One of the leading therapies for acute lymphoblastic leukemia (ALL) is the chemotherapeutic agent PEGylated E. coli-derived-l-asparaginase (PEG-ASNase). Due to the high risk of dose-limiting liver injury, characterized by clinically elevated levels of hepatic transaminases, PEG-ASNase therapy is generally avoided in adult patients. Our preclinical investigations have indicated that PEG-ASNase-induced liver injury is associated with the release of free fatty acids (FFAs) from white adipose tissue (WAT), suggesting potential lipotoxic effects. However, it remains uncertain whether PEG-ASNase directly induces hepatotoxicity or sensitizes hepatocytes to FFA-induced toxicity. Our results show that PEG-ASNase treatment results in hepatocyte apoptosis and lipid peroxidation. Ex vivo and in vitro studies in mouse and human WAT suggest that PEG-ASNase induces the expression of adipose triglyceride lipase (ATGL), activates the lipase, and stimulates adipose tissue lipolysis, suggesting that the FFAs from WAT may contribute to the observed liver injury. Moreover, treatment with PEG-ASNase sensitizes hepatocytes to FFA-induced lipotoxicity. Mechanistically, our RNA-sequencing (RNA-seq) analyses reveal that PEG-ASNase-induced sensitization to lipotoxicity is accompanied by the induction of Cyp2e1. We demonstrated that this sensitization effect is attenuated by both pharmacological and genetic inhibition of Cyp2e1. Our findings suggest that PEG-ASNase therapy induces WAT lipolysis and sensitizes hepatocytes to hepatic lipotoxicity in a Cyp2e1-dependent manner.

Objective To analyze medication patterns and the targets and pathways of core drug combinations in treatment of palpitation.Methods The prescriptions of Li Yaping for treatment of palpitation from March 2023 to March 2024 were collected,and frequency counts of drugs'nature and flavour,channel tropism,and efficacy were performed.Apriori algorithm,association rules,and clustering analysis were carried out using SPSS Modeler 18.0 and SPSS 26.0.The core drugs and disease targets were searched,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed on the targets of their therapeutic action for palpitation.Results A total of 220 prescriptions were collected,involving 192 flavors of traditional Chinese medicines,with a cumulative medication frequency of 3978 times,and 18 flavors of high-frequency medicines.The medicines were mainly tonics,sedative,and promoting blood circulation for removing blood stasis.The distribution of medicinal properties were mainly warm,cold and flat.The medicinal flavors were mainly sweet,bitter and pungent,and channel tropism were mostly heart,liver and spleen channel.Association rule analysis showed that Radix Angelicae Sinensis,Radix et Rhizoma Salviae Miltiorrhizae,Radix et Rhizoma Glycyrrhizae,Radix Ophiopogonis,and Radix Astragali were the core drugs.Cluster analysis showed that there was 3 cluster combinations.In the network pharmacology part,there were 181 targets intersected by drug combinations and diseases.KEGG analysis showed that the core drugs for palpitation mainly involved signaling pathways such as phosphoinositide 3-kinase/protein kinase B,hypoxia-inducible factor-1,mitogen-activated protein kinase,interleukin-17,etc.GO analysis obtained 1000 GO pathways,of which 760 were biological processes,93 were cellular components,and 147 were molecular functions.Conclusion In the treatment of palpitation,Li Yaping advocates benefiting qi and promoting yang,removing blood stasis and eliminating turbidity,and tranquilizing the mind,emphasizing the"two hearts in the same adjustment",and treating the heart and liver at the same time,taking into account the spleen and stomach,and the combination of core medicines can intervene in the course of palpitation through multi-components,multi-targets,and multi-pathways,which is of great significance for the treatment of palpitation in the clinical setting.

Objective:To evaluate the clinical efficacy of modified all-arthroscopic reconstruction of medial patella femoral ligament (MPFL) for the treatment of recurrent patellar dislocation.Methods:A retrospective case series study was conducted to analyze the clinical data of 38 patients (46 knees) with recurrent patellar dislocation, who were treated at First Affiliated Hospital of Shenzhen University from January 2017 to January 2020. The patients included 12 males (12 knees) and 26 females (34 knees), aged 14-40 years [(24.6±5.4)years]. All patients underwent the modified all-arthroscopic MPFL reconstruction procedure. The femoral tunnel locations were assessed by 3D-CT immediately after surgery. The MRI was performed at 6 and 12 months after operation to assess the healing morphology of the reconstructed MPFL. The Lysholm score and Kujala score were used to assess the knee function before operation, at 6 months after operation, at 12 months after operation and at the last follow-up. The time to return to sports as well as complications were observed.Results:All patients were followed up for 26-48 months [(32.4±8.6)months]. Postoperative 3D-CT examination showed that the femoral tunnels were located in the groove area of the medial epicondyle of the femur and the adductor tubercle. At 6 and 12 months after operation, MRI T2 images showed that the reconstructed MPFL had a low signal and well tensioned ligament tissue, indicating that the MPFL was healed well. The Lysholm scores at 6 and 12 months postoperatively and at the last follow-up were (81.1±12.0)points, (91.2±3.8)points, and (92.2±9.8)points, respectively, being significantly higher than the preoperative (52.4±10.6)points (all P<0.01). The Kujala scores at 6 and 12 months postoperatively and at the last follow-up were (85.4±3.9)points, (91.4±3.6)points, and (93.1±8.5)points, respectively, being significantly higher than the preoperative (55.2±6.8)points (all P<0.01). Compared with 6 months postoperatively, the Lysholm score and Kujala score were significantly improved at 12 months postoperatively and at the last follow-up (all P<0.05). All patients returned to sports, with the time to return to sports for 3-12 months [(8.7±2.3)months] after operation. One patient had poor wound healing but was healed after dressing changes. No wound infection, nerve injury, joint stiffness, patella re-dislocation or other complications occurred. Conclusion:For recurrent patellar dislocation, the modified all-arthroscopic MPFL reconstruction has advantages of accurate bone tunnel positioning, good ligament healing, good function recovery, early return to sports, and less postoperative complications.

SARS-CoV-2 main protease (M^pro) is one of the most extensively exploited drug targets for COVID-19. Structurally disparate compounds have been reported as M^pro inhibitors, raising the question of their target specificity. To elucidate the target specificity and the cellular target engagement of the claimed M^pro inhibitors, we systematically characterize their mechanism of action using the cell-free FRET assay, the thermal shift-binding assay, the cell lysate Protease-Glo luciferase assay, and the cell-based FlipGFP assay. Collectively, our results have shown that majority of the M^pro inhibitors identified from drug repurposing including ebselen, carmofur, disulfiram, and shikonin are promiscuous cysteine inhibitors that are not specific to M^pro, while chloroquine, oxytetracycline, montelukast, candesartan, and dipyridamole do not inhibit M^pro in any of the assays tested. Overall, our study highlights the need of stringent hit validation at the early stage of drug discovery.

In view of the high recognition error rate and long scanning time in the existing hospital scanning technology, a new hospital operating room scanning system is designed based on personal digital assistant (PDA). The PDA scanning device adopts PIC16F877A microcontroller of 8 bit for wireless transmission through RFID and bluetooth technology, the code scanning efficiency is greatly improved. In addition, in order to improve the accuracy of image analysis, this study also adopts the energy driven sampling classification algorithm (EDS-CA) to properly preprocess the medical data information received through PDA scanning, then constructs a function classifier, and improves the image processing efficiency according to the EDS-CA reduction process. The experimental results show that the average accuracy of the code scanning system designed in this study is 95%, which proves that PDA code scanning has good performance.
Algorithms ; Computers, Handheld ; Hospitals ; Operating Rooms ; Technology

To determine the effect of andrographolide (Andro) on angiogenesis of human umbilical vein endothelial cells (HUVECs).
 Methods: HUVECs were treated with different concentrations of Andro and the cell viability was detected with Cell Counting Kit-8 (CCK-8). HUVECs were treated with half lethal dose (IC50) of Andro. Matrigel was used to make capillary formation of HUVECs and the effect of Andro on capillary formation was evaluated by calculating the percentage of capillary formation. Moreover, the effects of Andro and the supernatant from cultured A549 tumor cells on capillary formation were evaluated by calculating the percentage of capillary formation. The effect of Andro on the expression of matrix metalloproteinase-9 (MMP-9) was determined with Western blot.
 Results: The cell viability of HUVECs decreased with the increase of Andro concentrations. IC50 was 20 μmol/L. The capillary formation of HUVECs was inhibited when treated with 20 μmol/L Andro for 24 hours. Moreover, Andro was able to antagonize the promotion of the capillary formation induced by the supernatant from cultured tumor cells. Andro could suppress the expression of MMP-9 and antagonize the capillary formation.
 Conclusion: Andro inhibits the capillary formation of HUVECs and can antagonize the promotion of angiogenesis induced by the supernatant from cultured tumor cells.
Capillaries ; drug effects ; Cell Survival ; Collagen ; Culture Media ; Diterpenes ; pharmacology ; Drug Combinations ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Laminin ; Matrix Metalloproteinase 9 ; metabolism ; Neovascularization, Pathologic ; enzymology ; etiology ; prevention & control ; Proteoglycans ; Tumor Cells, Cultured

Objective To explore the risk factors of early venous thromboembolism (VTE) based on Caprini risk assessment model among patients with thoracoscopic lobectomy for lung. Methods From June 2015 to December 2017, retrospective analysis was used to collect the data of 28 patients with pulmonary embolism one week after thoracoscopic lobectomy for lung of Shanghai Chest Hospital, Shanghai Jiaotong University, in observation group. And we selected 84 patients with the same operation in the same term by convenience sampling in control group according to the ratio of 1:3. Patients of two groups were scored with the Caprini risk assessment model. Single factor analysis and Logistic regression analysis were used to the risk factors in Caprini risk assessment model and related factors of lung lobectomy. Results The Caprini score of patients group in observation group was higher than that in control group with a significant difference (P＜0.01). The proportion of moderate risk and high risk in patients with VTE was 78.6% in observation group and was 20.2% in control group with a statistical difference in the risk classification (P＜ 0.01). Logistic regression analysis took patients in case group as dependent variable and 16 risk factors in clinical baseline information as the independent variable showed the body mass index≥25 kg/m2, smoking history, preoperative plasma D-dimer higher than the critical value had positive correlations with the risk of VTE after surgery (OR=13.354, 5.639, 3.084;P＜0.05). Conclusions The Caprini risk assessment model can well determine the risk factors of VTE among patients with thoracoscopic lobectomy for lung. The high risk factors of VTE of these patients may include long-term and heavy smoking, overweight and preoperative plasma D-dimer higher than the critical value.

Objective To strengthen the management of the handover and transfer process of surgical patients in the department of thoracic surgery, improve surgery and transfer efficiency and ensure transfer safety. Methods In 2015, Shanghai Chest Hospital, Shanghai Jiaotong University reconstructed a nursing team by building the surgical handover and transfer process, analyzed the needs of transferees and transferees and the factors contributing to low efficiency and high safety risks in transfer, rebuilt, optimized and standardized the existing surgical handover and transfer process in the department of thoracic surgery, and enhanced relevant training after the process was rebuilt. Totally 1591 transferred patients who received thoracic surgery between January and March 2015 were selected as a control group, while 2126 patients who received thoracic surgery from January to March 2016 were selected as an observation group. The handover and transfer efficiency before and after the rebuilt process was then compared, including time of handover delay for the first surgery, time of delay for consecutive surgery, the number of patients detained in operation rooms postoperatively as well as doctors and nurses′ satisfaction to the rebuilt process.Results After the process was rebuilt, the delay rate for the first surgery was 1.7%; the delay rate for consecutive surgery was 2.7%; the retention rate in recovery rooms was 2.8%, lower than the figures before the process was rebuilt (χ2=24.059, 63.146, 53.675;P＜0.01). Doctors and nurses′ satisfaction to the rebuilt process was ＞90%.Conclusions Management optimization by process reengineering helps to improve surgical handover and transfer efficiency, safety as well as doctors and nurses′ satisfaction.

Objective To explore the standardized management in hybrid operation room so as to guarantee the smooth completion of interventional operation.Methods A management model of standardized management in hybrid operating room was constructed along with providing pre-post training for related staff, ensuring intervention materials well-managed, instruments and equipment in good condition, rescue articles prepared completely.Results Nursing and security management during operations for 70 patients ran smoothly without any situations compromising patients' safety and with operations being accomplished smoothly. Conclusions The standardized management in hybrid operation room is the key to success in interventional operation. It has an important guiding significance for interventional operations of multiple injuries.

Objective To investigate of the risk factors for the death of severe fever with thrombocytopenia syndrome (SFTS),so as to set up SFTS critical score and evaluate its role in predicting the prognosis for patients with SFTS.Methods A total of 123 SFTS patients hospitalized in Ji′nan Hospital of Infectious Diseases affiliated to Shandong University from June 2011 to October 2014 were enrolled in this study.The univariate Logistic regression analysis was performed to analysis the risk factor for the death of SFTS.Then the SFTS critical score system was set up accordingly.The prognosis value of SFTS critical score was compared with the rapid emergency medicine score (REMS)and the acute physiology and chronic health evaluation Ⅱ (APACHEⅡ)by using receiver operator characteristic curve (ROC).Results Among all the patients,17 males and 14 females were in death group,and 45 males and 47 females were in survival group.The results of the univariate Logistic regression analyses indicated that the glasgow coma scale (GCS),lactate dehydrogenase,activated partial thromboplastin time,oxygen saturation were risk factors for the death of SFTS,with statistically significant difference (all P <0.05). All of the four parameters of SFTS critical scores in the death group were higher than those in the survival group,with statistically significant difference (all P <0.05 ).The REMS,APACHEⅡ score and SFTS critical score in the death group were significantly higher than those in the survival group (all P <0.01 ). The area under the curve (AUC)of REMS,APACHE Ⅱ scores and SFTS critical score were 0.734, 0.746 and 0.788,respectively.The Youden index of the SFTS critical scores was the highest among all three scores (P <0.01).If 15 .0 was used as the cut off value of SFTS critical score,the specificity and the sensitivity for predicting the death risk for the hospitalized patient were 74.2% and 76.1 %, respectively.Conclusion SFTS critical score,REMS and APACHEⅡ score can all effectively predict the prognosis for SFTS patients,among which,the SFTS critical score is the most convenient and has the best predictive value.