This paper summarizes Professor WANG Yaoxian's experience in treating diabetic kidney disease （DKD） from the perspective of spleen and stomach based on the "internal heat leading to concretions" theory. It is considered that internal heat leading to concretions constitutes the core pathogenesis of DKD， with the spleen and stomach serving as the source of internal heat； therefore， treatment should be based on regulating the spleen and stomach. In the early stage of DKD， dysfunction of the spleen and stomach leads to the initial generation of internal heat. Common syndrome patterns include gastrointestinal heat accumulation and constrained heat in the liver and stomach， for which modified Gegen Qinlian Decoction （葛根芩连汤） can be used to clear heat bind while modified Dachaihu Decoction （大柴胡汤） is used to clear stomach and soothe liver， respectively. In the middle stage of DKD， weakness of the spleen and stomach results in the initial formation of concretions and conglomerations. Common patterns include spleen deficiency with prevalence of dampness and deficiency of both the spleen and kidney. Treatment emphasizes strengthening the spleen and resolving dampness， raising yang and boosting the stomach with modified Shengyang Yiwei Decoction （升阳益胃汤）， or supplementing spleen and boosting kidney， dissipating bind and dispe-ring concretions with modified Shenqi Dihuang Decoction （参芪地黄汤）， respectively. In the late stage of DKD， it is characterized by spleen and stomach depletion， and rampant accumulation of turbidity and toxin， and the common syndrome patterns are damp-turbidity obstruction in the middle jiao （焦） and spleen-kidney yang deficiency. Treatment aims to remove turbidity and harmonize the stomach， or to warm the kidney and strengthen the spleen while elimina-ting turbidity， using modified Dahuang Gancao Decoction（大黄甘草汤） and Jupi Zhuru Decoction （橘皮竹茹汤） or modified Baoyuan Decoction （保元汤） and Lizhong Decoction （理中汤）， respectively. In clinical practice， appropriate formulas and medications are flexibly selected according to specific syndromes.

High-performance phototheranostics with combined photothermal therapy and photoacoustic imaging have been considered promising approaches for efficient cancer diagnosis and treatment. However, developing phototheranostic materials with efficient photothermal conversion efficiency (PCE), especially over the second near-infrared window (NIR-II, 1000-1700 nm), remains challenging. Herein, we report an ultraefficient NIR-II-activated nanomedicine with phototheranostic and vaccination capability for highly efficient in vivo tumor elimination and metastasis inhibition. The NIR-II nanomedicine of a semiconducting biradical oligomer with a motor-flexible design was demonstrated with a record-breaking PCE of 87% upon NIR-II excitation. This nanomedicine inherently features extraordinary photothermal stability, good biocompatibility, and excellent photoacoustic performance, contributing to high-contrast photoacoustic imaging in living mice and high-performance photothermal elimination of tumors. Moreover, a whole-cell vaccine based on a NIR-II nanomedicine with NIR-II-activated performance was further designed to remotely activate the antitumor immunologic memory and effectively inhibit tumor occurrence and metastasis in vivo, with good biosafety. Thus, this work paves a new avenue for designing NIR-II active semiconducting biradical materials as a promising theranostics platform and further promotes the development of NIR-II nanomedicine for personalized cancer treatment.

OBJECTIVE: To identify and validate novel biomarkers for the early diagnosis of sepsis-associated acute kidney injury (SA-AKI) and precise continuous renal replacement therapy (CRRT) using proteomics. METHODS: A prospective multicenter cohort study was conducted. Patients with sepsis admitted to five hospitals in Taizhou City of Zhejiang Province from April 2019 to December 2021 were continuously enrolled, based on the occurrence of acute kidney injury (AKI). Sepsis patients were divided into SA-AKI group and non-SA-AKI group, and healthy individuals who underwent physical examinations during the same period were used as control (NC group). Peripheral blood samples from participants were collected for protein mass spectrometry analysis. Differentially expressed proteins were identified, and functional enrichment analysis was conducted on these proteins. The levels of target proteins were detected by enzyme linked immunosorbent assay (ELISA), and the predictive value of target protein for SA-AKI were evaluated by receiver operator characteristic curve (ROC curve). Additionally, sepsis patients and healthy individuals were selected from one hospital to externally verify the expression level of the target protein and its predictive value for SA-AKI, as well as the accuracy of CRRT treatment. RESULTS: A total of 37 patients with sepsis (including 19 with AKI and 18 without AKI) and 31 healthy individuals were enrolled for proteomic analysis. Seven proteins were identified with significantly differential expression between the SA-AKI group and non-SA-AKI group: namely cystatin C (CST3), β ₂-microglobulin (β ₂M), insulin-like growth factor-binding protein 4 (IGFBP4), complement factor I (CFI), complement factor D (CFD), CD59, and glycoprotein prostaglandin D2 synthase (PTGDS). Functional enrichment analysis revealed that these proteins were involved in immune response, complement activation, coagulation cascade, and neutrophil degranulation. ELISA results demonstrated specific expression of each target protein in the SA-AKI group. Additionally, 65 patients with sepsis (38 with AKI and 27 without AKI) and 20 healthy individuals were selected for external validation of the 7 target proteins. ELISA results showed that there were statistically significant differences in the expression levels of CST3, β ₂M, IGFBP4, CFD, and CD59 between the SA-AKI group and non-SA-AKI group. ROC curve analysis indicated that the area under the curve (AUC) values of CST3, β ₂M, IGFBP4, CFD, and CD59 for predicting SA-AKI were 0.788, 0.723, 0.723, 0.795, and 0.836, respectively, all exceeding 0.7. Further analysis of patients who underwent CRRT or not revealed that IGFBP4 had a good predictive value, with an AUC of 0.84. CONCLUSIONS Based on proteomic analysis, CST3, β ₂M, IGFBP4, CFD, and CD59 may serve as potential biomarkers for the diagnosis of SA-AKI, among which IGFBP4 might be a potential biomarker for predicting the need for CRRT in SA-AKI patients. However, further clinical validation is required.
Humans ; Sepsis/complications* ; Acute Kidney Injury/blood* ; Proteomics ; Prospective Studies ; Biomarkers/blood* ; Male ; Female ; beta 2-Microglobulin/blood* ; Middle Aged ; Cystatin C/blood* ; Aged

This study investigates the pharmacokinetics and metabolic characteristics of three marine-derived piericidins as potential drug leads for kidney disease: piericidin A (PA) and its two glycosides (GPAs), glucopiericidin A (GPA) and 13-hydroxyglucopiericidin A (13-OH-GPA). The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate. Rapid absorption of PA and GPAs in mice was observed, characterized by short half-lives and low bioavailability. Glycosides and hydroxyl groups significantly enhanced the absorption rate (13-OH-GPA > GPA > PA). PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes (CYPs) and uridine diphosphoglucuronosyl transferases (UGTs). Glucuronidation emerged as the primary metabolic pathway, with UGT1A7, UGT1A8, UGT1A9, and UGT1A10 demonstrating high elimination rates (30%-70%) for PA and GPAs. This rapid glucuronidation may contribute to the low bioavailability of GPAs. Despite its low bioavailability (2.69%), 13-OH-GPA showed higher kidney distribution (19.8%) compared to PA (10.0%) and GPA (7.3%), suggesting enhanced biological efficacy in kidney diseases. Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability. In conclusion, this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.
Animals ; Male ; Mice ; Aquatic Organisms/chemistry* ; Biological Availability ; Cytochrome P-450 Enzyme System/metabolism* ; Glucuronosyltransferase/metabolism* ; Microsomes, Liver/metabolism* ; Molecular Structure ; Biological Products/pharmacokinetics* ; Pyridines/pharmacokinetics*

Objective:To explore the predictive value of the combined application of total prostate-specific antigen (TPSA), vascular endothelial growth factor A (VEGF-A), and interleukin (IL) in predicting postoperative biochemical recurrence in patients with prostate cancer.Methods:This study adopted a retrospective cohort research method. 202 male prostate cancer patients who visited Xi′an Gaoxin Hospital from April 2021 to January 2024 were selected as the research subjects. The age of the patients was 68(64, 71) years, and their postoperative conditions were classified into the non-recurrence group ( n=144) and the biochemical recurrence group ( n=58). The general clinical data and serumological test indicators SA, free prostate-specific antigen (FPSA), VEGF-A, IL-6, IL-17] were detected and compared between the two groups. Quantitative data with normal distribution were expressed as mean±standard deviation, and the comparison between groups was performed using the independent sample t-test; non-normal distribution quantitative data were expressed as M( Q1, Q3), and the comparison between groups was performed using the Mann-Whitney U test. The comparison between groups of count data was performed using the chi-square test. Through Spearman correlation analysis and multivariate Logistic regression analysis, the risk factors for biochemical recurrence after surgery in prostate cancer patients were screened out, and the efficacy of the combined prediction model based on TPSA, VEGF-A, and IL-17 was evaluated by receiver operating characteristic (ROC) curve, decision curve (DCA), and calibration curve. Results:The average tumor diameter, proportion of positive surgical margins, proportion of seminal vesicle invasion, and proportion of patients with Gleason score 3-5 in the biochemical recurrence group were significantly higher than those in the non-recurrence group ( P<0.05). The serumological indicators TPSA, VEGF-A, IL-6, IL-17 in the biochemical recurrence group were 44.28 (42.37, 48.57) ng/mL, (28.24±3.99) ng/mL, (39.14±2.95) ng/L and (66.64±6.04) pg/mL; those in the non-recurrence group were 41.25 (36.61, 43.56) ng/mL, (23.52±3.75) ng/mL, (37.19±4.19) ng/L, and (57.31±6.63) pg/mL. The biochemical recurrence group was higher than the non-recurrence group, and the difference was statistically significant ( P<0.05). Spearman correlation analysis and Logistic regression analysis found that TPSA, VEGF-A, and IL-17 were risk factors for biochemical recurrence after surgery in prostate cancer patients ( P<0.05); the DCA curve and calibration curve indicated that the combined prediction model based on TPSA, VEGF-A, and IL-17 had good accuracy (Hosmer-Lemeshow P=0.421), and the ROC curve suggested that the efficacy of the above indicators combined for predicting biochemical recurrence after surgery in prostate cancer patients was higher [AUC (95% CI)=0.899 (0.832-0.966)], and higher than the independent predictive efficacy of each indicator. Conclusion:Continuous monitoring of serum TPSA, VEGF-A, and IL-17 levels can effectively predict the risk of postoperative recurrence in prostate cancer patients and also provide biological markers for preventing disease recurrence.

Fatigue driving is one of the leading causes of traffic accidents, posing a significant threat to drivers and road safety. Most existing methods focus on studying whole-brain multi-channel electroencephalogram (EEG) signals, which involve a large number of channels, complex data processing, and cumbersome wearable devices. To address this issue, this paper proposes a fatigue detection method based on frontal EEG signals and constructs a fatigue driving detection model using an asymptotic hierarchical fusion network. The model employed a hierarchical fusion strategy, integrating an attention mechanism module into the multi-level convolutional module. By utilizing both cross-attention and self-attention mechanisms, it effectively fused the hierarchical semantic features of power spectral density (PSD) and differential entropy (DE), enhancing the learning of feature dependencies and interactions. Experimental validation was conducted on the public SEED-VIG dataset. The proposed model achieved an accuracy of 89.80% using only four frontal EEG channels. Comparative experiments with existing methods demonstrate that the proposed model achieves high accuracy and superior practicality, providing valuable technical support for fatigue driving monitoring and prevention.
Humans ; Electroencephalography/methods* ; Automobile Driving ; Fatigue/diagnosis* ; Accidents, Traffic/prevention & control* ; Signal Processing, Computer-Assisted ; Neural Networks, Computer ; Algorithms ; Prefrontal Cortex/physiology*

Objective To explore the value of low contrast dose and low flow rate one-stop craniocervical CT angiography(CT A)-cerebral CT perfusion(CTP)for detecting carotid atherosclerosis(CAS).Methods Totally 117 CAS patients were prospectively enrolled and divided into group A(n=19),B(n=52),C(n=46),and low contrast dose and low flow rate one-stop craniocervical CTA-brain CTP scanning,low contrast dose and low flow rate craniocervical CT A scanning,as well as conventional craniocervical CT A scanning were performed,respectively.Virtual monoenergetic images(VMI)of 40,50 and 60 keV were reconstructed in group A and B.The subjective and objective evaluations of image quality were compared among 3 groups.Results Subjective scores of image quality and diagnostic confidence of 40 and 50 keV VMI,and the diagnostic confidence of 60 keV VMI in group A and B were not significant different compared with those in group C(all P＞0.05).Signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of each segment of craniocervical blood vessels at 40 and 50 keV VMI in group A and B were all higher than those in group C(all P＜0.05).CNR of cavernous sinus segment of internal carotid artery(C5 segment),horizontal segment of middle cerebral artery(MCA)(A1 segment),lateral sulcus segment of MCA(M2 segment)and basilar artery(BA)segment in group A at 60 keV VMI were all higher than those in group C(all P＜0.05).SNR of C5 segment,A1 segment and BA segment,as well as CNR of BA segment of 60 keV VMI in group B were all higher than those in group C(all P＜0.05).Conclusion Low contrast dose and low flow rate one-stop craniocervical was feasible for detecting CAS.

Objective:To systematically compares the medial plantar venous flap (MPVF) and the lateral toe flap (LTF) reconstruction of digit-pulp defect, aiming to establish whether there exist significant differences between the 2 flaps in flap survival rate, two-point discrimination (TPD), score of Vancouver Scar Scale (VSS) and score of digit-pulp defect reconstruction evaluation.Methods:With a prospective cohort design, this study enrolled 36 patients who were admitted in Department of Hand Surgery, Longgang Eighth People's Hospital of Shenzhen for digit-pulp defects with bone or tendon exposure between January 2024 and September 2024. According to the random grouping method, participants were divided into 2 groups. The MPVF group comprised 18 patients (21 digits) of 13 males (15 digits) and 5 females (6 digits), aged 13-58 (mean 44±12) years. The MPVF group included 9 left and 12 right digits, with distribution as follows: 2 thumbs, 5 index fingers, 7 middle fingers, 5 ring fingers and 2 little fingers. The soft tissue defect area ranged from 2.0 cm × 1.0 cm to 9.2 cm × 3.3 cm (mean 6.69 cm 2± 6.69 cm 2). Flap dimensions ranged from 2.1 cm×1.1 cm to 9.5 cm×3.5 cm (mean 7.54 cm 2±7.22 cm 2). Donor sites were closed primarily or by full-thickness skin grafts harvested from the leg. The LTF group included 18 patients (21 digits) of 15 males (17 digits) and 3 females (4 digits), aged 22-62 (mean 41±12) years. The affected digits in LTF group comprised 12 left and 9 right digits, with a distribution of: 3 thumbs, 9 index fingers, 5 middle fingers, 2 ring fingers and 2 little fingers. The area of soft tissue defect ranges from 1.4 cm × 1.0 cm to 3.9 cm × 1.8 cm (mean 3.93 cm 2± 1.80 cm 2). Flap dimensions ranged from 1.5 cm×1.2 cm to 4.0 cm×1.9 cm (mean 4.52 cm 2±1.89 cm 2). Donor sites were closed primarily, or by full-thickness skin grafts harvested through extension of proximal wound extension or from calf for defect coverage. Patients were contacted for postoperative follow-up by telephone or WeChat to arrange a visit of outpatient clinic or a home visit by surgeon. Statistical analysis was conducted to compare the 2 groups regarding: gender, age and flap dimensions, flap survival rate at 2 weeks after surgery and TPD of flaps, VSS scores, and digit-pulp defect reconstruction evaluation scale scores at 4 months and 6 months postoperatively. P<0.05 indicates a statistically significant difference. Results:The comparative analysis revealed no statistically significant differences between 2 groups in baseline characteristics: gender distribution ( χ2=0.53, P=0.47), mean age ( t=0.75, P=0.46), flap dimensions ( t=1.86, P=0.08), confirming a demographic and surgical parameter equivalence in subsequent outcome comparisons ( P>0.05). All flaps survived at 2 weeks after surgery. All skin grafts at donor sites demonstrated complete viability with uneventful primary wound healing. At 4 months after surgey, the TPD in the MPVF group were 14.71 mm±1.90 mm and 7.81 mm±1.78 mm, respectively, compared to 14.48 mm±1.57 mm and 7.67 mm±1.39 mm in the LTF group at 6 months after surgery. The VSS scores were 1.67±1.11 and 1.29±0.72 for MPVF versus 1.86±1.15 and 1.38±0.81 for LTF at corresponding time points. The digit-pulp defects reconstruction evaluation scale scores showed 88.43±2.62 and 91.43±3.59 for MPVF versus 88.19±2.70 and 91.19±3.50 for LTF. Statistical analysis revealed no significant differences (all P>0.05) at 2 postoperative time points. Conclusion:The MPVF demonstrated non-inferior clinical efficacy to the LTF in reconstruction of digit-pulp defects, with comparable outcomes in flap survival rate at 2 weeks, and in TPD, VSS scores, digit-pulp defect reconstruction evaluation scale scores at 4 months and at 6 month after surgey.

Objective:To establish and evaluate the performance of a stable and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of six phytosterols in human plasma.Methods:The methodology was established, evaluated, and applied. A number of 136 healthy subjects were recruited from the Physical Examination Center of Suzhou Municipal Hospital from October 2023 to December 2023, meanwhile plasma phytosterols′ levels were validated in 5 patients with sitosterolemia. Taking deuterium isotope as internal standards, the clear separation was achieved using a Phenomenex C18 (2.1×100 mm, 2.6 μm) column. The mobile phase consisted of water and methanol at a flow rate of 0.4 ml/min with gradient elution, and the column temperature was 25 ℃. The experiments were performed on AB Sciex 6500+triple quadrupole mass spectrometry, and the linearity, limit of quantification, rate of recovery, precision, and stability of the method were evaluated. The testing method was further validated in the sitosterolemia patients.Results:The method had in-run and between-run coefficient of variation ranging 1.8%-12.5% and 2.6%-13.6%, respectively, which accorded with the precision requirements. The rates of recovery were 85.0%-105.1%, which accorded with the accuracy requirements. The samples showed good stability before and after handling stored at 4 ℃ for 72 hours. The plasma levels of sitosterol, campesterol, stigmasterol and cholestanol in sitosterolemia patients were apparently higher compared with those in the healthy group ( P<0.001). Conclusion:LC-MS/MS method for the quantitative measurement of plant sterols in human plasma has been established, which has convenient preprocessing and passed the performance evaluation including linearity, lower limit of quantification, recovery rate, precision and stability, and shown to be suitable for clinical application.