OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

OBJECTIVE: To assess the association of microribonucleic acid (miRNA) gene polymorphisms with the risk and clinicopathological characteristics of Crohn's disease (CD) and the influence of miRNA gene variants on the response to ustekinumab (UST) treatment among CD patients. METHODS: From January 2018 to February 2025, 312 patients diagnosed with CD and 527 gender- and age-matched normal controls were selected as the study subjects at the Department of Gastroenterology of the Second Affiliated Hospital of Wenzhou Medical University. Genotypes of miR-155 (rs767649), miR-21 (rs13137), miR-124 (rs531564) and miR-146a (rs57095329, rs2431697) were determined with multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) technique. The patients were divided into different subgroups according to the Montreal Classification Criteria for CD. Harvey-Bradshaw index (HBI) and simplified endoscopic score for CD were respectively applied to assess the clinical and endoscopic disease activity of CD. Unconditional logistic regression model was employed to analyze the distribution of miRNA gene polymorphisms between the two groups, as well as their influence on the clinicopathological characteristics of CD patients. Among them, 185 CD patients received first-line UST treatment, with the first sufficient dose of UST (6 mg/kg) administered intravenously. Based on the changes in HBI at week 8, the response of patients to UST treatment was evaluated. Unconditional logistic regression model was employed to analyze the distribution of miRNA gene polymorphisms between clinically responsive group (the decline of HBI ≥ 3 scores compared to week 0) and non-responsive group. All of the P values were adjusted by Bonferroni correction. This study has been approved by the Medical Ethics Committee of the Second Affiliated Hospital of Wenzhou Medical University (Ethics No.: 2025-K-12-01). RESULTS: No significant difference was found in the distribution of miRNA gene polymorphisms between the two groups (all P > 0.05). The variant genotype (TC+CC) of rs2431697 was more common among patients with terminal ileal-type and ileocolic-type CD than those with the colonic-type CD (OR = 4.98, 95%CI: 1.49~16.68, P = 0.009, adjusted P = 0.045). However, the opposite conclusion was drawn for the homozygous variant genotype (TT) of rs13137 and variant genotype (GC+CC) of rs531564 (OR = 0.37, 95%CI: 0.18~0.76, P = 0.007, adjusted P = 0.035; OR = 0.36, 95%CI: 0.18~0.73, P = 0.004, adjusted P = 0.020). Compared to patients with non-stricturing and penetrating CD, the variant genotype (AG+GG) and variant allele (G) of rs57095329 were more common in those with stricturing and penetrating CD (OR = 4.06, 95%CI: 2.46~6.71, P < 0.001, adjusted P < 0.005; OR = 3.12, 95%CI: 2.06~4.73, P < 0.001, adjusted P < 0.005). However, the frequencies of variant genotype (AT+TT) and variant allele (T) of rs13137 were lower among patients with stricturing and penetrating CD than in those without (OR = 0.25, 95%CI: 0.15~0.41, P < 0.001, adjusted P < 0.005; OR = 0.45, 95%CI: 0.33~0.63, P < 0.001, adjusted P < 0.005). Additionally, the variant genotype (AG+GG) and variant allele (G) of rs57095329 were more common among those with moderately to severely endoscopic activity than those with mildly endoscopic activity (OR = 2.01, 95%CI: 1.19~3.42, P = 0.009, adjusted P = 0.045; OR = 2.04, 95%CI: 1.28~3.25, P = 0.003, adjusted P = 0.015). In total 117 cases had shown clinical response by week 8, while 68 cases showed no response. Compared with t he clinically non-responsive group, the variant genotype (TC+CC) and variant allele (C) of rs2431697 were more common in the clinically responsive group (OR = 3.86, 95%CI: 1.80~8.32, P = 0.001, adjusted P = 0.005; OR = 2.60, 95%CI: 1.34~5.06, P = 0.005, adjusted P = 0.025). However, the variant genotype (TA+AA) of rs767649 was less frequent in the clinically responsive group than the non-responsive group (OR = 0.40, 95%CI: 0.21~0.74, P = 0.004, adjusted P = 0.020). The same conclusion was drawn for the variant genotype (AT+TT) and variant allele (T) of rs13137 when the clinically responsive group was compared with the non-responsive group (OR = 0.30, 95%CI: 0.14~0.63, P = 0.002, adjusted P = 0.010; OR = 0.54, 95%CI: 0.35~0.82, P = 0.005, adjusted P = 0.025). CONCLUSION Genetic polymorphisms of miRNAs are not associated with the risk of developing CD. The miR-146a (rs57095329) variant may increase the endoscopic activity of CD and the risk for stenosis or penetration. However, the miR-146a (rs2431697) variant may increase the risk of ileal involvement. The miR-21 (rs13137) variant may reduce the risk of ileal involvement and the risk of stenosis or penetration. The miR-124 (rs531564) variant may reduce the risk of ileal involvement. Among patients receiving UST treatment, the miR-146a (rs2431697) variant may increase the clinical response by week 8. However, both the miR-155 (rs767649) and miR-21 (rs13137) variants may decrease the clinical response by week 8.
Humans ; MicroRNAs/genetics* ; Crohn Disease/pathology* ; Male ; Female ; Adult ; Polymorphism, Single Nucleotide ; Middle Aged ; Asian People/genetics* ; Genetic Predisposition to Disease ; Genotype ; Young Adult ; Case-Control Studies ; Adolescent ; East Asian People

Processed electroencephalogram (EEG) indices, such as the Bispectral Index, have markedly influenced anesthesia practice as they translate brain activity into simple numerical indices. Nevertheless, as the manufacturing algorithms are not disclosed, the underlying neurophysiology remains obscured. Additionally, these indices are often affected by electromyographic contamination, pharmacological variability, and patient-specific EEG heterogeneity. In contrast, an EEG spectrogram, or density spectral array, preserves the frequency- and time-resolved structures of cortical oscillations. This information is presented in a form that is both physiologically meaningful and clinically interpretable. In this review, we trace the evolution of anesthesia from an index-based to a spectrogram-guided approach, and summarize the clinical rationale for adopting the latter. Key applications of this approach include the use of frontal alpha power as a biomarker of cortical stability and postoperative brain health, the identification of nociceptive arousal through alpha dropout and beta or delta arousal patterns, and individualized titration of multimodal or age-specific anesthetic management. Although current devices lack standardized quantitative alpha metrics and have limited sensitivity for low-frequency brain wave components, structured EEG education programs have proven to be effective in terms of fostering spectrogram literacy among anesthesiologists. By combining neurophysiological precision with bedside practicality, the EEG spectrogram represents a pivotal advance toward individualized, mechanism-based, and brain-protective anesthesia, transforming anesthetic monitoring from mere algorithmic abstraction to cortical insight.

ObjectiveThis paper aims to study the effects of four weeks of aerobic exercise combined with Anmeidan on the synaptic plasticity marker protein and synaptic ultrastructure of the hippocampus in the model rats with sleep deprivation， thereby investigating the possible mechanism of its action to improve the learning memory of rats with sleep deprivation. Methods50 Sprague-Dawley （SD） rats were randomly divided into blank control group （group C）， sleep deprivation group （group M）， aerobic exercise + sleep deprivation group （group MEX）， Anmeidan + sleep deprivation group （group MA， 18.18 g∙kg^-1∙d^-1）， and aerobic exercise + Anmeidan + sleep deprivation group （group MEXA， 18.18 g∙kg^-1∙d^-1）. Anmeidan was administered by gavage in the MA group for four weeks. Aerobic exercise was performed in the MEX group for four weeks. Anmeidan was administered by gavage in the MEXA group in combination with aerobic exercise for four weeks， and sleep deprivation was performed for 72 h by using the multi-platform water environment method. At the end of sleep deprivation， Morris water maze was used to assess the learning and memory ability of rats in each group， and hematoxylin-eosin （HE） staining was used to observe the morphological changes of rats' hippocampal neurons. A transmission electron microscope was used to observe the synaptic ultrastructure of rats' hippocampus. The expression levels of brain-derived neurotrophic factor （BDNF）， tyrosine kinase receptor B （TrkB）， cAMP-response element binding protein （CREB）， postsynaptic density-95 （PSD-95）， and synaptophysin （SYN） were detected by Western blot， and the real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the relative mRNA expression levels of BDNF， TrkB， and CREB in the rats' hippocampus. ResultsCompared with those in group C， rats in group M had significantly longer latency and total swimming distance on the platform （P<0.01） and a significantly reduced number of traversals across the platform as well as the residence time in the target quadrant （P<0.01）. Part of the hippocampal neurons damaged， with a reduced number， disorganized arrangement， fuzzy synaptic gaps， thinning of post-synaptic dense material， and uneven density of synaptic vesicles. The protein expression levels and relative mRNA expression levels of BDNF， TrkB， and CREB were significantly reduced （P<0.01）， and the protein expression levels of PSD-95 and SYN were significantly reduced （P<0.01）. Compared with those in group M， rats in MA， MEX， and MEXA groups showed a decrease in latency to platform and total distance swum， an increase in the number of traversals across the platform and residence time in the target quadrant （P<0.05， P<0.01）， a reduction in hippocampal neuronal damage， a better arrangement， a more intact synaptic structure， a thickening of post-synaptic dense material， a uniform density of synaptic vesicles， and an increase in the protein expression levels and mRNA expression levels of BDNF， TrkB， and CREB （P<0.05， P<0.01）. The protein expressions of PSD-95 and SYN rose （P<0.05， P<0.01）. ConclusionAerobic exercise combined with Anmeidan can improve learning memory in rats with sleep deprivation， and its mechanism of action may be related to the modulation of the BDNF/TrkB/CERB signalling pathway， up-regulation of the expression of PSD-95 and SYN， and improvement of synaptic structural damage. The combination of interventions is superior to single exercise or drugs.

The development of polysaccharide conjugate vaccines, which convert polysaccharide antigens into T-cell-dependent immunogens through covalent conjugation with protein carriers, represents a critical strategy for enhancing immune protection in infants and young children. Globally licensed conjugate vaccines currently employ carrier proteins including Tetanus Toxoid, Diphtheria Toxoid, and Cross-Reacting Material 197. Recent advances have focused on three key areas: novel carrier protein discovery, optimized conjugation strategies, and evaluation of immune interference during co-administration of multivalent formulations. These efforts aim to achieve broader serotype coverage, prolonged protective efficacy, and simplified immunization schedules. This review synthesizes recent progress in carrier protein development, encompassing vaccine design principles, manufacturing processes, safety profiles, and epidemiological effectiveness. Furthermore, it critically examines current selection criteria for carrier proteins, their clinical applications, and persistent challenges, providing strategic insights to inform future conjugate vaccine development and immunization policy optimization in China.

Objective To observe the effects of Yuebi Decoction on adriamycin-induced nephrotic syndrome(NS)and adhesion molecule levels in rats;To explore the possible mechanism of its inhibition of NS edema.Methods A NS rat model was established by a one-time tail vein injection of 6.5 mg/kg adriamycin.The rats were randomly divided into normal group,model group,prednisone group and Yuebi Decoction group.The prednisone group and Yuebi Decoction group were given 5 mg/kg prednisone and 22.2 g/kg Yuebi Decoction by gavage,respectively.The normal group and the model group were given an equal amount of normal saline by gavage,once a day for 2 consecutive weeks.The wet and dry weight ratios of skin and kidney were detected,24 hour urine total protein quantification(24 hUTP)and the contents of blood urea nitrogen(BUN),serum creatinine(SCr),total cholesterol(TC),albumin(ALB),hemoglobin(HB)were detected,HE and PAS staining was used to observe the morphology of renal tissue,ELISA was used to detect vascular cell adhesion molecule-1(VCAM-1)and intercellular adhesion molecule-1(ICAM-1)contents in renal tissue,the positive expressions of VCAM-1 and ICAM-1 were detected by immunohistochemistry,the expressions of VCAM-1,Rac1,signal transducer and activator of transcription 3(STAT3)and p-STAT3 proteins were detected by Western blot.Results Compared with the normal group,the wet dry weight ratio of the skin and kidney of the model group rats significantly increased(P<0.01),and the 24 hUTP,SCr,BUN and TC contents significantly increased(P<0.01),while the ALB and HB contents significantly decreased(P<0.01);with glomerular balloon atrophy,the renal tubules exhibit protein casts,inflammatory cell infiltration in renal interstitium,and significant increase in the contents of VCAM-1,ICAM-1 and protein expressions of VCAM-1,Rac1,p-STAT3 in renal tissue(P<0.01).Compared with the model group,the wet dry weight ratio of the skin and kidneys of rats in the prednisone group and Yuebi Decoction group was significantly reduced(P<0.05,P<0.01),and the 24 hUTP,SCr,BUN and TC were significantly reduced(P<0.01),while the contents of ALB and HB significantly increased(P<0.01);the infiltration of inflammatory cells in renal tissue was reduced,the protein casts decreased,and the contents of VCAM-1 and ICAM-1 in renal tissue,as well as the expressions of VCAM-1,Rac1 and p-STAT3 proteins significantly decreased(P<0.05,P<0.01).Conclusion Yuebi Decoction can alleviate edema,reduce urine protein,and improve capillary permeability in NS rats.Its mechanism is related to inhibiting the Rac1/STAT3 signaling pathway and reducing the expression of renal tissue adhesion molecules.

A microchannel-based electrochemiluminescence(ECL)sensor was developed for detection of tetracycline(TC)utilizing luminol/H2O2 as ECL reporting system.The low excitation potential of luminol/H2O2 effectively mitigated the impact of clamping voltage,thereby enhancing the detection performance of the microchannel-based ECL sensor.The microchannel modified with TC aptamer selectively recognized and captured target TC.The positively charged TC reduced the surface charge density within the microchannel,thereby increasing the ionic current in the microchannel,leading to change of ECL signal of system.The experimental conditions such as electrolyte concentration,TC-aptamer concentration,and reaction time between TC and TC-aptamer were optimized.Under optimal conditions,the difference of ECL signal in the absence and presence of TC(?ECL)exhibited a good linear relationship with TC concentration in the range from 1.00 ng/mL to 200 ng/mL,with a detection limit as low as 0.69 ng/mL.The sensor had good selectivity and was successfully used in detection of TC in milk samples.

A method for simultaneous determination of 21 kinds of Aconitum alkaloids(ATS)in biological specimens and infused liquor using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was developed.The biological samples were pretreated with methanol-acetonitrile(1∶2,V/V)for protein precipitation,while infused liquors were diluted 100-fold with acetonitrile,followed by centrifugation,and filtration by a 0.22-μm membrane.Chromatographic separation was carried out on an EC-C18 column using gradient elution with the mixture of 10 mmol/L ammonium acetate and 0.2%formic acid as mobile phase A and acetonitrile as mobile phase B.With this method,all the analytes were separated within 9.5 min.The samples were detected in positive ESI mode with dynamic multiple reaction monitoring(MRM)and quantified via external standard calibration.The results showed that the concentrations of the analytes in the range of 2-1000 ng/mL had excellent linearity(R2>0.9992)with the peak area.The developed method was successfully used for detection of 21 kinds of aconitum alkaloids,with limits of detection of 0.5-2 ng/mL,quantification limits of 2-6 ng/mL,intra/inter-day precision≤6.0%,spiked recoveries of 89.4%-100.9%,extraction recoveries of 74.2%-104.4%,and matrix effects ranging from-11.1%to 9.2%in blood/urine.The method was applied to detection of 12 samples from 4 fatal aconite poisoning cases,and all 21 kinds of ATS with total alkaloid concentrations of 0.04-4.18 μg/mL in blood and 154.96-422.83 μg/mL in medicinal liquors were detected.Tissue distribution revealed that the order of concentrations from highest to lowest is as follows:urine(157.22 μg/mL)>gastric contents(51.37 μg/mL)>kidney(21.6 μg/g)>whole blood(4.18 μg/mL)>liver(0.03 μg/g).This method showed many advantages such as simple pretreatment,low detection limits,accurate quantification,broad analyte coverage,and superior anti-interference capability in complex matrices,proving ideal for forensic and toxicological analysis of aconitum alkaloids.

Fluorescent probes L1 to L5 containing two recognition sites based on Schiff base were prepared for detection of Al3+.The probes were constituted by introducing two salicylaldehyde derivatives through hydrazide groups on isophthalic hydrazide.Among them,a fast turn-on fluorescence probe L1 for Al3+with high fluorescence quantum yield was found.The recognition performance and mechanism of probe L1 to Al3+were studied by multiple analysis methods.The results showed that probe L1 could rapidly and highly selectively recognize Al3+by fluorescent enhancement at 446 nm and the detection limit was as low as 4.65 nmol/L,and it was found that L1 complexed with Al3+in the molar ratio of 1:1.In addition,the calculation results of density functional theory(DFT)showed that two binding sites in the probe molecule connected two different Al3+,and each Al3+connected two adjacent probe molecules.Using quinine sulfate as a reference,the fluorescence quantum yield of L1-Al3+complex was as high as 30%.Probe L1 could also be applied to the detection of Al3+in real water samples.

Objective:To investigate the feasibility and clinical value of artificial intelligence-assisted compressed sensing (ACS) technology in accelerating MR simulation (MR-sim) for radiotherapy of nasopharyngeal carcinoma (NPC).Methods:Thirty patients with NPC scheduled to receive radical radiotherapy at Sun Yat-sen University Cancer Center were prospectively enrolled. All patients underwent head and neck MR-sim on a 3.0 T scanner, with axial T 1 weighted imaging (WI), T 2WI, contrast-enhanced T 1WI, and fat-suppressed contrast-enhanced T 1WI images acquired using both ACS and parallel imaging (PI) techniques. Paired-sample t tests or rank-sum tests were used to compare scan time, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of MR-sim images between the two techniques. A 5-point Likert scale was applied to evaluate tumor lesion visualization, lesion margin clarity, artifacts, and overall image quality, with chi-square tests used to compare subjective image quality scores between the two techniques. Tumor target volumes were delineated on MR-sim images obtained by both ACS and PI techniques after fusion with CT simulation images, and consistency was assessed using the Dice similarity coefficient (DSC). Results:For both individual sequences and overall protocols, ACS significantly reduced MR-sim acquisition time compared with PI ( P < 0.001). The total acquisition time with ACS was (378.60±17.07) s versus (694.93±17.07) s with PI, representing a 45.52% time reduction. SNR, CNR, tumor lesion identification, margin clarity, artifacts, and overall image quality scores of MR-sim images did not differ significantly between ACS and PI ( P > 0.05). Tumor target volumes delineated from ACS- and PI-based MR-sim images showed high consistency after fusion with CT simulation images ( P > 0.05), with mean DSC values of primary tumors and metastatic cervical lymph nodes approaching 1. Conclusion:Compared with conventional MR acceleration methods (PI), ACS enables faster MR-sim acquisition in NPC without compromising image quality or the accuracy of tumor target delineation.