Objective To explore the research hotspots and development trends of Ziziphi Spinosae Semen in the past 20 years,and to provide reference for related research.Methods Literatures on Ziziphi Spinosae Semen were searched from January 1,2000 to December 31,2022 in CNKI,Web of Science Core Collection Database.VOS viewer software was used to visually analyze the citation frequency,research institutions and keyword hotspots of English literatures.CiteSpace software was used to visually analyze research institutions,authors,emergence keywords and keyword overlap time of Chinese literatures,and Microsoft Excel 2021 software was used to analyze of annual publication trends and publication volume of Chinese and English literatures,and download frequency of Chinese literatures.Results A total of 4 872 Chinese and 128 English literatures were included,with an overall upward trend in the number of annual publications.The research institutions with the highest number of publications in Chinese and English were Shandong University of Traditional Chinese Medicine and Tianjin University of Commerce,and the authors with the highest number of publications were DU Chenhui and XIE Junbo,respectively.The most frequent keywords in Chinese literatures were"Ziziphi Spinosae Semen","composed"and"application of compound therapy",and in English literatures were"performance","oxidative stress".Conclusion From 2000 to 2022,the research hotspots of Ziziphi Spinosae Semen mainly focused on the chemical composition,pharmacological effects and clinical application analysis,compatibility research,formulation and preparation.Quality control and evaluation of Ziziphi Spinosae Semen,and the research on the mechanism of preventing and treating insomnia with Ziziphi Spinosae Semen may become future research directions.

Objective:To study and screen the differential expression of inflammatory proteins in diabetes skin ulcers and common skin ulcers, so as to provide experimental basis for further research on anti-inflammatory and healing drug targets of diabetes skin ulcers.Methods:The tissues of 11 patients with diabetes skin ulcer, 12 patients with common skin ulcer and 11 patients with normal skin were collected from the First Hospital of Hunan University of Chinese Medicine. The levels of inflammatory protein Toll like receptor 4 (TLR4), nuclear factor κB (NF-κB), pro-inflammatory factor interferon -γ (IFN -γ), tumor necrosis factor - α (TNF -α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1β (IL-1β), macrophage chemotactic protein-1 (MCP-1), anti-inflammatory factors epidermal growth factor (EGF), interleukin-4 (IL-4), and interleukin-10 (IL-10) were detected in three groups of tissues using enzyme-linked immunosorbent assay (ELISA).Results:Compared with normal tissues, the concentrations of TLR4, NF-κB, IFN -γ, TNF -α, IL-1β, IL-6, IL-8, MCP-1 and EGF in common ulcer skin tissues and diabetes ulcer tissues were higher, and the concentrations of IL-10 were lower, with statistically significant differences (all P<0.05); Compared with the normal tissue, the concentration of IL-4 in diabetes ulcer tissue was lower, the difference was statistically significant ( P<0.05); Compared with ordinary ulcer skin tissue, the concentrations of TLR4, NF-κB and MCP-1 in diabetes ulcer tissue were higher, and the concentrations of IL-4 were lower, with statistically significant differences (all P<0.05). Conclusions:The skin ulcer in diabetes patients will have inflammatory reaction, and high glucose promotes the inflammatory reaction of skin ulcer, which may be related to the abnormal expression of TLR4, NF-κB, MCP-1 and IL-4. TLR4/NF-κB signal pathway and inflammatory factors MCP-1 and IL-4 may be the target of the inflammation regulation of diabetes skin ulcer.

ObjectiveA rapid method for identification of chemical constituents in Baoyuantang reference sample was established in order to clarify the material basis of this formula. MethodBased on ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） and self-established database information， the chemical components in Baoyuantang were systematically characterized and identified. The chromatography was performed on a Waters ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with mobile phase of 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） for gradient elution（0-3 min， 2%-19%B； 3-8 min， 19%B； 8-8.1 min， 19%-22%B； 8.1-14 min， 22%-29%B； 14-16 min， 29%B； 16-32 min， 29%-45%B； 32-32.1 min， 45%-90%B； 32.1-35 min， 90%-95%B； 35-36 min， 95%-98%B； 36-37 min， 98%-2%B； 37-40 min， 2%B）. Based on electrospray ionization（ESI）， continuum data format was collected in both positive and negative ion modes with a scanning range of m/z 50-1 500. Chemical constituents in the decoction of Baoyuantang were systematically analyzed by UNIFI 1.9.4 software matching， control comparison， The Encyclopedia of Traditional Chinese Medicine（ETCM） database search and literature reports. ResultA total of 229 components were identified under negative ion mode and 181 under positive ion mode， with a total of 322 components after removing duplicates， including 116 triterpene saponins， 66 flavonoids， 19 organic acids， 6 gingerphenols， 6 gingerols， 5 gingerones， 10 amino acids， 7 saccharides， 5 coumarins and 82 other components. Among them， 83， 141， 39， 35 and 38 components were attributed to Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Astragali Radix， Cinnamomi Cortex and Zingiberis Rhizoma Recens， respectively. ConclusionIn this study， the rapid characterization and identification of multi-class components in Baoyuantang was realized， and it was confirmed that the material basis of this formula was mainly triterpenoid saponins， flavonoids， gingerols and organic acids， and the chemical composition was attributed and analyzed， which provided a reference for the subsequent quality control research.

Candidiasis has a high morbidity and mortality worldwide,and its main causative agent is Candi-da albicans.At present,the treatment effect of candidiasis is not ideal due to the shortcomings of antifungal drugs,such as toxicity,drug resistance,single route of administration,and high price.In order to overcome this situation,metal nanoparticles with antifungal activity and the potential to deliver antifungal drugs have been extensively studied.In this paper,the mechanism and application of gold,silver,copper and iron nanoparticles against Candida albicans are reviewed.Compared with traditional antifungal drugs,metal nanoparticles exert antifungal effects through a multi-target mechanism,which minimizes the emergence of antifungal resistance.Cytotoxicity limits the application of metal nanoparticles,but green synthesis can reduce the cytotoxicity of metal nanoparticles and improve antimicrobial properties.

Ziziphi spinosae semen mainly contains contents of saponins,flavonoids,alkaloids and aliphatic acids.Meanwhile,it has a variety of activities such as sedative-hypnotic,anti-anxiety,anti-depression,nerve protection,cardiovascular and cerebrovascular protection,liver protection,and antioxidant,which is widely used in medicine,food,health food and other fields.The chemical constituents,pharmacological action and clinical application of Ziziphi spinosae semen were systematically summarized in this paper by reviewing the literature,in order to provide theoretical guidance for the sustainable development of the resources and the rational use of Ziziphi spinosae semen.

Heat stress refers to a series of stress reactions such as heat balance disturbance and physiological dysfunction when the body is exposed to the thermal environment for a long time. Studies have found that heat stress can damage intestinal morphology, such as length of intestinal villi, number of goblet cells, and depth of the crypt, affecting the digestion and absorption functions. It also can increase the permeability of the intestinal barrier by damaging the tight junction of the intestinal epithelium, which in turn allows endotoxin and bacteria to enter the blood circulation from the intestinal cavity to cause a systemic inflammatory response. At the same time, heat stress can disrupt the homeostasis of intestinal microbiota, increase pathogenic bacteria, and change downstream metabolites such as short-chain fatty acids. In addition, heat stress can inhibit the occurrence of hippocampal neurons and reduce the number of neurons; decrease the density of synapses; damage important organelles of neurons; induce inflammation of the central nervous system, and then lead to cognitive dysfunction. The brain-gut axis is a two-way signal axis between the intestine and the brain. Intestinal microorganisms and the intestinal barrier can participate in central nervous system regulation, and the brain can change the intestinal homeostatic function and affect the quality of the intestinal barrier through the hypothalamic-pituitary-adrenal axis (HPA axis). The interaction plays an essential role in the body's homeostasis. Therefore, this article reviewed current understandings on the impacts of heat stress on the gut and cognitive function, aiming to provide a reference for subsequent research.

ObjectiveTo analyze the blood-transition constituents of Bergeniae Scopulosae Rhizoma extract based on the serum pharmacochemical method. MethodUltra-high performance liquid chromatography-quadrupole/electrostatic field orbital trap high resolution mass spectrometry （UHPLC-Q Exactive Focus MS/MS） technique was used to compare the chromatogram differences of Bergeniae Scopulosae Rhizoma extract， blank serum and drug-containing serum， according to the retention time， relative molecular weight and the ratio with primary and secondary ion fragments provided by MS， the prototype components and metabolites of Bergeniae Scopulosae Rhizoma extract were analyzed in serum of rats after oral administration. The detection conditions were as follows：the mobile phase of methanol （A）-0.1% formic acid solution （B） for elution gradient （0-40 min， 5%-95%A； 40-45 min， 95%A）， the flow rate of 0.3 mL·min^-1， the injection volume of 1 µL， heated electrospray ionization， detection range of m/z 80-1 200， positive and negative ion scanning modes. ResultAfter oral administration， a total of 35 components were detected in the serum， of which 6 were prototype components and 29 were metabolites of prototype components. The 6 prototype components were identified as arbutin， mallonanoside A， bengenin， ardimerin， salicylic acid and ellagic acid. The 29 metabolites were mainly metabolites from compound containing structural units such as gallic acid， mallonanoside A， bengenin， catechin， and ellagic acid， and their metabolic pathways were mainly glucuronidation， sulfation， methylation and others， which by phase Ⅱ metabolism. ConclusionThe components absorbed into the blood and their metabolites may be the pharmacodynamic components of Bergeniae Scopulosae Rhizoma. Among them， mallonanoside A， bengenin and ellagic acid can not only enter the blood as prototype components， but also exert their efficacy through phase Ⅱ metabolism. Most of the other chemical components in Bergeniae Scopulosae Rhizoma may be transformed into simple structures such as gallic acid， bengenin and catechin by hydrolysis， and then further metabolized by phase Ⅱ.

Polyporus umbellatus， as a traditional Chinese medicine for promoting diuresis and clearing dampness， mainly contains steroids and polysaccharides. It is usually used to treat diseases of urinary system. In this paper， the research progress of the effective components， pharmacological mechanisms and clinical use of P. umbellatus in diuresis-promotion and dampness- clearance is reviewed. Steroids such as ergosterone， peroxyergosterone， ergosta-7，22-dien-3-one and P. umbellatus polysaccharide PPS1， PPS2， PPS3， GUMP-1-1 and GUMP-1-2 promote diuresis and eliminate dampness through diuresis， renal protection， anti- inflammatory， bacteriostatic and immunomodulatory effects. Traditional Chinese medicine compound preparations such as P. umbellatus powder， P. umbellatus decoction， and Wuling powder have significant effects in treating urinary tract infections， lithiasis， renal edema and lesions， which providing reference for the further development and application of P. umbellatus.

Objective:To evaluate the performance of an artificial intelligent (AI)-based automated digital cell morphology analyzer (hereinafter referred as AI morphology analyzer) in detecting peripheral white blood cells (WBCs).Methods:A multi-center study. 1. A total of 3010 venous blood samples were collected from 11 tertiary hospitals nationwide, and 14 types of WBCs were analyzed with the AI morphology analyzers. The pre-classification results were compared with the post-classification results reviewed by senior morphological experts in evaluate the accuracy, sensitivity, specificity, and agreement of the AI morphology analyzers on the WBC pre-classification. 2. 400 blood samples (no less than 50% of the samples with abnormal WBCs after pre-classification and manual review) were selected from 3 010 samples, and the morphologists conducted manual microscopic examinations to differentiate different types of WBCs. The correlation between the post-classification and the manual microscopic examination results was analyzed. 3. Blood samples of patients diagnosed with lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms were selected from the 3 010 blood samples. The performance of the AI morphology analyzers in these five hematological malignancies was evaluated by comparing the pre-classification and post-classification results. Cohen′s kappa test was used to analyze the consistency of WBC pre-classification and expert audit results, and Passing-Bablock regression analysis was used for comparison test, and accuracy, sensitivity, specificity, and agreement were calculated according to the formula.Results:1. AI morphology analyzers can pre-classify 14 types of WBCs and nucleated red blood cells. Compared with the post-classification results reviewed by senior morphological experts, the pre-classification accuracy of total WBCs reached 97.97%, of which the pre-classification accuracies of normal WBCs and abnormal WBCs were more than 96% and 87%, respectively. 2. The post-classification results reviewed by senior morphological experts correlated well with the manual differential results for all types of WBCs and nucleated red blood cells (neutrophils, lymphocytes, monocytes, eosinophils, basophils, immature granulocytes, blast cells, nucleated erythrocytes and malignant cells r>0.90 respectively, reactive lymphocytes r=0.85). With reference, the positive smear of abnormal cell types defined by The International Consensus Group for Hematology, the AI morphology analyzer has the similar screening ability for abnormal WBC samples as the manual microscopic examination. 3. For the blood samples with malignant hematologic diseases, the AI morphology analyzers showed accuracies higher than 84% on blast cells pre-classification, and the sensitivities were higher than 94%. In acute myeloid leukemia, the sensitivity of abnormal promyelocytes pre-classification exceeded 95%. Conclusion:The AI morphology analyzer showed high pre-classification accuracies and sensitivities on all types of leukocytes in peripheral blood when comparing with the post-classification results reviewed by experts. The post-classification results also showed a good correlation with the manual differential results. The AI morphology analyzer provides an efficient adjunctive white blood cell detection method for screening malignant hematological diseases.