OBJECTIVE To evaluate the comprehensive value of novel oral anticoagulant drugs （NOACs） after major orthopedic surgery. METHODS The evaluation evidence was collected through literature research； evidence and value：impact on decision-making （EVIDEM） framework was introduced to integrate the evaluation process； the multi-criteria decision analysis （MCDA） method was used to construct a multi-dimensional evaluation system； the weights assigned to each evaluation criterion were determined by the combination of Delphi method and analytic hierarchy process， and the rivaroxaban， dabigatran and apixaban were comprehensively evaluated. RESULTS The clinical comprehensive evaluation system of NOACs after major orthopedic surgery was successfully established， and the final clinical comprehensive evaluation weights of NOACs （rivaroxaban， dabigatran， apixaban） after major orthopedic surgery were calculated， with scores of 0.399 7 for rivaroxaban， 0.244 4 for apixaban， and 0.355 9 for dabigatran， indicating that rivaroxaban demonstrated the highest overall clinical value. Among them， rivaroxaban had the highest weight score in the evaluation of pharmaceutical characteristics， cost-effectiveness and other attributes in a single dimension. In terms of efficacy and safety evaluation， apixaban had the highest weighting score. CONCLUSIONS Among NOACs， rivaroxaban is more suitable for routine anticoagulation management after major orthopedic surgery， especially in terms of pharmacological properties， cost-effectiveness and other attributes.

Multiple myeloma (MM) is a hematological malignancy that poses significant treatment challenges due to its heterogeneity and propensity for relapse and progression. In the last two decades, the therapeutic landscape of MM has changed dramatically, but the disease remains largely incurable, with many patients facing treatment resistance. This review evaluates the current status of MM treatments, emphasizing the limitations of traditional therapies and the emerging role of immunotherapy in improving patient outcomes. It highlights the importance of achieving and maintaining minimal residual disease negativity and a balanced immune response as key treatment goals. Furthermore, it discusses the advancements in immunotherapies that are improving the prospects for patients, particularly those with relapsed or refractory disease. Innovative strategies, such as chimeric antigen receptor T-cell therapy, bispecific antibodies, and bispecific T cell engagers, have shown significant promise by targeting the malignant cells and the bone marrow microenvironment, which are essential for disease persistence and resistance to therapy. Future research should focus on refining MM treatment strategies, including the integration of immunotherapy into earlier treatment lines and the development of predictive biomarkers for personalized treatment approaches, ultimately enhancing patient outcomes.

Objective To investigate the clinical efficacy of esmolol combined with atorvastatin on se-vere sepsis complicated with cardiac insufficiency.Methods This study was a prospective,double-blind,ran-domized controlled clinical trial.A total of 153 patients with severe sepsis complicated with cardiac insufficien-cy admitted to this hospital from January 2021 to December 2022 were selected and divided into groups A,B,and C by random number table method,with 51 cases in each.Patients in group A were given routine symp-tomatic supportive treatment after admission.On this basis,patients in group B and group C were given esmo-lol,esmolol+atorvastatin,respectively.The hemodynamic indexes,serological indexes and clinical prognosis of the three groups before and after intervention were compared.Results There was no significant difference in baseline data,and hemodynamic and serological indexes of three groups before intervention(P＞0.05).Compared with before intervention,after five days of intervention,heart rate,systemic vascular resistance in-dex(SVRI),blood levels of creatine kinase-MB(CK-MB),cardiac troponin Ⅰ(cTn Ⅰ),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and high sensitive C-reactive protein(hs-CRP)in three groups were de-creased,while the values of cardiac index(CI)were increased,and the differences were statistically significant(P＜0.05).After five days of intervention,the heart rate,SVRI,blood levels of CK-MB,cTn Ⅰ,TNF-α,IL-6,and hs-CRP in group C were lower than those in group A and group B,and the levels in group B were lower than those in group A;the value of CI in group C was higher than that in group A and group B,and group B was higher than that in group A,the differences were statistically significant(P＜0.05).After intervention,the length of stay in intensive care unit(ICU)in group C was the shortest,and that in group B was shorter than that in group A,the difference was statistically significant(P＜0.05).There was no significant difference in 28 d mortality among the three groups(P＞0.05).Conclusion Esmolol combined with atorvastatin can signif-icantly inhibit the inflammatory response in patients with severe sepsis complicated with cardiac insufficiency,relieve myocardial injury and promote rehabilitation,and the therapeutic effect is better than esmolol alone.

ObjectiveIn view of the standardization of clinical diagnosis and treatment of the acute abdomen and the inheritance of diagnosis and treatment experience of prestigious veteran traditional Chinese medicine（TCM） doctors， a diagnosis and treatment reasoning algorithm based on association rule mining under incomplete evidence（AMIE）+ random walk was proposed to provide information services and technical support for primary doctors by recommending personalized diagnosis and treatment plans based on medical records. MethodThe experience of diagnosis and treatment of acute abdomen of prestigious veteran TCM doctors and the text data of clinical diagnosis and treatment guidelines of integrated TCM and western medicine were collected to complete the task of knowledge extraction and construct acute abdomen knowledge graph based on Neo4j. On the basis of ontology-supported rule-based reasoning， the rule reasoning based on similar syndromes was used to expand the syndrome combinations whose Jaccard similarity was greater than the threshold in the syndrome recommendation results. The semantic path coverage algorithm was used to calculate the semantic similarity between the symptom nodes. The symptom nodes were divided into 10 categories， and the symptom nodes in the same category were extended. The random walk algorithm was used to search the symptom nodes connected with the syndrome， and the connection rules between the syndrome and symptom nodes were extended to realize the knowledge reasoning of AMIE+ random walk. ResultThe acute abdomen knowledge graph included 1 320 nodes and 2 464 relationships. According to the link prediction evaluation index of knowledge reasoning， the reasoning results of the three algorithms in the auxiliary diagnosis and treatment of acute abdomen were compared. The AMIE+ random walk algorithm complemented the knowledge graph by extending the similar syndrome connection rules and the syndrome-symptom connection rules. Compared with the knowledge reasoning algorithm based on ontology rules， the area under the curve （AUC） was 15.18% higher and the accuracy was 30.36% higher， which achieved more accurate and effective knowledge inference. ConclusionThis study used knowledge graph technology to visualize the diagnosis and treatment of acute abdomen with TCM and western medicine， assisting primary clinicians in intuitively viewing the diagnosis and treatment process and data relationship. The proposed diagnosis and treatment reasoning algorithm can realize the personalized diagnosis and treatment plan recommendation at the level of "disease-syndrome-diagnosis-treatment-prescription"， which can assist primary doctors in disease diagnosis and treatment and clinical decision-making， contribute to the knowledge sharing and application of diagnosis and treatment experience and clinical guidelines of prestigious veteran TCM doctors， improve the level of primary clinical diagnosis and treatment， and promote the normalization and standardization of the diagnosis and treatment process of acute abdomen with integrated TCM and western medicine.

Objective:To evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation(auto-HSCT)for the treatment of multiple myeloma(MM)in elderly patients aged over 65 years.Methods:In this retrospective analysis, the efficacy and safety of auto-HSCT for the treatment of MM was examined in 28 patients aged >65 years diagnosed and treated at Soochow Hopes Hematology Hospital between March 1, 2020 and October 31, 2022.The functions of the major organs of these patients were evaluated before transplantation.Results:The 28 patients had a median age of 67(66-72)at the time of transplantation, a median number of 2.985 × 10 6/kg(2.036-9.5 × 10 6/kg)of collected CD34+ hematopoietic stem cells, and a median number of 2(1-3)days of collection.The median time to neutrophil implantation after hematopoietic stem cell transfusion was 10(9-14)days, and the median platelet implantation time was 11(10-29)days.The median follow-up time was 25 months, but the median progression-free survival time was not reached.The 1-year PFS rate was 89.3% and 2-year PFS rate was 76.3%, with 2 patients' starting point of PFS set at the time of pre-transplantation re-induction therapy because needed salvage auto-HSCT.The overall survival time was not reached, the 1-year overall survival rate was 100.0%, and the 2-year overall survival rate was 90.5%. Conclusions:Auto-HSCT is a safe and effective treatment for elderly MM patients aged over 65 years after screening and assessment.

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

At present, non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in the world. Recent studies have shown that varying degrees of central nervous system dysfunction can occur during the progression of NAFLD, including cognitive impairment and emotional imbalance. This article summarizes the main risk factors for NAFLD-related cognitive impairment at different stages, so as to provide a basis and ideas for the early prevention and clinical treatment of this disease.

To investigate the efficacy and safety of total oral regimen containing ixazomib in multidrug-resistant relapsed and refractory multiple myeloma(RRMM). A total of 38 patients were retrospectively analyzed from August 2018 to January 2020 in the First Affiliated Hospital of Soochow University. The overall response rate (ORR)was 36.8%. Among them, the very good partial response (VGPR) or better rate was 23.7%, and the complete response (CR) rate was 5.3%. The ORR was 41.7% in patients receiving ixazomib-lenalidomide-dexamethasone (IRD) regimen. Median PFS was 5 months and median OS was 7.5 months. The ORR was 50% after second-line therapy, 40% after third-line therapy and 12.5% after forth-line therapy or more. The ORR was 29.0% in bortezomib-refractory patients, 38.0% in lenalidomide-refractory patients, 21.4% in bortezmoib & lenalidomide dual refractory patients. Grade 3-4 hematological adverse events (AEs) were reported in 21% patients. Common hematological AEs included lymphopenia, neutropenia, thrombocytopenia. Other usual AEs were fatigue and diarrhea. No grade 3-4 peripheral neuropathy was recorded. In the treatment of relapsed/refractory multiple myeloma patients with multidrug resistance, the total oral regimens containing ixazomib demonstrate reliable efficacy and safety. Early administration of ixazomib at first or second relapse is suggested for more favorable clinical outcome.

MicroRNAs(miRNAs)are important regulators of gene expression.The large-scale detection and profiling of miRNAs have been accelerated with the development of high-throughput small RNA sequencing(sRNA-Seq)techniques and bioinformatics tools.However,generating high-quality comprehensive miRNA annotations remains challenging due to the intrinsic complexity of sRNA-Seq data and inherent limitations of existing miRNA prediction tools.Here,we present iwa-miRNA,a Galaxy-based framework that can facilitate miRNA annotation in plant species by combining computational analysis and manual curation.iwa-miRNA is specifically designed to generate a comprehensive list of miRNA candidates,bridging the gap between already annotated miRNAs provided by public miRNA databases and new predictions from sRNA-Seq datasets.It can also assist users in selecting promising miRNA candidates in an interactive mode,contributing to the accessibility and reproducibility of genome-wide miRNA annotation.iwa-miRNA is user-friendly and can be easily deployed as a web application for researchers without programming experience.With flexible,interactive,and easy-to-use features,iwa-miRNA is a valu-able tool for the annotation of miRNAs in plant species with reference genomes.We also illustrate the application of iwa-miRNA for miRNA annotation using data from plant species with varying genomic complexity.

Objective:This study aimed to evaluate the efficacy and safety of lenalidomide combined with bortezomib and dexamethasone (VRD) in the treatment of newly diagnosed multiple myeloma (MM) .Methods:A total of 150 newly diagnosed patients with MM diagnosed in The First Affiliated Hospital of Soochow University from November 2018 to February 2021 and received VRD as the induction regimen were included to evaluate the safety and efficacy of VRD induction therapy for newly diagnosed MM.Results:The median follow-up was 22 months, two patients (1.3%) died early after treatment, and 148 patients (98.7%) completed induction therapy. 116 patients (77.3%) were mobilized to collect autologous hematopoietic stem cells, 101 cases (87.1%) were qualified in the collection, of which 48 cases (41.4%) were excellent in the collection. The 3-year progression-free survival (PFS) rate was 59%, and the 3-year overall survival (OS) rate was 83%. After induction, complete remission (CR) /stringent CR rate was 54.4%, ≥ very good partial remission rate was 77.3%, overall response rate was 86.0%, and minimal residual disease negative rate was 46.0%. There was no statistically significant difference in the efficacy of cytogenetic high-risk patients compared with standard risk patients ( P=0.456) . The median PFS time of cytogenetic high-risk patients was shorter than that of standard risk patients (not reached vs 33 months, P=0.014) . There was no statistically significant difference in the median OS time (not reached vs not reached, P=0.072) . The highest incidence of hematological adverse events was thrombocytopenia (72%) , followed by neutropenia (42%) and anemia (20%) . The highest incidence of non-hematological adverse events was peripheral neuritis (56.7%) . The main digestive tract symptoms include constipation (30.0%) and diarrhea (17.3%) . Upper respiratory tract infection (23.3%) and lung infection (7.3%) are the main infections. The incidence of adverse thrombocytopenia (90.0% vs 63.7%, P=0.001) , neutropenia (54.2% vs 36.3%, P=0.038) , anemia (33.3% vs 13.7%, P=0.005) , diarrhea (27.1% vs 12.7%, P=0.030) , limb edema (20.8% vs 3.9%, P=0.030) , fever (20.8% vs 4.9%, P=0.006) , thrombosis (8.3% vs 0, P=0.016) , and renal function deterioration (20.8% vs 3.9%, P=0.030) in patients with renal insufficiency was higher than that in patients with normal renal function. Conclusion:The VRD regimen has a significant effect on newly diagnosed MM, does not affect the hematopoietic stem cell collection, and has controllable adverse events; however, the incidence of adverse events was higher in patients with renal insufficiency.