The theory of constitution in traditional Chinese medicine （TCM） has emerged as a new discipline in recent years. Constitution plays a vital role in the onset，progression，transformation，and prognosis of diseases. At present，some clinical scholars have adopted a novel diagnostic and treatment model of "constitution differentiation-disease identification-syndrome differentiation"，in which constitution is regarded as a core element throughout the diagnostic and therapeutic process. Constitution is closely associated with etiology，onset，pathogenesis，syndrome differentiation，and treatment. Against this background，the construction of animal models based on constitution holds far-reaching significance for advancing clinical research. This paper focuses on the construction and evaluation of rodent models with Qi-deficiency constitution，aiming to explore how to further induce Qi-deficiency syndromes and related disease states on the basis of Qi-deficiency constitution models，thereby developing an integrated animal model that embodies the trinity of "constitution-disease-syndrome". The establishment of this model not only provides a solid experimental foundation for the development of new therapies and drugs in TCM targeting specific constitutions，diseases，and syndromes，but also greatly promotes the modernization and scientific advancement of TCM theory. By comprehensively applying multidisciplinary technologies and methods，the study evaluates the model's validity，reliability，and practicality，with the aim of opening new avenues for future research in TCM and promoting the development of the field.

The theory of constitution in traditional Chinese medicine （TCM） has emerged as a new discipline in recent years. Constitution plays a vital role in the onset，progression，transformation，and prognosis of diseases. At present，some clinical scholars have adopted a novel diagnostic and treatment model of "constitution differentiation-disease identification-syndrome differentiation"，in which constitution is regarded as a core element throughout the diagnostic and therapeutic process. Constitution is closely associated with etiology，onset，pathogenesis，syndrome differentiation，and treatment. Against this background，the construction of animal models based on constitution holds far-reaching significance for advancing clinical research. This paper focuses on the construction and evaluation of rodent models with Qi-deficiency constitution，aiming to explore how to further induce Qi-deficiency syndromes and related disease states on the basis of Qi-deficiency constitution models，thereby developing an integrated animal model that embodies the trinity of "constitution-disease-syndrome". The establishment of this model not only provides a solid experimental foundation for the development of new therapies and drugs in TCM targeting specific constitutions，diseases，and syndromes，but also greatly promotes the modernization and scientific advancement of TCM theory. By comprehensively applying multidisciplinary technologies and methods，the study evaluates the model's validity，reliability，and practicality，with the aim of opening new avenues for future research in TCM and promoting the development of the field.

Objective To compare the clinical efficacy of neuroendoscope-assisted evacuation and navigation-assisted puncture drainage in treating thalamic hemorrhage breaking into the ventricle. Methods A retrospective analysis was conducted on the clinical data of 93 patients with thalamic hemorrhage breaking into the ventricle at Taihe Hospital of Wannan Medical College between January 2022 and February 2024. The patients received neuroendoscope-assisted removal of thalamic hematoma combined with contralateral extraventricular drainage (n＝44, neuroendoscope group) and navigation-assisted thalamic hematoma puncture drainage combined with contralateral extraventricular drainage (n＝49, navigation group), respectively. The treatment efficacy, surgical situation, and prognosis between the two groups were compared. Results The neuroendoscope group had longer operation duration, more intraoperative blood loss, higher hospitalization costs than the navigation group (P＜0.05). The neuroendoscope group had higher hematoma clearance rate 3rd after surgery and shorter length of stay than the navigation group (P＜0.05). There was no significant difference in the incidence of intracranial infection after surgery between the two groups. The neuroendoscope group had higher Glasgow coma scale (GCS) score at 1 week after surgery and Glasgow outcome scale (GOS) score at 3 months after surgery (P＜0.01). Conclusions Compared with navigation-assisted puncture, neuroendoscope-assisted evacuation can improve the thalamic hemorrhage clearance rate, shorten the length of stay, and improve the prognosis of patients.

OBJECTIVE To investigate the mechanism by which Naozhenning granules （NZN） improve learning and memory impairment in a rat model of multiple cerebral concussion （MCC）. METHODS The MCC rat model was established using the closed controlled cortical impact method. The experiment was set up with a blank group （normal saline）， a model group （normal saline）， a piracetam group （positive control group， 0.324 g/kg）， and high-， medium-， and low-dose NZN groups （5.4， 2.7， 1.35 g/kg）， with 11 rats in each group. Drugs or normal saline were administered by gavage once daily for 28 consecutive days. General condition and body weight were monitored throughout the experiment. The sucrose preference rate and novel object recognition index were measured； Evans blue （EB） extravasation in the cerebral cortex was detected； pathological changes of cortical neurons were observed； the levels of B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， interleukin-6 （IL-6）， IL-10， and tumor necrosis factor-α （TNF-α） in the cerebral cortex were determined； and the phosphorylation levels of AMP-activated protein kinase （AMPK）， glycogen synthase kinase 3β （GSK3β）， and Tau protein were detected. RESULTS Compared with the blank group， the model group showed poor mental state， sluggish response to external stimuli， reduced food and water intake， decreased limb flexibility， and disheveled fur. Body weight， sucrose preference rate， and novel object recognition index were significantly decreased （ P ＜0.05）； EB extravasation in the cerebral cortex was significantly increased （ P ＜0.05）， with severe neuronal damage. The positive area ratio of Bax protein， IL-6 and TNF-α levels， and Tau protein phosphorylation level were all significantly increased （ P ＜0.05）， whereas the positive area ratio of Bcl-2 protein， IL-10 level， and AMPK and GSK3β protein phosphorylation levels were significantly decreased （ P ＜0.05）. Compared with the model group， all NZN dose groups showed improvements in general condition and pathological damage， with quantitative indices partially restored， and the differences in quantitative indices in high-dose NZN group were statistically significant （ P ＜0.05）. CONCLUSIONS NZN can effectively improve learning and memory impairment in MCC model rats. The mechanism may be related to activating the AMPK/GSK3β pathway， inhibiting inflammatory response， reducing Tau protein phosphorylation level， and then repairing the neuronal injury.

Asthma is a chronic inflammatory respiratory disease involving multiple cells and cellular components， characterized by recurrent episodes of wheezing， shortness of breath， chest tightness， and coughing， significantly impacting patients' quality of life. The phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway， as a crucial hub in intracellular signaling， is widely involved in the regulation of cell growth， proliferation， survival， metabolism， and a series of pathophysiological processes. Its regulatory role in the pathological progression of asthma is particularly significant， specifically in promoting airway inflammation， mediating epithelial mesenchymal transition， accelerating airway remodeling， regulating cell autophagy， inducing mucus hypersecretion， and influencing immune response balance. This study analyzed potential molecular targets of the PI3K/Akt pathway， including activators such as cysteine proteinase inhibitor 1（CST1）， found in inflammatory zone 1（FIZZ1） and free fatty acid receptor 1（FFAR1）， and inhibitors such as human β-defensin-3（hBD-3）， disintegrins， metalloproteinase 33（ADAM33） and interleukin-27（IL-27）， and initially revealed the potential molecular mechanisms of traditional Chinese medicine（TCM） in asthma intervention. Based on this， the authors systematically summarized the efficacy and specific mechanisms of TCM monomers， compounds， and external treatments for asthma by regulating the PI3K/Akt signaling pathway through literature review and analysis， aiming at establishing a robust foundation for the wide application and advanced development of TCM in asthma treatment， offering innovative insights for clinical research and drug development of asthma.

Asthma is a chronic inflammatory respiratory disease involving multiple cells and cellular components， characterized by recurrent episodes of wheezing， shortness of breath， chest tightness， and coughing， significantly impacting patients' quality of life. The phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway， as a crucial hub in intracellular signaling， is widely involved in the regulation of cell growth， proliferation， survival， metabolism， and a series of pathophysiological processes. Its regulatory role in the pathological progression of asthma is particularly significant， specifically in promoting airway inflammation， mediating epithelial mesenchymal transition， accelerating airway remodeling， regulating cell autophagy， inducing mucus hypersecretion， and influencing immune response balance. This study analyzed potential molecular targets of the PI3K/Akt pathway， including activators such as cysteine proteinase inhibitor 1（CST1）， found in inflammatory zone 1（FIZZ1） and free fatty acid receptor 1（FFAR1）， and inhibitors such as human β-defensin-3（hBD-3）， disintegrins， metalloproteinase 33（ADAM33） and interleukin-27（IL-27）， and initially revealed the potential molecular mechanisms of traditional Chinese medicine（TCM） in asthma intervention. Based on this， the authors systematically summarized the efficacy and specific mechanisms of TCM monomers， compounds， and external treatments for asthma by regulating the PI3K/Akt signaling pathway through literature review and analysis， aiming at establishing a robust foundation for the wide application and advanced development of TCM in asthma treatment， offering innovative insights for clinical research and drug development of asthma.

OBJECTIVE To study the effects of peripheral blood-derived exosomes （Exo） intervened by Naozhenning （NZN） on injury of neuron cells HT22 induced by microglia BV-2 cells. METHODS Wistar rats were selected to prepare peripheral blood- derived Exo intervened by NZN （66.83 g/kg）， referred to as NZN-Exo； peripheral blood-derived Exo intervened by normal saline and piracetam （PLXT， 1.62 g/kg） were prepared using the same method， denoted as KB-Exo and PLXT-Exo respectively， and all Exo were subsequently identified. Meanwhile， BV-2 cells were stimulated with 1 μg/mL lipopolysaccharide （LPS） to prepare LPS- stimulated supernatant， and non-LPS-stimulated supernatant was prepared following the same protocol. HT22 cells were divided into four groups: KB-Exo group （treated with non-LPS-stimulated supernatant+KB-Exo）， model group （treated with LPS-stimulated supernatant+KB-Exo）， PLXT-Exo group （treated with LPS-stimulated supernatant+PLXT-Exo）， and NZN-Exo group （treated with LPS-stimulated supernatant+NZN-Exo）， with the concentration of the corresponding Exo in all groups being 50 μg/mL. After 24 hours of culture， the proliferation of HT22 cells was detected by the CCK-8 assay and EdU assay； the apoptosis of HT22 cells was detected； the microstructure of HT22 cells was observed； the contents of interleukin-1β （IL-1β）， IL-10， nuclear factor-κB （NF- κB）， and tumor necrosis factor-α （TNF-α） in HT22 cells were measured， as well as the expression levels of TNF-α， NOD-like receptor thermal protein domain associated protein 3 （NLRP3）， Caspase-1， B-cell lymphoma-2（ Bcl-2）， and Bcl-2-associated X protein （Bax）. RESULTS KB-Exo， PLXT-Exo and NZN-Exo were successfully prepared， and all Exo exhibited typical cup-shaped contours and membrane-enclosed characteristics. Compared with KB-Exo group， model group showed significantly decreased cell proliferation rates （detected by CCK-8 and EdU）， intracellular IL-10 levels， and Bcl-2 protein expression levels （P＜0.05）； while the cell apoptosis rate， intracellular levels of IL-1β， TNF-α， and NF-κB， as well as the expression levels of NLRP3， TNF-α， Caspase-1， and Bax proteins were significantly increased （P＜0.05）. Additionally， in the model group， the cells showed volume swelling， incomplete cell membrane， nucleolar rupture， significant swelling and deformation of mitochondria， and severe vacuolization. Compared with model group， the above quantitative indicators in the PLXT-Exo group and NZN-Exo group were significantly reversed （P＜0.05）， with large and round cell nuclei， intact nuclear membranes， and reduced mitochondrial vacuolization. CONCLUSIONS Peripheral blood-derived Exo intervened by naozhenning can alleviate the injury of neuronal cells HT22 by inhibiting inflammatory responses and cell apoptosis.

Objective To analyze the impact of chronic obstructive pulmonary disease(COPD)on coronary plaque burden in elderly patients.Methods A total of 120 COPD patients admitted to the Hongqi Hospital Affiliated to Mudanjiang Medical University from January 2022 to December 2024 were prospectively enrolled and served as the COPD group.Another 120 healthy volunteers were recruited as the control group during the same period.The general clinical data and coronary plaque burden were compared between the two groups.Pearson linear correlation analysis was used to investigate the correlation between forced expiratory volume in the first second(FEV1)and coronary plaque burden as well as left ventricular ejection fraction(LVEF).Multiple linear regression analysis was employed to identify the influencing factors of total coronary plaque bur-den and calcified plaque burden.Results The COPD group had significantly larger smoking ratio and higher levels of high-sensitivity C-reactive protein(hs-CRP)and IL-6,but obviously lower LVEF and FEV1 levels than the control group(P＜0.01).Notably increased total coronary plaque burden(38.30±8.22 vs 24.61±5.56,P＜0.01),calcified plaque burden(21.11±6.57 vs 12.54±3.65,P＜0.01)and non-calcified plaque burden(17.19±5.39 vs 12.07±3.92,P＜0.01)were observed in the COPD group than the control group.FEV1 was negatively correlated with coro-nary plaque burden,calcified plaque burden,and non-calcified plaque burden,and positively corre-lated with LVEF(P＜0.01).Multiple linear regression analysis showed that FEV1 and IL-6 were influencing factors for both total coronary plaque burden(P＜0.01)and coronary calcified plaque burden(P＜0.01),and FEV1 was an influencing factor of non-calcified plaque burden in coronary arteries(P＜0.01).Conclusion COPD promotes the development of coronary plaque burden.So,for COPD patients,it is necessary to strengthen the monitoring and early prevention of coronary plaque burden.

Objective To investigate whether vertebrobasilar dolichoectasia(VBD)and three vascular endothelial injury factors correlate with white matter hyperintensity(WMH)and lacunar infarction(LI)in patients with cerebral small vessel disease(CSVD).Methods Patients with CSVD hospitalized at the Brain Disease Center of the First Affiliated Hospital of Henan University of Chinese Medicine from March 2023 to March 2024 were prospectively and consecutively included in this study.Baseline clinical data,including gender,age,body mass index,hypertension,diabetes mellitus,coronary artery disease,atrial fibrillation,hyperlipidemia,hyperhomocysteinemia,hyperuricemia,carotid plaque,history of previous stroke,smoking,alcohol consumption,and other vascular risk factors.The patients were categorized into CSVD with VBD group and CSVD without VBD group.Imaging assessments were performed within 24 h of enrollment,including evaluating the WMH severity using Fazekas scale score(mild WMH:1-2,moderate WMH:3-4,severe WMH:5-6),imaging characteristics of LI and vertebrobasilar artery parameters on three dimensional time of flight magnetic resonance angiography images(including bilateral vertebral artery diameters,basilar artery diameters,standard basilar artery length[BAL],and bending length of the basilar artery).A basilar artery diameter ≥4.5 mm or vertebral artery diameter ≥4.0 mm was defined as dilatation.BAL ≥29.5 mm was defined as elongation,and a basilar artery bending length ≥ 10.0 mm was defined as curvature.Patients meeting at least one of these criteria(dilatation,elongation,and curvature)were included in the CSVD with VBD group.Levels of interleukin-6(IL-6),soluble intercellular adhesion molecule-1(sICAM-1),and von Willebrand factor(vWF)levels were measured on the second day of enrollment.To analyze the influencing factors of VBD in CSVD patients and examine the correlation between vertebrobasilar artery imaging parameters,the levels of three vascular endothelial injury factors(IL-6,sICAM-1,vWF),and the severities of WMH and LI in patients with CSVD.Results A total of 88 patients with CSVD,aged 40-80 years,with a mean age of(64±10)years,were included in this study,with 50patients in the CSVD with VBD group and 38patients in the CSVD without VBD group.(1)Univariate analysis showed no statistically significant differences in clinical baseline data or the three endothelial injury factor levels between the two groups(all P＞0.05).After adjusting for age and gender,variables with P＜0.1 in the univariate analysis(male,smoking history)were further examined using multivariate Logistic regression analysis,which showed that neither male gender(OR,2.656,95％CI 0.647-10.907,P=0.175)nor smoking history(OR,0.992,95％CI 0.255-3.866,P=0.991)significantly increased the risk of VBD in CSVD patients.(2)There were no statistically significant differences in bilateral vertebral artery diameters or BAL among different severity of WMH or between patients with or without LI(all P＞0.05).The basilar artery bending length was significantly smaller in patients with mild and moderate WMH CSVD than those with severe WMH CSVD(2.49[1.60,4.58]mm,5.24[2.28,6.02]mm,6.99[5.19,8.93]mm,respectively;both P＜0.05).(3)Univariate analysis showed that IL-6,sICAM-1,and vWF levels were significantly higher in patients with moderate and severe WMH CSVD compared to patients with mild WMH CSVD(all P＜0.05).IL-6 and sICAM-1 levels were significantly higher in patients with severe WMH CSVD compared to patients with moderate WMH CSVD(both P＜0.05).The levels of IL-6,sICAM-1,and vWF were significantly higher in CSVD patients with LI than those in CSVD patients without LI(all P＜0.05).(4)After adjusting for confounders such as gender,age,and smoking history,the multifactorial Logistic ordered regression analysis,using patients with mild WMH CSVD as the reference indicated that high IL-6(OR,2.358,95％CI 1.268-4.387,P=0.007),sICAM-1(OR,2.077,95％CI 1.430-3.016,P＜0.01),and vWF(OR,1.437,95％CI 1.058-1.951,P=0.020)levels were significant risk factors for the occurrence of moderate WMH in patients with CSVD,as well as significant risk factors for severe WMH in patients with CSVD(IL-6[OR,5.340,95％CI 2.555-11.163,P＜0.01],sICAM-1[OR,16.004,95％CI3.692-69.379,P＜0.01],and vWF[OR,1.748,95％CI 1.267-2.412,P=0.001]);a long basilar artery bending length was an risk factor for the development of moderate(OR,1.287,95％CI 1.032-1.603,P=0.025)and severe(OR,1.639,95％CI 1.280-2.099,P＜0.01)WMH in CSVD patients.(5)After adjusting for confounding factors such as gender,age,and smoking history,multifactorial Logistic ordered regression analysis identified that high IL-6(OR,1.536,95％CI 1.074-2.198,P=0.019),sICAM-1(OR,2.066,95％CI 1.465-2.913,P＜0.01),vWF(OR,1.423,95％CI 1.078-1.879,P=0.013)levels are significant influential factors for the development of LI in CSVD patients.Conclusions Longer basilar artery bending length was associated with more severe WMH in patients with CSVD.Elevated levels of IL-6,sICAM-1,and vWF were associated with development of LI and more severe WMH in patients with CSVD.

Objective To evaluate the ability of longitudinal changes in urinary extracellular domain of neurotrophin receptor p75(p75ECD)to serve as a prognostic biomarker of severity,progression and survival time in patients with amyotrophic lateral sclerosis(ALS).Methods Forty patients with ALS attended follow-up appointments at 3-to 6-month interval,and 51 healthy control(HC)volunteers were recruited.The concentrations of urinary p75ECD were tested by a sandwich ELISA.The ALSFRS-r was used to quantify the severity of ALS.The change rate of urinary p75ECD(Δp75ECD)was calculated as the average monthly change during the period between the first and the last sampling.Results The concentration of urinary p75ECD was higher at the last follow-up than at baseline(P=0.002 3).Spearman analysis showed that there was a negative correlation between urinary p75ECD and ALSFRS-r score(r=-0.35,P=0.001 3);the course of ALS in the fast-changing Δp75ECD group was shorter than that in the slow-changing group(P=0.015 8);the Δp75ECD and course of ALS showed a negative correlation(r=-0.39,P=0.014),and the Δp75ECD in the fast-progression ALS group was significantly higher than in the slow-progression group(P=0.001 6).There was a positive correlation between Δp75ECD and progression in ALS patients(r=0.34,P=0.005).Kaplan-Meier survival analysis showed a longer median survival time in those with slow-changing Δp75ECD(P=0.03).Conclusion The change rate of urinary p75ECD has shown great potential as a biomarker for the prognosis of the severity,progression and survival time of ALS.