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 the prevalence trend and spatiotemporal distribution characteristics of congenital heart disease in China.Methods:Data on the incidence of congenital heart disease in China and provinces from 2002 to 2021 were collected through publicly available literature and reports. Joinpoint regression was used to assess the temporal trend of the incidence of congenital heart disease. Spatial autocorrelation analysis and spatiotemporal scanning statistics were used to analyze the spatial aggregation of hotspots and clustering areas of congenital heart disease occurrence.Results:The incidence of congenital heart disease in China showed a continuously increasing trend from 2002 to 2021, with an average annual increase of 15.33% (AAPC=15.33%, P<0.001). Except for areas with missing data, 25 provinces showed an increasing trend (all AAPC>0, all P<0.05), while there was no significant change in Guangdong and Guangxi ( P=0.397 and 0.081). The results of global autocorrelation analysis showed that the occurrence of congenital heart disease had a certain clustering distribution, with the Global Moran′s I>0 in 2005, 2006 and 2016, which were 0.23, 0.26 and 0.23 ( P=0.027, 0.017 and 0.022). The results of local spatial autocorrelation showed that Hunan, Jiangxi and Fujian were high-high clustering areas, while the central and southwestern regions were low-low clustering areas. The results of segmental spatiotemporal scanning showed that eight clustering areas were found in four time periods ( P≤0.001), and the clustering areas showed a trend of gradually expanding from none to certain coverage. Conclusion:From 2002 to 2021, the overall trend of congenital heart disease in China has been on the rise, with a certain degree of spatial aggregation. The clustering areas of spatiotemporal scanning have gradually increased, and the scope has gradually expanded.

Objective:To analyze the prevalence trend and spatiotemporal distribution characteristics of congenital heart disease in China.Methods:Data on the incidence of congenital heart disease in China and provinces from 2002 to 2021 were collected through publicly available literature and reports. Joinpoint regression was used to assess the temporal trend of the incidence of congenital heart disease. Spatial autocorrelation analysis and spatiotemporal scanning statistics were used to analyze the spatial aggregation of hotspots and clustering areas of congenital heart disease occurrence.Results:The incidence of congenital heart disease in China showed a continuously increasing trend from 2002 to 2021, with an average annual increase of 15.33% (AAPC=15.33%, P<0.001). Except for areas with missing data, 25 provinces showed an increasing trend (all AAPC>0, all P<0.05), while there was no significant change in Guangdong and Guangxi ( P=0.397 and 0.081). The results of global autocorrelation analysis showed that the occurrence of congenital heart disease had a certain clustering distribution, with the Global Moran′s I>0 in 2005, 2006 and 2016, which were 0.23, 0.26 and 0.23 ( P=0.027, 0.017 and 0.022). The results of local spatial autocorrelation showed that Hunan, Jiangxi and Fujian were high-high clustering areas, while the central and southwestern regions were low-low clustering areas. The results of segmental spatiotemporal scanning showed that eight clustering areas were found in four time periods ( P≤0.001), and the clustering areas showed a trend of gradually expanding from none to certain coverage. Conclusion:From 2002 to 2021, the overall trend of congenital heart disease in China has been on the rise, with a certain degree of spatial aggregation. The clustering areas of spatiotemporal scanning have gradually increased, and the scope has gradually expanded.

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 explore the effects of Balint Group on the emotional stability of residents during the standardized training and the improvement of doctor-patient relationship and communication ability, so as to provide a basis for incorporating the activities of Balint Group into the daily management of the standardized training of residents and as an important course in post competency.Methods:From February to December 2021, a simple randomized controlled study was conducted at the First Affiliated Hospital of Suzhou University, 40 residents were selected and assigned to two groups. Twenty residents were enrolled in the "experimental group" to participate in the closed Balint group activities; another 20 residents did not participate in the Balint group activities and were treated as the "control group". Tools of Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Set the stage, Elicit information, Give information, Understand the patient's perspective, and End the encounter (SEGUE) were applied to evaluate the emotional state, doctor-patient relationship management, and doctor-patient communication skills of residents in the two groups in the third month, sixth month and ninth month of participating in the Balint group. SPSS 22.0 software was used for t test, and comparison among three or more groups was conducted by analysis of variance. Repeated measures data involving two factors were analyzed by repeated measures analysis of variance. Results:In the assessment of anxiety state, the scores in the experimental group decreased gradually from the sixth month to the ninth month, and there was a significant difference in the interaction effect between time and group ( F=14.57, P<0.001). In the assessment of depressive state, there was a significant difference in the interaction effect between time and group ( F=33.25, P<0.001), and the depression self-score in the experimental group decreased gradually, with an gradually increased difference between the two groups. Compared with the control group, the experimental group had significantly improvements in three dimensions of information collection, information giving, and understanding of patients. The total SEGUE score in the experimental group was improved significantly after nine months of training compared with the baseline value [(107.20±2.16) vs. (92.55±4.37), t=7.26, P<0.001]. The repeated measures analysis of variance showed that there were significant differences between the two groups in terms of information giving ( F=3.01, P=0.045) and total SEGUE score ( F=6.29, P=0.002) under the assessment of interaction between time and group. Conclusions:Balint groups can alleviate residents' anxiety and depression and play an important role in maintaining stable mood. Balint groups have an advance effect on improving residents' doctor-patient communication skills, especially in information collection, information feedback and giving, and understanding of patients.

Objective:To explore the effects of Balint Group on the emotional stability of residents during the standardized training and the improvement of doctor-patient relationship and communication ability, so as to provide a basis for incorporating the activities of Balint Group into the daily management of the standardized training of residents and as an important course in post competency.Methods:From February to December 2021, a simple randomized controlled study was conducted at the First Affiliated Hospital of Suzhou University, 40 residents were selected and assigned to two groups. Twenty residents were enrolled in the "experimental group" to participate in the closed Balint group activities; another 20 residents did not participate in the Balint group activities and were treated as the "control group". Tools of Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Set the stage, Elicit information, Give information, Understand the patient's perspective, and End the encounter (SEGUE) were applied to evaluate the emotional state, doctor-patient relationship management, and doctor-patient communication skills of residents in the two groups in the third month, sixth month and ninth month of participating in the Balint group. SPSS 22.0 software was used for t test, and comparison among three or more groups was conducted by analysis of variance. Repeated measures data involving two factors were analyzed by repeated measures analysis of variance. Results:In the assessment of anxiety state, the scores in the experimental group decreased gradually from the sixth month to the ninth month, and there was a significant difference in the interaction effect between time and group ( F=14.57, P<0.001). In the assessment of depressive state, there was a significant difference in the interaction effect between time and group ( F=33.25, P<0.001), and the depression self-score in the experimental group decreased gradually, with an gradually increased difference between the two groups. Compared with the control group, the experimental group had significantly improvements in three dimensions of information collection, information giving, and understanding of patients. The total SEGUE score in the experimental group was improved significantly after nine months of training compared with the baseline value [(107.20±2.16) vs. (92.55±4.37), t=7.26, P<0.001]. The repeated measures analysis of variance showed that there were significant differences between the two groups in terms of information giving ( F=3.01, P=0.045) and total SEGUE score ( F=6.29, P=0.002) under the assessment of interaction between time and group. Conclusions:Balint groups can alleviate residents' anxiety and depression and play an important role in maintaining stable mood. Balint groups have an advance effect on improving residents' doctor-patient communication skills, especially in information collection, information feedback and giving, and understanding of patients.

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