ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

Objective:To analyze the research status and development trend of successful aging at home and abroad, so as to provide references for the study of population aging in China.Methods:The literatures on successful aging included in China National Knowledge Infrastructure and Web of Science core collection from the establishment of database to April 2023 were retrieved, and CiteSpace software was used to analyze.Results:A total of 199 Chinese articles and 517 English articles were included. The number of articles published at home and abroad was generally on the rise, the published journals had certain authority, and a core group of domestic authors had been formed.Conclusions:Research hotspots at home and abroad involve influencing factors, study population, cognitive function, etc. This field is in the stage of discipline development and application diffusion. Physical and mental health of the elderly, successful aging at work, and healthy aging are the future development trends. In the future, international exchanges and cooperation should be strengthened, combined with the actual situation in China, further improve the related theories of successful aging and build a more scientific and localized successful aging system, so as to provide guidance for solving the problem of population aging.

Objective To establish a mouse model of spleen deficiency and dampness stagnation syndrome combining atopic dermatitis(AD)and explore the feasibility of modeling by comparing 2,4-dinitrochlorobenzene(DNCB)-induced atopic dermatitis model of mouse,"external dampness+improper diet+irrigation of senna"-induced spleen deficiency and dampness stagnation syndrome model of mouse,as well as both in combination of model mouse.Methods The construction of a mouse(Balb/c)with spleen deficiency and dampness stagnation syndrome was explored by using the method of"external dampness+improper diet+irrigation of senna",and then DNCB was applied to induce the AD-like lesions in Balb/c mice to establish a mouse model of spleen deficiency and dampness stagnation syndrome combining atopic dermatitis.The general condition and body weight of mice in each group were observed,and the symptoms of spleen deficiency and dampness were scored.The severity of AD was evaluated by comparing the skin lesion degree,EASI score,transcutaneous water loss value(TEWL),spleen index and thymus index.The levels of creatinine,glucose,total cholesterol,triglyceride,gastrin,and amylase were measured.Results(1)During the modeling period of spleen deficiency and dampness stagnation syndrome,compared with the normal group,spleen deficiency and dampness stagnation syndrome group,spleen deficiency and dampness stagnation syndrome combined with atopic dermatitis group showed obesity,listlessness,filthy and greasy hair,diarrhea,and poor cleanliness around the anal.After combining with the application of the atopic dermatitis model,the body weight of the mice in atopic dermatitis group(P＜0.001),spleen deficiency and dampness stagnation syndrome group(P＜0.05)and spleen deficiency and dampness stagnation syndrome combined with atopic dermatitis group(P＜0.001)decreased sharply compared with the normal group.(2)Compared with the atopic dermatitis group,the degree of skin lesions,EASI score(P＜0.05)and TEWL(P＞0.05)were higher in the spleen deficiency and dampness stagnation syndrome combined with atopic dermatitis group.(3)Compared with the normal group,the spleen index of the atopic dermatitis group increased(P＜0.001)and the thymus index decreased(P＜0.001).Compared with the atopic dermatitis group,the spleen index(P＞0.05)and thymus index(P＜0.05)of the spleen deficiency and dampness stagnation syndrome combined with atopic dermatitis group decreased.(4)The results of serum biochemical indexes showed that compared with the normal group,the levels of creatinine(P＜0.01),glucose(P＜0.001),total cholesterol(P＞0.05),triglyceride(P＞0.05)and gastrin(P＜0.001)in the spleen deficiency and dampness stagnation syndrome group were increased,and the level of amylase was decreased(P＜0.01).Compared with the atopic dermatitis group,the levels of creatinine(P＞0.05),glucose(P＜0.05),total cholesterol(P＞0.05),triglyceride(P＞0.05),gastrin(P＜0.001)increased and the level of amylase decreased(P＞0.05).Conclusion A mouse model of spleen deficiency and dampness stagnation syndrome combining atopic dermatitis,which was induced by the combination of DNCB and"external dampness+improper diet+irrigation of senna",can not only show obvious TCM indications of spleen deficiency and dampness syndrome,but also show the characteristics of AD.This model can be used as a reliable animal model of combination of disease and syndrome.It provides reference for further study on pathological mechanism,pharmacodynamic evaluation and pharmacological mechanism of spleen deficiency and dampness stagnation syndrome combining atopic dermatitis.

Skin modeling of transdermal drug delivery system refers to experimental models that mimic the structure and function of human skin to explore and evaluate absorption,penetration,and efficacy of medicines in transdermal drug delivery.It provides an alternative to traditional human skin experiments and reduces the use of human skin in medical research,which is convenient,controllable,and cost effective.For skin models of transdermal drug delivery systems,this article introduces commonly used animal skin models,artificial skin models,and recombinant human skin models from the perspective of the transdermal absorption pathway of medicines,and analyzes their advantages,disadvantages,and applications so provide references the research and development of transdermal formulations and topical therapies.

Objective A serum proteomic approach was used to explore the targets of action of Peitu Qingxin Granules(composed of Rhizoma Atractylodis Macrocephalae,Forsythiae Fructus,Imperatae Rhizoma,Pseudostellariae Radix,etc.)in the treatment of atopic dermatitis.Methods Five patients with atopic dermatitis were selected and treated with Peitu Qingxin Granules for 12 weeks,and five healthy volunteers were used as controls.The clinical core evaluation indexes of atopic dermatitis patients after treatment,including Eczema Area and Severity Index/Scoring Atopic Dermatitis(EASI/SCORAD),Pruritus Score,Patient-Oriented Eczema Measure(POEM),and quality of life index,were assessed.Serum samples were examined using data-independent acquisition-mass spectrometry(DIA-MS)technology,and serum differential proteins between atopic dermatitis patients and healthy people,as well as serum differential proteins in atopic dermatitis patients before and after treatment with Peitu Qingxin Granules were screened according to P＜0.05 and Fold Change>1.2.GO function enrichment analysis and KEGG pathway enrichment analysis were performed on the differential proteins.Results(1)Compared with the pre-treatment period,the clinical core evaluation indexes of patients with atopic dermatitis,including the EASI/SCORAD,Pruritus Score,POEM,and quality-of-life index,were significantly improved after treatment,and the differences were all statistically significant(P＜0.05,P＜0.01).(2)A total of 28 differential proteins were analyzed in the healthy control group and atopic dermatitis group,of which 12 proteins expressions were increased and 16 proteins were decreased,including ALAD(δ-aminolevulinic acid dehydrogenase),LTA4H(leukotriene A-4 hydrolase),CA1(carbonic anhydrase 1),F11(coagulation factor XI),and LCP1(lymphocyte cytoplasmic protein 1),etc..The main signaling pathways involved are PI3K-AKT signaling pathway,lipids and atherosclerosis,ECM-receptor interaction,platelet activation,NF-κB signaling pathway,and neutrophil extracellular trap formation.(3)A total of 12 different proteins were analyzed in atopic dermatitis patients before and after treatment with Peitu Qingxin Granules,of which 8 proteins were increased and 4 proteins were decreased,including ALAD,FGA(fibrinogen α-chain),IGHV3-64D,and IGHV3-38.They were mainly involved in signaling pathways such as lipids and atherosclerosis,complement pathway,Staphylococcus aureus infection,NF-κB signaling pathway,fluid shear stress and atherosclerosis.(4)The expressions of three protein targets including ALAD,FGA and IGHV3-64D,were significantly down-regulated in patients with atopic dermatitis and significantly up-regulated after treatment with Peitu Qingxin Granules.Conclusion The differentially expressed proteins ALAD,FGA and IGHV3-64D may be the action targets of Peitu Qingxin Granules in the treatment of atopic dermatitis,which lays the foundation for further experimental validation.

Objective To discuss the nursing cooperation method in CT-guided pulmonary nodule localization using indocyanine green combined with methylene blue.Methods A total of 81 patients,who needed to receive pulmonary nodule localization before thoracoscopic resection,were enrolled in this study.The nursing cooperation measures,including the preparation and injection of indocyanine green combined with methylene blue,breathing mode coordination,position management,precise localization coordination,and psychological care,were analyzed.Results Successful nodule localization was accomplished in all patients.No statistically significant difference in the incidence of adverse events existed between the patients with different clinical characteristics(P＞0.05).The gender,age,lesion site,nodule size,nodule-pleura distance,posture during puncturing and needle path route were not the factors influencing the occurrence of adverse reactions in patients receiving CT-guided pulmonary nodule localization using indocyanine green combined with methylene blue.Conclusion In performing CT-guided pulmonary nodule localization using indocyanine green combined with methylene blue,the nursing cooperation method carries generality and stability,which is suitable for patients with different clinical characteristics.

Objective To observe the effect of group biofeedback in patients with residual schiz-ophrenia(RS).Methods A total of 127 patients with RS were selected as study objects,and ran-domly divided into control group(n=63)and observation group(n=64).The control group re-ceived routine nursing,and the observation group received group biofeedback based on the control group.The Positive and Negative Symptom Scale(PANSS),Personal and Social Performance Scale(PSP)and Self-awareness Inventory(SAI)Questionnaire(treatment compliance)scores were com-pared between the two groups.Results After 12 weeks of intervention,the score of the positive symptoms,the score of negative symptoms and the total score of PANSS in the observation group were significantly lower than those in the control group(P＜0.05).The number of patients with PSP scores greater than 70 to 100 and greater than 30 to 70 in the observation group was significantly more than those in the control group,and the number of patients with PSP score of 0 to 30 was significantly less than that in the control group(P＜0.05).The SAI score of the observation group after interven-tion was significantly higher than that before intervention and control group,and the number of com-pleted biofeedback therapy in the observation group was significantly more than that in the control group(P＜0.05).Conclusion Group biofeedback can promote symptom relief and improve treat-ment compliance in patients with RS.

Objective To observe the effect of group biofeedback in patients with residual schiz-ophrenia(RS).Methods A total of 127 patients with RS were selected as study objects,and ran-domly divided into control group(n=63)and observation group(n=64).The control group re-ceived routine nursing,and the observation group received group biofeedback based on the control group.The Positive and Negative Symptom Scale(PANSS),Personal and Social Performance Scale(PSP)and Self-awareness Inventory(SAI)Questionnaire(treatment compliance)scores were com-pared between the two groups.Results After 12 weeks of intervention,the score of the positive symptoms,the score of negative symptoms and the total score of PANSS in the observation group were significantly lower than those in the control group(P＜0.05).The number of patients with PSP scores greater than 70 to 100 and greater than 30 to 70 in the observation group was significantly more than those in the control group,and the number of patients with PSP score of 0 to 30 was significantly less than that in the control group(P＜0.05).The SAI score of the observation group after interven-tion was significantly higher than that before intervention and control group,and the number of com-pleted biofeedback therapy in the observation group was significantly more than that in the control group(P＜0.05).Conclusion Group biofeedback can promote symptom relief and improve treat-ment compliance in patients with RS.

Gastric cancer (GC) is associated with high morbidity and mortality rates. Thus, early diagnosis is important to improve disease prognosis. Endoscopic assessment represents the most reliable imaging method for GC diagnosis; however, it is semi-invasive and costly and heavily depends on the skills of the endoscopist, which limit its clinical applicability.Therefore, the search for new sensitive biomarkers for the early detection of GC using noninvasive sampling collection methods has attracted much attention among scientists.Urine is considered an ideal biofluid, as it is readily accessible, less complex, and relatively stable than plasma and serum. Over the years, substantial progress has been made in screening for potential urinary biomarkers for GC. This review explores the possible applications and limitations of urinary biomarkers in GC detection and diagnosis.