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 explore the safety and efficacy of shunt reduction using the Interlock-35 fibered interlocking detachable coil (IDC) occlusion system in the treatment of refractory hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS).Methods:From August 2022 to December 2023, at the Department of Gastroenterology of the Air Force Medical Center, the clinical data of patients with refractory HE after TIPS who were treated with shunt reduction using the Interlock-35 fibered IDC occlusion system were retrospectively collected, which included portal vein pressure gradient (PVPG), HE grades, blood ammonia levels, prothrombin time (PT), liver function parameters, and other related indicators. The primary indicators related to the efficacy of the shunt reduction included symptom improvement, and changes in PVPG, blood ammonia levels, and Child-Pugh score. The safety of shunt reduction was analyzed based on the incidence of complications such as gastrointestinal bleeding and ascites during the follow-up period. Paired t-test was used for statistical analysis. Results:A total of 21 patients were enrolled. Prior to shunt reduction, there were 5 cases with HE of grade 3 and 16 cases with HE of grade 2. Before operation, the blood ammonia was (103.14±27.69) mol/L; and the liver function Child-Pugh grade of 1 case was classified as grade A, 16 cases as grade B, and 4 cases as grade C. Shunt reduction was performed between 7 and 1 879 d, with a median time of 99 (54, 806) d after TIPS. The procedure was technically successful in all patients, with a total of 25 coils implanted. Before shunt reduction, the PVPG was (14.02±5.28) cmH 2O (1 cmH 2O=0.098 kPa), after shunt reduction procedure, the PVPG increased to (25.05±6.04) cmH 2O, and the difference was statistically significant ( t=-11.26, P<0.001). After operation, 16 patients returned to the hospital for follow-up examinations, with a median follow-up time of 114 (46, 195) d, the blood ammonia levels, PT, and Child-Pugh scores during the follow-up were all lower than those before operation ((78.19±27.85) μmol/L vs. (105.00±30.53) μmol/L, (14.09±1.65) s vs. (15.41±2.35) s, and 6.88±1.59 vs. 8.13±1.75, respectively), and the differences were statistically significant ( t=2.23, 3.23, and 2.61; P=0.040, <0.001, =0.020). There was no statistically significant in PVPG between during follow-up and immediately post-procedure ((28.91±6.20) cmH 2O vs. (25.22±5.92) cmH 2O, P>0.05). During the follow-up period, HE symptoms disappeared in 12 patients among the 16 patients who returned to hospital for follow-up, however gastrointestinal bleeding occurred in 5 patients and ascites occurred in 3 patients; additionally, 4 patients experienced intermittent HE symptoms (grade 1 in 3 cases, grade 2 in 1 case). After operation, 5 patients were followed up via telephone, among them, 3 patients died, and 2 patients experienced intermittent HE (grade 1) which could be spontaneously restored with dietary adjustments and(or) medication. Conclusions:Interlock-35 fibered IDC occlusion system for shunt reduction is a feasible and effective treatment for refractory HE after TIPS. It can effectively improve symptoms and decrease liver function score. After shunt reduction, early follow-up and adjustment of flow reduction can help reduce the occurrence of severe complications.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.

Aim To investigate the regulatory mecha-nisms of donepezil on the expression and enzymatic ac-tivity of cytochrome P450 3A4(CYP3A4),elucidate the synergistic impact of hypoxia on CYP3A4 function,and reveal its potential association with drug-induced cardiotoxicity,particularly QT interval prolongation.Methods Western blot,co-immunoprecipitation,and gene knockdown techniques were employed to evaluate the effects of donepezil and hypoxia on CYP3A4 pro-tein expression.CYP3A4 enzymatic activity was as-sessed using an in vitro incubation system with rat liver microsomes combined with high-performance liquid chromatography(HPLC),and the half-maximal inhib-itory concentration(IC50)was determined.Results Donepezil(10 μmol·L-1)and hypoxia reduced CYP3A4 protein expression to 31.75％and 45.90％of the control levels,respectively.Both interventions activated the gp78-mediated ubiquitin-proteasome path-way,significantly increasing CYP3A4 ubiquitination levels by 2.1-fold compared to the control group,thereby promoting proteasomal degradation.Donepezil inhibited CYP3A4 enzyme activity with an IC50 of 83.4μmol·L-1,and hypoxia synergistically enhanced this inhibitory effect,reducing the IC50 to 20.79 μmol·L-1.Conclusion Donepezil downregulates CYP3A4 function through dual mechanisms involving ubiquitin-mediated proteasomal degradation and direct enzymatic inhibition.Hypoxia potentiates this effect,leading to impaired metabolism of CYP3A4 substrate drugs,ele-vated plasma drug concentrations(1.6-2.3-fold in-crease compared to normal metabolic conditions),and an increased risk of QT interval prolongation and other forms of cardiotoxicity.

Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.

Objective:To analyze the preferences of medical staff in TCM hospitals in Beijing regarding the achievements transformation of hospital traditional Chinese medicine preparations,and to provide a reference for formulating incentive policies.Methods:233 medical staff from five TCM hospitals in Beijing were taken as the research objects,and surveyed with a questionnaire designed based on the discrete choice experiment(DCE).Mixed logit models and latent class models were then used to analyze their transformation preferences.Results:The mixed Logit model revealed that seven key attributes significantly influenced medical staff's preferences for the achievements transformation of traditional Chinese medicine preparations(P<0.05).Latent class analysis identified three distinct preference groups among respondents:an organization-dependent group(27.0%),a pro-transformation group(61.4%),and a conservative group(11.6%).Conclusions:Medical Staff preferred transformation conditions that increased monthly income;utilized"human use+re-experimentation";involved the hospital's achievements transformation department as the entity;were funded by the hospital;offered a 70%profit share;enabled promotion three years earlier,and assigned patents to the hospital.The study recommends implementing diverse incentive measures and developing differentiated strategies tailored to the distinct Medical Staff categories to facilitate the transformation of hospital traditional Chinese medicine preparations into new drugs.

Purpose To quantitatively compare the diffusion parameters of mono-and biexponential diffusion-weighted imaging models,and to obtain optimal sets of b-values in diffusion-weighted MRI for obtaining monoexponential apparent diffusion coefficient(ADC)close to perfusion-insensitive intravoxel incoherent motion(IVIM)model ADC(ADCIVIM)in identifying of pulmonary solid benign and malignant lesions.Materials and Methods IVIM was performed in 40 patients with solid nodule and masse in Xi'an Gaoxin Hospital from July 2021 to August 2022 using a 3.0T MR imager.Two experienced diagnostic radiologists subjectively evaluated the IVIM images.A single index model was used to calculate ADC values(ADC0-1 000,ADC20-1 000,ADC50-1 000,ADC80-1 000,ADC150-1 000,ADC300-1 000,ADC500-1 000,ADC300,500,1 000,ADC300,800,1 000,ADC300,500,ADC300,800 and ADC300,1 000).The reference standard ADCIVIM value were calculated using a double-exponential model.The physician's measurements between two physicians were measured.The malignant and benign groups were compared and receiver operator characteristic curve for all parameters were analyzed.Results The measurement consistency of ADC values under b value sets and ADCIVIM was very good,and the intraclass correlation coefficient was more significant than 0.75.The differences between ADCIVIM and ADC values in each b group were statistically significant(t=-6.016--2.500,all P<0.05).The area under the curve(AUC)of ADCIVIM was the largest(0.906),with an optimal threshold of 1.271×10-3 mm2/s,a sensitivity of 80.0%and a specificity of 93.0%.The diagnostic efficacy close to ADCIVIM were ADC300,800(AUC=0.891),ADC50-1 000(AUC=0.827)and ADC300,800,1 000(AUC=0.795),respectively.The optimal threshold of ADC300,800 was 1.140×10-3 mm2/s,the sensitivity and specificity were 80.0%and 93.7%,respectively.Conclusion Combining b-values 300 s/mm2 and 800 s/mm2 is recommended as routine scanning parameters for identifying the insensitive monoexponential ADC between benign and malignant solid pulmonary lesions.

Purpose To explore the value of quantitative parameters(T2* value,R2* value)of three-dimensional multi-echo ultrashort echo time technique for the differential diagnosis of benign and malignant pulmonary nodules and masses(PNMs).Materials and Methods The MRI data of 68 patients with PNMs in Xi'an Gaoxin Hospital from July 2021 to October 2022 were retrospectively analyzed,and PNMs were grouped into benign(34 cases)and malignant(34 cases)categories using histopathology or clinical follow-up as the reference standard.Two observers respectively outlined the regions of interest on three-dimensional multi-echo ultrashort echo time-T2* and R2* maps,and quantitatively measured the T2* and R2* values.The intraclass correlation coefficient(ICC)was used to evaluate the consistency of the measured values.Differences in the above indicators between the two groups of PNMs were analyzed,and their diagnostic efficacy was assessed.The predictive probability of the combined two indicators was computed,the receiver operating characteristic curve was plotted,and the area under the curve(AUC)was calculated.Results The measurement results of each parameter of PNMs in the benign and malignant groups by the two observers were consistent(ICC>0.75).The T2* value of the malignant group was higher than that of the benign group(Z=-5.158,P<0.001),and the R2* value was lower than that of the benign group(Z=-4.845,P<0.001),and the differences were statistically significant.The AUC of the T2* value was 0.864(95%CI 0.775-0.953,P<0.001),with a maximum Youden index of 0.677,a threshold of 9.675 ms,a sensitivity of 76.5%,and a specificity of 91.2%.The AUC of the R2* value was 0.842(95%CI 0.746-0.937,P<0.001),with a maximum Youden index of 0.647,and a threshold of 109.15/s,with a sensitivity of 73.5%and a specificity of 91.2%.The AUC of the combined diagnosis of T2* and R2* values was 0.867(95%CI 0.779-0.955,P<0.001),with a maximum Youden index of 0.677,a sensitivity of 82.4%,and a specificity of 85.3%.There was no statistically significant difference in the pairwise comparison of T2* values,R2* values,and their combined AUC(all P>0.05).Conclusion The T2* value and R2* value of the three-dimensional multi-echo ultrashort echo time technique,as well as the combination of the two indicators,are all helpful in differentiating benign and malignant PNMs,providing imaging support for the preoperative non-invasive and precise differentiation of PNMs and optimizing clinical diagnosis and treatment decisions.

Objective Metabolomics combined with machine learning algorithms was used to systematically study the preoperative serum metabolites of patients with early postoperative cognitive dysfunction(POCD)after heart valve replacement,so as to screen biomarkers that may predict early POCD after heart valve replacement and explore the corresponding metabolic regulatory mechanisms.Methods A total of 60 patients underwent heart valve replacement under extracorporeal circulation were selected and divided into early-POCD group(group P)and non-POCD group(group N)according to whether POCD occurred or not.Metabolomic analysis was performed on preoperative serum samples of patients in group P and group N to screen the differential metabolites and metabolic pathways.The biomarkers related to early POCD were identified by random forest algorithm.Results A total of 532 differential metabolites were detected by metabonomics analysis,and 5 biomarkers were screened by random forest algorithm,namely quinoline,3'-sialyllactose,sphingomyelin(d18∶1/20∶0),lysophosphatidylcholine[P-18∶1(9Z)]and 25-hydroxycholesterol.Among them,the main metabolic pathways were phenylalanine metabolism,primary bile acid biosynthesis,ascorbic acid and aldonate metabolism,pentose and glucuronate interconversion,tryptophan metabolism,drug metabolism-cytochrome P450,porphyrin and chlorophyll metabolism.Conclusion Many metabolic pathways in patients with early POCD after heart valve replacement under extracorporeal circulation have changed before operation,which may lead to the occurrence of early POCD.Quinoline,3'-sialyllactose,sphingomyelin(d18∶1/20∶0),lysophosphatidylcholine[P-18∶1(9Z)]and 25-hydroxycholesterol may be biomarkers for predicting early POCD.