Objective We aim to analyse semaglutide related adverse events in real-world,overall and by gender and age subgroups and compare the differences of different gender and age patients in adverse events,in order to supply references for security usage in the clinic.Methods OpenVigil 2.1 was used to search FDA Adverse Event Reporting System for semaglutide related adverse events from the establishment of the databases to April 2023.According to age and gender,patients were divided into 18-64 years old group and≥65 years old group,male group and female group.We selected ten adverse events which we interested(nausea,diarrhoea,vomiting,pancreatitis,cholecystitis,cholelithiasis,hypoglycaemia,diabetic retinopathy,acute kidney injury and thyroid cancer/medullary thyroid cancer)and analyzed overall and each group of semaglutide adverse events.Results A total of 5 330 cases and 15 558 adverse events were collected.2 935 patients aged 18-64 old group years with 8 553 adverse events;2 395 patients aged≥65 years old group with 7 005 adverse events.2 231 male group patients with 6 195 adverse events;3 059 female group patients with 9 277 adverse events.The sex of 40 patients was unknown.Nausea(1 089 cases/7.00％),vomiting(775 cases/4.98％)and diarrhoea(545 cases/3.50％)remained the most common adverse events.The constituent ratio of pancreatitis was significantly higher in patients aged 18-64 years old group than in patients aged 65 years old group(P＜0.05);the constituent ratio of diarrhoeaand cholelithiasis was significantly lower in patients aged 18-64 years old group than patients aged≥65 years old group(P＜0.05).The constituent ratio of diarrhoea,vomiting,pancreatitis,cholecystitis,cholelithiasis,diabetic retinopathy,and acute kidney injurywas significantly higher in male group patients than in female group(P＜0.05).Conclusion Nausea,diarrhoea and vomiting remined the most common adverse events of semaglutide.Male should be more concerned about gastrointestinal,pancreatitis,gallbladder events,retinopathy and acute kidney injury.Elderly patients should be more alert diarrhoea and cholelithiasis.

Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.

Objective To investigate the relationship between insomnia,gastrointestinal symptoms,and glycosylated hemoglobin(HbA1c)levels in individuals diagnosed with type 2 diabetes mellitus(T2DM),as well as the related influencing factors.Methods A total of 910 T2DM patients treated in our multicenter from January 2022 to December 2022 were enrolled in this study.General information(gender,age,smoking and drinking history,exercise,course of disease,treatment and complications),HbA1c,Athens Insomnia Scale(AIS)scores and Gastrointestinal Symptoms Rating Scale(GSRS)scores of patients were collected.The differences of sleep and gastrointestinal symptoms between groups were analyzed,and the correlation between the differences and HbA1c was analyzed.Furthermore,the risk factors for non-standard HbA1c were analyzed.Results The AIS score and GSRS score in the HbA1c control group were less than those in the non-standard group(P＜0.01).Insomnia was reported by 37.0％of T2DM patients,and the HbA1c level in the insomnia group was significantly higher than that in the non-insomnia group(10.00％±2.38％vs.8.26％±1.73％,P＜0.01).Gastrointestinal symptoms were present in 57.5％of T2DM patients,and the HbA1c levels in the group with gastrointestinal symptoms were significantly higher than those in the group without gastrointestinal symptoms(9.26％±2.23％vs.8.43％±1.98％,P＜0.01).Furthermore,26.3％of T2DM patients experienced both insomnia and gastrointestinal symptoms.Remarkably,the HbA1c levels in the group with both insomnia and gastrointestinal symptoms were significantly higher than those in the group without either condition(10.18％±2.44％vs.8.45％±1.86％,P＜0.01).Correlation analysis demonstrated a significant association between sleep quality,gastrointestinal function,and HbA1c levels(P＜0.01).The logistic regression analysis result revealed that age,GSRS score,AIS score,and the presence of insomnia combined with gastrointestinal symptoms were independent risk factors for predicting HbA1c≥6.5％(P＜0.01).Having both insomnia and gastrointestinal symptoms concurrently was the strongest risk factor for substandard HbA1c control,and the risk of blood sugar control may increase about 5 times when both appear together.Conclusion Insomnia and gastrointestinal symptoms are common comorbidities in T2DM patients,showing a cross-interfering relationship,and they appear together with poor blood sugar control,interact causally,and amplify each other.

[Objective] To establish a real-time fluorescence quantitative PCR nucleic acid detection method of human parvovirus B19 and validate the method systematically. [Methods] Specific primers and probes for the highly conserved regions of the three genotypes of B19 virus were designed, and B19 quantitative amplification standard curves were established. The accuracy, precision (repeatability and intermediate precision), linear range, quantification limit, detection limit, specificity, anti cross contamination, genotyping and anti-interference ability of this method were verified. [Results] When the quantitative reference range for B19 virus was 2.0×10¹ to 1.0×10⁸ IU/mL, a double logarithmic regression analysis was performed between the measured values and the theoretical values, and the regression equation R²≥0.98 showed good linear correlation. The quantification limit was 20 IU/mL, with a detection rate of 100%. The detection limit was 10 IU/mL, and the detection rate is 95.23%. Three genotypes of B19 virus samples can be effectively detected. The plasma of seven non B19 pathogens, including hepatitis A virus, hepatitis B virus, hepatitis C virus, human immuno-deficiency virus, human cytomegalovirus, hepatitis E virus and Treponema pallidum, was non reactive and has good species specificity. Simultaneously, in the presence of seven other concurrent pathogens, positive samples with a weak positive concentration of E3 IU/mL could be stably detected, and the B19 nucleic acid testing method was not interfered with. When the hemoglobin concentration was 431 mg/dL, triglycerides (1 269 turbidity) and unconjugated bilirubin concentration was 20 mg/dL, this method was non reactive for all three common plasma interfering substances. In the presence of three common plasma interfering substances, positive samples with a weak positive concentration of E3 IU/mL could be stably detected, and the B19 nucleic acid testing method was not interfered with. The deviation between the detection values of standard substances at two concentration levels of S1 (E5 IU/mL) and S2 (E4 IU/mL) and the target values were≤±0.5 log value. The CV values of positive sample 1 (concentration level E5 IU/mL) and positive sample 2 (concentration level E4 IU/mL) for daily precision confirmation and continuous 5-day intra-day precision confirmation were both≤5%. [Conclusion] This method has strong specificity, high sensitivity, wide linear range, stability, reliability and high accuracy, and can be used for the detection of human parvovirus B19 nucleic acid in plasma.

Objective:To construct a representative index system for evaluating pediatric orthopedic nursing quality, providing a basis for hospital pediatric orthopedic nursing quality assessment and monitoring.Methods:From April to July 2023, using the "structure-process-outcome" three-dimensional quality structure model as the theoretical framework, a literature review was conducted, and an item pool was formulated. Through two rounds of Delphi method expert consultations, the hierarchical analysis method was finally employed to determine the indicators and their weights at each level.Results:The effective recovery rates of the questionnaire of the two rounds of expert consultations were 100% (20/20), the authority coefficients of experts were 0.87 and 0.88, the coefficients of variation were 0.00 to 0.27 and 0.00 to 0.24. The Kendell harmony coefficients of the second and third indicators in the two rounds of inquiry were 0.140, 0.166 and 0.192, 0.161(all P<0.05). The final pediatric orthopedic nursing quality evaluation index system included 3 primary indicators, 21 secondary indicators and 83 tertiary indicators. Among the primary indicators, the weight of process quality was the highest at 0.493 4, followed by outcome quality at 0.310 8, and the lowest was structural quality at 0.195 8. In the secondary indicators, "assessment criteria of limb blood circulation" had the highest weight at 0.099 8. Conclusions:The constructed pediatric orthopedic nursing quality evaluation index system covers key aspects and is more operationally feasible. It provides better guidance for nursing interventions and quality control.

Human-animal interaction has a long-standing tradition dating back to ancient times. With the rapid advancements in intelligent chips, wearable devices, and machine algorithms, the intelligent interaction between animals and electronic technology, facilitated by electronic devices and systems for communication, perception, and control, has become a reality. These electronic devices aim to implement an animal-centric working mode to enhance human understanding of animals and promote the development of animal intelligence and creativity. This article takes medium-sized and large animals as research objects, with the goal of developing their ability enhancement, and introduces the concept of “intelligent animal augmentation system (IAAS)”. This concept is used to describe the characteristics of such devices and provides a comprehensive overview of existing animal and computer interface solutions. In general, IAAS can be divided into implantable and non-implantable types, each composed of interface platforms, perception and interpretation, control and instruction components. Through various levels of enhancement systems and architectural patterns, intelligent interaction between humans and animals can be realized. Although existing IAAS still lack a complete independent interaction system architecture, they hold great promise and development space in the future. Not only can they be applied as substitutes for cutting-edge devices and transportation equipment, but they are also expected to achieve cross-species information interaction through intelligent interconnection. Additionally, IAAS can promote bidirectional interaction between humans and animals, playing a significant role in advancing animal ethics and ecological protection. Furthermore, the development of interaction models based on animal subjects can provide insightful research experiences for the design of human-computer interaction systems, thereby contributing to the more efficient realization of the ambitious goal of human-machine integration.

The importance of evaluating the oxygen supply system of the medical aircraft was introduced.With considerations on the characteristics of the oxygen supply system of the medical aircraft during its development and application,an oxygen supply system effectiveness evaluation method was proposed based on the analytic hierarchy process and the experience of experts in the field of medical aircraft,which involved in seven evaluation indexes of total oxygen supply,pipeline airtight-ness,single-nozzle flow adjustment characteristics,single-nozzle outlet pressure adjustment characteristics,disassembly and assembly,mechanical operation and fixation ability.The effectiveness evaluation method proposed was of significance for accurately grasping the changes in the performance of the oxygen supply system.References were provided for the ground maintenance of the oxygen supply system of the medical aircraft.[Chinese Medical Equipment Journal,2024,45(1):89-92]

Objective:To explore the protective mechanism of tea polyphenols (TP) on mouse oral cancer.Methods:A total of 50 mice were divided into control group, model group, TP group, Selisistat group, TP+ Selisistat group, with 10 mice in each group. The control group was gavaged with physiological saline, while the model group, TP group, Selisistat group, and TP+ Selisistat group were gavaged with 300 mg/L 4-NQO to establish a mouse oral cancer model. Physiological saline, 200 mg/kg TP, 0.01 mg/kg Selisistat, and 200 mg/kg TP+ 0.01 mg/kg Selisistat were gavaged respectively. The weight changes of each group of mice were compared; HE staining was used to observe the morphology of mouse oral tumor tissue; Enzyme linked immunosorbent assay was used to detect the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in serum; Immunoblotting and immunohistochemistry were used to detect the expression of silencing information regulatory factor (Sirt1) and nuclear factor E2 related factor 2 (Nrf2) proteins in mouse oral tissues.Results:Compared with the control group, the model group mice had a decrease in body weight [(23.19±1.36)g], a decrease in serum SOD level [(91.64±8.75)U/ml], an increase in MDA level [(5.18±0.46)nmol/ml], a decrease in Sirt1 (0.38±0.05) and Nrf2 (0.36±0.05) protein expression in oral tissue, and an increase in Nrf2 acetylation level (0.84±0.11) (all P<0.05). Compared with the model group, the TP group mice had an increase in body weight [(25.28±1.25)g], elevated serum SOD levels [(121.24±10.68)U/ml], decreased MDA levels [(3.89±0.42)nmol/ml], increased expression of Sirt1 (0.61±0.09) and Nrf2 (0.58±0.06) proteins in oral tissue, and decreased Nrf2 protein acetylation levels (0.39±0.05); The Selisistat group mice showed a decrease in body weight [(21.41±1.07)g], a decrease in serum SOD levels [(72.16±7.43)U/ml], an increase in MDA levels [(5.87±0.41)nmol/ml], a decrease in Sirt1 (0.23±0.04) and Nrf2 protein (0.24±0.03) expression in oral tissue, and an increase in Nrf2 acetylation levels (1.12±0.14) ( P<0.05). The body weight [(23.32±1.27)g], serum SOD levels [(92.58±8.13)U/ml], and oral Sirt1 (0.41±0.06) and Nrf2 (0.38±0.05) protein expression in the TP+ Selisistat group mice were higher than those in the Selisistat group, while MDA [(5.11±0.38)nmol/ml] and Nrf2 acetylation levels (0.82±0.09) were lower than those in the Selisistat group (all P<0.05). Conclusions:Tea polyphenols can alleviate oral tissue damage and alleviate oxidative stress in mice with oral cancer, and their mechanism may be related to the upregulation of the Sirt1/Nrf2 pathway.

Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.

AIM To explore the effects of Buyang Huanwu Decoction on mitochondrial oxidative damage and PKCε-Nampt pathway in rats following cerebral ischemia reperfusion(I/R).METHODS The rats were randomly divided into the sham operation group,the model group,Buyang Huanwu Decoction group(14.3 g/kg)and edaravone group(3 mg/kg).Except those of the sham operation group,SD rats of other groups were induced into models of brain I/R injury by MCAO method,followed by corresponding drug administration 24 hours after operation.After 7 days of administration,the rats had their neurological deficit evaluated by neurological function scoring;thier expression of neuron marker MAP-2 detected by immunofluorescence staining;their neuron damage observed and the oxidative damage evaluated through assessment of their ROS levels and MDA and SOD activities;their changes of mitochondrial membrane potential detected by fluorescent probe JC-1;their ratio of NAD+/NADH detected using modified enzyme circulation method;their expressions of PKCε,p-PKCε and Nampt proteins detected with Western blot;and their positive expressions of p-PKCε and Nampt proteins detected with immunohistochemistry method.RESULTS Compared with the model group,Buyang Huanwu Decoction group shared decreased cerebral infarction volume and neurological function score(P<0.05);increased cerebral fluorescence intensity of MAP-2(P<0.05);reduced neuronal damage,decreased cerebral levels of ROS and MDA(P<0.05);increased SOD activity,mitochondrial membrane potential and NAD+/NADH ratio(P<0.05);and increased protein expressions of p-PKCε and Nampt(P<0.05).CONCLUSION Buyang Huanwu Decoction can improve mitochondrial function and reduce brain I/R injury in rats by activating their PKCε-Nampt signaling pathway.