ObjectiveTo systematically identify the chemical constituents of Xuefu Zhuyutang（XFZY） and quantitatively determine its main components， aiming to elucidate its pharmacodynamic material basis and provide a scientific foundation for improving its quality control standards. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was employed for qualitative analysis of XFZY， and the identification of compounds was accomplished by comparing their retention times， secondary MS fragment ion information， 52 reference standards and relevant databases， followed by attribution of their herbal sources. A total of 22 representative compounds were screened out， and UPLC-quadrupole-linear ion trap mass spectrometry（UPLC-Q-TRAP-MS/MS） was applied for quantitative analysis of the compounds in the formula. ResultsA total of 77 compounds were identified in XFZY， including 31 flavonoids mainly derived from Aurantii Fructus， Glycyrrhizae Radix et Rhizoma， Persicae Semen， Carthami Flos， Bupleuri Radix， Paeoniae Radix Rubra and Achyranthis Bidentatae Radix， 24 terpenoids mainly derived from Platycodonis Radix， Glycyrrhizae Radix et Rhizoma， Paeoniae Radix Rubra and Rehmanniae Radix， 9 phenylpropanoids and their derivatives mainly derived from Chuanxiong Rhizoma， Angelicae Sinensis Radix and Rehmanniae Radix， 4 phenolic acids mainly derived from Chuanxiong Rhizoma， Angelicae Sinensis Radix and Paeoniae Radix Rubra， 3 saccharides mainly derived from Rehmanniae Radix and Achyranthis Bidentatae Radix， and 6 other compounds mainly derived from Persicae Semen， Rehmanniae Radix and Angelicae Sinensis Radix. The results of quantitative analysis showed that the contents of protocatechuic acid， hydroxypaeoniflorin， amygdalin， vanillic acid， paeoniflorin， liquiritin apioside， liquiritin， isoquercitrin， naringin， cosmosiin， hesperidin， neohesperidin， isoliquiritin， liquiritigenin， naringenin， benzoylpaeoniflorin， hesperetin， isoliquiritigenin， formononetin， glycyrrhizic acid， nobiletin and ligustilide in XFZY were determined to be 0.12， 1.57， 54.53， 0.29， 36.17， 4.29， 4.84， 0.09， 46.67， 0.04， 3.44， 31.95， 0.82， 0.10， 0.11， 0.43， 0.07， 0.03， 0.01， 8.24， 0.13， 1.81 mg·g^-1. ConclusionThe qualitative method established in this study enables rapid and sensitive analysis of the chemical constituents in XFZY. Among the identified compounds， 52 are confirmed by reference standards， ensuring the accuracy of identification. The quantitative analysis of 22 key components provides a reliable experimental basis for the pharmacodynamic material basis research and quality control standard improvement of XFZY.

Objective: To understand the epidemiological and etiological characteristics of food poisoning event occurred in a school in Hangzhou, Zhejiang, so as to provide reference for the scientific management of related emergencies. Methods: By determining the nature of the event through epidemiological investigation, a case control study was carried out to spot suspicious food in May 2024. The hygienic investigation was conducted to find out possible pollution links and factors, patients and canteen practitioners anal swab, canteen retention samples, catering link daub and other specimens were collected ,for rapid pathogen screening. And the suspected pathogen Clostridium perfringens (CP) were isolated and identified according to the screening results, and toxin gene detection and whole genome sequencing and cluster analysis of CP isolated strains were carried out. Results: The incident resulted in 45 people experiencing gastrointestinal symptoms, such as diarrhea and abdominal pain. The suspicious food was tomato scrambled eggs and corn ribs provided by the student canteen for lunch on May 29. A hygiene investigation found that there was a risk of contamination in the food processing, preparation and storage. A total of 46 anal swabs and 10 canteen retention samples were positive for CP 16 S, 59 strains of CP were isolated from 27 samples, 10 cases and 1 practitioner isolate were positive for CPE ( cpe ) (F mode), and their whole genome evolution analysis was conducted based on the same source. Conclusions The food poisoning event is caused by CP infection carrying CPE ( cpe ) (F mode), and the possible sources of outbreak are the carriers of the CP by employees. It is recommended that cafeteria staff strengthen training on common foodborne diseases and conduct regular monitoring of pathogens.

OBJECTIVES: To fabricate an injectable composite microsphere hydrogel reinforced with silk fibroin/hyaluronic acid microspheres, achieving synergistic enhance-ment of mechanical robustness and biofunctionality. METHODS: Methacrylated hyaluronic acid (HAMA) and thiolated silk fibroin (TSF) were synthesized. Monodisperse microspheres generated via microfluidics were UV-cured (420 nm) through thiol-ene click reaction. These microspheres were embedded in a TSF/HAMA matrix to form photo-cured composites. The grafting rate of TSF and HAMA was characterized by H1-NMR; particle size distribution of microsphere hydrogels in soybean oil was observed by optical microscopy; gel point of composite microsphere hydrogels was determined by advanced extensional rheometer; microscopic morphology of microsphere hydrogels was observed by scanning electron microscopy; elemental distribution of microsphere hydrogels was detected by X-ray energy dispersive spectroscopy; tunability of composite microsphere hydrogels was observed by inverted confocal microscopy; mechanical properties of composite microsphere hydrogels were tested by compression testing; swelling ratio, degradation rate and water retention rate of composite microsphere hydrogels were measured by gravimetric method. Cytotoxicity of the composite microsphere hydrogels was determined by Calcein-AM/propidium iodide dual staining and CCK-8 assay; cell migration capability was observed by scratch assay. RESULTS: The grafting rates of HAMA and TSF was 48.03% and 17.99%, respectively. Microsphere hydrogels with particle sizes of (43.3±1.2), (78.1±3.0), and (130.8±1.9) μm were prepared. The gel time of the composite microsphere hydrogels was 48-115s. The laser confocal imaging confirmed dynamic regulation characteristics of the composite microsphere hydrogels. The compressive strength of the composite microsphere hydrogels reached 22.7 kPa and maintained structural integrity at 40% strain after 20 compression cycles. The composite microsphere hydrogels exhibited differential deswelling behaviors in simulated physiological environments, and reducing microsphere particle size could significantly enhance its stability under moist conditions. The degradation rate of the composite microsphere hydrogels was (49.1±0.9)% after 200 h, and water retention rate was maintained at 40%-60% after 96 h. Biocompatibility assays confirmed >95% cell viability and unimpaired cell migration abilities. CONCLUSIONS The TSF/HAMA composite microsphere hydrogel developed in this study has characteristics of rapid fabrication, adjustable mechanical properties, enhanced environmental stability and excellent biocom-patibility, thus providing a new material solution for tissue repair and regenerative medicine.
Fibroins/chemistry* ; Hydrogels/chemistry* ; Microspheres ; Hyaluronic Acid/chemistry* ; Humans

Interfering hepatitis B virus (HBV) capsid assembly holds promise as a therapeutic approach for chronic hepatitis B (CHB). Novel anti-HBV agents are urgently needed to overcome drug resistance challenges, with targeted protein degradation (TPD) emerging as a hopeful strategy. Herein, we report the first degradation of HBV core protein (HBC), a multifunctional structural protein, using small-molecule degraders developed by hydrophobic tagging (HyT) technology. Structure-activity relationship (SAR) analysis identified compound HyT-S7, featuring an adamantyl group, exhibiting potent inhibitory activity (EC₅₀ = 0.46 μmol/L, HepAD38 cells) and degradation ability (DC₅₀ = 3.02 ± 0.54 μmol/L) in a dose- and time-dependent manner. Mechanistic studies demonstrated that the autophagy-lysosome pathway was a potential driver of HyT-S7-induced HBC degradation. Remarkably, HyT-S7 effectively degraded 11 drug-resistant mutants, including highly resistant strains P25G and T33N, to Phase III drug GLS4. Furthermore, cellular thermal shift assay, surface plasmon resonance assay, and molecular dynamics simulations revealed the precise mode of HyT-S7 binding to HBC with the adamantyl group potentially mimicking protein misfolding to facilitate HBC degradation. This first proof-of-concept study highlights the potential of HyT-mediated TPD in HBC as a promising avenue for discovering novel HBV and other antiviral agents with favorable drug resistance profiles.

Sennoside A (SA), a typical prodrug, exerts its laxative effect only after its transformation into rheinanthrone catalyzed by gut microbial hydrolases and reductases. Hydrolases have been identified, but reductases remain unknown. By linking a photoreactive group to the SA scaffold, we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling (ABPP). From lysates of an active strain, Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), 397 proteins were enriched and subsequently identified using mass spectrometry (MS). Among these proteins, chromate reductase/nicotinamide adenine dinucleotide (NADH) phosphate (NADPH)-dependent flavin mononucleotide (FMN) reductase/oxygen-insensitive NADPH nitroreductase (nfrA) was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource (UniProt) database screening. We also determined that recombinant nfrA could reduce SA. Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

Objective:To investigate the effect of ear acupoint bean pressing on gastrointestinal motility and related hormones after laparoscopic surgery in patients with hysteromyoma,and to explore the therapeutic mechanism of ear acupoint bean pressing.Methods:Patients undergoing laparoscopic myomectomy in the Department of Gynecology of The People's Hospital Affiliated to Fujian Univer-sity of Traditional Chinese Medicine from May 2022 to December 2023 were randomly divided into an experimental group and a control group,with 57 patients in each group.The experimental group was treated with postoperative routine nursing and ear acupoint bean pressing(targeting the spleen,stomach,and sympathetic),and the control group was treated with postoperative routine nursing and sham ear acupoint bean pressing(containing no Vaccaria seed,targeting the spleen,stomach,and sympathetic).After the intervention,the time to first postoperative passing of flatus and defecation,clinical efficacy,and changes in gastrointestinal hormone levels were compared between the two groups.Results:The time to first postoperative passing of flatus[20.31(17.52,22.38)h vs.21.51(18.53,28.15)h]and defecation[35.32(31.47,39.17)h vs.38.12(33.44,42.78)h]in the experimental group was lower than that in the control group(P<0.05),and the clinical efficacy was better than that in the control group(P<0.05).There were no significant differ-ences in motilin(MTL),gastrin(GAS),somatostatin(SS),and substance P(SP)levels between the two groups before operation(P>0.05).The MTL and GAS levels were increased and the SS and SP levels were decreased after operation.The MTL[(451.52±54.33)pg/mL vs.(476.24±56.35)pg/mL]and GAS[150.50(133.93,164.52)pg/mL vs.173.44(154.45,184.63)pg/mL]levels at 24 h after operation in the experimental group were lower than those in the control group(P<0.05),and the SS[38.34(33.24,40.23)pg/mL vs.33.36(29.13,38.76)pg/mL]level at 24 h after operation was higher than that in the control group(P<0.05),with no significant change in the SP level(P>0.05).The results of repeated measures analysis of variance and generalized estimation equation showed that there were significant differences in the time effect and interaction effect of MTL(P<0.05),a significant difference in the time effect of SP(P<0.05),and significant differences in the time effect,intergroup effect,and interaction effect of GAS and SS(P<0.05).Conclusion:Ear acupoint bean pressing has significant effect on abdominal distension after laparoscopic surgery in patients with hysteromyoma,ef-fectively regulates the level of gastrointestinal motility related hormones,and promotes the recovery of gastrointestinal function.

Objective:Laboratory evaluation of the relationship between cerebrospinal fluid and plasma indicators and intrathecal immunoglobulin G(IgG) synthesis in patients with neurological diseases, and establishment of a new diagnostic method for intrathecal IgG synthesis.Methods:This study retrospectively analyzed the content of IgG in cerebrospinal fluid samples and blood albumin in blood samples, and other test results of 410 patients with neurological diseases who visited Beijing Tiantan Hospital from 2019 to 2022. According to the results of oligoclonal bands in cerebrospinal fluid, patients were divided into intrathecal IgG synthesis group and non-intrathecal IgG synthesis group. The Mann Whitney U test was used for inter group comparison, and a bilateral test with P<0.05 indicates a statistically significant difference. Include indicators with differences between groups in logistic regression analysis, construct a predictive model, and compare it with the established quantitative formula IgG index. Results:There were significant differences in 10 indicators, including cerebrospinal fluid leukocyte count and 24-hour intrathecal IgG synthesis rate, between the intrathecal IgG synthesis group and the non-intrathecal IgG synthesis group, with P<0.05. The area under the curve (AUC) of intrathecal IgG synthesis was higher than the IgG index (AUC=0.920, 0.809, Z=31.178, P<0.001), the sensitivity was higher than the IgG index (0.825, 0.618), and the specificity was lower than the IgG index (0.876, 0.908). Conclusion:The combination of 10 indicators such as cerebrospinal fluid white blood cell count and 24-hour intrathecal IgG synthesis rate can improve the diagnostic efficacy and sensitivity of intrathecal IgG synthesis.

Objective To understand the reliability of caloric test results through the analysis of the pod shape dia-gram types of caloric test and to provide a more accurate and reliable basis for vestibular system function evaluation.Meth-ods The results of caloric test in 528 patients from July 2021 to May 2022 in vertigo diagnosis and treatment center were analyzed.According to pod pattern and unilateral weakness(UW),the patients were divided into five groups:cold and warm test symmetrical group,left and right side asymmetry group,single value significant abnormal group,bilateral hypo-plasia group and pod morphology unable to be classified group.Unreliable data can be identified by comparing,explaining,and summarizing the results of UW of different groups,so as to reduce the interference of unreliable data to clinical diagno-sis and treatment.Results Cold and warm test symmetric group(n=439)included patients with symmetry of bilateral vestibular function(n=273)and decreased vestibular function of one side(n=166).Left and right symmetrical groups in-eluded pationts with bilateral symmetric vestibular function(n=11)and unilateral reduction(n=13).Single value signifi-cant abnormal group showed cases with unilateral vestibular function reduction(n=25)and bilateral symmetric vestibular function(n=11).Bilateral hypolasion group showed cases with bilateral symmetric vestibular function(n=25)and unilat-eral reduction(n=9).Pod morphology unclassified group(n=5)suggested varions interference factors.Conduson When the function of the peripheral vestibular is symmetrical and normal,we should be alert to the existence of temperature effect,and should consider the inspection of the perfusion apparatus and the calibration of the irrigation temperature.When the function of the peripheral vestibular shows unilateral weakness,repeating the irrigation is recommended when the single value of the caloric test significantly increases or decreases.If there is no change,repeating the irrigation at the same tem-perature in the other ear or even repeating the whole caloric test are recommended.The UW value could not truly reflect the state of peripheral vestibular function when the caoric test produces bilateral weakness.Therefore,water irrigation could be used to make a correct judgment based on the medical history and other auxiliary examinations.It is of great significance to judge the effectiveness of caloric test comprehensively by combining the morphology of pod diagram with UW value.

Based on the discussions in the The Inner Canon of Yellow Emperor （《黄帝内经》）， it is proposed that in the course of the disease， "bind" represents the initial stage of pulmonary nodules， while "accumulation" represents the final form. In terms of the pathogenesis， "two colds interacting" represented by "body cold" and "cold fluid retention" are the prerequisites for the formation of pulmonary nodules， while "disorder of qi" represented by "fainting" is the core of the formation. The specific manifestation is the disturbance of pivot of shaoyang （少阳） or shaoyin （少阴）， resulting in a complex of cold and heat， and then phlegm and stasis are suddenly generated and further formed into nodules. Therefore， the treatment principle should be to regulate the cardinal mechanism， dissolve phlegm and blood stasis. Depending on the complex degree of cold and heat， it is suggested to use Chaihu Guizhi Decoction （柴胡桂枝汤）， Chaihu Guizhi Ganjiang Decoction （柴胡桂枝干姜汤）， or Chaihu Xianxiong Decoction （柴胡陷胸汤） for disturbance of shaoyang pivot， while for shaoyin pivot dysfunction， modified Mahuang Fuzi Xixin Decoction （麻黄附子细辛汤） or Shengjiang Powder （升降散） can be used.

Objective: To explore and validate the potential targets of Paeoniae Radix Alba (P. Radix, Bai Shao) in protecting against chemical liver injury through network pharmacology, molecular docking technology, and in vitro cell experiments. Methods: Network pharmacology was used to identify the common potential targets of P. Radix and chemical liver injury. Molecular docking was used to fit the components, which were subsequently verified in vitro. A cell model of hepatic fibrosis was established by activating hepatic stellate cell (HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1. The cells were exposed to different concentrations of total glucosides of paeony (TGP), the active substance of P. Radix, and then evaluated using the cell counting kit-8 assay, enzyme-linked immunosorbent assay, and western blot. Results: Analysis through network pharmacology revealed 13 key compounds of P. Radix, and the potential targets for preventing chemical liver injury were IL-6, AKT serine/threonine kinase 1, jun proto-oncogene, heat shock protein 90 alpha family class A member 1 (HSP90AA1), peroxisome proliferator activated receptor gamma (PPARG), PTGS2, and CASP3. Gene Ontology (GO) enrichment analysis indicated the involvement of response to drugs, membrane rafts, and peptide binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation. Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1, PTGS2, PPARG, and CASP3. Different concentrations of TGP can inhibit the expression of COL-Ⅰ, COL-Ⅲ, IL-6, TNF-α, IL-1β, HSP-90α, and PTGS2 while increasing the expression of PPAR-γ and CASP3 in activated HSC-LX2 cells. Conclusion P. Radix primarily can regulate targets such as HSP90AA1, PTGS2, PPARG, CASP3. TGP, the main active compound of P. Radix, protects against chemical liver injury by reducing the inflammatory response, activating apoptotic proteins, and promoting the apoptosis of activated HSCs.