Incidence of thrombotic disease is very high, and this disease can result in high mortality and high disability rate. Prevention and treatment of the disease mainly include:antiplatelet, anticoagulation and thrombolysis. Choice of anti?thrombotic treatment based emphasizes on individuation. As a direct inhibitor of factor Xa, Rivaroxaban exert its anticoagu?lant activity without antithrombinⅢbut is ineffective to theⅩa in prothrombin complex, which can be used as a substitute of traditional anticoagulant. In this paper, applications of Rivaroxaban on treating symptomatic venous thromboembolic dis?ease, postoperative venous thrombosis and cardiovascular thrombosis are reviewed.

[Objective] To investigate the effects of mitochondrial unfolded-protein response (UPRmt) on the aggregation toxicity of Aβ protein in Alzheimer's disease (AD).[Methods] By cloning the mitochondrial outer membrane tomm-22,inner membrane E04A4.5 and atfs-1 genes of Caenorhabditis elegans (C.elegans) and constructing the L4440 interference vectors,HT115 competent cells were transformed to prepare tomm-22,E04A4.5 and atfs-1 RNAi bacteria.The effects of tomm-22 and E04A4.5 RNAi on the process of paralysis were investigated through transgenic AD disease models CL4176 and CL2006.The life span of wild type N2 C.elegans was observed after RNAi of tomm-22 and E04A4.5.The regulatory role of ATFS-1 signaling by atfs-1 RNAi in inhibition of Aβ protein aggregation was detected.The dynamic changes of UPRmt in transgenic SJ4100 nematode and the autophagy level in transgenic DA2123 nematodes were analyzed by tomm-22 and E04A4.5 RNAi.[Results] We successfully established the UPRmt model by cloning mitochondrial tomm-22 and E04A4.5 of C.elegans and further constructing RNAi bacteria,and showed that they can suppress aggregation toxicity of Amyloid-β (Aβ) protein in AD model CL4176,and slow down paralysis process.The life span of wild type N2 was significantly shortened after feeding with the tomm-22 and E04A4.5 RNAi bacteria.At the same time,the progressive paralysis AD model CL2006 shows a delayed paralysis in the early stage of life cycle but get acceleration in the late.These results illustrate that the UPRmt can alleviate the mitochondrial stress and improve the function of mitochondria at least in the short term.The atfs-1 RNAi confirmed that delayed paralysis process of AD model CL4176 is not directly related to the ATFS-1 signal.However,tomm-22 and E04A4.5 RNAi can gradually increase the UPRmt response and induce the expression level of autophagy-related molecules LGG-1,suggesting that tomm-22 and E04A4.5 RNAi may play a role in delaying the AD disease process by enhancing the activity of autophagy in C.elegans.[Conclusions] The study found that the UPRmt can inhibit the accumulation of A β protein by coordinating the signal transduction between mitochondria and nucleus,and can help to restore mitochondria and even intracellular protein homeostasis for protecting the normal physiological function of cells,and also provides new targets for prevention and treatment of neurodegenerative diseases such as AD.

Objective To explore the impact of Th17 cells adoptive immunity on tumor growth of diffuse large B cell lymphoma (DLBCL)-bearing mice.Methods The CD4+ CD62L+ na(i)ve T cells purified by Mini MACS immunomagnetic beads were stimulated under the condition of TGF-β, IL-6, anti-IFN-γ, anti-IL-4, IL-23.IL-17 expression was detected by ELISA.SCID mice were inoculated with DLBCL cells line SUDHL-4 to estaldish the model of DLBCL-bearing mice, and then they received Th17 cells adoptive immunotherapy at the 0, 8 th or 18th day (3 groups in total, 5 mice pre-group).The tumor volume and the survival of tumor model were observed.Results Formation of tumor nodules in mice was observed at about the 8th day after the mice received the Th17 SUDHL-4 cells.The tumors volume of DLBCL-bearing mice that had received Th17 cells adoptive immunotherapy was obviously smaller than that of the mice had not (P ＜ 0.05).The survival time of the tumor-bearing mice that had received Th17 cells adoptive immunotherapy was also longer than that of the tumor-bearing mice had not (P ＜ 0.05).Conclusion Th17 cells adoptive immunotherapy displays an anti-tumor effect on DLBCL-bearing mice.

Objective:To collect the imaging data and related materials of the patients with in-stent restenosis (ISR)after coronary artery stent operation with intravascular ultrasound (IVUS),and to analyze the risk factors of ISR,and to propose the reasonable intervention strategies.Methods:Fifty patients with ISR were divided into ISR ≤ 50% drug group (n = 14 )and ISR > 50% drug group (n = 36),including drug-coated balloon therapy group (n=16)and stent treatment group (n=20);IVUS virtual organization technology was used to compare the plaque area,location,tissue composition,thrombus and other factors of the patients in various groups after treatment;the data changes after 6 months of follow-up were analyzed.Results:The IVUS results showed the plaque areas and plaque loads of the ISR patients treated with intervention were significantly reduced compared with before operation (P <0.05);the plaque compression degree of the patients in drug-coated balloon therapy group was lower than that in stent treatment group (P <0.05),but the differences were not found between drug-coated balloon therapy group and stent treatment group in fibrous tissue components and calcified tissue proportion (P >0.05).Conclusion:The ISR rate is higher in the patients with high degree of fiber components,plaque composition heterogeneity and distribution of diffuse tortuous and calcified lesions.ISR has no significant correlation with the plaque wall thickness and lipid content and plaque instability and necrotic tissue proportion.

Objective:To construct and verify the occurrence model of acute respiratory distress syndrome (ARDS) using lung injury prediction score (LIPS) combined with acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and oxygenation index (PaO 2/FiO 2). Methods:Using a prospective cohort study method, 244 patients with complete medical records who were admitted to the intensive care unit (ICU) of Peking University Third Hospital from December 2020 to July 2022 were selected as research objects according to the inclusion and exclusion criteria. They were divided into training set (173 cases) and validation set (71 cases). Patients' gender, age, body mass index (BMI), various causes (shock, sepsis, craniocerebral injury, pulmonary contusion, multiple trauma, aspiration, pneumonia, acute abdomen, hypoproteinemia, acidosis, major surgery, etc.), underlying diseases (diabetes, malignant tumor, cerebrovascular disease, liver disease, kidney disease) and laboratory test indicators were collected. According to the above data, the LIPS score, APACHE Ⅱ score, sequential organ failure assessment (SOFA) and PaO 2/FiO 2, etc within 24 hours after admission to the ICU were calculated. Univariate analysis was used to screen the influencing factors for the occurrence of ARDS, and the factors with P < 0.2 were included in the multivariate Logistic regression analysis to screen out the independent predictive factors for the occurrence of ARDS. According to the results of multivariate Logistic regression analysis, the risk score of patients with ARDS was obtained to construct the risk prediction model of ARDS, the receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated. The established ARDS prediction model was externally validated, and ROC curves were drawn to evaluate the predictive accuracy of the prediction model for the occurrence of ARDS in critically ill patients, and the AUC of the validation set was calculated to analyze the predictive performance of each risk factor on the occurrence of ARDS. Results:A total of 173 patients were enrolled in the training set, including 121 patients without ARDS and 52 patients with ARDS; 77 cases of acute abdomen, 64 cases of sepsis, 60 cases of shock, 51 cases of acidosis, 40 cases of hypoproteinemia, 37 cases of diabetes, 34 cases of craniocerebral injury, 34 cases of abnormal liver function, 28 cases of multiple trauma, 23 cases of malignant tumor, 23 cases of spinal orthopedic surgery, 17 cases of obesity, 12 cases of pneumonia, 11 cases of pulmonary contusion, and 7 cases of chronic kidney disease, chemotherapy in 6 cases, and aspiration in 2 cases. The rates of shock, sepsis, acute abdomen, acidosis, abnormal liver function, lung contusion, pneumonia and aspiration, gender, age, LIPS score, APACHE Ⅱ score, and SOFA score in the ARDS group were significantly higher than those in the non-ARDS group (all P < 0.05), moreover, PaO 2/FiO 2 ratio was significantly lower than that of non-ARDS group ( P < 0.01). Multivariate Logistic regression analysis showed that LIPS score, APACHE Ⅱ score, and PaO 2/FiO 2 ratio were independent risk factors for ARDS in ICU patients with high risk factors for ARDS, and the odds ratio ( OR) was 1.768 [95% confidence interval (95% CI) was 1.380-2.266], 1.242 (95% CI was 1.089-1.417), 0.985 (95% CI was 0.978-0.991), all P < 0.05. ROC curve analysis showed that the AUC of the ARDS prediction model training set was 0.920, the sensitivity was 86.5%, and the specificity was 86.8%; the AUC of the verification set was 0.896, the sensitivity was 96.8%, and the specificity was 76.6%. Conclusion:LIPS score, APACHE Ⅱ score and PaO 2/FiO 2 are independent risk factors for the occurrence of ARDS in ICU patients with high risk factors for ARDS. The ARDS risk prediction model established based on these three indicators has a good predictive ability for the occurrence of ARDS in critically ill patients, wihich needs to be verified by multicenter cohort studies.

Objective To explore the impact of arterial injury on distal limb blood supply in lower limb trauma. Meth?ods Retrospective analysis of 93 patients with different levels of lower limb arterial injury admitted to our hospital from June 2014 to August 2017. There were 84 males and 9 females aged 43.54±9.90 years (ranging 25-65 years). Revascularization was performed through open reduction. Patients were divided into three groups according to their arterial injury locations. Proximal ves?sels were along the superficial femoral artery, from its beginning to the point where it was divided into the descending genicular ar?tery and direct periosteal branches. Intermediate vessels were from the dividing point on the superficial femoral artery to the popli?teal artery before it was divided into the medial inferior genicular artery. Distal vessels were from the dividing point on the poplite?al artery to the distal end of the peroneal artery. The duration from injury to revascularization in the three groups were 13.67±5.99 h, 11.15±4.43 h, and 11.92±5.48 h, respectively. There was no significant difference between groups (F=1.564, P=0.215). ISS in the three groups were 13.00±3.74, 12.77±3.81, and 11.50±3.99, respectively. There was no significant difference between groups (F=1.445, P=0.241). The following items were compared among the three groups, postoperative creatine kinase, arterial blood lac?tate and limb compartment cut. Results Creatine kinase of the intermediate vascular group was 8 743.15±6 968.48 u/L, proximal vascular group 1 467.67±1 810.27 u/L, distal vascular group 2 893.51±1 304.56 u/L. The data of intermediate vascular group were higher than those of proximal and distal vascular groups with significant difference among the groups (F=22.587,P=0.000). The lactate of the intermediate vascular group was 3.20 ± 1.51 mmol/L, proximal vascular group 1.63 ± 0.46 mmol/L, distal vascular group 1.85±0.69 mmol/L with significant difference among the groups (F=20.612,P=0.000). The compartment cut of the intermedi?ate vascular group was incised in 24, but not in 15. The proximal vascular group was not incised in 18, while 15 was incised and 21 not incised in distal vascular group. The rates of compartment cut were 61.5%, 0 and 41.7%, respectively with significant differ? ences (χ2=19.156, P=0.000). Conclusion In lower limb injuries, the intermediate vascular (from the superficial femoral artery after it is divided into the descending genicular artery and direct periosteal branches to the popliteal artery before it is divided into the medial inferior genicular artery) injury leads to the most severe distal limb ischemia.

Objective:To investigate the mechanism of curcumin in the treatment of diabetic retinopathy (DR) by network pharmacology and molecular docking.Methods:The compounds targets of curcumin were predicted by SEA and SwissTargetPrediction databases, and the DR target genes were obtained by CTD database.The different genes were mapped and matched by Venny database to screen their intersections.The intersecting genes were submitted to GeneMANIA database to construct a protein-protein interaction network.WebGestalt database was used to conduct enrichment analysis and AutoDock Vina was used to perform molecular docking of the core targets.Results:A total of 52 targets of curcumin, 1 599 targets of DR and 48 intersecting targets were detected.The core targets were serine/threonine-protein kinase 1 (AKT1), tumor necrosis factor-α (TNF-α), epidermal growth factor receptor (EGFR), signal transduction and activator of transcription 3 (STAT3) and heat shock protein 90 alpha family class A member 1 (HSP90AA1). Enrichment analysis suggested that these targets were mainly associated with signaling pathways, including the EGFR tyrosine kinase inhibitor resistance signaling pathway, hypoxia-inducible factor-1 (HIF-1) signaling pathway, interleukin (IL)-17 signaling pathway and advanced glycosylation end product-the receptor of advanced glycosylation end product (AGE-RAGE) signaling pathway.Conclusions:Curcumin may play an important role in the treatment of DR by regulating multiple signaling pathways to inhibit the inflammatory response and combat oxidative stress.

Objective:To investigate the diagnostic value of an intelligent assisted grading algorithm for nuclear cataract using anterior segment optical coherence tomography (AS-OCT) images.Methods:A diagnostic test study was conducted.AS-OCT image data were collected from 939 cases of 1 608 eyes of nuclear cataract patients at the Shanghai Tenth People's Hospital of Tongji University from November 2020 to September 2021.The data were obtained from the electronic case system and met the requirements for clinical reading clarity.Among them, there were 398 cases of 664 male eyes and 541 cases of 944 female eyes.The ages of the patients ranged from 18 to 94 years, with a mean age of (65.7±18.6) years.The AS-OCT images were labelled manually from one to six levels according to the Lens Opacities Classification System Ⅲ (LOCS Ⅲ grading system) by three experienced clinicians.This study proposed a global-local cataract grading algorithm based on multi-level ranking, which contains five basic binary classification global local network (GL-Net).Each GL-Net aggregates multi-scale information, including the cataract nucleus region and original image, for nuclear cataract grading.Based on ablation test and model comparison test, the model's performance was evaluated using accuracy, precision, sensitivity, F1 and Kappa, and all results were cross-validated by five-fold.This study adhered to the Declaration of Helsinjki and was approrved by Shanghai Tenth People's Hospital of Tongji University (No.21K216).Results:The model achieved the results with an accuracy of 87.81%, precision of 88.88%, sensitivity of 88.33%, F1 of 88.51%, and Kappa of 85.22% on the cataract dataset.The ablation experiments demonstrated that ResNet18 combining local and global features for multi-level ranking classification improved the accuracy, recall, specificity, F1, and Kappa metrics.Compared with ResNet34, VGG16, Ranking-CNN, MRF-Net models, the performance index of this model were improved.Conclusions:The deep learning-based AS-OCT nuclear cataract image multi-level ranking classification algorithm demonstrates high accuracy in grading cataracts.This algorithm may help ophthalmologists in improving the diagnostic accuracy and efficiency of nuclear cataract.

Objective: To investigate the pregnancy and neonatal outcomes in twin pregnancies and the association with chorionicity and modes of conception in order to provide evidence for early prevention and reduction of complications and life quality improvement of twin neonates. Methods: This study retrospectively enrolled 756 women with twin pregnancies who gave birth at Peking University Third Hospital from January 1, 2014 to December 31, 2015. Clinical features of the mothers and newborns were collected, the pregnancy and neonatal outcomes were analyzed. Impacts of chorionicity and different modes of conception on the outcomes were also evaluated. Two independent-sample t test and Chi-square test were used as statistical methods. Results: Twin pregnancies accounted for 6.7% (756/11 169) of all deliveries in the hospital during the study period and the preterm birth rate was 59.4% (449/756). Twenty five women underwent fetal reduction (3.3%, 25/756) and intrauterine death occurred in 85 pregnancies (11.2%, 85/756). Eventually 1 400 babies were born alive (92.6%, 1 400/1 512). Subgroup analysis suggested that compared with dichorionic diamniotic (DCDA) pregnancies, monochorionic diamniotic (MCDA) cases showed younger maternal age at conception [(30.5±4.2) vs (32.9±4.0) years, t=-7.412], smaller gestational age at delivery [(34.1±3.1) vs (35.7±2.2) weeks, t=-7.325] and higher preterm birth rate [78.4% (174/222) vs 51.5% (263/511), χ²=46.554], all P<0.05. Moreover, the incidence of neonatal complications, including respiratory distress syndrome [18.3% (40/219) vs 8.0% (21/261), χ²=11.210], neonatal pneumonia [18.3% (40/219) vs 8.8% (23/261), χ²=9.331] and sepsis [6.8% (15/219) vs 1.5% (4/261), χ²=8.854], etc. was higher in the MCDA group than those in the DCDA group, resulting in a higher mortality rate [7.8% (17/219) vs 1.1% (3/261), χ²=13.042] in the MCDA pregnancies, all P<0.05. Compared with spontaneously conceived twin pregnancies, women underwent in vitro fertilization-embryo transfer were older at conception [(33.4±3.8) vs (30.6±4.4) years, t=-6.095], delivered at a greater gestational age [(35.8±2.1) vs (35.2±2.6) weeks, t=-2.452] and had a lower preterm birth rate [49.2% (206/419) vs 63.5% (54/85), χ²=5.838] in the DCDA group, all P<0.05. No significant differences in the incidence of neonatal diseases were observed between the two subgroups. Conclusions The incidence of preterm birth is high in twin pregnancies. Compared with DCDA twin pregnancies, MCDA twin pregnancies are associated with more adverse outcomes due to higher incidence of neonatal diseases. In vitro fertilization-embryo transfer does not increase the incidence of preterm birth and the neonatal outcomes were comparable to those of spontaneously conceived ones.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.