Travelling wave structures for lossless ion manipulations(TW-SLIM)employ travelling wave electric fields to propel ions forward,enabling exceptionally long transmission paths and holding great potential for applications in material transportation and separation.In this study,different from previous studies focusing on the transport performance of macromolecules such as proteins in TW-SLIM,the transmission performance of small molecules(<200 amu)was investigated and analyzed in the turning TW-SLIM through the COMSOL simulation platform,to explore the influence of electrostatic field of protective electrode and radio frequency(RF)electric field on ion transport efficiency,and obtain the optimal value.Compared to macromolecules,small molecules required lower voltage amplitudes from guard electrodes but stricter requirements in terms of the peak-to-peak amplitude and frequency of RF voltage for lossless transmission.Using dimethyl methylphosphonate(DMMP)as a sample and testing it on the TW-SLIM experimental platform,when the protective voltage amplitude was 5 V and the peak-to-peak voltage of the radio-frequency electrode was 440 V at 1.5 MHz,the ion transmission efficiency reached 100%,achieving lossless transmission.The experimental results provided valuable references for application of TW-SLIM in separation and detection of small molecular substances,such as explosives and drugs.

The electrocatalytic nitrate reduction reaction(NO3RR)presents a sustainable pathway for large-scale ammonia production,yet it faces significant challenges due to proton supply limitations caused by the high energy barrier for water dissociation,which slows ammonia(NH3)generation.Herein,a palladium(Pd)-modified copper-cobalt(CuCo)hollow fiber penetration electrode that enabled H2 injection through its hollow structures,thereby enhancing proton availability for NO3RR was developed.The active Pd component efficiently dissociated H2,facilitating active hydrogen(*H)spillover and speeding up the cascade NO3RR process on Cu and Co sites.As a result,a half-cell energy efficiency of 39.53%and an NH3 Faradaic efficiency(FE)of 97.11%±1.17%at-0.1 V(vs RHE)were achieved,comparable to state-of-the-art systems.Importantly,the H2-assisted approach prevented the oxidation of active Cu and Co phases,demonstrating exceptional stability with less than 5.6%decay in current density(267 mA/cm2)and retention of NH3 FE at 94.8%after over 70 h of electrolysis.These findings offered valuable insights into proton supply pathways and design of NO3RR electrodes.

PURPOSE: Septic shock is associated with high mortality and poor outcomes among sepsis patients with coagulopathy. Although traditional statistical methods or machine learning (ML) algorithms have been proposed to predict septic shock, these potential approaches have never been systematically compared. The present work aimed to develop and compare models to predict septic shock among patients with sepsis. METHODS: It is a retrospective cohort study based on 484 patients with sepsis who were admitted to our intensive care units between May 2018 and November 2022. Patients from the 908th Hospital of Chinese PLA Logistical Support Force and Nanchang Hongdu Hospital of Traditional Chinese Medicine were respectively allocated to training (n=311) and validation (n=173) sets. All clinical and laboratory data of sepsis patients characterized by comprehensive coagulation indexes were collected. We developed 5 models based on ML algorithms and 1 model based on a traditional statistical method to predict septic shock in the training cohort. The performance of all models was assessed using the area under the receiver operating characteristic curve and calibration plots. Decision curve analysis was used to evaluate the net benefit of the models. The validation set was applied to verify the predictive accuracy of the models. This study also used Shapley additive explanations method to assess variable importance and explain the prediction made by a ML algorithm. RESULTS: Among all patients, 37.2% experienced septic shock. The characteristic curves of the 6 models ranged from 0.833 to 0.962 and 0.630 to 0.744 in the training and validation sets, respectively. The model with the best prediction performance was based on the support vector machine (SVM) algorithm, which was constructed by age, tissue plasminogen activator-inhibitor complex, prothrombin time, international normalized ratio, white blood cells, and platelet counts. The SVM model showed good calibration and discrimination and a greater net benefit in decision curve analysis. CONCLUSION The SVM algorithm may be superior to other ML and traditional statistical algorithms for predicting septic shock. Physicians can better understand the reliability of the predictive model by Shapley additive explanations value analysis.
Humans ; Shock, Septic/blood* ; Machine Learning ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Sepsis/complications* ; ROC Curve ; Cohort Studies ; Adult ; Intensive Care Units ; Algorithms ; Blood Coagulation ; Critical Illness

OBJECTIVE: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). METHODS: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. RESULTS: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. β-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). CONCLUSIONS YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. β-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.
Humans ; Microcirculation/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Stomach Neoplasms/physiopathology* ; Emulsions ; Male ; Plant Oils/administration & dosage* ; Brucea/chemistry* ; Middle Aged ; Female ; Drug Combinations ; Human Umbilical Vein Endothelial Cells/metabolism* ; Seeds/chemistry* ; Injections ; Vascular Endothelial Growth Factor A/metabolism* ; Aged ; Network Pharmacology

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Wastewater-based epidemiology has emerged as a transformative surveillance tool for estimating substance consumption and monitoring disease prevalence, particularly during the COVID-19 pandemic. It enables the population-level monitoring of illicit drug use, pathogen prevalence, and environmental pollutant exposure. In this perspective, we summarize the key challenges specific to the Chinese context: (1) Sampling inconsistencies, necessitating standardized 24-hour composite protocols with high-frequency autosamplers (≤ 15 min/event) to improve the representativeness of samples; (2) Biomarker validation, requiring rigorous assessment of excretion profiles and in-sewer stability; (3) Analytical method disparities, demanding inter-laboratory proficiency testing and the development of automated pretreatment instruments; (4) Catchment population dynamics, reducing estimation uncertainties through mobile phone data, flow-based models, or hydrochemical parameters; and (5) Ethical and data management concerns, including privacy risks for small communities, mitigated through data de-identification and tiered reporting platforms. To address these challenges, we propose an integrated framework that features adaptive sampling networks, multi-scale wastewater sample banks, biomarker databases with multidimensional metadata, and intelligent data dashboards. In summary, wastewater-based epidemiology offers unparalleled scalability for equitable health surveillance and can improve the health of the entire population by providing timely and objective information to guide the development of targeted policies.
China/epidemiology* ; Humans ; Wastewater/analysis* ; COVID-19/epidemiology* ; Public Health ; Wastewater-Based Epidemiological Monitoring ; SARS-CoV-2

The cobalt sulphide nickel ternary material(NiCo2S4)prepared by hydrothermal method in this work was combined with multi-walled carbon nanotubes(MWCNT)for constructing an electrochemical sensor for quantitative detection of rutin.The morphology and crystal of the electrochemical materials were characterized by scanning electron microscopy and X-ray diffractometer,and the electrochemical behavior of the glassy carbon electrode(GCE)modified with NiCo2S4/MWCNT composites was investigated.The experimental results showed that the electrochemical redox process of two electrons and two protons occurred on the surface of modified electrode NiCo2S4/MWCNT/GCE.Under the optimized conditions,the linear range for detection of rutin by square-wave voltammetry(SWV)using this sensor was 0.06-14.8 μmol/L and the detection limit was 14.3 nmol/L.The electrochemical sensor was sensitive,simple and low-cost,with good reproducibility and reliable stability,and could be used for detection of rutin in real samples such as compound rutin tablets and color chrysanthemi tablets,with spiked recoveries of 99.5%-102.0%.

Objective To investigate the role and clinical significance of fine-needle aspiration combined with next-generation sequencing 18 genes detection in the diagnosis of thyroid cancer.Methods The samples were tested by liquid-based cytology and next-generation sequencing.Cytological diagnosis was based on the 3rd edition Bethesda system for reporting thyroid cytopathology.Histological diagnosis was based on the fifth WHO classification criteria for thyroid neoplasms.Results Among 97 thyroid specimens,8 cases(8.25%)were unsatis-fied,44 cases(45.36%)had benign lesions,9 cases(9.28%)had atypical cells of unknown significance,4 cases(4.12%)had suspected follicular or oncocytic tumors.Suspected papillary carcinoma was found in 10 cases(10.31%)and papillary carcinoma in 22 cases(22.68%).A total of 52 cases(53.61%)were mutated,and 10 gene muta-tions were detected,among which BRAF gene mutation had the highest detection rate 63.46%(33/52).BRAF gene mutation was associated with gender,age and cytological diagnosis(P<0.05).Cytology combined with next-generation sequencing improved the diagnostic accuracy(97.0%vs.81.8%),having higher diagnostic efficiency.Conclusion Thyroid fine-needle aspiration cytology combined with next-generation sequencing can promote early diagnosis of thyroid cancer and provide basis for individual treatment of patients.

The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.

Objective:To study the clinical safety and validity of retrograde new endoscopic field of vision in miniature pigs.Methods:6 live miniature pigs were selected as study subjects,En-doscopic Retrograde New View(ERNV)was selected.The performance,image quality and intraoper-ative and postoperative complications were evaluated.To evaluate whether all the experimental ani-mals could complete the relevant endoscopy.Verify ERNV's operating performance,including whether the duodenoscope can enter the biliary tract smoothly,and made sure whether the injection,suction,and instrument channels were unobstructed.Choledochoscope image clarity,color resolu-tion,image deformation and distortion,accurate evaluation of lumen conditions and clear observation of mucosal surface conditions were analyzed.Whether there were operant injuries such as bleeding and perforation,as well as adverse events such as respiratory depression and cardiac arrest.The sur-vival status and adverse reactions of all pigs were observed.Results:The choledochoscope was successfully inserted into the bile duct of 6 miniature pigs.The product had good operation perfor-mance and could enter the bile duct through the duodenoscope smoothly.The injection,suction and instrument channels were relatively smooth.In addition,the endoscopic images are clear,with better color resolution,and without image deformation and distortion,which can realize accurate evaluation of the conditions in the lumen and observe the mucosal surface conditions more clearly.No bile duct stenosis or dilatation occurred in all miniature pigs,and the bile duct mucosa was smooth,without hyperemia and edema,and no abnormal thickening or bending of mucous vessels.During the exami-nation,there were no operational injuries such as bleeding and perforation,and no adverse events such as respiratory depression and cardiac arrest occurred.The vital signs of all miniature pigs tended to be stable after operation,and the survival state was good,and there were no complications such as cholangitis,bleeding and perforation.Conclusion:ERNV has good clinical safety and efficacy,ex-cellent operation performance and excellent image quality,and is worthy of clinical application.