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.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

Objective To report the diagnosis,treatment,and verification process of a patient with sex development disorder whose chromosomal karyotype and genetic test results are inconsistent,and conduct a literature review to improve the understanding of the mosaic status of sexual development disorders.Methods A 14-year-old patient presented with primary amenorrhea on April 3,2020,at the First Affiliated Hospital of Hebei North University,exhibiting female sexual characteristics.The patient underwent ultrasonic/magnetic resonance imaging of gonads,assessment of gonadal axis function,chromosomal karyotype,and molecular genetic testing,as well as pelvic exploration,malignant gonads resection,and hormone replacement therapy,resulting in drug-induced menstruation.During the diagnosis and treatment,it was found that the patient's chromosomal karyotype analysis was inconsistent with the molecular genetic test results.Subsequently,samples from the three germ layer cells were taken,and fluorescence in situ hybridization(FISH)was used to detect the sex chromosomes in each germ layer cell.XY probes were used to label the gonadal pathological sections to explore the distribution differences of the Y chromosome in the gonads,and changes in anti-Müllerian hormone(AMH)levels before and after surgery were compared.Databases such as Wanfang and PubMed were searched to summarize relevant cohort study literature and understand the current status of research on this disease.Results The patient's body exhibited a significant differences between the 45,X and 46,XY cell lines in different germ layers and within the same layer tissues.The proportion of 45,X in buccal mucosal cells derived from the ectoderm was 30%(6/20),in peripheral blood lymphocytes derived from the mesoderm was 9.7%(11/114),and in bladder shed cells derived from endoderm was 20.4%(22/108).The gonadal pathological sections labeled with XY probes indicated a mosaic state with a reduced Y-chromosome;where the epididymal structure area had a 45,X cell line mosaic of 50.0%,and the malignant area had a normal"Y"content.After gonadal resection,AMH levels significantly dropped from 7.28 pmol/L to＜0.07 pmol/L.Literature review revealed that patients with 45,X/46,XY have a complex phenotype spectrum,most with features of Turner syndrome,and female phenotypes are at risk of gonadal tumors.Conclusions In the diagnosis of difficult cases of sex development disorders,when performing peripheral blood karyotype testing,the number of counted cells and analyzed cells should be increased as much as possible,and multi-germ layer cell sampling should be performed.Gonads with a high"Y"mosaic rate are more prone to malignancy in the abdominal cavity.Detecting AMH levels can distinguish cryptorchidism and anorchidism in sexual development disorders with Y chromosomes.

Objective To explore the correlation of bilateral knee joint strength asymmetry with balance,walking ability,and motor function in hemiplegic stroke patients,providing a reference for clinical assessment of stroke patients.Methods A total of 46 hemiplegic stroke patients admitted to the Rehabilitation Medicine Department of People's Hospital of Shijiazhuang from February to December 2023 were selected.According to the Berg Balance Scale(BBS)scores,patients were divided into Group A(BBS score≤20,n=23)and Group B(BBS score>20,n=23).The peak torque and differences of bilateral knee flexors and extensors were compared between two groups.Isokinetic technology was used to assess the differences in peak torque of bilateral knee joints at 60°/s and 120°/s.BBS,Functional Ambulation Classification(FAC),and Fugl-Meyer Assessment of Lower Extremity(FMA-LE)were used to evaluate patients'balance,walking ability,and lower limb motor function.The correlation between bilateral knee joint peak torque and its difference with the scores of three functional scales was analyzed.Results The peak torque of knee flexors and extensors at 60°/s in group A was significantly lower than that in group B(P<0.05).At both 60°/s and 120°/s the differences in peak torque between the healthy and affected sides of knee flexors and extensors were greater than those in group B(P<0.05).At 60°/s,the difference in peak torque of bilateral knee extensors in hemiplegic stroke patients was negatively correlated with the scores of BBS,FAC,and FMA-LE(r=-0.569,-0.582,-0.606,P<0.01),as did the knee flexors(r=-0.534,-0.386,-0.458,P<0.05).At 120°/s,similar negative correlations were observed for both knee extensors(r=-0.304,-0.304,-0.443,P<0.05)and flexors(r=-0.337,-0.349,-0.370,P<0.05).Conclusions Bilateral knee joint strength asymmetry in hemiplegic stroke patients is negatively correlated with balance and walking ability.The difference in strength between the two sides of knee joint may be one of the clinical indicators for evaluating the motor function of stroke patients.

Objective:To investigate the effect of insulin-like growth factor 1 (IGF-1) on acute lung injury in septic mice and its underlying molecular mechanism.Methods:Twenty SPF male C57BL/6J mice aged 6-8 weeks were randomly (random number) divided into the sham-operated group, sham-operated + IGF-1 group, sepsis group and sepsis + IGF-1 group, with 5 mice in each group. IGF-1 [60 μg/(kg·d)] was injected via the tail vein for 3 consecutive days in the sham-operated + IGF-1 group and sepsis + IGF-1 group, and mice in the sham-operated group and sepsis group were injected with an equal volume of saline. The tissue of the upper lobe of the right lung was taken to calculate the wet-to-dry ratio, and the upper lobe of the left lung was subjected to HE staining to analyze pathological changes and evaluate lung injury. The levels of interleukin (IL)-6 and IL-1β in the bronchoalveolar lavage fluid (BALF) and serum of mice were detected by ELISA. The expression of p-PI3K, PI3K, p-AKT and AKT in lung tissues was determined via Western blotting. The quantitative data with a normal distribution and homogeneity of variance were compared between the two groups by two independent sample t test. Results:Lung volume was reduced in the sepsis group than in the sham-operated group, obvious surface congestion, dark red color, large bruises and hemorrhagic foci were observed under the pericardium, and the wet-to-dry ratio was significantly elevated ( P<0.05). Compared with the sepsis group, the sepsis + IGF-1 group had slightly increased lung volume, less congestion, darker red color, fewer bruises and hemorrhagic foci, and a lower wet-to-dry ratio ( P<0.05). There was no significant change in lung tissue morphology in the sham-operated + IGF-1 group compared with the sham-operated group. HE staining and lung histopathological scores showed that lung tissue was significantly damaged in the sepsis group than the sham-operated group ( P<0.001), and the pathological score of lung tissue was less damaged in the sepsis + IGF-1 group compared with the sepsis group ( P<0.01). The ELISA results demonstrated that the serum levels of IL-6 and IL-1β were markedly decreased in the sepsis + IGF-1 group than in the sepsis group [(26.22±1.60) pg/mL vs. (45.61±7.85) pg/mL, P<0.05; (87.99±11.80) pg/mL vs. (181.26±10.11) pg/mL, P<0.001]. Moreover, the IL-6 and IL-1β contents in the BALF of the sepsis + IGF-1 group were notably lower than those in the BALF of the sepsis group [(7.67±0.42) pg/mL vs. (20.25±0.43) pg/mL, P<0.001; (17.00±6.08) pg/mL vs. (108.61±5.18), pg/mL P <0.001]. Western blot analysis revealed that the expression of p-PI3K, PI3K, p-AKT and AKT in the lung tissues of mice in the sepsis+IGF-1 group were markedly lower than that in the sepsis group [(0.71±0.05) vs. (1.21±0.09), P<0.05; (0.57±0.08) vs. (1.24±0.22), P<0.01; (0.29±0.07) vs. (1.10±0.04), P<0.001; (0.65±0.17) vs. (1.19±0.07), P<0.01]. Conclusion:IGF-1 ameliorates sepsis-induced acute lung injury in mice, and its protective effect may be achieved by inhibiting the PI3K/AKT pathway.

Fear of disease progression(FoP)is a common psychological state among patients with coronary heart dis-ease(CHD),which exists throughout the course of disease and seriously affects the prognosis.High level of FoP not only harms the mental health of patients but also do not benefit their rehabilitation after discharge.This concept was first proposed by foreign researchers studying the psychological state of cancer patients.In recent years,there have been numerous studies on the influencing factors and qualitative aspects of FoP in CHD patients,while related inter-vention studies remain few.This paper reviews the concept,scales and related influencing factors of FoP,providing ideas for medical staff to provide targeted interventions for CHD patients.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Combined seawater Hf and Nd isotope compositions have been applied as reliable tracers of water mass mixing and weathering input changes.The establishment of standardized synchronous extraction methods for Fe-Mn oxyhydroxide in sediments,which serve as effective carriers for isotopic signals of ancient seawater,is a prerequisite and key for paleoceanography research.The research material of this study was the surface sediments of the Western Arctic Ocean obtained from China's 7th Arctic Scientific Expedition,and a reliable simultaneous Nd-Hf isotope extraction method in Fe-Mn oxyhydroxide fraction was established through systematic optimization of pretreatment procedures and key extraction parameters.This research focused on analyzing the effects of pretreatment(Milli-Q water pre-wash)and key extraction parameters(leaching time,solution/solid ratios,concentration of EDTA-2Na,and concentration of mixed solution of hydroxyamine hydrochloride(HH)and acetic acid(HAc))on element extraction efficiency and isotopic composition.The experimental results indicated that the Milli-Q water pre-wash was not necessary,Fe-Mn oxyhydroxide extraction could be directly performed.Nd extraction amount in Fe-Mn oxyhydroxide fraction was not sensitive to changes in extraction conditions,while the Hf extraction amount was significantly affected by leaching time,solution/solid ratios and concentration of EDTA-2Na.The optimal conditions for synchronously extracting Nd-Hf isotopes were as follows:adding 20 mL of a mixed solution of 0.005 mol/L HH+1.5%HAc+0.03 mol/L EDTA-2Na per gram of sample,and reaction at room temperature for 3 h under shaking.Through systematic verification of 87Sr/86Sr ratio,εNd value,εHf value,Al/Nd ratio and Al/Hf ratio,it was confirmed that this method could effectively avoid interferences from residual components and accurately obtain Nd-Hf isotope signals of ancient seawater preserved in sediments.The standardized method established in this work provided reliable technical support for reconstructing water mass mixing between the Arctic,North Atlantic,and North Pacific Oceans and riverine input histories.It also provided important reference for the extraction methods of Nd and Hf isotopes from marine sources in sediments from other sea areas around the world.