ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

ObjectiveTo explore the effect of serum containing Zhenwutang on myocardial mast cell apoptosis induced by angiotensin Ⅱ （AngⅡ） and the mechanism of the correlation between apoptosis and mitochondrial autophagy. MethodsIn this experiment， AngⅡ and serum containing Zhenwutang with different concentrations were used to interfere with H9C2 cardiomyocytes for 24 h， and the survival rate of H9C2 cardiomyocytes was detected by cell counting kit-8 （CCK-8） to screen the optimal concentration for the experiment. Enzyme-linked immunosorbent assay （ELISA） was used to detect the content of B-type natriuretic peptide （BNP） in cell culture supernatant， and immunofluorescence was used to detect the cell surface area to verify the construction of the myocardial mast cell model. Subsequently， the experiment was divided into a blank group （20% blank serum）， a model group （20% blank serum + 5×10^-5 mol·L^-1 AngⅡ）， low-， medium-， and high-dose （5%， 10% and 20%） serum containing Zhenwutang groups， an autophagy inhibitor group （1×10^-4 mol·L^-1 3-MA）， and autophagy inducer group （1×10^-7 mol·L^-1 rapamycin）. The apoptosis level of H9C2 cells and the changes of mitochondrial membrane potential were detected by flow cytometry. The lysosomal probe （Lyso Tracker） and mitochondrial probe （Mito Tracker） co-localization was employed to detect autophagy. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect Caspase-3， Caspase-9， B-cell lymphoma 2 （Bcl-2）， Bcl-2-related X protein （Bax）， and cytochrome C （Cyt C） in apoptosis-related pathways and the relative mRNA expression of ubiquitin ligase （Parkin）， phosphatase and tensin homolog （PTEN）-induced kinase 1 （PINK1）， and p62 protein in mitochondrial autophagy-related pathways. Western blot was used to detect cleaved Caspase-3， cleaved Caspase-9， Bax， Bcl-2， and Cyt C in apoptosis-related pathways， phosphorylated ubiquitin ligase （p-Parkin）， phosphorylated PTEN-induced kinase 1 （p-PINK1）， p62， and Bcl-2 homology domain protein Beclin1 in mitochondrial autophagy-related pathways， and the change of microtubule-associated protein 1 light chain 3 （LC3） Ⅱ/Ⅰ ratio. ResultsCCK-8 showed that when the concentration of AngⅡ was 5×10^-5 mol·L^-1， the cell activity was the lowest， and there was no cytotoxicity. At this concentration， the surface area of cardiomyocytes was significantly increased （P<0.01）， and the content of BNP in the supernatant of culture medium was significantly increased （P<0.05）. Therefore， AngⅡ with a concentration of 5×10^-5 mol·L^-1 was selected for the subsequent modeling of myocardial mast cells. Compared with the blank group， the model group and the autophagy inhibitor 3-MA group had a significantly increased apoptosis rate （P<0.01） and significantly decreased mitochondrial membrane potential （P<0.01）. The results of immunofluorescence co-localization showed that compared with the blank group， the model group had a significantly decreased number of red and green fluorescence spots. The results of Real-time PCR showed that compared with that in the blank group， the relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 in the model group was significantly up-regulated （P<0.01）， while the relative mRNA expression of Bcl-2， Parkin， and PINK1 was significantly down-regulated （P<0.01）. In addition， the relative protein expression of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 was significantly up-regulated （P<0.01）. The LC3Ⅱ/Ⅰ was significantly decreased， and the relative protein expression of Bcl-2， p-Parkin， p-PINK1， and Beclin1 was significantly down-regulated （P<0.01）. Compared with the model group， the serum containing Zhenwutang groups and the autophagy inducer group had significantly decreased apoptosis rate （P<0.01）， and the decrease ratio of mitochondrial membrane potential is significantly lowered （P<0.01） in a dose-dependent manner. Additionally， both red and green fluorescence spots became more in these groups. In the 3-MA group， the number of red and green fluorescence spots decreased significantly. The relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 was significantly down-regulated （P<0.05， P<0.01）， while that of Bcl-2， Parkin， and PINK1 was significantly up-regulated （P<0.01）. In the serum containing Zhenwutang groups， the relative protein expression levels of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 were significantly down-regulated （P<0.05，P<0.01）. The LC3Ⅱ/Ⅰ was significantly increased， and the relative protein expression levels of Bcl-2， p-Parkin， p-PINK1， and Beclin1 were significantly up-regulated （P<0.01）. ConclusionThe serum containing Zhenwutang can reduce the apoptosis of myocardial mast cells and increase mitochondrial autophagy. This is related to the inhibition of intracellular Bax/Bcl-2/Caspase-3 apoptosis pathway and regulation of Parkin/PINK1 mitochondrial autophagy pathway.

Objective To analyze the epidemiological characteristics of norovirus outbreaks in Haidian District, Beijing, and to provide a reference for epidemic prevention and control. Methods Descriptive epidemiological methods were used to organize and statistically analyze the norovirus outbreak data reported from 2016 to 2022. Results A total of 26 outbreaks of norovirus were reported in Haidian District, with a total of 1595 cases and an attack rate M (Q_R) of 8.23 (16.33)%. There were 24 cases of norovirus type GII (92.31%), 1 case of type GI (3.85%), and 1 case of mixed infection of virus type GI/GII (3.85%). The highest number of reported outbreaks occurred in March and April, with 17 cases, accounting for 65.38%. The highest number of reported cases was in November and December, with 785 cases, accounting for 44.92%. The case age M (Q_R) was 18 (14) years old. The detection rate of positive samples in different age groups had statistical significance（χ²=12.021, P=0.007). The 26 outbreaks were mainly distributed in collective units such as schools, preschool institutions, and enterprises and institutions. There were a total of 11 outbreaks related to foodborne transmission, with 923 cases, accounting for 57.87%. Diarrhea was positively correlated with the age of the cases (r_s=0.572, P<0.001), while vomiting was negatively correlated with the age of the cases (r_s=-0187, P<0.001). The time interval between the onset of acute gastroenteritis symptoms in the first case and the reporting of the epidemic was positively correlated with the duration of the epidemic (r_s=0.586, P=0.002). Conclusion It is necessary to strengthen the prevention and control of norovirus in schools (primary and secondary schools and colleges), strictly implement health monitoring and regular screening for kitchen workers, carry out publicity and education, detect cases as early as possible, report the epidemic in a timely manner, and effectively reduce the scale of the epidemic and prevent its spread.

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

Objective To investigate the effect of spontaneous hypertension on the remodeling of cardiac and aortic tissues in rats, with special attention to the changes in the content of collagen fibers, elastic fibers and secreted Frizzled-related protein 2 （sFRP2） in cardiac and aortic tissues. Methods 28-week-old SHR rats （Spontaneously Hypertensive rats） and WKY （Wistar-Kyoto rats） of the same age were selected as experimental animals. Cardiac load was assessed by calculating the cardiac weight index. Collagen fibers and elastic fibers were isolated from the rat thoracic aorta by hot alkali method, and their content was determined by biochemical analysis. In addition, pathological evaluation of tissue sections of the left ventricle and thoracic aorta were performed by H&E staining, Sirius red staining, and lichen red staining. Western blotting was used to determine the expression level of sFRP2 protein in cardiac tissues. Results Compared with WKY rats, the heart weight index of SHR rats increased significantly （P<0.001）, and the results of biochemical analysis and staining of pathological sections showed that the content of collagen fibers in the aorta in the SHR group was higher than that in the WKY group, while the content of elastic fibers was lower, but the difference did not have statistical significance. The content of collagen fibers in the heart of the SHR group was significantly higher than that in the WKY group （P<0.01）. Western blotting showed that there was no significant difference in the expression level of sFRP2 protein in heart tissues between the two groups. Conclusion The remodeling of cardiac and aortic tissues in a rat model of spontaneous hypertension may involve complex molecular mechanisms, not just changes in the content of collagen fibers and elastic fibers. The detailed mechanism of the progression of spontaneous hypertension and target organs damage still need further investigation.

ObjectiveTo investigate the level of hepatitis B surface antibody (anti-HBs) among preschool children (aged 3‒6 years) and primary and secondary school students in Tonglu County, Zhejiang Province, to evaluate the effectiveness of hepatitis B vaccination, and to provide a basis for hepatitis B prevention and control in the region. MethodsAs part of the 2023 Tonglu County Urban and Rural Residents Health Examination Program, blood samples were collected during health check-ups. Fingertip blood samples were obtained from preschool children, while venous blood samples were collected from primary and secondary school children. The anti-HBs levels in blood (positive + / negative -) were qualitatively tested using hepatitis B surface antibody test kits (latex method). The differences in anti-HBs positivity rates among different age groups were analyzed. ResultsBetween April 1, 2023 and June 30, 2023, a total of 52 919 individuals were surveyed, including 11 973 preschool children and 40 946 primary and secondary school students. The overall anti-HBs positivity rate was 39.74%, with the highest positivity rate observed among preschool children (60.20%). Age was negatively correlated with the anti-HBs positivity rate (P<0.001). No significant gender differences in anti-HBs positivity rates were observed. The anti-HBs positive rate in rural areas was higher than that in urban areas, with statistically significant differences across school grade groups (primary grades 1‒3, grades 4‒6, middle school, and high school) (P<0.001). ConclusionThe anti-HBs positivity rate among preschool and school-age children in Tonglu County decreases with age and remains relatively low. It is recommended to strengthen the monitoring of hepatitis B antibody levels and promote health education among preschool and school-age children. Children who have not completed the full hepatitis B vaccination should receive timely catch-up vaccination.

Chinese medicinal materials serve as the material foundation of traditional Chinese medicine （TCM） culture. The sustainable development of Chinese medicinal material resources is a focal point in the modernization of TCM. With the increasing scarcity of Chinese medicinal material resources， the expansion of new Chinese medicinal material resources has become a crucial means for the sustainable utilization of these resources. New Chinese medicinal material resources refer to natural resources that have been newly discovered or developed， possessing potential medicinal value or healthcare functions， which fall outside the traditional application scope of herbal medicines. These resources have not yet been widely recognized or applied within the framework of traditional TCM theory. They specifically include artificial substitutes for endangered medicinal materials， new medicinal parts of medicinal plants， medicinal materials with expanded clinical applications， and foreign medicinal resources. The rational compatability and formulation of new Chinese medicinal material resources are essential pathways for integrating them into the TCM system. Due to the weak foundational research on new Chinese medicinal material resources in China， the characteristics of these resources that align with the TCM theory are not yet fully understood， posing numerous constraints on formulating prescriptions based on the traditional compatibility principles of TCM. This paper integrates the traditional formulation theory of TCM with modern data integration methods， proposing four formulation models for new TCM resources： synergistic compatibility， substitutive compatibility， symptom-based compatibility， and efficacy semantic compatibility. These models provide new insights for the application of new Chinese medicinal material resources， not only facilitating their rational use in clinical practice but also offering theoretical support for the development and compatibility research of these resources.

Chinese medicinal materials serve as the material foundation of traditional Chinese medicine （TCM） culture. The sustainable development of Chinese medicinal material resources is a focal point in the modernization of TCM. With the increasing scarcity of Chinese medicinal material resources， the expansion of new Chinese medicinal material resources has become a crucial means for the sustainable utilization of these resources. New Chinese medicinal material resources refer to natural resources that have been newly discovered or developed， possessing potential medicinal value or healthcare functions， which fall outside the traditional application scope of herbal medicines. These resources have not yet been widely recognized or applied within the framework of traditional TCM theory. They specifically include artificial substitutes for endangered medicinal materials， new medicinal parts of medicinal plants， medicinal materials with expanded clinical applications， and foreign medicinal resources. The rational compatability and formulation of new Chinese medicinal material resources are essential pathways for integrating them into the TCM system. Due to the weak foundational research on new Chinese medicinal material resources in China， the characteristics of these resources that align with the TCM theory are not yet fully understood， posing numerous constraints on formulating prescriptions based on the traditional compatibility principles of TCM. This paper integrates the traditional formulation theory of TCM with modern data integration methods， proposing four formulation models for new TCM resources： synergistic compatibility， substitutive compatibility， symptom-based compatibility， and efficacy semantic compatibility. These models provide new insights for the application of new Chinese medicinal material resources， not only facilitating their rational use in clinical practice but also offering theoretical support for the development and compatibility research of these resources.

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.