ObjectiveTo improve the accuracy of discrete element method in simulating the processing of traditional Chinese medicine（TCM） powder system under low shear conditions. MethodsIn this study， extract powders of Tongsaimai tablets and Qige granules were used as the research objects， the angle of repose（AOR） and effective angle of internal friction of the two materials were determined by AOR test method and shear cell test method. Based on the Hertz-Mindlin with JKR V2 contact model and particle scaling theory， taking the particle-particle restitution coefficient（A）， particle-particle static friction coefficient（B）， particle-particle rolling friction coefficient（C）， particle-steel restitution coefficient（D）， particle-steel static friction coefficient（E）， particle-steel rolling friction coefficient（F） and Johnson-Kendall-Roberts（JKR） surface energy（G） as test factors， the simulated contact parameters of Tongsaimai tablets extract powder were first calibrated with a single reference value using AOR as the reference value， and then the simulated contact parameters of Tongsaimai tablets extract powder as well as Qige granules extract powder were co-calibrated with AOR and effective angle of internal friction as the joint reference value， respectively. Then， Plackett-Burman design was used to screen the critical contact parameters that have a significant effect on the simulated reference value， and the steepest ascent design was used to determine the optimal range of the critical contact parameters， finally， the regression model between the critical contact parameters and the simulated reference values was established through the design of the response surface test， and the critical contact parameters were calibrated based on the regression model and the desirability function approach. ResultsThe optimal combination of discrete elemental contact parameters A-G for Tongsaimai tablets extract powder under a single reference value was 0.100， 0.718， 0.616， 0.100， 0.400， 0.250 and 0.075 J·m^-2， which was validated to have relative errors of 0.10% and -8.64% for the simulated AOR and the simulated effective angle of internal friction， respectively. And the optimal combination of discrete elemental contact parameters A-G for Tongsaimai tablets extract powder at the joint reference values was 0.100， 0.682， 0.598， 0.100， 0.521， 0.294 and 0.075 J·m^-2， which was verified to have relative errors of 0.10% and -0.18% for the simulated AOR and the simulated effective angle of internal friction， respectively. The optimal combination of discrete elemental contact parameters A-G for Qige granules extract powder at the joint reference values was 0.150， 0.370， 0.330， 0.150， 0.500， 0.500 and 0.100 J·m^-2， which was verified to have relative errors of 2.70% and -1.30% for the simulated AOR and the simulated effective angle of internal friction， respectively. Compared with the single reference value method， the joint calibration method not only increased the number of the critical contact parameters for characterizing particle-device interactions， but also was more accurate and reliable. ConclusionCompared with the results of single reference value calibration， the results obtained by the method of joint calibration of discrete element simulation contact parameters with AOR and effective angle of internal friction as the reference values are more accurate， which can provide more accurate and reliable simulation physical property data for the simulation experiments of TCM extract powder under low shear process conditions.

Objective To investigate the rate of greater omentum metastasis in gastric cancer(GC). Methods General informations of patients with GC who underwent radical gastrectomy at Shanghai Ruijin Hospital in May 2020 were collected, and their clinicopathological characteristics were analyzed to find risk factors of greater omentum metastasis. Recurrence and survival were also assessed. Results A total of 59 patients with GC were included in the study, of which 2(3.4%) had greater omentum metastasis. One patient presented a pathological stage of pT4aN3bM0 and another ypT4bN1M0. The 3-year overall survival rate of patients in the study was 87.9%. Conclusions The rate of greater omentum metastasis was relatively low, and patients with greater omentum metastasis had an more advanced pathological stage. To further validate this clinical issue, a prospective randomized controlled clinical study should be conducted between radical gastrectomy with omentectomy and omentum-preserving radical gastrectomy.

Objective Currently, there is no commercially available quantitative detection kit for the main Felis domestic allergen (Fel d 1) in China. To establish a rapid detection method for Fel d 1, this study aims to prepare monoclonal antibodies against Fel d 1 protein. Methods The codon preference of Escherichia coli was utilized to optimize and synthesize the Fel d 1 gene. The prokaryotic expression plasmid pET-28a-Fel d 1 was constructed and used to express and purify the recombinant Fel d 1 protein. Subsequently, the recombinant protein was immunized into BALB/c mice and monoclonal antibodies (mAbs) were prepared by the hybridoma technique. An indirect ELISA was established using the recombinant Fel d 1 as the coating antigen, and hybridoma cell lines were screened for positive clones. The specificity and antigenic epitopes of the mAbs were confirmed by Western blot analysis. Finally, the selected hybridoma cells were injected into the peritoneal cavities of BALB/c mice for large-scale monoclonal antibody production. Results The recombinant plasmid pET-28a-Fel d 1 was successfully constructed, and soluble Fel d 1 protein was obtained after optimizing the expression conditions. Western blot and antibody titer assays confirmed the successful isolation of two hybridoma cell lines, 7D11 and 5H4, which stably secreted mAbs specific to Fel d 1. Antibody characterization revealed that the 5H4 mAb was of the IgG2a subtype and could recognize the amino acid region 105-163 of Fel d 1, while the 7D11 mAb was the IgG1 subtype and could recognize the amino acid region 1-59. Conclusion The high-purity recombinant Fel d 1 protein produced in this study provides a promising alternative for clinical immunotherapy of cat allergies. Furthermore, the monoclonal antibody prepared in this experiment lays a material foundation for the in-depth study of the biological function of Fel d 1 and the development of ELISA detection.
Animals ; Antibodies, Monoclonal/biosynthesis* ; Mice, Inbred BALB C ; Cats ; Mice ; Allergens/genetics* ; Glycoproteins/genetics* ; Enzyme-Linked Immunosorbent Assay ; Hybridomas/immunology* ; Recombinant Proteins/genetics* ; Female ; Antibody Specificity

Based on the theory of the liver's"using bitter herbs to nourish or purge"from Huangdi Neijing,this paper systematically elucidates the theoretical foundation for treating functional constipation from liver.Focusing on the physiological characteristic of"liver desires to disperse"and the pathological manifestation of"liver bitterness and urgency,"combined with the"liver communicates with the large intestine"theory,this paper establishes a diagnostic and therapeutic framework for managing functional constipation by regulating liver function.The pathological evolution of functional constipation manifests in three distinct stages:in the early stage,liver qi stagnation leads to large intestine qi obstruction,where damaged by an excess of seven emotions resulting in symptoms such as difficult defecation,abdominal bloating,and hypochondriac pain;in the middle stage,liver depression transforms into fire,scorching bodily fluids to generate dryness,thereby creating a pathological interplay of stagnation,fire,and dryness,which is marked by anal heat,dry mouth,and yellow urine;in the late stage,yin deficiency in liver and kidney causes large intestine malnutrition,resulting in a complex pathological state where yin deficiency,collateral blockage,dryness accumulation,and blood stasis intertwine,clinically manifesting as pellet-like stools(resembling sheep feces)and soreness and weakness of the waist and knees.In treatment,the formula design follows the principle of"sweetness to relieve,acridity to tonify,and sourness to purge,"with treatment principles varying across stages.In the early stage,the focus is on dispersing liver and regulating qi,and unblocking the zang-fu viscera;in the middle stage,the priority shifts to clearing heat-fire,nourishing large intestine,and promoting fluid production;whereas,in the late stage,the emphasis lies on nourishing yin,unblocking collaterals,and promoting blood circulation.This staged treatment of functional constipation overcomes the limitations of solely focusing on nourishing large intestine and facilitating feces excretion,thereby advancing the treatment of different stages based on syndrome differentiation and personalized treatment.It provides theoretical support for improving patients' intestinal function and enhancing overall health outcomes.

Objective To establish and validate a risk model for predicting heart failure(HF)in patients with hypertension.Methods The clinical data of 1500 patients with hypertension in Department of Cardiology of Tianjin Union Medical Center from January 2019 to December 2021 were retrospectively collected.The dataset was randomly partitioned into a training set(n=1050)and a valida-tion set(n=450)at a ratio of 7∶3.Then,the patients of training set were segmented into heart failure group(n=144)or non-heart failure group(n=906).The univariate Logistic regression,least absolute shrinkage and selection operator(LASSO)regression model and multivariate Logistic regression analysis were used for screening the risk factors and developing model.The R software was used to con-struct a nomogram.The discrimination ability of the model was determined by the area under the receiver operating characteristic curve(AUC),the calibration degree was evaluated by the calibration plot and Hosmer-Lemeshow goodness-of-fit test.Decision curve analy-sis(DCA)was performed to assess the clinical utility.Results This study showed that age,coronary heart disease,uric acid(UA),red blood cell distribution width(RDW),blood urea nitrogen/albumin ratio(BAR)and neutrophil to lymphocyte ratio(NLR)are inde-pendent predictors of the development of HF in patients with hypertension.A predictive model was constructed using the above six predic-tive factors.In the training set,the model had an AUC value of 0.864(95％CI;0.831-0.896),Hosmer-Lemeshow goodness of fit test showedx2=10.29,P=0.25.In the validation set,the AUC value was 0.842(95％CI:0.794-0.891),Hosmer-Lemeshow goodness of fit test showedx2=10.48,P=0.23.The clinical decision analysis also showed that the nomogram model had a better clinical perform-ance and could bring net clinical benefits to the patients.Conclusion This study successfully constructs a predictive model for the risk of HF in adults with hypertension and it can effectively identify patients at high risk of HF and formulate targeted intervention measures,thereby providing a basis for performing early prevention and treatment and improving prognosis.

Objective:To investigate the additional value of 99Tc m-hydrazinonicotinamide (HYNIC)-Tyr3-octreotide (TOC) SPECT/CT imaging in the diagnosis and treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods:A total of 54 patients (28 males and 26 females, age: (52.6±11.7) years) who underwent enhanced CT (MR) and 99Tc m-HYNIC-TOC SPECT/CT in People′s Hospital of Zhengzhou University between December 2017 and June 2023 were analyzed retrospectively. Surgical pathology or biopsy was the gold standard of patients′ diagnosis (primary tumors), and comprehensive evaluation based on pathology, imaging and follow-up results was used as the diagnostic criteria of lesions. McNemar χ2 test was used to compare the diagnostic efficacy of different imaging methods. Results:Pathological results showed that 43 of the 54 patients were with GEP-NETs and 11 were with non-neuroendocrine tumors (NETs). The sensitivities of enhanced CT and enhanced MR in the diagnosis of patients with GEP-NETs were 65.1%(28/43) and 60.0%(15/25) respectively, which increased to 93.0%(40/43) and 92.0%(23/25) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 8.64, 4.90, P values: 0.002, 0.021). There were 22 and 15 patients showing atypical enhancement on enhanced CT and enhanced MR respectively. The sensitivities of these two methods for GEP-NETs in patients with atypical enhancement were 54.5%(12/22) and 8/15 respectively, which increased to 95.5%(21/22) and 14/15 with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 5.82, 4.17, P values: 0.012, 0.031). Compared with enhanced CT, the detection rates of liver and bone metastatic lesions were improved significantly from 90.8%(158/174) and 55.2%(32/58) to 96.6%(168/174) and 87.9%(51/58) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 5.79, 9.82, P values: 0.013, 0.001). Compared with enhanced MR, the detection rate of bone metastases was improved significantly from 56.0%(14/25) to 88.0%(22/25) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2=4.08, P=0.039). After 99Tc m-HYNIC-TOC imaging, stages were changed in 7.0%(3/43) of patients and a greater number or extent of metastases were detected in 11.6%(5/43) of patients. 99Tc m-HYNIC-TOC imaging detected additional recurrent or metastatic lesions in 40.0%(8/20) of patients during follow-up compared to enhanced CT. Conclusion:99Tc m-HYNIC-TOC imaging can provide an added value for diagnosing GEP-NETs with atypically enhanced CT(MR), and in the detection of liver metastasis and early bone metastasis, thus helping the optimization of clinical treatment strategies.

Objective To investigate the status and influencing factors of type 2 diabetes mellitus(T2DM)patients' fear of complications,and to provide a reference for formulating targeted intervention measures.Methods From April to November 2024,370 patients with T2DM in 2 tertiary general hospitals in Daqing City were selected by convenience sampling method.General data questionnaire,Fear of Complications Questionnaire,Self-Perceived Burden Scale,Psychological Capital Questionnaire,Mishel Uncertainty in Illness Scale and Family Apgar Index Questionnaire were used for investigation.Univariate analysis and binary Logistic regression were performed to analyze the influencing factors.Results A total of 364 valid questionnaires were collected,with an effective recovery rate of 98.38％.The score of Fear of Complications Questionnaire was(23.47±7.47),and the incidence of fear of complications was 22.25％.Logistic regression analysis showed that medical payment methods,the number of complications,positive psychological capital and family care were the influencing factors of FoC in T2DM patients.Conclusion The fear of complications in T2DM patients is at a moderate level.Nursing staff should pay attention to the early assessment of patients' fear of complications,promptly identify and take effective measures to reduce the level of patients' fear of complications,improve their quality of life.

Objective:To mine the adverse event (AE) risk signals of semaglutide and liraglutide in weight management populations, and provide references for the safe use of these drugs in relevant patients.Methods:The reporting odds ratio (ROR) method, proportional reporting ratio (PRR) method, Bayesian confidence propagation neural network (BCPNN) method, and empirical Bayesian geometric mean (EBGM) method were used to mine the AE risk signals of semaglutide and liraglutide in weight management populations from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the 1st quarter of 2010 to the 4th quarter of 2023. Adverse events that met the criteria of all 4 mining methods were considered as risk signals. The adverse events were classified and statistically analyzed using the system organ class (SOC) and preferred term (PT) of the 26.1 version of the Medical Dictionary for Regulatory Activities 26.1 version, and the identified risk signals were analyzed. Results:During the set period, 2 292 AE reports for semaglutide for weight management (excluding diabetes) and 2 973 for liraglutide were retrieved. The semaglutide-related AE reports involved 83 PTs, among which 57 were already recorded in the instructions and 26 were not. Among the 26 PTs not recorded in the labels, the top 5 PTs in terms of AE report numbers were increased appetite, hunger, panic attack, binge eating, and feeling cold; the top 5 PTs in terms of ROR values were lack of satiety, hunger-induced ketoacidosis, myoglobinuria, binge eating, and bulimia. The liraglutide-related AE reports involved 74 PTs, among which 60 were already recorded in the instructions and 14 were not. Among the 14 PTs not recorded in the labels, the top 5 PTs in terms of AE report numbers were weight gain, increased appetite, binge eating, weight fluctuation, and pancreatic cyst; the top 5 PTs in terms of ROR values were lack of satiety, binge eating, hepatic adenoma, increased appetite, and pancreatic cyst. Three PTs of severe AEs that were not recorded in the labels for semaglutide were identified, namely, olfactory abnormality, ketoacidosis, and panic attack. One PT of severe AE that was not recorded in the labels for liraglutide was identified, namely, metastatic pancreatic cancer. Conclusion:The AE risk signals of semaglutide and liraglutide in weight management include AEs not recorded in the labels, and some are even serious AEs, which need to be identified and prevented in clinical practice.

Objective:To mine the adverse event (AE) risk signals of semaglutide and liraglutide in weight management populations, and provide references for the safe use of these drugs in relevant patients.Methods:The reporting odds ratio (ROR) method, proportional reporting ratio (PRR) method, Bayesian confidence propagation neural network (BCPNN) method, and empirical Bayesian geometric mean (EBGM) method were used to mine the AE risk signals of semaglutide and liraglutide in weight management populations from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the 1st quarter of 2010 to the 4th quarter of 2023. Adverse events that met the criteria of all 4 mining methods were considered as risk signals. The adverse events were classified and statistically analyzed using the system organ class (SOC) and preferred term (PT) of the 26.1 version of the Medical Dictionary for Regulatory Activities 26.1 version, and the identified risk signals were analyzed. Results:During the set period, 2 292 AE reports for semaglutide for weight management (excluding diabetes) and 2 973 for liraglutide were retrieved. The semaglutide-related AE reports involved 83 PTs, among which 57 were already recorded in the instructions and 26 were not. Among the 26 PTs not recorded in the labels, the top 5 PTs in terms of AE report numbers were increased appetite, hunger, panic attack, binge eating, and feeling cold; the top 5 PTs in terms of ROR values were lack of satiety, hunger-induced ketoacidosis, myoglobinuria, binge eating, and bulimia. The liraglutide-related AE reports involved 74 PTs, among which 60 were already recorded in the instructions and 14 were not. Among the 14 PTs not recorded in the labels, the top 5 PTs in terms of AE report numbers were weight gain, increased appetite, binge eating, weight fluctuation, and pancreatic cyst; the top 5 PTs in terms of ROR values were lack of satiety, binge eating, hepatic adenoma, increased appetite, and pancreatic cyst. Three PTs of severe AEs that were not recorded in the labels for semaglutide were identified, namely, olfactory abnormality, ketoacidosis, and panic attack. One PT of severe AE that was not recorded in the labels for liraglutide was identified, namely, metastatic pancreatic cancer. Conclusion:The AE risk signals of semaglutide and liraglutide in weight management include AEs not recorded in the labels, and some are even serious AEs, which need to be identified and prevented in clinical practice.