ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture （消肿止痛合剂， XZM） in the treatment of diabetes foot ulcer （DFU）. MethodsFifty SD rats were randomly divided into blank group， model group， XZM group， inhibitor group， XZM plus inhibitor group （combination group）， with 10 rats in each group. Except for the blank group， rats were fed with high-sugar， high-fat， high-cholesterol diet， intraperitoneally injected with streptozotocin， and subjected to skin defect to establish DFU model. After successful modeling， the XZM group and the combination group were given 1 ml/（100 g·d）of XZM by gavage， while the blank group， model group， and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later， the inhibitor group and the combination group were intraperitoneally injected with 5 mg/（kg·d） of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration， the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin （HE） staining. The microvascular density （MVD） in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction （RT-PCR） and western blotting were used to detect the mRNA and protein levels of Notch1 homolog （Notch1）， Delta-like ligand 4 （Dll4）， Delta-like ligand 4 （VEGF）， and angiopoietin 2 （Ang-2）， respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group， the epidermis exhibited excessive keratinization， vacuolar cytoplasm， and a large number of inflammatory cells infiltrating the tissue， while in the XZM group， a large amount of scab formation was observed in the epidermis， with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group， partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group， the MVD in the wound tissue increased in the model group， as well as the mRNA expression and protein levels of Notch1 and Dll4， while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the MVD in the wound tissue of all medication groups significantly increased， and the mRNA and protein levels of Notch1 and Dll4 decreased， while VEGFA and Ang-2 mRNA expression and protein levels increased （P＜0.05 or P＜0.01）. Compared to the XZM group， the inhibitor group and the combination group showed decreased MVD in wound tissue， increased Notch1 and Dll4 mRNA and protein levels， and decreased expression of VEGFA and Ang-2 mRNA and proteins （P＜0.05 or P＜0.01）. ConclusionXZM can effectively promote wound healing in DFU rats， and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue， therey promoting angiogenesis.

Objective: To investigate the environmental contamination of norovirus in nurseries and primary/secondary schools, so as to provide a scientific basis for effective prevention and control measures. Methods: A total of 483 external environmental samples were collected from 34 cluster outbreaks of norovirus gastroenteritis in kindergartens and primary/secondary schools in Linhai City from 2021 to 2024. Pathogen detection was conducted using a rapid nucleic acid extraction kit and realtime fluorescence RT-PCR, and the results were analyzed using the χ2 test or Fishers exact test. Results: Among the collected external environmental samples, the total positive rate of surface contamination was 13.66%. The positive rates in kindergartens and primary/secondary schools were 12.20% and 15.82%, respectively. In kindergartens, the five surfaces with the highest detection rates were desks/chairs (23.33%), toilet stool troughs (20.69%), urinal troughs (12.00%), washbasins/sinks (11.11%), and toilet mops (9.38%). In primary/secondary schools, the top five were toilet stool troughs (38.30%), urinal troughs (23.53%), toilet door handles (13.04%), toilet mops (12.50%), and drinking cups (11.11%). The difference in positive detection rates among different external environments in primary/secondary schools was statistically significant (Fishers exact probability test, P<0.01). The positive detection rate in sanitary toilets was higher than that in classroom environments (χ2=17.38), while the positive detection rate in classroom environments of kindergartens was higher than that in primary/secondary schools (χ2=5.42)(P<0.05). Conclusions Norovirus exhibits a high contamination rate in nurseries and schools, particularly in restroom areas. Strengthening sanitation and disinfection in highrisk environments, and improving hygiene awareness among children and staff, are essential for the effective prevent and control of norovirus.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

Cough variant asthma （CVA） is a chronic respiratory disease with cough as its main symptom. The occurrence of CVA is closely related to non-specific airway inflammation， and its pathogenesis involves environmental， genetic， immune， and other factors. In recent years， the advantages of traditional Chinese medicine （TCM） in the treatment of CVA have attracted the attention of experts and scholars in China and abroad， especially its prominent role in regulating immune balance， relieving cough symptoms in CVA patients， and reducing recurrence. T Helper cells 1 （Th1）， T helper cells 2 （Th2）， T helper cells 17 （Th17）， and regulatory T cells （Treg） are derived from CD4⁺ T cells. Immune imbalance of Th1/Th2 and Th17/Treg is a new hotspot in the pathogenesis of CVA and a potential key target in the treatment of CVA by TCM. Th cell subsets are in dynamic balance under physiological conditions， maintaining respiratory immune homeostasis in which pro-inflammatory cytokines and anti-inflammatory cytokines are balanced. Immature helper T cells （Th0） can be differentiated into Th1， Th2， Th17， Treg， and other cell subsets due to cytokine types in the microenvironment in the stage of CVA maturation. The proliferation of Th2 cells leads to eosinophilic airway inflammation. Excessive differentiation of Th17 cells induces neutrophil airway inflammation. Th1/Th2 and Th17/Treg cells are mutually restricted in number and function， and the immune imbalance of Th1/Th2 and Th17/Treg is easy to aggravate the generation of inflammatory response. Restoring immune balance is particularly important for the airway anti-inflammatory therapy of CVA. In this paper， the imbalance of Th1/Th2 and Th17/Treg and the pathogenesis of CVA were systematically expounded. Meanwhile， the latest research on the regulation of immune imbalance by TCM compound， single TCM， and its effective ingredients in the treatment of CVA was reviewed. It provides ideas and references for revealing the scientific connotation of TCM regulating immune balance therapy of CVA， as well as the development of clinical treatment and basic research of CVA.

Objective:To explore the mechanism of zoledronic acid (ZOL) affects osteogenic differentiation and bone formation through the regulation of sirtuin 3 (SIRT3) / P53 expression.Methods:Bone marrow mesenchymal stem cells (BMSCs) were induced to differentiate into osteogenic cells, the expression of SIRT3 in the cells was detected, and the targeting regulation relationship between SIRT3 and P53 was analyzed. The intracellular expressions of SIRT3 and P53 were intervened and ZOL was used to treat the cells. MTT method, Western blot method and kit were used to detect cell viability, osteogenesis-related genes Osteoprotegerin (OPG), runt-related transcription factor 2 (Runx2) expression, alkaline phosphatase (ALP) activity and alizarin red S (ARS) staining, respectively. Ovariectomy (OVX) was used to construct a rat model and explore the effect of ZOL on the progression of osteoporosis (OP) in vivo.Results:ZOL promoted osteogenic differentiation of BMSCs. The expression of SIRT3 was down-regulated in the serum of OP patients (0.78±0.23) compared with that of healthy subjects (1.00±0.26 vs. 0.78±0.23. t=3.85, P<0.001). During the osteogenic differentiation of BMSCs, the expression level of SIRT3 gradually increased with the prolonged induction of osteogenesis. Compared with the p53 protein expression and BMSCs activity in the control group, SIRT3 knockout could increase the expression level of p53 protein (0.59±0.05 vs. 1.01±0.11. t=6.02, P=0.004) but inhibited the activity of BMSCs (100.00±8.41 vs. 51.26±5.59. t=8.36, P=0.001). After ZOL treatment, the inhibitory effect of SIRT3 on cell viability (49.61±5.11 vs. 87.61±7.31. t=7.38, P=0.002) and osteogenesis was relieved, and the level of P53 was inhibited (1.10±0.10 vs. 0.69±0.04. t=6.59, P=0.003). P53 overexpression partially offseted the effects of ZOL on cell viability (84.61±6.52 vs. 66.54±5.47. t=3.68, P=0.021) and osteogenesis. Compared with the sham surgery group, the OVX group showed inhibition of osteogenesis in rats, and ZOL treatment significantly improved osteogenic inhibition. ZOL treatment increased the expression level of SIRT3 protein in bone tissue of OVX rats, but inhibited the expression level of P53. Conclusion:ZOL promoted osteogenic differentiation and bone formation of BMSCs by promoting the ubiquitination and degradation of P53 by SIRT3.

With the advent of an aging society,Alzheimer's disease(AD)has gradually become a major ailment affecting the elderly.AD is a neurodegenerative disorder associated with cognitive impairments.In AD patients,brain network connections are disrupted,and their topological properties are also affected,leading to the disintegration of anatomical and functional connections.Anatomical connections can be tracked and evaluated using structural magnetic imaging(MRI)and diffusion tensor imaging(DTI),while functional connections are detected through functional MRI to assess their connectivity status.This review incorporates the findings of previous scholars and summarizes the current research of AD.It mainly discusses the imaging characteristics of large-scale brain network changes in AD patients,so as to provide researchers with scientific and objective imaging markers for AD prediction and early diagnosis,as well as future research.

Cerebral small vessel disease(CSVD)is a slowly progressive cerebrovascular disease caused by structural and functional disorders of small vessels and vascular neural units in the brain,and CSVD imaging markers may be evidence as manifestations of brain aging.Clinically,the onset of CSVD is not limited to individuals in middle-to-old age.Young patients without typical vascular risk factors may also have imaging markers,such as enlarged perivascular space and white matter hyperintensity.The diagnosis and treatment of these cases must be approached seriously.Compared with Western medicine,traditional Chinese medicine(TCM)has an advantage in treating disorders related to emotions,sleep,and cognition in patients with CSVD.Regarding CSVD,there are commonalities between anatomical structures,physiological functions,pathogenic mechanisms,and xuanfu and collateral theories in TCM.We combined the xuanfu and abnormal collateral theory and classified CSVD into three clinical stages:early-stage,dysfunction in xuanfu and stagnation in the qi collaterals;middle-stage,endogenous toxins and damage to the blood vessels;and late-stage,kidney and marrow deficiency and toxins damaging the brain collaterals.Different treatment strategies,such as promoting qi circulation,calming the mind,and dredging collaterals in the early stage;dispelling pathogenic factors and promoting blood circulation in the middle stage;tonifying the kidney and replenishing the marrow and removing toxins from collaterals in the late stage,are applied at different stages to offer novel perspectives on TCM treatment for CSVD.