The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To develop a risk assessment model related to ferroptosis,to explore the effects of ferroptosis on cervical cancer survival,to obtain differentially expressed ferroptosis-related genes in cervical cancer,and to predict microRNAs(miRNAs)targeting genes.Methods First,a ferroptosis-related gene dataset was defined using FerrDb,the Molecular Signatures Database,and a collection of ferroptosis-related genes in existing studies.Cervical cancer data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus databases were downloaded for differential analysis,and differentially expressed(DE)ferroptosis-related genes were screened out.Second,the risk score model was developed by least absolute shrinkage and selection operato regression analysis,and the cervical cancer data in the TCGA database were divided into two groups:high risk and low risk groups according to the score.The scoring model was evaluated by Kaplan-Meier analysis,subject working curves,clinical characteristics and immunoassays.Finally,miRNA for potential regulation of target genes was predicted by miRDB,TargetScan and starBase databases.Results A total of 28 DE ferroptosis-related genes were obtained in the cervical cancer data.The results showed that patients in the high-risk group had shorter overall survival(0.76 year vs 1.00 year,P＜0.001)and higher levels of infiltration of immunosuppressive cell infiltration than those in the low-risk group.The expression of the ferroptosis-related gene SQLE was significantly increased in cervical cancer.Finally,through database prediction,miR-579-3p was found to be the potential regulator of the expression of squalene epoxidase(SQLE).Conclusion In this study,a risk scoring model of ferroptosis gene for predicting the prognosis of cervical cancer was developed,and the potential miRNA miR-579-3p for regulating the expression of ferroptosis-related gene SQLE in cervical cancer was screened.

The Piezo protein is a non-selective mechanosensitive cation channel that exhibits sensitivity to mechanical stimuli such as pressure and shear stress. It converts mechanical signals into bioelectric activity within cells, thus triggering specific biological responses. In the digestive system, Piezo protein plays a crucial role in maintaining normal physiological activities, including digestion, absorption, metabolic regulation, and immune modulation. However, dysregulation in Piezo protein expression may lead to the occurrence of several pathological conditions, including visceral hypersensitivity, impairment of intestinal mucosal barrier function, and immune inflammation.Therefore, conducting a comprehensive review of the physiological functions and pathological roles of Piezo protein in the digestive system is of paramount importance. In this review, we systematically summarize the structural and dynamic characteristics of Piezo protein, its expression patterns, and physiological functions in the digestive system. We particularly focus on elucidating the mechanisms of action of Piezo protein in digestive system tumor diseases, inflammatory diseases, fibrotic diseases, and functional disorders. Through the integration of the latest research findings, we have observed that Piezo protein plays a crucial role in the pathogenesis of various digestive system diseases. There exist intricate interactions between Piezo protein and multiple phenotypes of digestive system tumors such as proliferation, apoptosis, and metastasis. In inflammatory diseases, Piezo protein promotes intestinal immune responses and pancreatic trypsinogen activation, contributing to the development of ulcerative colitis, Crohn’s disease, and pancreatitis. Additionally, Piezo1, through pathways involving co-action with the TRPV4 ion channel, facilitates neutrophil recruitment and suppresses HIF-1α ubiquitination, thereby mediating organ fibrosis in organs like the liver and pancreas. Moreover, Piezo protein regulation by gut microbiota or factors like age and gender can result in increased or decreased visceral sensitivity, and alterations in intestinal mucosal barrier structure and permeability, which are closely associated with functional disorders like irritable bowel sydrome (IBS) and functional consitipaction (FC). A thorough exploration of Piezo protein as a potential therapeutic target in digestive system diseases can provide a scientific basis and theoretical support for future clinical diagnosis and treatment strategies.

To explore the protective mechanisms of a novel molybdenum disulfide (MoS₂) nanozyme in alleviating inflammation-related endothelial cell injury by regulating mitochondrial dynamic, flower like-MoS₂ nanosheets were prepared by hydrothermal method, and its antioxidant enzyme-mimic activities were assessed via electron spin resonance (ESR) spectroscopy. It was shown that MoS₂ nanosheets had strong scavenging ability for hydroxyl radical (·OH) and singlet reactive oxygen species (¹O₂) in a dose-dependent manner. Using an in vitro lipopolysaccharide (LPS)-induced vascular endothelial cell injury model, the protective roles of MoS₂ nanozyme on cytotoxicity and apoptosis of endothelial cells were examined by MTT and Annexin V-FITC/PI assay, respectively. Mitochondrial fission/fusion of endothelial cell were observed by Mito-Tracker green probe. Reactive oxygen species (ROS) probe DCFH-DA and superoxide anion probe DHE were used to detect the level of oxidative stress in vitro. Plasmid GFP-LC3 transfection using colocalization analysis was applied to assess the autophagy of endothelial cells. The results showed that MoS₂ nanozyme could significantly reduce the cytotoxicity and apoptosis of endothelial cells stimulated by LPS, and prevent the impairment mitochondrial dynamics of endothelial cells, thus maintaining mitochondrial dynamics. In addition, MoS₂ nanozyme was also shown to alleviate LPS-mediated endothelial mitochondrial autophagy, thus protecting endothelial cells from inflammatory stress. These results established that MoS₂ nanozyme protected endothelial cells injury from inflammatory stress by regulating mitochondrial dynamics and mitochondrial autophagy of endothelial cells, which is expected to expand the use of MoS₂ nanozyme in the prevention and treatment of inflammation-related vascular endothelial diseases.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:To explore the application effect of microsurgical thinning optimized anterolateral thigh flap in the repair of limb tumor wounds.Methods:A retrospective analysis was conducted on the clinical data of patients with limb tumors at the Microsurgery and Reconstruction Department of Xuzhou Renci Hospital from January 2019 to January 2021. All patients underwent surgical resection of the lesions and were repaired with microsurgical thinning optimized anterolateral thigh flap. The outpatient follow-up was conducted after surgery. One year after surgery, limb function and appearance were evaluated using the Musculoskeletal Tumor Society (MSTS) bone tumor limb salvage surgery limb energy scale and efficacy satisfaction score. The total score is 30 points, and a higher score indicates better function. The limb appearance was evaluated using a satisfaction score scale, with a total score of 5-10 points being satisfactory, 0-4 points being average, and -5 to -1 points considered unsatisfactory. Descriptive methods were used for statistical analysis, and normally distributed measurement data were expressed as Mean±SD.Results:A total of 11 patients were included, comprising 7 males and 4 females, aged between 19 and 55 years, with an average age of 31.5 years. Among them, there were 3 cases of dermatofibrosarcoma protuberans, 4 cases of invasive fibroma, 1 case of mucinous fibrosarcoma, 2 cases of malignant fibrous histiocytoma, and 1 case of squamous cell carcinoma of the skin. The tumor lesion ranged from 5.5 cm × 8.0 cm to 9.0 cm × 19.0 cm, and the tumor resection range during surgery was from 6.5 cm × 9.0 cm to 10.0 cm × 20.0 cm. The size of the skin flap ranged from 7.5 cm × 11.0 cm to 10.0 cm × 22.5 cm. The average thickness of the flap before thinning was 2.2 cm (1.6-3.5 cm), and the average thickness after thinning was 1.2 cm (0.9-1.7 cm). One case of superficial necrosis occurred at the edge of the flap measuring 1.5 cm × 2.0 cm after surgery, and the wound healed after dressing changes. One case of arterial crisis occurred 48 hours after surgery, and thrombus formation was detected at the distal end of the anastomosis during exploration. After reanastomosis, blood flow was restored. The remaining flaps survived well, and the incisions healed in one stage. The average postoperative follow-up period was 14.5 months (12-18 months) with no tumor recurrence. The MSTS score for limb function was (25.2±2.1) points, and the satisfaction score for limb appearance efficacy was (7.4±1.6) points, with a satisfaction rate of 10 out of 11.Conclusion:The application of microsurgical thinning optimized anterolateral thigh flap in the plastic surgery of limb tumors can restore satisfactory limb function and appearance, making it an ideal surgical method.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the expression of CD123 in children with acute lymphoblastic leukemia(ALL)and its effect on the clinical characteristics and prognosis of children with B-lineage acute lymphoblastic leukemia(B-ALL).Methods A retrospective analysis was conducted on the clinical data of 251 children with ALL who were admitted to the Department of Hematology and Oncology,Children's Hospital of Kunming Medical University,from December 2019 to June 2022.According to the expression of CD123 at initial diagnosis,the children were divided into CD123+group and CD123-group,and the two groups were compared in terms of clinical characteristics and treatment outcome.The factors influencing the prognosis were analyzed.Results Among the 251 children with ALL,there were 146 children(58.2%)in the CD123+group.The B-ALL group had a significantly higher positive expression rate of CD123 than the acute T lymphocyte leukemia group(P<0.05).Compared with the CD123-group,the CD123+group had significantly lower peripheral blood leukocyte count and percentage of juvenile cells and a significantly higher proportion of children with high hyperdiploid karyotype or an age of 1-10 years,with a relatively low proportion of children with E2A-PBX1 fusion gene(P<0.05).The multivariate Cox proportional-hazards regression model analysis showed that compared with the>10 years group,the 1-10 years group had a significantly higher overall survival rate(P<0.05),and compared with the high risk group,the moderate risk group had a significantly higher event-free survival rate in children with B-ALL(P<0.05).Conclusions CD123 is widely expressed in children with B-ALL,and positive expression of CD123 might be an indicator for good prognosis in children with B-ALL,which is of great significance for evaluating the efficacy of remission induction therapy and survival prognosis of children with B-ALL.

Objective To investigate the effects of propranolol on the proliferation,apoptosis,migration,and tube formation ability of human umbilical vein endothelial cells(HUVEC),as well as its impact on the expression of sex-determining region Y-box 18(SOX18),matrix metalloproteinase-7(MMP-7),and vascular endothelial growth factor A(VEGFA).Methods HUVEC were treated with different concentrations of propranolol,and cell viability was assessed using the CCK-8 method to determine the optimal concentration and treatment duration.The experiment consisted of a control group and groups treated with different concentrations of propranolol(50,100,150 μmol/L).Apoptosis,migration,and tube formation of HUVEC were observed using flow cytometry,wound healing assays,and tube formation assays.Western blot and real-time quantitative PCR were used to detect the expression levels of SOX18,MMP-7,and VEGFA proteins and mRNA.Results Compared to the control group,the apoptosis rate in the propranolol treatment groups increased significantly(P<0.05),and it rose significantly with increasing drug concentration(P<0.05).The wound healing rate decreased in the propranolol treatment groups,and both the number of tube formation nodes and total tube length were reduced(P<0.05).The expression levels of SOX18,MMP-7,and VEGFA proteins and mRNA were downregulated in the propranolol treatment groups(P<0.05).Conclusions Propranolol can inhibit the proliferation,migration,and tube formation ability of HUVEC and promote cell apoptosis,resulting in decreased expression levels of SOX18,MMP-7,and VEGFA.

Objective:To provide reference for hospital drug selection and clinical rational drug selection,through evaluating the nutritional value of six commonly used balanced compound amino acid injection (BCAA) in clinical practice,including 18AA (250 mL:12.5 g),18AA-I (250 mL:17.5 g),18AA-Ⅱ(250 mL:21.25 g),18AA-IV (250 mL:8.7 g),18AA-V (250 mL:8.06 g),and 18AA-V-SF (250 mL:8.06 g). Methods:Based on the whole egg protein model,the nutritional value of six varieties of BCAA from two aspects were evaluated,including the first limiting amino acid chemical score (CS),value of essential amino acid (EAA) and the comprehensive quality of total EAA (both essential amino acid index and closeness to standard protein). Results:The first limiting amino acid CS value from high to low was 18AA-Ⅱ>18AA>18AA-V=18AA-V-SF>18AA-I=18AA-Ⅳ. Total EAA comprehensive quality:the essential amino acid index from high to low was 18AA-Ⅱ>18AA>18AA-I>18AA-Ⅳ>18AA-V=18AA-V-SF. The closeness to whole egg protein from high to low was 18AA-Ⅱ=18AA=18AA-I>18AA-Ⅳ>18AA-V=18AA-V-SF. Ultimately,the nutritional value of the 6 varieties of BCAA decreased from high to low:18AA-Ⅱ>18AA>18AA-I>18AA-Ⅳ>18AA-V=18AA-V-SF. Conclusions:Among the six varieties of BCAA,18AA-Ⅱ has the highest nutritional value and the highest amino acid content in the same liquid volume,making it the preferred drug for patients with normal liver and kidney function.