To investigate the risk factors for acute kidney injury (AKI) following the use of amphotericin B deoxycholate and to develop a predictive model to guide clinical monitoring and intervention.

Objective To construct an index system for assessment of schistosomiasis transmission risk following natural disasters such as rainstorms, floods, earthquakes, mudslides, and landslides, so as to provide insights into rapid identification of schistosomiasis transmission risk post-disasters and formulation of targeted schistosomiasis control strategies. Methods An initial framework for the index system for assessment of schistosomiasis transmission risk following natural disasters was drafted through literature review, brainstorming, and focus group discussions. Two rounds of expert correspondence consultations were conducted using the Delphi method to refine and finalize the system, and the degrees of expert activeness, authority and endorse ment, and consensus were evaluated. In addition, the weights of each index were calculated using the analytic hierarchy process. Results A total of 18 experts participated in the consultation. The expert positive coefficients were 100.00% and 94.44% for two rounds of consultations, with authority coefficients of 0.92 and 0.94, respectively. The coefficients of coordination on the index importance, rationality and operability were 0.209, 0.185, 0.222 and 0.407, 0.214, 0.257 for two rounds of consultations, respectively, and all consistency tests were statistically significant (χ² = 246.771 to 505.278, all P values < 0.001). Following two rounds of expert consultations, an index system consisting of 6 first-level indicators, 15 second-level indicators, and 49 third-level indicators was ultimately constructed. In terms of first-level indicators, “disaster situation”, “previous epidemics”, “healthcare guarantee”, “response capacity” and “emergency recovery” had the highest weights, each at 18.18%. Regarding second-level indicators, “Schistosoma japonicum infections in animals”, “S. japonicum infections in snails” and “medical treatment” had the highest weights, each at 7.35%. In terms of third-level indicators, ten items had the highest weights, including “identification of schistosomiasis cases”, “detection of S. japonicum infections in wild feces”, “detection of S. japonicum infections in snails”, “reserves of schistosomiasis diagnostic/testing reagents and consumables”, “reserves of chemotherapy agents for human and animal schistosomiasis”, “reserves of cercariacides”, “periodical surveillance on schistosomiasis”, “identification of schistosomiasis transmission risk and timely response”, “normal provision of diagnosis and treatment services” and “post-disaster schistosomiasis surveillance”, each at 2.40%. Conclusion A scientific, systematic, and practical index system has been constructed for assessment of schistosomiasis transmission risk following natural disasters, which may provide insights into rapid post-disaster identification of schistosomiasis transmission risk, formulation of targeted schistosomiasis control strategies and optimization of resource allocation.

ObjectiveTo identify potential influencing factors of urate crystal deposition at ankle/foot in patients with hyperuricemia （HUA）， and to analyze the predictive value of inflammatory indicators for urate crystal deposition in patients with different traditional Chinese medicine （TCM） syndromes， so as to provide potential reference for clinical risk assessment and individualized TCM intervention. MethodsA retrospective study was carried out with the enrollment of 231 HUA patients from The Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2021 and December 2024. The enrolled patients were further divided into a crystal deposition-positive group （143 cases） and a crystal deposition-negative group （88 cases） according to the results of dual-energy computed tomography （CT）. Sociodemographic data， living habits， serum uric acid levels， and inflammatory indicators of the enrolled patients were collcted， and TCM syndrome differentiation was performed. Furthermore， univariate analysis was used to compare inter-group differences in clinical characteristics. MMultivariate Logistic regression was applied to identify the influencing factors of urate crystal deposition. In addition， the receiver operating characteristic （ROC） curves were plotted to evaluate the predictive efficacy of inflammatory indicators for crystal deposition across different TCM syndromes. ResultsThere were statistically significant inter-group differences in the proportion of males， age， body mass index， proportion of mental labor， rate of low water intake， and rate of high-sugar beverage consumption （P<0.05），whereas no significant difference in low exercise intensity was found between the two groups. Furthermore， compared with the negative group， the positive group had higher serum uric acid level， neutrophil-to-lymphocyte ratio （NLR）， and platelet-to-lymphocyte ratio （PLR）， but lower systemic immune-inflammation index （SIRI） （P<0.05）. Regarding the distribution of TCM syndromes， the positive group was dominated by the dampness-heat accumulation syndrome （55/143，38.46%）， while the negative group was mainly characterized by the phlegm-turbidity obstruction syndrome （44/88，50.00%）. Multivariate Logistic regression analysis revealed that high-sugar beverage consumption， elevated NLR， and elevated PLR were risk factors for urate crystal deposition ［odd ratio （OR） = 8.002， 5.377， 1.034， respectively； 95% CI 1.572-40.732， 2.179-13.270， 1.013-1.054，all P<0.05］， while SIRI was a protective factor （OR = 0.869， 95% CI 0.778-0.971， P<0.05）. In the positive group， patients with the dampness-heat accumulation syndrome exhibited the highest NLR， while the lowest PLR and SIRI， showing statistically significant differences with those of other syndromes （all P<0.05）. In addition， ROC curve analysis indicated that for the dampness-heat accumulation syndrome， the combined "NLR + PLR" model had an area under the curve （AUC） of 0.901 （95% CI 0.850-0.951， P<0.01）， with a sensitivity of 89.1% and a specificity of 79.5%； for the blood stasis-heat obstruction syndrome， the combined "NLR + PLR" model had an AUC of 0.880 （95% CI 0.825-0.934， P<0.01）， with a sensitivity of 100.0% and a specificity of 67.3%； for the liver-kidney Yin-deficiency syndrome， the single PLR model had an AUC of 0.842 （95% CI 0.731-0.952， P<0.01）， with a sensitivity of 83.3% and a specificity of 84.0%. ConclusionUrate crystal deposition in HUA patients exhibits intimate associations with high-sugar beverage consumption as well as elevated NLR and PLR levels. Meanwhile， TCM syndrome differentiation has potential correlation with inflammatory characteristics. The inflammatory indicator-based prediction model constructed based on TCM syndromes exhibits good predictive value.

Background Microparticles (MPs) are one of the main medium of inflammatory reaction with an important role in atherosclerotic progression. Studies on association of air pollution exposure and levels of peripheral blood MPs are limited among human. Objective To evaluate the effects of short-term exposure to air pollution on levels of peripheral blood MPs. Method A panel of 73 healthy adults was followed with 4 repeated follow-ups in Beijing, China, from November 2014 to January 2016. During each visit, we collected questionnaire information, fasting venous blood, urine, and exposures to fine particulate matter (PM_2.5), black carbon, nitric oxide, nitrogen dioxide, nitrogen oxide, sulfur dioxide, carbon monoxide, and ozone. We used linear mixed-effect models to analyze associations of air pollution exposure with levels of total MPs (TMPs) and MPs derived from various cells. Stratified analysis was conducted by levels of C-reactive protein (CRP) and malondialdehyde (MDA). Results The results showed significant associations between air pollution exposure and peripheral blood TMPs at 2 h-6 d prior to the follow-ups (P<0.05), while no statistical associations were found for MPs derived from different cell types. Significant increases in TMPs of 7.8% (95%CI: 0.7%, 15.3%) and 14.3% (95%CI: 2.8%, 27.2%) were observed with each interquartile range (IQR) increase in PM_2.5 (IQR=64.9 μg·m⁻³) at prior 18 h and NO (IQR=40.5 μg·m⁻³) at prior 48 h. Among participants with low levels of CRP and MDA, significantly positive associations were observed between air pollution exposure and levels of TMPs (P<0.05). Conclusion Short-term exposure to air pollution is significantly associated with increased levels of circulating MPs in healthy adults, and in people with lower systemic inflammation, peripheral blood MPs levels are more easily affected after exposure to air pollutants.

[Objective] To evaluate the efficacy and safety of sacral neuromodulation (SNM) in the treatment of patients with benign prostatic hyperplasia (BPH) complicated with underactive bladder (UAB) who respond poorly to transurethral resection of the prostate (TURP). [Methods] A retrospective analysis was performed on 10 patients with BPH and UAB treated with TURP by the same surgeon in Zhongda Hospital Southeast University during Jan.2018 and Jan.2023.The residual urine volume was not significantly relieved after operation, and the maximum urine flow rate and urine volume per discharge were not significantly improved.All patients underwent phase I SNM, and urinary diaries were recorded before and after surgery to observe the average daily frequency of urination, volume per urination, maximum urine flow rate, and residual urine volume. [Results] The operation time was (97.6±11.2) min.During the postoperative test of 2-4 weeks, if the residual urine volume reduction by more than 50% was deemed as effective, SNM was effective in 6 patients (60.0%). Compared with preoperative results, the daily frequency of urination [(20.2±3.8) times vs. (13.2±3.2) times], volume per urination [(119.2±56.7) mL vs. (246.5±59.2) mL], maximum urine flow rate [(8.7±1.5) mL/s vs. (16.5±2.6) mL/s], and residual urine volume [(222.5±55.0) mL vs. (80.8±16.0) mL] were significantly improved, with statistical significance (P<0.05). There were no complications such as bleeding, infection, fever or pain.The 6 patients who had effective outcomes successfully completed phase II surgery, and the fistula was removed.During the follow-up of 1 year, the curative effect was stable, and there were no complications such as electrode displacement, incision infection, or pain in the irritation sites.The residual urine volume of the other 4 unsuccessful patients did not improve significantly, and the electrodes were removed and the vesicostomy tube was retained. [Conclusion] SNM is safe and effective in the treatment of BPH with UAB patients with poor curative effects after TURP.

Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the"therapeutic module"of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Structural optimization of lead compounds is a crucial step in drug discovery.One optimization strategy is to modify the molecular structure of a scaffold to improve both its biological activities and absorption,distribution,metabolism,excretion,and toxicity(ADMET)properties.One of the deep molecular generative model approaches preserves the scaffold while generating drug-like molecules,thereby accelerating the molecular optimization process.Deep molecular diffusion generative models simulate a gradual process that creates novel,chemically feasible molecules from noise.However,the existing models lack direct interatomic constraint features and struggle with capturing long-range dependencies in macromolecules,leading to challenges in modifying the scaffold-based molecular structures,and creates limitations in the stability and diversity of the generated molecules.To address these challenges,we propose a deep molecular diffusion generative model,the three-dimensional(3D)equivariant diffusion-driven molecular generation(3D-EDiffMG)model.The dual strong and weak atomic interaction force-based long-range dependency capturing equivariant encoder(dual-SWLEE)is introduced to encode both the bonding and non-bonding information based on strong and weak atomic interactions.Addi-tionally,a gate multilayer perceptron(gMLP)block with tiny attention is incorporated to explicitly model complex long-sequence feature interactions and long-range dependencies.The experimental results show that 3D-EDiffMG effectively generates unique,novel,stable,and diverse drug-like molecules,highlighting its potential for lead optimization and accelerating drug discovery.

Objective: This study aims to investigate the therapeutic effects and underlying mechanisms of Xuanfei Baidu Decoction (XFBD) in a mouse model of dampness-heat toxin pneumonia. By exploring how XFBD exerts its effects, we seek to deepen our understanding of its role in treating pulmonary diseases and to address the current knowledge gap regarding its mechanisms of action, thereby supporting its clinical application. Methods: Ultra-high-performance liquid chromatography and high-resolution mass spectrometry (HRMS) were employed to analyze the chemical constituents of XFBD. The protective effects of XFBD were evaluated using a dampness-heat toxin-induced mouse model, established through dampness-heat exposure and HCoV-229E infection. XFBD was administered orally, followed by assessments including lung index measurement, micro-CT imaging, viral load quantification, cytokine analysis, and histological evaluation via hematoxylin-eosin staining. Proteomics and single-cell transcriptomic analyses were conducted to explore the potential mechanisms underlying XFBD’s pharmacological effects. A cellular model of HCoV-229E infection was developed to investigate changes in the cAMP/PKA signaling pathway. Molecular docking and surface plasmon resonance (SPR) experiments confirmed the strong binding affinity between key XFBD components and PKA. Finally, PKA activators and inhibitors were applied in vitro to validate these mechanistic findings. Results: In vivo studies demonstrated that XFBD significantly reduced the lung index, improved the structural integrity of lung and tongue tissues, and decreased levels of proinflammatory mediators, including IL-6, IL-8, and TNF-α. Proteomic and single-cell transcriptomic analyses showed that the differentially expressed proteins after XFBD treatment were primarily associated with inflammatory responses and immune regulation. The cAMP/PKA signaling pathway was identified as a key mechanism underlying these therapeutic effects. Notably, Western blot, ELISA, molecular docking, and SPR analyses confirmed that XFBD elevated cAMP levels and p-PKA expression, thereby activating the cAMP/PKA signaling pathway in vitro. Conclusion: This study demonstrated that XFBD significantly alleviates symptoms in mice with dampness-heat toxin pneumonia. Its therapeutic effects are mediated, at least in part, through activation of the cAMP/PKA signaling pathway. These findings provide compelling evidence that XFBD is an effective herbal remedy against HCoV-229E infection.

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

Objective:To investigate microstructural alterations in the optic chiasm and optic radiations of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) based on diffusion kurtosis imaging (DKI).Methods:This study was a cross-sectional study. Retrospective analyses were conducted on the clinical and imaging data of 63 patients with relapsing-remitting MS (RRMS) and 62 patients with NMOSD diagnosed at First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023. According to the occurrence of optic neuritis (ON), they were categorized into ON-positive MS (ON+MS) group (40 cases), ON-negative MS (ON-MS) group (23 cases), ON-positive NMOSD (ON+NMOSD) group (40 cases) and ON-negative NMOSD (ON-NMOSD) group (22 cases). In addition, 40 healthy controls were enrolled during the same period. DKI data of all subjects were collected, and DKI post-processing was performed to obtain fractional anisotropy (FA), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) values of the optic chiasm and bilateral optic radiations. The scores of the mini-mental state examination (MMSE), montreal cognitive assessment (MoCA), and expanded disability status scale (EDSS) were obtained. The Kruskal-Wallis test was used to analyze the differences in DKI parameters of the optic chiasm and bilateral optic radiation among the 5 groups, and the Holm-Bonferroni method was employed for multiple comparison correction in pairwise comparisons.Results:There were statistically significant overall differences in the DKI parameters of the optic chiasm and bilateral optic radiations among healthy control group, ON+MS group, ON-MS group, ON+NMOSD group, and ON-NMOSD group (all P0.05). The FA value of the optic chiasm in ON+NMOSD group was significantly lower than that of healthy control group and ON-MS group, as well as ON-NMOSD group ( P0.05). The FA value of the left optic radiation in ON+NMOSD group was lower than that in healthy control group and the ON-MS group. The RK value of the optic chiasm in ON+MS group was lower than that in the healthy control group and ON-NMOSD group ( P0.05). The MK and RK values of the left optic radiation in ON-MS group were significantly lower than those in the ON+NMOSD group and ON-NMOSD group ( P0.05). Conclusions:NMOSD and RRMS patients demonstrate varying degrees of microstructural damage in the optic chiasm and optic radiations. Differences of DKI parameters suggest different pathological mechanisms of visual pathway damage between NMOSD and MS, which may be helpful for early detection of occult visual pathway lesions.