This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

Traditional Chinese medicine(TCM) resources are an important foundation for the theory and practice of TCM. Rare and endangered TCM, as a significant component of these resources, plays an essential role. Conducting research on substitutes for rare and endangered TCM resources is of great significance for alleviating resource shortages, promoting the sustainable utilization of TCM, and advancing TCM modernization. This paper reviews the conservation achievements of rare and endangered Chinese medicinal materials in China and organizes the substitution methods for these materials. Currently, the main substitution approaches include introduction and domestication, tissue culture, varietal replacement, and artificial synthesis. Furthermore, this paper proposes the following approaches for researching the application scenarios of rare and endangered medicinal materials, i.e., tracing the historical context of their use to clarify foundational principles; verifying disease classifications to strengthen the clinical application scenarios of these materials; analyzing the evolution patterns of prescription formulations to strengthen the mining of the compatibility application scenarios of rare and endangered medicinal materials; scientifically evaluating to strengthen the application scenario research and development of endangered Chinese patent medicine industry. These efforts aim to promote the scientific substitution and sustainable utilization of rare and endangered medicinal materials and their substitutes.
Drugs, Chinese Herbal/chemistry* ; Humans ; Medicine, Chinese Traditional ; China ; Plants, Medicinal/growth & development* ; Endangered Species ; Conservation of Natural Resources ; Animals

Placental maternal vascular perfusion defect(MVM)is a series of pathological manifesta-tions involving placental parenchyma and placental maternal vascular abnormalities,representing recognizable injury patterns reflecting placental maternal vascular abnormalities.Preeclampsia(PE)is a common pregnan-cy complication that occurs after 20 weeks of pregnancy,characterized by hypertension and/or proteinuria.It is one of the important causes of morbidity and mortality in pregnant women and perinatal infants.MVM is the manifestation of maternal vascular abnormalities on placental tissue,while PE is a clinical manifestation of ma-ternal vascular abnormalities.Through a review of relevant literature and based on the consensus of Amster-dam Placenta Symposium Group,this article starts from the common pathological mechanism of MVM and PE,and reviews the significance and future research directions of placental pathological examination for PE pa-tients.

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

OBJECTIVES: To study the effect of prophylactic phenytoin (PHT) or levetiracetam (LEV) on busulfan (BU) blood concentration in children undergoing hematopoietic stem cell transplantation. METHODS: Pediatric patients conditioned with BU plus cyclophosphamide and fludarabine at the First People's Hospital of Chenzhou from September 2023 to February 2025 were retrospectively included. Patients were grouped by prophylactic antiepileptic regimen into PHT (n=24) and LEV (n=26). BU blood concentrations at the end of infusion (0 hour) and at 1, 2, and 4 hours post-infusion were compared between groups. RESULTS: At 0 hour post-infusion, BU blood concentrations did not differ significantly between groups (P>0.05). At 1, 2, and 4 hours post-infusion, BU blood concentrations were higher in the LEV group than in the PHT group (P<0.05). The area under the concentration-time curve from 0 to ∞ (AUC_0-∞) was greater in the LEV group (P<0.001), and the attainment rate of AUC_0-∞ was higher in the LEV group than in the PHT group (73% vs 21%, P<0.001). No significant differences were observed between groups in time to hematopoietic engraftment or in the incidence of BU-related adverse drug reactions (P>0.05). CONCLUSIONS Compared with PHT, LEV prophylaxis is associated with higher BU blood concentration and a higher AUC_0-∞ attainment rate. There is no observed difference in BU efficacy or safety between PHT and LEV.
Humans ; Levetiracetam/therapeutic use* ; Busulfan/pharmacokinetics* ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child ; Child, Preschool ; Phenytoin/pharmacology* ; Infant ; Retrospective Studies ; Anticonvulsants/pharmacology* ; Adolescent

OBJECTIVE: To retrospectively analyze the clinical data of newly diagnosed acute myeloid leukemia (AML) patients treated with venetoclax combined with azacitidine (Ven/Aza) or standard "3+7" regimen and similar regimens, collect real-world study data, compare the treatment response and adverse events between the two regimens, as well as perform survival analysis. METHODS: To retrospectively analyze the efficacy, survival, and adverse reactions of newly diagnosed AML patients treated with Ven/Aza (24 cases) and "3+7" regimens (117 cases ) in our hospital from September 2009 to March 2023, as well as factors influencing outcomes. A propensity score matching (PSM) was performed on age and Eastern Cooperative Oncology Group performance status (ECOG PS) to obtain a 1:1 matched cohort of 20 pairs, and the efficacy and survival before and after the matching were compared. RESULTS: The median age of patients in the Ven/Aza group was 69 years, while that in the "3+7" group was 56 years (P <0.001). Objective remission rate (ORR) was 62.5% in Ven/Aza group and 74.8% in "3+7" group (P >0.05). The median overall survival (OS) in the Ven/Aza group was 522 days, while that in the "3+7" group was 1 002 days (P >0.05). After controlling the two variables of age and ECOG PS, a PSM cohort of 20 pairs was obtained, in which the ORR was 65% in Ven/Aza group and 60% in "3+7" group (P >0.05). The median OS was 522 days and 629 days, and median progression-free survival (PFS) was 531 days and 198 days between the two groups, respectively. There were no statistically significant differences in OS and PFS between the two groups (both P >0.05). Additionally, the incidence of adverse events in the Ven/Aza group was significantly reduced. CONCLUSION The overall cohort shows that the "3+7" regimen has advantages in efficacy and survival, but Ven/Aza regimen is relatively safer. After performing PSM on age and ECOG PS, the Ven/Aza group showed improved efficacy, and a longer median PFS compared to "3+7" group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Retrospective Studies ; Sulfonamides/administration & dosage* ; Azacitidine/administration & dosage* ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Aged ; Middle Aged ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

AIM:To investigate the therapeutic ef-fect of crocetin on diabetic lower limb ischemia and explore its underlying mechanism.METHODS:Male C57BL/6J mice aged 8 weeks were used to es-tablish a diabetic mouse model through intraperito-neal injection of streptozotocin(STZ).Following successful induction of diabetes,femoral artery li-gation(FAL)surgery was performed to create a model of diabetic lower limb ischemia.Fourteen days after STZ injection,the mice were treated with crocetin(3 mg/kg and 6 mg/kg)by gavage for 21 consecutive days.Post-FAL surgery,Doppler flowmetry was employed to assess blood flow in the mice of each group.Immunofluorescence stain-ing techniques were utilized to observe the expres-sion levels of platelet-endothelial cell adhesion molecule(CD31),α-smooth muscle actin(α-SMA),and inflammatory-related factors including tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),in-terleukin-6(IL-6),and transforming growth factor-β(TGF-β)in the gastrocnemius muscle of diabetic mice with lower limb ischemia.RESULTS:Com-pared to the normal group,the model group exhib-ited significantly elevated blood glucose levels and significantly reduced lower limb blood flow(P＜0.05).While CD31 and α-SMA expression showed no significant change,the expression levels of TNF-α,IL-1β,IL-6,and TGF-β were significantly in-creased(P＜0.05,P＜0.01,P＜0.05,P＜0.05).Com-pared to the model group,crocetin-treated groups showed no significant change in blood glucose lev-els but demonstrated significantly increased lower limb blood flow(P＜0.05).The high-dose crocetin group(6 mg/kg)significantly enhanced CD31 andα-SMA expression(P＜0.0001,P＜0.05)and signifi-cantly reduced the expression levels of IL-1β,IL-6,and TGF-β(P＜0.001,P＜0.05,P＜0.05).CONCLU-SION:Crocetin may exert its beneficial effects on diabetic lower limb ischemia through anti-inflam-matory and angiogenic mechanisms.

Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

Objective To observe brain structural changes in preterm infants and to analyze associated clinical risk factors based on 3D T1 structural MRI.Methods Brain 3D T1 structural MRI data of 82 preterm infants(preterm group)and 50 term infants(term group)were analyzed.Cortical morphology,including cortical thickness,surface area,sulcal depth and gyrification index were compared between groups.Spearman partial correlation analysis was used to explore the correlations of cortical structural changes and perinatal clinical variables.Results Compared with those in term group,increased cortical thickness of the right caudal middle frontal gyrus,reduced surface area of the left inferior parietal lobule,left precuneus and bilateral supramarginal gyrus,as well as decreased gyrification index in the right superior temporal gyrus,right lateral occipital gyrus,left inferior parietal lobule and left parahippocampal gyrus were observed in preterm group(all FDR corrected P＜0.05).No significant difference of sulcal depth was found between groups(all P＞0.05).Cortical surface area in bilateral supramarginal gyrus of preterm infant lowly-weakly negatively(rs=-0.327,-0.267,both P＜0.05)correlated,while the gyrification index in left parahippocampal gyrus of preterm infant weakly and positively(rs=0.221,P=0.045)correlated with maternal gestational diabetes mellitus.The surface area of left inferior parietal lobule,left precuneus,left supramarginal gyrus and right supramarginal gyrus in preterm infant weakly and negatively correlated with maternal infection during pregnancy(rs=-0.284—-0.224,all P＜0.05).Meanwhile,cortical thickness of the right caudal middle frontal gyrus and surface area of the right supramarginal gyrus in preterm infant lowly and negatively correlated with premature rupture of membranes(rs=-0.311,-0.301,both P＜0.05).Conclusion 3D T1 structural MRI was useful for detecting abnormal cortical morphology of preterm infants.Maternal gestational diabetes,infection during pregnancy and premature rupture of membranes might be risk factors for abnormal brain structure in newborns.

Objective:To investigate the changes of the epidemiology and clinical characteristics of human metapneumovirus (hMPV) among children with acute lower respiratory tract infection (ALRTI) before and after the discontinuation of non-pharmaceutical interventions (NPI) during coronavirus disease 2019 epidemic.Methods:This was a retrospective cohort study. Children hospitalized at The Second Affiliated Hospital and Yuying Children′s Hospital of Wenzhou Medical University between January 2021 and December 2023, who were diagnosed with ALRTI by nasopharyngeal secretion testing for respiratory pathogens nucleic acid were enrolled. Clinical and laboratory data were collected. Children admitted between January 1, 2021 and January 7, 2023 were classified as the pre-NPI withdrawal group (abbreviated as pre-withdrawal group), while those admitted from January 8, 2023 afterward were classified as the post-NPI withdrawal group (abbreviated as post-withdrawal group). Nasopharyngeal secretions from the enrolled children were tested for 13 respiratory pathogens using polymerase chain reaction-capillary electrophoresis fragment analysis, and bacterial cultures were also performed. Statistical analyses were performed using the Mann-Whitney U test or chi-square test. Results:A total of 30 855 ALRTI cases were enrolled, with 1 679 of hMPV-positive. In the pre-withdrawal group, there were 861 cases with an age of onset of 2.0(1.0, 3.0) years, and the highest proportion was in the 1 to <3 years age group, accounting for 35.3%(304/861). In the post-withdrawal group, there were 818 cases with an age of onset of 3.0(2.0, 4.0) years, and the highest proportion was in the 3 to <5 years age group, accounting for 39.2%(321/818).The age of onset in the post-withdrawal group was significantly older than that in the pre-withdrawal group ( Z=7.69, P<0.001) .The hMPV detection rate was higher in the pre-withdrawal group than that in post-withdrawal group (5.75%(861/14 984) vs 5.15%(818/15 871); χ2=5.25, P=0.022). In the pre-withdrawal group, the epidemic peaks occurred in winter and spring, with the highest rates in January 2022(25.2%(224/890)) and March 2022 (21.6%(186/860)). In the post-withdrawal group, the epidemic peak shifted to spring and summer, and the detection rate became increased since April 2023(10.8%(136/1 258)). The post-withdrawal group showed lower rates of wheezing, shortness of breath, cyanosis, respiratory support, severe pneumonia, intensive care unit admission, and shorter hospital stays compared to the pre-withdrawal group ( χ2=69.09, 31.63, 12.97, 57.96, 55.73, 5.48 and Z=7.11, respectively, all P< 0.05).In the pre-withdrawal group, 412 cases (47.9%(412/861)) had other pathogens detected, compared to 445 cases (54.4%(445/181)) in the post-withdrawal group, indicating a significantly higher rate of co-infections in the post-withdrawal group ( χ2=7.20, P<0.05). The most commonly detected pathogens in both groups were Mycoplasma pneumoniae (MP), rhinovirus, and Streptococcus pneumoniae. However, the post-withdrawal group showed significantly higher detection rates of MP and influenza virus, but lower bacterial detection rates compared to the pre-withdrawal group ( χ2=39.41, 9.70, 5.63, respectively, all P<0.05). The detection rate of Haemophilus influenzae was 2.1%(17/818) in the post-withdrawal group which lower than that (6.7%(58/861)) in the pre-withdrawal group, and the difference was statistically significant ( χ2=21.32, P<0.001). Conclusions:In 2023, following the withdrawal of NPI, the epidemic peak of hMPV in Wenzhou area is delayed to spring and summer. The age of children with hMPV-associated ALRTI increases, with the majority being 3 to <5 years old. The overall severity of the disease decreases. However, the detection of mixed pathogens increases, with MP being the most common, while bacterial detection decreases.