 3 groups by the age of onset according to the age segmentation of the World Health Organization. Counting variables were presented as frequency (percentage). Quantitative results were presented as mean±standard deviation, or median, inter quartile range. Differences between groups were analyzed by analysis of variance, the Mann-Whitney test or the chi-square test, depen-ding on the distribution of the variables.Results:Six hundred and eighty-two SSc patients were included. Accor-ding to the age of onset, they were divided into three groups: youth group (18-44 years old), middle-aged group (45-59 years old) and elderly group (over 60 years old). There were 361 patients in the youth group,245 patients in the middle age group and 76 patients in the elderly group. The mean age of onset was (43.8±12.1) years. The variables with significant different among the groups were as the following: left ventricular diastolic dysfunction [14.0%(14/100), 38.8%(39/98), 65.4%(17/26); χ2=30.756, P<0.001]; cardiac arrhythmias [1.9% (7/361), 3.7% (9/361), 7.9% (6/76), χ2=7.38, P=0.024), Raynaud's phenomenon [94.7% (342/361), 89.4%(219/245), 89.5%(68/76), χ2=6.73, P=0.035], loss of finger pad substance [36.9%(133/360), 25.4% (62/244), 18.4% (14/76), χ2=15.184, P=0.001]; digital ulcer [31.0% (112/361), 23.0% (56/244), 15.8% (12/76), χ2=9.86, P=0.007]; arthritis [16.3%(59/361), 13.5%(33/245), 5.3%(4/76), χ2=6.49, P=0.039], digital contracture [11.6%(42/361), 5.7%(14/245), 9.2%(7/76), χ2=6.10, P=0.047]; positive anti-RNP antibody [32.3% (116/359), 20.7% (50/241), 17.3% (13/75), χ2=14.06, P=0.001]; and positive anti-centromere antibody [8.9% (32/351), 18.4%(45/239), 23.7%(18/76), χ2=17.78, P<0.001] were significantly different between the young age group and elder group. Conclusion:The predominant age of disease onset of SSc is middle and young age. Elder onset SSc patients are more likely to have left ventricular diastolic dysfunction, and young onset patients are more likely to have microvascular lesions, which needs more attentions by clinicians.

Objective:To evaluate the differences in clinical characteristics between different genders of Chinese patients with systemic sclerosis(SSc).Methods:The data of SSc patients registered in Chinese Rheumatism Data Center between August 2008 and June 2020 were retrospectively analyzed.Results:A total of 1 844 patients with SSc were enrolled in the study. The ratio of males to females was 289 to 1 555. The onset age was (48.6±13.7) years in males and (45.5±13.1) years in females( P<0.001). Male patients represented shorter disease duration [2.0(0.0, 4.0)years vs.3.0(1.0, 7.0) years, P<0.001],higher proportion of diffuse cutaneous SSc (dcSSc) [63.0% (182/289)vs.44.2%(688/1 555), P<0.001]. Although more man patients experienced smoking [47.4%(137/289) vs. 1.7%(27/1 555), P<0.001] and exposure to harmful environments [7.6%(22/289) vs. 2.1%(33/1 555), P<0.001], there was no statistically significant difference in interstitial lung disease between male and female patients [69.3%(181/261) vs. 74.5%(1 085/1 457), P=0.084].Otherwise, Raynaud′s phenomenon [87.7% (1 364/1 555) vs.75.4%(218/289), P<0.001], arthritis [11.1%(173/1 555) vs.6.9%(20/289), P=0.032], gastroesophageal reflux disease [22.0%(342/ 1 555) vs.13.1%(38/289), P=0.001], and leucopoenia [10.7(161/1 511)% vs. 6.1%(17/279), P=0.019] were more common in female patients, but finger ulcer was less common [22.5%(350/1 555) vs. 30.4%(88/289), P=0.004]. Antinuclear antibody(ANA) positivity rate [85.6%(1 310/1 531) vs. 78.6%(221/281), P=0.003], anti-RNP antibody positivity rate [23.1%(342/1 479) vs.14.0%(38/271), P=0.001], anti-SSA antibody positivity rate [28.2%(419/1 487) vs.13.9%(38/274), P<0.001] were higher in female patients. Physician′s global assessment(PGA) scores [1.4 (1.0, 2.0) vs. 1.0 (0.3, 1.6), P<0.001] and modified Rodnan Skin Score(mRSS) [18.0 (9.5, 28.0) vs. 14.0 (5.0, 28.0), P=0.003] were higher in males. Conclusion:Even though male SSc patients account for a small proportion, more extensive skin involvement, finger ulcers and higher PGA are manifested in males. Physicians need pay attention to these clinical disparities between different genders in SSc.

Objective:To investigate the effect of usage of transthoracic echocardiography(TTE) on the prognosis of patients after acute kidney injury (AKI) in intensive care unit (ICU).Methods:The clinical data of patients with AKI in the Medical Information Mart for Intensive Care (MIMIC-Ⅲ v1.4) database was collected retrospectively, and the patients were divided into TTE group (with TTE within 24 hours of AKI diagnosis) and No-TTE group (without TTE examination or first TTE examination was more than 24 hours after AKI diagnosis). Propensity score matching (PSM) was utilized to balance the baseline variables between the two groups and Cox regression analysis was used to evaluate the independent risk factors for 28-day all-cause mortality (the primary outcome). Moreover, after PSM, the effects of TTE usage on the second outcomes (including the volumes of intravenous fluid and urine output in the first, second and third 24-hour after the diagnosis of AKI; the total number of mechanical ventilation-free days, renal replacement therapy-free days and vasopressor-free days within 28 days after ICU admission; use of diuretics after the diagnosis of AKI; reduction in serum creatinine within 48 hours after the diagnosis of AKI; and the length of ICU stay and hospital stay) were also evaluated.Results:Among 23 945 eligible AKI patients, 3 365 patients (14.1%) patients received TTE within 24 hours after the diagnosis of AKI and finally there were 3 361 patients in TTE group and No-TTE group included in this study after PSM based on the ratio of 1∶1. After PSM, all variables in the two groups were well balanced (standardized mean difference<0.1, respectively). Before and after PSM, patients in TTE group had lower 28-day all-cause mortality compared with patients in No-TTE group (10.76% vs 13.04%, χ2=13.535, P<0.001; 10.65% vs 18.80%, χ2=88.932, P<0.001), and Kaplan-Meier survival curves also revealed that patients in the TTE group had higher cumulative survival rate compared with patients in No-TTE group (Log-rank χ2=15.438, P<0.001; Log-rank χ2=75.360, P<0.001, respectively). Multivariate Cox regression analysis showed that TTE was an independent influencing factor for 28-day all-cause mortality before and after PSM ( HR=0.80, 95% CI 0.73-0.89, P<0.001; HR=0.58, 95% CI 0.51-0.65, P<0.001). And all subgroup analyses showed the similar results. Compared with patients in the No-TTE group, patients in the TTE group had higher volume of intravenous fluid on the first day and the second day after the diagnosis of AKI (both P<0.01). Patients in the TTE group had higher volume of urine output on the first day and the third day after the diagnosis of AKI (both P<0.01). The patients in the TTE group had a significantly lower duration of vasopressor-free and mechanical ventilation-free (both P<0.01). The usage of diuretic was significantly higher in the TTE group compared with that in the No-TTE group (54.1% vs 44.2%, χ2=65.609, P<0.001). With respect to serum creatinine, the reduction in serum creatinine within 48 hours after the diagnosis of AKI was higher in the TTE group than that in the No-TTE group [36.6(23.0, 97.2) μmol/L vs 30.1(14.2, 61.9) μmol/L, Z=-9.549, P<0.001]. Moreover, TTE group had shorter ICU stay than that in the No-TTE group [5.03(3.40, 8.90) d vs 5.37(3.77, 10.00) d, Z=-6.589, P<0.001]. There were no significant difference between the two groups in other secondary outcomes (all P>0.05). Conclusions:Timely TTE utilization after AKI incident is associated with better clinical outcomes for ICU patients.

Objective:To observe the effect of methylphenidate hydrochloride (MPH) combined with mentalization-based family therapy (MBFT) on clinical efficacy and social function in children with attention deficit hyperactivity disorder (ADHD).Methods:Sixty-four children with ADHD diagnosed in Wuxi Children's Hospital and Affiliated Hospital of Jiangnan University from June 2019 to May 2021 were selected and divided into observation group ( n=32) and control group ( n=32) according to the random number table.Children in both groups received methylphenidate hydrochloride extended-release tablets, while those in the observation group were given additional MBFT.The duration of treatment was 12 weeks in both groups.The parent symptom questionnaire (PSQ), swanson nolan and pelham-version Ⅳ (SNAP-Ⅳ) parent Al scale, and Weiss impairment functional scale (WFIRS-P) were used to evaluate the effectiveness of treatment.Statistical analysis was performed by SPSS 25.0 statistical software.In particular, the χ2 test was used for counting data and the paired sample t test was used for comparison of measurement data between the two groups before and after treatment. Results:(1) All the PSQ dimension scores of patients in the observation group and the control group after treatment were significantly lower than those before treatment (all P<0.01). Compared with the control group after treatment, the PSQ dimension scores of personality and behavior problems ((1.25±0.15), (0.94±0.18), t=7.484, P<0.001), learning problems ((1.57±0.16), (1.32±0.20), t=5.522, P<0.001), psychosomatic disorders ((0.56±0.11), (0.44±0.13), t=3.986, P<0.001), impulse hyperactivity ((1.76±0.23), (1.54±0.25), t=3.663, P<0.001), anxiety ((0.94±0.12), (0.76±0.11), t=6.255, P<0.001) and hyperactivity index ((1.74±0.19), (1.51±0.16), t=5.238, P<0.001) decreased significantly in the observation group after treatment.(2) Compared with the pre-treatment period, the SNAP-Ⅳ scale scores of attention deficit, impulsivity-hyperactivity and oppositional defiance were significantly lower in both groups after treatment (all P<0.01); and compared with the control group, the SNAP-Ⅳ scale scores of the above three dimensions were significantly lower in the observation group (all P<0.01). (3) All six dimensions (family, learning and school, life skills, self-management, social activities, and risk-taking activities)of the WFIRS-P scale were significantly lower in the children in the observation group after treatment compared with those before treatment (all P<0.01), and all the six dimensions of the WFIRS-P scale were significantly lower in the observation group compared with those in the control group (all P<0.01). Conclusion:Methylphenidate hydrochloride extended-release tablets combined with MBFT can significantly improve the clinical symptoms and social function of children with ADHD.

Ex vivo-expanded mesenchymal stem cells(MSCs)have been demonstrated to be a heterogeneous mixture of cells exhibiting varying proliferative,multipotential,and immunomodu-latory capacities.However,the exact characteristics of MSCs remain largely unknown.By single-cell RNA sequencing of 61,296 MSCs derived from bone marrow and Wharton's jelly,we revealed five distinct subpopulations.The developmental trajectory of these five MSC subpopulations was mapped,revealing a differentiation path from stem-like active proliferative cells(APCs)to multipotent progenitor cells,followed by branching into two paths:1)unipotent preadipocytes or 2)bipotent prechondro-osteoblasts that were subsequently differentiated into unipotent prechondro-cytes.The stem-like APCs,expressing the perivascular mesodermal progenitor markers CSPG4/MCAM/NES,uniquely exhibited strong proliferation and stemness signatures.Remarkably,the prechondrocyte subpopulation specifically expressed immunomodulatory genes and was able to sup-press activated CD3+T cell proliferation in vitro,supporting the role of this population in immunoregulation.In summary,our analysis mapped the heterogeneous subpopulations of MSCs and identified two subpopulations with potential functions in self-renewal and immunoregulation.Our findings advance the definition of MSCs by identifying the specific functions of their heteroge-neous cellular composition,allowing for more specific and effective MSC application through the purification of their functional subpopulations.