ObjectiveTo compare the differences between the ultrafiltration method and the dextran gel filtration method during the purification of Tfn-modified PCL micelles by using purification efficiency and micelle purity as indicators. MethodsCoumarin-6 （C6） was used as a fluorescent probe and was loaded into HOOC-PEG-PCL to form PCL micelles by the film-dispersion method. Tfn was then conjugated to the surface of PCL micelles via an amidation reaction， resulting in two types of micelles： Tfn/PCL_H and Tfn/PCL_L. The pharmaceutical properties of the two types of micelles were characterized. The micelles were then purified through ultrafiltration method and dextran gel method respectively， and the efficiency of the two methods， along with the purity of the final micelles， was compared. The density of Tfn on the surface of PCL micelles was also calculated. ResultsThe hydrated diameter of PCL micelles was approximately 73 nm， and the C6 loading efficiency was around 0.046%. The size increased to 134 nm and 158 nm for Tfn/PCL_L and Tfn/PCL_H， respectively. The micelle population was monodisperse. The purification results showed that， for the ultrafiltration method， after two and one rounds of purification， the Tfn/C6 ratio stabilized at 23.6 and 3.4 for Tfn/PCL_H and Tfn/PCL_L， respectively. For the dextran gel filtration method， the Tfn/C6 ratio reached 23.7 for the Tfn/PCL_H group after two rounds of purification. However， for the Tfn/PCL_L group， the Tfn/C6 ratio increased during four rounds of dextran gel purification， and a significant difference （P = 0.042 4） was observed between the first and last filtrations. The density of Tfn in the final micelles were calculated. For the ultrafiltration method， the Tfn density of Tfn/PCL_H and Tfn/PCL_L were 94.9% and 13.8%， respectively. For the dextran gel filtration method， the density of the two micelles were 95.6% and 14.4%， respectively. For Tfn/PCL_L group， the density results revealing a statistically significant difference （P=0.000 2）. ConclusionThe purification efficiency of the two methods is comparable. However， the purity of the final micelles shows a significant difference， with the dextran gel filtration method resulting in higher purity， particularly for the Tfn/PCL_L micelles.

Objective To collect oral exhaled odor spectrum of patients of chronic atrophic gastritis(CAG)with yin deficiency syndrome and detect their gut microbiota;To elucidate the mechanism of odor changes from the perspective of gut microbiota changes;To provide a basic research for the objectification of TCM olfactory diagnosis in CAG.Methods Totally 110 patients with CAG,including 55 patients with CAG yin deficiency syndrome,55 patients with CAG non-yin deficiency syndrome,and 30 healthy individuals were collected.The electronic nose technology was used to collect the oral exhaled odor spectrum of all subjects,and an improved Transformer model was used to identify the breath odor spectrum of CAG yin deficiency syndrome patients and healthy individuals,CAG non-yin deficiency syndrome patients and healthy individuals,CAG yin deficiency syndrome patients and CAG non-yin deficiency syndrome patients.At the same time,16S rRNA high-throughput sequencing method was used to detect the gut microbiota of the subjects'fecal samples,and the correlation analysis between the odor spectrum characteristics of CAG yin deficiency syndrome and gut microbiota was conducted.Results ① Analysis and recognition of odor spectrum characteristic.Amplitude characteristics:The response curves A,C,D,G,H,I and J of the odor spectrum in the CAG yin deficiency syndrome group and the CAG non-yin deficiency syndrome group were all lower in amplitude than those in the healthy group(P<0.01,P<0.05).Slope characteristics:The slopes of response curves A,B,C,D,E,G,H,I and J in the odor spectrum of the CAG yin deficiency syndrome group and the CAG non-yin deficiency syndrome group were lower than those of the healthy group(P<0.01,P<0.05).Pattern recognition:The accuracy of pattern recognition between the CAG yin deficiency syndrome group and the healthy group reached 0.904,with an area under ROC curve(AUC)of 0.91;the accuracy of pattern recognition between the CAG non-yin deficiency syndrome group and the healthy group reached 0.885,AUC=0.89;the accuracy of pattern recognition between the CAG yin deficiency syndrome group and the CAG non-yin deficiency syndrome group reached 0.747,AUC=0.75.② Species composition:At the genus level,compared with the healthy group,the abundance of Actinomyces,Escherichia-Shigella and Tyzzerella in the CAG yin deficiency syndrome group increased(P<0.05),while the abundance of Prevotella,Sutterella and Subdoligranulum decreased(P<0.05);the abundance of[Ruminococcus]_gnavus_group and Escherichia-Shigella in the CAG non-yin deficiency syndrome group increased significantly(P<0.01),while the abundance of Prevotella and Subdoligranulum decreased(P<0.05).Compared with the CAG yin deficiency syndrome group,the non-yin deficiency syndrome group showed significant enrichment of the Dialister(P<0.05).③ Correlation analysis between odor spectrum characteristics and gut microbiota in CAG yin deficiency syndrome:This study identified 17 bacterial genera that showed positive and negative correlations with the amplitude and slope characteristics of the odor spectrum in CAG yin deficiency syndrome,namely Lachnospiraceae_NK4A136_group,Lachnospiraceae_ND3007_group,Faecalibacterium,UCG-002,UCG-005,Coprococcus,CAG-352,Parabacteroides,Actinomyces,Streptococcus,Anaerostipes,Blautia,Dorea,[Eubacterium]_hallii_group,Phascolarctobacterium,Clostridium_sensu_stricto_1,Enterobacter.The above-mentioned bacterial genera could be classified into the following bacterial families:Trichomonas,Clostridia,Porphyromonas,Actinobacteria,Ruminococcus,Streptococcus,Bacteroidetes,Clostridium,Veillonellaceae and Enterobacteriaceae.Conclusion The use of electronic nose technology can accurately identify the oral exhaled odor of patients with CAG yin deficiency syndrome,CAG non-yin deficiency syndrome,and healthy individuals;the odor spectrum characteristics of patients with CAG yin deficiency syndrome are correlated with multiple bacterial genera,and the changes in related metabolites and gases produced by the disruption of their gut microbiota may be one of the biological bases for the changes in oral exhaled odor in CAG yin deficiency syndrome.

Objective To observe the value of non-contrast CT radiomics extreme gradient boosting(XGBoost)model based on SHAP method for predicting acute necrotic collection(ANC)around acute pancreatitis(AP).Methods A total of 307 patients with initially clinically diagnosed AP were retrospectively enrolled.The optimal radiomics features of peripheral pancreatic tissue volume of interest(VOI)were extracted and screened based on automatic segmentation on the first non-contrast CT,and the evaluation results of modified CT severity index(MCTSI)score of AP severity based on first enhanced CT were recorded.The patients were divided into peripancreatic ANC group(ANC group)and acute peripancreatic fluid collection(APFC)group according to follow-up abdominal CT.XGBoost method was used to construct radiomics model,MCTSI model and combined model for predicting AP ANC based on the optimal radiomics features,MCTSI and their combination,respectively.The diagnostic efficacy of each model was evaluated using 5-fold cross-validation method,and the contribution of each variable to combined model was analyzed with SHAP method.Results Among 307 cases,there were 134 cases in ANC group and 173 in APFC group.Totally 6 optimal radiomics features were screened based on the first non-contrast CT.The area under the receiver operating characteristic curve(AUC)of radiomics model,MCTSI model and combined model was 0.936,0.693 and 0.917,respectively.The AUC of MCTSI model was lower than that of radiomics model and combined model(Z=-3.485,-2.824,both P＜0.01),while no significant difference of AUC was found between radiomics model and combined model(Z=-0.817,P=0.415).The contribution of optimal radiomics features to combined model were all higher than that of MCTSI score.Conclusion Non-contrast CT radiomics XGBoost model could effectively predict AP ANC.

Non-human primate animal models are core tools for the study of highly pathogenic microorganisms and are irreplaceable in the fields of pathology and drug discovery.However,anatomical sampling of non-human primate infection models in high-level biosafety laboratories carries potential risk and related risk assessment and control measures require clarification.Based on biosafety regulations and practical experience,we systematically discuss the risk control strategies of anatomical operations with respect to personal protection,instrument selection,anatomical specifications,documentation,and personnel training.Our review will help to improve the management of high-level biosafety laboratories,reduce the risk of pathogen escape and human infection,and provide support for the safe research of highly pathogenic microorganisms.

Objective:To explore the latent classes of intrinsic capacity and their influencing factors among hospitalized older adults, providing a basis for developing targeted intervention strategies.Methods:A convenience sampling method was used to recruit 371 hospitalized older adults from Beijing Hospital between April 2022 and July 2023. The integrated care for older people comprehensive assessment tool was used to assess the intrinsic capacity of hospitalizd older adults, along with grip strength tests. Latent class analysis (LCA) was employed to classify the intrinsic capacity of hospitalizd older adults, and multinomial Logistic regression analysis was conducted to explore the influencing factors of different latent classes.Results:Among the 371 older adults, 78.98% (293/371) exhibited declines in various dimensions of intrinsic capacity, with impairment detection rates of 36.39% (135/371) in cognition, 34.23% (127/371) in mobility, 21.02% (78/371) in vitality, 33.69% (125/371) in psychological well-being, and 47.98% (178/371) in sensory function. The LCA results identified three latent classes of intrinsic capacity: high mobility-moderate sensory group (39.08%, 145/371) , low cognition-high mobility group (26.68%, 99/371) , and low mobility group (34.23%, 127/371) . Multinomial Logistic regression analysis revealed that age, gender, monthly family income, polypharmacy, and grip strength were influencing factors of the latent classes of intrinsic capacity ( P<0.05) . Conclusions:The intrinsic capacity of hospitalized older adults is heterogeneous. It is essential to promptly identify the characteristics of intrinsic capacity in different groups, with particular attention to older adults in the low cognition-high mobility group and low mobility group, and implement targeted interventions to prevent and improve adverse outcomes.

ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy， to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian， and meanwhile， the contents of four index components（geniposide， paeoniflorin， hesperidin and paeonol） were quantitatively analyzed by high performance liquid chromatography（HPLC）. Nonalcoholic fatty liver disease（NAFLD） rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group， model group， lovastatin group（1.8 mg·kg^-1）， combined decoction group（1.26 g·kg^-1） and single decoction group（1.18 g·kg^-1）. After successful modeling， lovastatin group， combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day， and the control group and model group were given equal amounts of normal saline by intragastric administration， after 4 weeks of administration， the serum and liver tissues were collected， and the contents of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C） and high-density lipoprotein cholesterol（HDL-C） in serum of rats were detected， and the liver pathological examination was carried out by hematoxylin-eosin（HE） staining and oil red O staining， so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian， and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide， paeoniflorin， hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples（P<0.01）. The pharmacodynamic results showed that compared with the model group， both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats， reduce the serum levels of AST， ALT， TC， TG and LDL-C， increase the serum level of HDL-C， and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However， there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition， but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.

Objective:To explore the latent classes of intrinsic capacity and their influencing factors among hospitalized older adults, providing a basis for developing targeted intervention strategies.Methods:A convenience sampling method was used to recruit 371 hospitalized older adults from Beijing Hospital between April 2022 and July 2023. The integrated care for older people comprehensive assessment tool was used to assess the intrinsic capacity of hospitalizd older adults, along with grip strength tests. Latent class analysis (LCA) was employed to classify the intrinsic capacity of hospitalizd older adults, and multinomial Logistic regression analysis was conducted to explore the influencing factors of different latent classes.Results:Among the 371 older adults, 78.98% (293/371) exhibited declines in various dimensions of intrinsic capacity, with impairment detection rates of 36.39% (135/371) in cognition, 34.23% (127/371) in mobility, 21.02% (78/371) in vitality, 33.69% (125/371) in psychological well-being, and 47.98% (178/371) in sensory function. The LCA results identified three latent classes of intrinsic capacity: high mobility-moderate sensory group (39.08%, 145/371) , low cognition-high mobility group (26.68%, 99/371) , and low mobility group (34.23%, 127/371) . Multinomial Logistic regression analysis revealed that age, gender, monthly family income, polypharmacy, and grip strength were influencing factors of the latent classes of intrinsic capacity ( P<0.05) . Conclusions:The intrinsic capacity of hospitalized older adults is heterogeneous. It is essential to promptly identify the characteristics of intrinsic capacity in different groups, with particular attention to older adults in the low cognition-high mobility group and low mobility group, and implement targeted interventions to prevent and improve adverse outcomes.

Objective To observe the value of non-contrast CT radiomics extreme gradient boosting(XGBoost)model based on SHAP method for predicting acute necrotic collection(ANC)around acute pancreatitis(AP).Methods A total of 307 patients with initially clinically diagnosed AP were retrospectively enrolled.The optimal radiomics features of peripheral pancreatic tissue volume of interest(VOI)were extracted and screened based on automatic segmentation on the first non-contrast CT,and the evaluation results of modified CT severity index(MCTSI)score of AP severity based on first enhanced CT were recorded.The patients were divided into peripancreatic ANC group(ANC group)and acute peripancreatic fluid collection(APFC)group according to follow-up abdominal CT.XGBoost method was used to construct radiomics model,MCTSI model and combined model for predicting AP ANC based on the optimal radiomics features,MCTSI and their combination,respectively.The diagnostic efficacy of each model was evaluated using 5-fold cross-validation method,and the contribution of each variable to combined model was analyzed with SHAP method.Results Among 307 cases,there were 134 cases in ANC group and 173 in APFC group.Totally 6 optimal radiomics features were screened based on the first non-contrast CT.The area under the receiver operating characteristic curve(AUC)of radiomics model,MCTSI model and combined model was 0.936,0.693 and 0.917,respectively.The AUC of MCTSI model was lower than that of radiomics model and combined model(Z=-3.485,-2.824,both P＜0.01),while no significant difference of AUC was found between radiomics model and combined model(Z=-0.817,P=0.415).The contribution of optimal radiomics features to combined model were all higher than that of MCTSI score.Conclusion Non-contrast CT radiomics XGBoost model could effectively predict AP ANC.

ObjectiveAutoimmune thyroiditis （AIT） is a complex and immune-mediated disorder， with no established treatment protocol. Both Western and traditional Chinese medicine （TCM） focus on the pathogenesis and treatment of AIT. This study evaluated the clinical consistency of existing AIT animal models based on the diagnostic criteria of both Western and TCM， using a novel evaluation method. Additionally， it proposed recommendations and future prospects for improving these models. MethodsA comprehensive literature review was conducted on existing AIT animal models， using databases and the diagnostic criteria of both Western and TCM. Core and accompanying symptoms of these models were scored based on the diagnostic criteria of both Western and TCM， and clinical consistency was assessed. ResultsMice are the primary experimental animals used in AIT modeling. Modeling methods include vaccine immunization， iodine induction， heterologous thyroid antigen immunization， and a combination of high iodine water and antigen immunization. The average consistency of clinical syndromes based on TCM and Western medicine is 40%， 60%， 54%， and 63%， with the highest consistency observed in the combined high iodine water and antigen immunization model. Pathological models based on TCM are less common， with the liver-stagnation-spleen-deficiency rat model showing high clinical consistency. While most models are designed according to Western medical theory， meeting the surface and structural effectiveness criteria of Western medicine. However， there is a lack of fine-tuning and clear differentiation of TCM syndromes. ConclusionCurrent AIT syndrome-disease combination animal models primarily reflect the pathological features of Western medicine， with limited integration of TCM syndromes. Future research should aim to combine the syndrome characteristics of TCM with the pathological features of Western medicine， creating multi-factor and dynamic syndrome-disease models. Such models would better facilitate an experimental platform that conforms to the theories of TCM， providing more comprehensive support and guidance for the pathogenesis and treatment strategies of AIT.

Non-human primate animal models are core tools for the study of highly pathogenic microorganisms and are irreplaceable in the fields of pathology and drug discovery.However,anatomical sampling of non-human primate infection models in high-level biosafety laboratories carries potential risk and related risk assessment and control measures require clarification.Based on biosafety regulations and practical experience,we systematically discuss the risk control strategies of anatomical operations with respect to personal protection,instrument selection,anatomical specifications,documentation,and personnel training.Our review will help to improve the management of high-level biosafety laboratories,reduce the risk of pathogen escape and human infection,and provide support for the safe research of highly pathogenic microorganisms.