Abstract Adverse childhood experiences (ACEs) exposure is a pressing and severe global public health issue. Children and adolescents exposed to multiple ACEs are highly susceptible to toxic stress and impaired physiological functioning, which significantly jeopardize their physical and mental health. Effective prevention and intervention strategies can reduce the prevalence of ACEs and mitigate their severe impacts, thereby minimizing the long term detrimental consequences on future outcomes. The review provides a comprehensive review of intervention strategies across four dimensions: individual, family, school, and public services/policy, so as to establish a theoretical foundation for implementing effective interventions for children and adolescents exposed to adverse childhood experiences.

Objective To investigate the species of sandflies and the prevalence of Leishmania infections in sandflies from selected areas of northern and northwestern China, so as to provide insights into identification of leishmaniasis vectors and assessment of epidemiological trends of leishmaniasis in China. Methods Sandfly samples were collected from Mentougou District of Beijing Municipality, Xiangning County in Linfen City of Shanxi Province, Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, and Payzawat County of Karamay District of Karamay City, Gaochang District of Turpan City in Xinjiang Uygur Autonomous Region from July 2023 to July 2024. Approximately 100 intact female sandfly samples were randomly selected from each site and the species of sandflies was identified according to morphological characteristics and molecular assays. Female sandflies originating from the same habitat were grouped into pools of 10 individuals. Leishmania infection was detected using polymerase chain reaction (PCR) assay targeting the internal transcribed spacer 1 (ITS-1) gene, and the prevalence of Leishmania infection was calculated in sandflies from different sampling sites using the minimum infection rate (MIR) method. In addition, positive amplicons were sequenced and subjected to phylogenetic analysis. Results A total of 6 155 sandflies were collected from different environments at sampling sites across the six aforementioned regions from July 2023 to July 2024. Phlebotomus chinensis (96.00%) was the dominant sandfly species in Mentougou District, Beijing Municipality, with a small proportion of Ph. sergenti (4.00%), and only Ph. chinensis was found in Xiangning County, Linfen City, Shanxi Province. Ph. wui was the only sandfly species detected in Ejin Banner, Alxa League, Inner Mongolia Autonomous Region, and Payzawat County, Kashgar City, Xinjiang Uygur Autonomous Region, and Ph. caucasicus (97.70%) was the dominant sandfly species in Karamay District, Karamay City, Xinjiang Uygur Autonomous Region, with a small proportion of Ph. wui (2.30%), while Ph. alexandri was the only species in Gaochang District, Turpan City, Xinjiang Uygur Autonomous Region. A total of 40, 60, 34, 18, 18, and 22 pools of sandfly samples were tested from Mentougou District in Beijing Municipality, Xiangning County in Linfen City of Shanxi Province, Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, Payzawat County in Kashgar City, Karamay District in Karamay City, and Gaochang District in Turpan City of Xinjiang Uygur Autonomous Region, respectively. L. infantum was detected in Ph. chinensis samples from Mentougou District in Beijing Municipality, and Xiangning County of Linfen City in Shanxi Province, with MIR of 0.25% to 1.00%, and L. donovani was detected in Ph. wui from Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, and Payzawat County in Kashgar City of Xinjiang Uygur Autonomous Region, with MIR of 0.56% to 0.88%; however, no Leishmania infection was detected in Ph. caucasicus from Karamay District in Karamay City or Ph. alexandri from Gaochang District in Turpan City of Xinjiang Uygur Autonomous Region. Phylogenetic analysis showed that the Leishmania ITS-1 gene sequences obtained from Mentougou District in Beijing Municipality and Xiangning County in Linfen City of Shanxi Province were clustered into the same clade with the reference sequences of L. infantum ITS-1 gene, while the Leishmania ITS-1 gene sequences obtained from Ejin Banner in Alxa League of Inner Mongolia Autonomous Region and Payzawat County in Kashgar City of Xinjiang Uygur Autonomous Region were clustered into the same clade with the reference sequences of L. donovani ITS-1 gene. Conclusions There are variations in sandfly species in selected areas of northern and northwestern China, and variations in the species of Leishmania infecting sandflies. Improved surveillance of sandfly vectors and targeted control strategies with adaptations to geographical features and leishmaniasis vectors are recommended.

ObjectiveThis study employs a special conformational engineering (CE) technology to construct an α-chymotrypsin-like active center, which includes a catalytic triad, an oxyanion hole, and a substrate-binding site, on silver nanoparticles (AgNPs), thereby creating an AgNP-based artificial hydrolase with high catalytic activity. This study provides a new approach for the design of highly efficient artificial enzymes and enzyme-mimicking. MethodsAgNPs were chosen as the scaffold to build the an α-chymotrypsin-like active center. A special CE procedure enables the designed peptide, Triad5, to adopt an α‑helical conformation on AgNPs, with the key catalytic residues located on one side of the α-helix forming a catalytic active center with a catalytic triad, an oxyanion hole, and a substrate-binding site. The CE procedure consists of three steps, including conformation induction via trifluoroethanol (TFE), conformation stabilization on AgNPs via Ag-S bonds, and TFE removal via lyophilization. Circular dichroism (CD) spectra were used to confirm the formation and stabilization of the α-helix conformation. Mutations of the key residues combined with stopped-flow kinetic experiments were used to demonstrate the indispensability of each key residue and the synergistic effects among the catalytic triad, the oxyanion hole, and the substrate-binding site. ResultsCD spectra show that the designed Triad5 alone is in random coil conformation; when conjugated on AgNPs, Triad5 still remains largely unstructured; but after the CE treatment, Triad5 adopts a typical α-helical conformation on AgNPs as designed, thus produces an AgNP-based artificial hydrolase, Silverzyme. Silverzyme exhibits extremely high hydrolytic activity towards p-nitrophenyl acetate (p-NPA), with an extremely high catalytic turnover number per active site of 3.5 s^-1, which is even higher than that of α-chymotrypsin. As a comparison, the AgNP-Triad5 conjugate without CE treatment shows much lower catalytic activity than Silverzyme, highlighting the important role of the right conformation of the active center for the catalytic activity and the power of the CE treatment. When the key residues of the catalytic triad of Silverzyme were mutated to alanine, the overall catalytic efficiency of this mutant dropped by about 2 orders of magnitude, unambiguously demonstrating the key role of the designed catalytic triad. Similarly, when the residues for the oxyanion hole were deleted, the mutant with the intact catalytic triad also showed significantly decreased catalytic activity, highlighting the indispensable role of the oxyanion hole for the catalytic activity. Unexpectedly, when both the catalytic triad and the oxyanion hole were kept intact, a slight change of the binding site also resulted in significantly decreased catalytic activity, indicating that the designed binding site is at the right position to align the substrate in the right orientation in the active center for catalytic hydrolysis. These results confirm the synergy among the catalytic triad, the oxyanion hole, and the substrate-binding site, indicating successful mimicking of the active center of α-chymotrypsin. Moreover, Silverzyme shows better thermal stability than α-chymotrypsin, and can even hydrolyze the tough non-activated ester diethyl phthalate, a priority pollutant by the United States Environmental Protection Agency (USEPA). ConclusionThis study successfully mimicked the complex catalytic active center of α-chymotrypsin using a conformational engineering strategy, and produced a highly active artificial hydrolase with a well-defined structure and catalytic mechanism. The findings highlight the significant potential of conformational engineering.

Objective:To study and establish the UPLC fingerprint and multi-index content determination methods of Hedyotidis chrysotricahae Herba; To provide a reference for the quality control of Hedyotidis chrysotricahae Herba.Methods:The chromatographic column was ACQUITY UPLC HSS T3 (100 mm×2.1 mm,1.8 μm). The mobile phase was acetonitrile-0.1% phosphoric acid solution with gradient elution; the detection wavelength was 254 nm; the flow rate was 0.30 ml/min and column temperature was 35 ℃. The method could determine content and fingerprint of rutin, Kaempferol-3-O-rutinoside, Narcissoside, Neochlorogenic aci, Chlorogenic Acid, Cryptochlorogenic acid and have quality analysis to 17 batches of Hedyotidis chrysotricahae Herba based on the variance of fingerprint, similarity evaluation, clustering analysis along with principal component analysis (PCA) at the same time.Results:The common pattern of UPLC specific chromatogram of Hedyotidis chrysotricahae Herba was established. The 11 common peaks were marked out, among which 7 peaks were identified. 17 batches Hedyotidis chrysotricahae Herba could be divided into 4 categories according to different origins. Quality content of six indicators of Hedyotidis chrysotricahae Herba was in slight difference between different origins, among which the content quality of Hedyotidis chrysotricahae Herba from Duyun in Guizhou Province was the highest.Conclusion:The established UPLC fingerprint and content determination method of 6 indicators from the study can be used for the quality control of Hedyotidis chrysotricahae Herba, which can also provide a theoretical basis for the standard improvement of Hedyotidis chrysotricahae Herba.

Objective To investigate the diagnostic value of magnetic resonance imaging(MRI)-based intratumoral and peritumoral radiomics of prostate cancer(PCa)for bone metastases.Methods A total of 211 patients diagnosed with PCa by biopsy pathology at Gansu Provincial People's Hospital from January 2018 to January 2023 were retrospectively analyzed.These patients were randomly divided into a training set(n=147)and a validation set(n=64)in a 7:3 ratio.Regions of interest(ROIs)were delineated from the patients'T2-weighted imaging(T2WI),diffusion-weighted imaging(DWI),and apparent diffusion coefficient imaging(ADC)sequences to extract radiomic features.Z-score(normalization)and the LASSO algorithm were used for feature dimensionality reduction,selection,and construction.A predictive model was then built using a logistic regression(LR)machine learning classifier.The receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to assess the model's performance.Calibration curves and decision curves(DCA)were plotted to evaluate the model's fit and clinical net benefit.Results Radiomic features were extracted from the tumor and peritumoral regions in each patient's T2WI,DWI,and ADC images,with a total of 312 features from each region.The LASSO regression model ultimately identified 10 intratumoral radiomic features closely related to bone metastasis,including 2 T2 sequence features,7 DWI features,and 1 ADC sequence feature;and 9 peritumoral radiomic features,including 4 T2 sequence features,3 DWI features,and 2 ADC sequence features.The predictive model based on intratumoral radiomic features achieved an AUC of 0.845(95%CI 0.747-0.943),while the predictive model based on peritumoral radiomic features had an AUC of 0.818(95%CI 0.716-0.919).A combined nomogram model incorporating intratumoral features,peritumoral radiomic features,and clinical features(including Gleason score,total prostate specific antigen,and body mass index)yielded an AUC of 0.936(95%CI 0.902-0.970).Calibration curves indicated that the combined model had good fit,and DCA demonstrated that the combined model provided better clinical net benefit.Conclusions Peritumoral radiomics has excellent predictive value for bone metastasis in newly diagnosed PCa.Combining with intratumoral radiomics features and clinical features,it significantly enhances the predictive capability of the model.

Objective To explore the effectiveness of drawing-based method in medical courses and their impact on students' learning habits,academic performance,and comprehensive competencies,in order to meet the demand for high-quality,interdisciplinary,and innovative talent,and provide theoretical support for integrating aesthetic education into medical training.Methods A questionnaire survey was conducted among medical students(n=310)at Dalian Medical University,covering the frequency of using drawing method and their effects on learning outcomes,innovation ability,and humanistic qualities.Data were analyzed using the Chi-square test and Fisher's exact test(P＜0.05).Results Totally 93.6％of students approved of using drawing method for learning medical courses,with 70.8％having developed a habit of drawing-based learning.Students with stronger drawing skills were more inclined to use drawing method and supported their application in teaching.The frequency of drawing-based learning was positively correlated with anatomy scores(P＜0.05).Students generally agreed that drawing method enhanced knowledge comprehension,learning interest,long-term memory,innovation ability,critical thinking,and humanistic qualities.However,students with weaker drawing skills perceived drawing method as potentially increasing learning burdens and being less efficient,but this perception significantly decreased with increased drawing frequency(P＜0.05).Conclusion Drawing methods are widely used in medical courses and effectively improve learning outcomes and comprehensive competencies.Drawing proficiency and frequency are key factors influencing students' acceptance and learning effectiveness.Future efforts should focus on promoting drawing method,strengthening students' drawing skills,and optimizing learning processes to deepen the integration of aesthetic education in medical training.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

Objective:To explore the efficacy and safety of intravascular lithotripsy (IVL) for the treatment of calcified lesions in lower limb peripheral artery disease (PAD).Methods:A literature search was conducted on PubMed, Web of Science, Cochrane Library, and Embase, including studies related to IVL for calcified lesions in PAD published from January 2016 to December 2024. Data on patient baseline characteristics, lesion information, IVL procedural parameters, changes in vascular stenosis, and complication occurrence were extracted and included. The Methodological Index for Non-Randomized Studies (MINORS) was used to assess the quality of the included studies. The meta-analysis was performed using STATA 15.1 software. The heterogeneity of different studies was evaluated using Cochran′s Q test. The publication bias was assessed through funnel plots and Egger test.Results:A total of nine studies were included (1 983 patients, 2 387 lesions). The meta-analysis demonstrated that regarding efficacy, after IVL treatment, the average reduction in vascular stenosis was 52.1% (95% CI 45.3%-58.9%). Regarding safety, the incidence of flow-limiting dissection was only 0.6% (95% CI 0.1%-1.4%), and the perforation rate was 0.4%-0.5%, with no events of severe amputation or death. In combined treatments, the usage rate of drug-coated balloons reached 51.2%, and the stent implantation rate was 20.4%. Conclusions:IVL can effectively reduce the degree of vascular stenosis in calcified lesions and has a high safety profile. Combined treatment with drug-coated balloons can reduce the dependence on stents.

Objective To compare the intestinal injury induced by different intensities of waveshock in rats exposed to extremely cold environment and to preliminarily explore the characteristics of the injury.Methods Sixty healthy male SD rats(2 months old,weighing 200～250 g)were randomly divided into 6 groups(n=10):blank control group,low-temperature control group,5.0 MPa shock control group,and low-temperature+4.0,4.5 and 5.0 MPa shock groups.The rats in the experimental groups were pre-treated in a-10℃low-temperature environment for 30 min and then subjected to intestinal injury by using BST-I biological shock tube with different driving pressures.At 3,8,and 24 h after injury,the serum levels of IL-6,TNF-α,intestinal fatty acid binding protein(I-FABP),and diamine oxidase(DAO)were detected,and the survival of rats within 24 h was recorded.At 24 h after injury,the rats were anesthetized and dissected,the characteristics of intestinal injury were observed,and pathological examination was performed.The differences of intestinal injury were compared among the 6 groups to explore the characteristics of intestinal injuries after different intensities of shockwave in rats after exposure to extremely cold environment.Results Compared with the blank control group,the other 5 groups exhibited different severities of intestinal injury,and the rats in the low-temperature+different shock groups were more prone to intestinal edema and trauma.The mortality rate was significantly increased in the low-temperature+5.0 MPa shock group(P<0.05).Pathological and serological studies found that dual effects of very cold environment and blast injury resulted in intestinal mucosal hemorrhage,edema,and disintegration of lamina propria in the experimental rats.The indicators of intestinal mucosal injury and intestinal inflammatory factors were also significantly increased when compared with the blank control group,and significant differences were among the groups with increment of shock intensity(P<0.05).Conclusion Exposure to very cold environment combined with abdominal blast injury increases mortality rate in rats,manifested by elevated serological indicators and intestinal inflammatory factors,as well as varying severities of intestinal wall edema and submucosal bleeding.Furthermore,the severity of the injury is positively related to the impact intensity,with worsened as the impact intensity increasing.