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.

Bruton's tyrosine kinase inhibitors (BTKi) are a class of novel small-molecule targeted antitumor drugs used to treat B-cell malignancies. However, safety issues associated with BTKi may lead to treatment interruption, compromising their efficacy. To promote the standardized management of safety in BTKi treatment, Evidence-Based Pharmacy Professional Committee of the Chinese Pharmaceutical Association, Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association, Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society, Expert Committee on Lymphoma of Chinese Society of Clinical Oncology, Expert Committee on Leukemia of Chinese Society of Clinical Oncology, Integrated Cancer Cardiology Branch of China Anti-Cancer Association, Hematology Branch of the Chinese Medical Association, and Hospital Pharmacy Professional Committee of the Cross-Straits Medicine Exchange Association formulated the Evidence-based Expert Consensus on the Clinical Management of Safety of Bruton′s Tyrosine Kinase Inhibitors (2024), which was published in the Chinese Journal of Cancer Research in June 2024. It covered 9 clinical issues in the following 3 domains: (1) the management of common adverse reactions of BTKi such as bleeding, cardiovascular events, hematological toxicity, infections, rashes, diarrhea, and arthralgia; (2) the management of drug-drug interactions; (3) management guidance for special populations. This consensus provides evidence-based recommendations for the safety management of BTKi medication in clinical practice. This article provides an interpretation and evidence summary of the consensus in Chinese, aiming to facilitate its implementation in China, enhance the safety management of BTKi treatment, and improve patient outcomes.

Objective To investigate the application value of ultrasound guidance combined with X-ray fluoroscopy for percutaneous transhepatic biliary drainage(PTBD).Methods A total of 157 patients with obstructive jaundice who underwent PTBD were selected and then divided into a control group(75 cases)and an observation group(82 cases)according to different guidance methods.The control group underwent puncture and catheterization of the biliary system under the guidance of traditional X-ray fluoroscopy.Meanwhile,the observation group underwent the puncture to the biliary system under ultrasound guidance and the catheterization under X-ray fluoroscopy.The success rates of puncture,operation and initial needle puncture,puncture times,operation time,X-ray fluoroscopy time,radiation dose and complication rate were compared between the two groups.Results Puncture and catheterization were successful in both groups,and the success rates of puncture and operation were all 100％.In the observation group,the success rate of initial needle puncture was 90.24％(74/82),which was higher than 74.67％(56/75)in the control group;the mean puncture times was 1.14,which was less than 1.77 in the control group;the mean operation time was 30.02 min,which was less than 40.09 min in the control group;the mean X-ray fluoroscopy time was 4.03 min,which was less than 6.61 min in the control group;the mean radiation dose was 49.08 mGy,which was less than 82.29 mGy in the control group,and all the differences above between the two groups were statistically significant(P＜0.05).In the observation group,there were 2 cases with biliary hemorrhage,3 cases with biliary infection,and 5 cases with biliary fistula(including 2 cases of secondary biliary peritonitis);while the control group had 10 cases with biliary hemorrhage,15 cases with biliary infection,13 cases with biliary fistula and 9 cases with biliary peritonitis,and the differences between the two groups were statistically significant(P＜0.05).Conclusion Ultrasound guidance combined with X-ray fluoroscopy for PTBD is safe and effective,with significantly short operation time,low radiation dose and fewer complications,which has a certain popularity value in different level hospitals.

Objective:To analyze the results of next generation sequencing (NGS) gene testing in liquid-based cytological specimens of lung adenocarcinoma cavity and evaluate the clinical efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment.Methods:Liquid based cytological specimens of 222 cases of lung adenocarcinoma with cavity effusion and 201 cases of metastatic lymph node biopsy were collected. Specimens were obtained from the Cytology Laboratory of the Cancer Hospital of the Chinese Academy of Medical Sciences. The collection period was from January 2018 to December 2022. The results of NGS gene detection were compared. The clinical efficacy of 91 patients treated with EGFR-TKI was evaluated, and the survival curve was analyzed by Kaplan-Meier and other statistical methods.Results:The mutation rates of cancer-related genes detected by NGS were 82.0% (182/222) vs 79.1% (159/201), ( P=0.455) in liquid-based cytological specimens and histological specimens of metastatic lymph node biopsy, respectively. However, the mutation rate of EGFR T790M was significantly higher in cavity effusion than in lymph node biopsy specimens [12.2%(27/222)＞3.5%(7/201), P=0.001]. The results of gene mutation were identical in 10 of the 13 cases with cavity effusion and metastatic lymph node biopsy, and the agreement rate of EGFR was 84.6%(11/13). In 3 inconsistent cases, EGFR mutations were detected in 2 cavity effusion cases that were not detected by lymph node biopsy. Results of genetic analysis of fluid-based cytological samples of 91 patients with cavity effusion were evaluated after drug treatment with EGFR-TKI. The mean progression-free survival (PFS) of the patients was 11.4 months (95% CI: 9.9-12.9). The mean PFS of patients harboring EGFR mutation was 12.3 months (95% CI: 10.8-13.9), and the mean PFS of EGFR wild type was 4.1 months (95% CI: 2.1-6.2). Conclusions:The results of NGS gene detection in liquid-based cytological specimens of lung adenocarcinoma patients with cavity effusion show that the PFS time is similar to that of histological specimens after clinical treatment with EGFR-TKI, which proves the reliability of NGS gene detection results in liquid cytological specimens. NGS gene testing appears higher sensitivity in cavity liquid-based samples than in metastatic lymph node samples.

Objective:To investigate the predictive value of refeeding syndrome (RFS) and its influencing factors for 30-day intensive care unit (ICU) readmission in critically ill patients.Methods:A prospective cohort study was conducted. Critically ill patients admitted to the department of critical care medicine, department of respiratory and critical care medicine, and department of neurology at Tianjin Medical University General Hospital from January to April in 2025 were enrolled. Patients were assessed for RFS according to the American Society for Parenteral and Enteral Nutrition (ASPEN) criteria. General information within 24 hours of ICU admission was collected via the electronic medical record system. Treatment details and 30-day ICU readmission status were dynamically recorded. Participants were divided into readmission and non-readmission groups based on whether ICU readmission occurred within 30 days. Intergroup comparisons were performed to identify differences. Multivariate Logistic regression was used to analyze the relationship between RFS and its influencing factors with 30-day ICU readmission. Receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive performance of risk factors.Results:A total of 196 critically ill patients were enrolled, among whom 25 (12.76%) were readmitted to ICU within 30 days and 171 (87.24%) were not. Significant differences were observed in the readmission group compared with the non-readmission group, including significantly higher rates of nasogastric decompression, higher acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, a higher incidence of RFS, and a longer duration of nasogastric decompression. Multivariate Logistic regression analysis showed that RFS was an independent risk factor for 30-day ICU readmission [odds ratio ( OR) = 5.756, 95% confidence interval (95% CI) was 1.603-20.670, P = 0.007]. APACHEⅡ score showed a positive correlation trend with 30-day ICU readmission ( OR = 1.057, 95% CI was 0.991-1.127, P = 0.092). ROC curve analysis showed that the combined prediction model incorporating RFS and APACHEⅡ score had an area under the ROC curve (AUC) of 0.766 (95% CI was 0.668-0.864), with a sensitivity of 88.0% and a specificity of 62.0%, which was significantly superior to a single indicator (the AUC of RFS and APACHEⅡ score was 0.639 and 0.624, respectively). Conclusions:RFS significantly increases the risk of 30-day ICU readmission in critically ill patients. A combined model incorporating RFS and APACHEⅡ score demonstrates good predictive efficacy for 30-day ICU readmission in critically ill patients.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

Objective:Kawasaki disease shock syndrome（KDSS）and macrophage activation syndrome（MAS）are both severe forms of Kawasaki disease. The coexistence of these two critical illnesses is extremely rare，which can be life-threatening in severe cases. The purpose of this study is to summarize the clinical features of children with KDSS complicated with MAS，and provide a basis for precise diagnosis and treatment.Methods:A retrospective analysis was conducted on the clinical manifestations，laboratory tests，imaging characteristics，treatment，and prognosis of 10 children with KDSS and MAS admitted to Beijing Children's Hospital，Capital Medical University from January 2021 to June 2024.Results:Among the 10 children，six were male and four were female，and the age of onset was three months to eleven years old. Acute kidney injury was observed in five patients. Laboratory tests revealed significant increases in serum ferritin，C-reactive protein，B-type natriuretic peptide，aspartate aminotransferase，alanine aminotransferase，creatinine，triglycerides，and interferon-γ，while platelet count and albumin were significantly decreased. Six patients had cardiac enlargement，three had reduced ejection fraction，seven had pericardial effusion，and seven had coronary artery damage. All children were treated with immunoglobulin and methylprednisolone pulse therapy，as well as vasoactive drug infusion to improve circulation and maintain blood pressure. All children were discharged after clinical improvement，and most had a good prognosis.Conclusion:Children with KDSS may develop MAS，which present a complex and rapidly progressing condition often accompanied by a significant increase in ferritin levels. Early diagnosis and treatment can lead to a favorable prognosis.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

Soy is a vital source of plant carbohydrates.However,it poses significant allergenic risks,particularly to young children and animals.Among the various proteins in soy,β-conglycinin,which con-stitutes approximately 30％of total soy carbohydrates,is a primary allergen.Undigested β-conglycinin can lead to intestinal damage by inhibiting cell growth,disrupting the cytoskeleton,and inducing apopto-sis.It can also enter the lymphatic and circulatory systems,triggering allergic reactions.Conventional ELISA methods for detecting β-conglycinin rely on polyclonal or monoclonal antibodies,which are limited by their large molecular weight,difficulty in accessing the protein core,and sensitivity to acidic and bas-ic conditions.To address these limitations,this study aimed to develop nanobodies(Nbs)against β-con-glycinin.Nbs,derived from the variable regions of heavy-chain antibodies found in camelids,have a mo-lecular weight approximately one-tenth that of conventional antibodies.They offer advantages such as small size,stable structure,high specificity,and strong affinity.A female alpacas was immunized five times using β-conglycinin,which showed a heavy chain antibody potency of 1∶16 000 by ELISA.Pe-ripheral blood lymphocytes were subsequently isolated and total RNA was extracted.The variable region of the heavy-chain antibody was amplified via PCR,and recombinant plasmids were constructed and transformed into the E.coli competency strain ER2738.The resulting library contained about 3.5×108 CFU/mL,which increased to 1.15×1012 PFU/mL after phage rescue,with a 100％Nbs gene insertion rate,indicating high diversity.Its Nbs phage output was significantly enriched by four rounds of solid-phase elution with an enrichment rate of 155.9.Four rounds of solid-phase panning yielded 35 positive clones,all of which shared the same amino acid sequence upon sequencing.The selected Nb was ex-pressed in a prokaryotic system,and its binding ability to β-conglycinin was confirmed using Western blotting and ELISA.The results demonstrated excellent specificity and affinity.This research lays the groundwork for developing a rapid and efficient detection method for β-conglycinin using Nbs,potentially enhancing food safety and allergen management.

Objective:To explore the short-term clinical effects of deep cervical lymph node-venous anastomosis in the treatment of Alzheimer’s disease (AD).Methods:A prospective exploratory study was conducted on the treatment of AD patients using the cervical deep lymph node-venous anastomosis technique in Scar and Wound Treatment Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from September to October 2024. The patients underwent high-frequency ultrasound to locate deep cervical lymph nodes and the external jugular vein. Under general anesthesia, bilateral deep cervical lymph node-venous anastomoses were performed. Indocyanine green (ICG) lymphography was conducted via subcutaneous injection behind the ear to visualize lymph nodes in levels Ⅱ and Ⅲ. After making a skin incision along the posterior margin of the sternocleidomastoid muscle, the external jugular vein, internal jugular veins, and associated lymph nodes were exposed. Adjacent veins were selected for anastomosis of lymph node. Using microsurgical techniques, end-to-side or end-to-end anastomosis was completed for lymph nodes in levels Ⅱ and Ⅲ. Preoperative assessments included the mini-mental state examination (MMSE, a higher score indicates better cognitive function), Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog, a higher score indicates greater impairment of cognitive function), Alzheimer’s disease cooperative study scale for activities of daily living (ADCS-ADL, a higher score indicates better ability to perform daily activity), and neuropsychiatric inventory (NPI, a higher score indicates more severe behavioral and emotional symptom). Postoperative follow-up included the same scales to observe changes in cognitive function, activities of daily living, and emotional communication.Results:Four patients (1 male, 3 females, aged 58-79 years) with AD were included. All were diagnosed based on cerebrospinal fluid biomarkers. All patients successfully underwent bilateral deep cervical lymph node-venous anastomoses. On average, 4.3 (2-7 per person) anastomoses were performed per patient. Surgical procedures lasted an average of 6.5 h (5.5-8.5 h) with minimal blood loss (less than 50 ml). Patients resumed normal activity within 6 hours postoperatively and were discharged after an average of 4.1 d (3.5-5.0 d). Postoperative complications included one case each of aspiration pneumonia, lower limb venous thrombosis, and transient delirium, all of whom resolved without long-term effects. Clinical symptoms, including memory decline, mood swings, and anxiety, showed varying degrees of improvement. Patients reported enhanced quality of life, emotional stability, and social engagement, confirming the procedure’s safety and potential cognitive benefits. At one month postoperatively, the MMSE scores of the four patients increased by an average of 0.8 points compared to preoperative levels. Additionally, the two patients who completed the ADAS-Cog assessments showed a decrease in their scores (reduced by 1.0 points and 11.3 points, respectively, compared to preoperative scores), indicating a certain degree of improvement in cognitive function during this period. The ADCS-ADL and NPI scores of four patients varied significantly, without showing any clear pattern.Conclusion:Lymphovenous anastomosis of the deep cervical lymph node-venous anastomosis may provide a new surgical intervention approach for AD, but further large-scale studies and long-term follow-up are needed to validate its safety and effectiveness.