ObjectiveTo investigate whether Shixiaosan can improve neurological function and inhibit ferroptosis in rats with cerebral ischemia-reperfusion injury （CIRI） by regulating the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） pathway. MethodsA rat model of CIRI was established using the intraluminal filament method. Briefly， cervical blood vessels were separated， branches of the external carotid artery were ligated， and the common carotid artery and internal carotid artery were clamped. A nylon filament was inserted through the opening of the external carotid artery to the origin of the middle cerebral artery to block blood flow and induce cerebral ischemia. After 60-120 min of ischemia， the filament was withdrawn to restore blood flow， and the external carotid artery incision was ligated. The rats were divided into a CIRI group， a Shixiaosan low-dose （-L） group （intragastric administration of 1.26 g·kg^-1 Shixiaosan）， a Shixiaosan high-dose （-H） group （intragastric administration of 2.52 g·kg^-1 Shixiaosan）， a donepezil hydrochloride tablet （DON） group （intragastric administration of 0.45 mg·kg^-1 DON）， and a Shixiaosan -H + Nrf2 inhibitor （ML385） group （intragastric administration of 2.52 g·kg^-1 Shixiaosan combined with intraperitoneal injection of 30 mg·kg^-1 ML385）. An additional 12 rats underwent cervical artery separation followed by incision suturing and served as the control group. Equal volumes of double-distilled water were administered to the CIRI and control groups. Neurological function impairment was assessed using the modified Garcia JH score. Magnetic resonance imaging was used to determine the cerebral infarct volume ratio. Hematoxylin-eosin （HE） staining and Prussian blue staining were performed to observe neuronal injury and iron accumulation in the ischemic penumbra， respectively. Transmission electron microscopy was used to examine the ultrastructure of neuronal mitochondria in the ischemic penumbra. Commercial kits were used to measure ferrous iron （Fe²⁺）， malondialdehyde （MDA）， reduced glutathione （GSH） content， and reactive oxygen species （ROS） activity in the ischemic penumbra. The BODIPY （581/591） C11 fluorescent probe was used to detect intracellular lipid peroxidation levels. Western blot was performed to detect protein expression levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFRC）， ferritin heavy chain （FHC）， and ferritin light chain （FLC） in the ischemic penumbra. ResultsCompared with the control group， the CIRI group exhibited neuronal injury in the ischemic penumbra， characterized by reduced neuron numbers， nucleolar shrinkage， and interstitial edema. Marked iron accumulation was observed in the tissue. Neuronal mitochondria showed atrophy and rupture， with reduced mitochondrial cristae and increased membrane density. The cerebral infarct volume ratio， Fe²⁺ content， MDA content， ROS activity， and lipid peroxidation levels were increased， whereas the modified Garcia JH score， GSH content， and protein expression levels of Nrf2， SLC7A11， GPX4， FHC， and FLC were decreased， and TFRC protein expression was increased （P<0.05）. Compared with the CIRI group， the Shixiaosan -L group， Shixiaosan -H group， and DON group showed attenuated neuronal injury in the ischemic penumbra， reduced iron accumulation， alleviated mitochondrial damage， decreased cerebral infarct volume ratio， Fe²⁺ and MDA contents， ROS activity， and lipid peroxidation levels， as well as increased modified Garcia JH scores， GSH content， and protein expression levels of Nrf2， SLC7A11， GPX4， FHC， and FLC， while TFRC protein expression was decreased （P<0.05）. The magnitude of changes in all indicators was greater in the Shixiaosan -H group than in the Shixiaosan -L group （P<0.05）. Compared with the Shixiaosan -H group， all measured indicators in the Shixiaosan -H + ML385 group showed opposite trends （P<0.05）. ConclusionShixiaosan may inhibit ferroptosis and restore neurological function in rats with CIRI by activating the Nrf2/SLC7A11/GPX4 pathway.

ObjectiveTo explore the function and related molecular mechanisms of magnoflorine against colon cancer via network pharmacology， molecular docking， and in vitro cell experiments. MethodsIn this study， the canonical SMILES of magnoflorine was obtained from the PubChem database， and the potential targets of magnoflorine were predicted by the Swiss Target Prediction database， while the disease targets of colon cancer were obtained from the DisGeNET， GeneCards and OMIM databases. The intersecting targets between magnoflorine's predicted targets and colon cancer disease targets were taken， and a protein-protein interaction （PPI） network was constructed and analyzed. The DAVID online database was employed to conduct Gene Ontology （GO） and KEGG pathway enrichment analyses on core targets. The top five key targets screened were docked with magnoflorine using AutoDock software. Finally， cellular experiments including CCK-8 assays， EdU experiments， cell scratch assays， and Transwell assays were conducted to validate the results from network pharmacology and molecular docking. Results44 key targets of magnoflorine in resisting colon cancer were acquired. The molecular docking results showed that magnoflorine had a strong binding activity with the core target signal transducer and activator of transcription 3 （STAT3） in the top five of the PPI network. Cellular experiments confirmed that magnoflorine could inhibit the proliferation and migration of colon cancer cells by suppressing the JAK/STAT3 signaling pathway. ConclusionMagnoflorine may inhibit the proliferation and migration of colon cancer cells by regulating the JAK/STAT3 signaling pathway.

ObjectiveTo investigate the effect of Semaphorin 3A （Sema3A） on the progression of pathological cardiac hypertrophy. MethodsWild-type C57BL 6J mice， Sema3A global overexpressing （Sema3A/Cre-ER^TM） mice， and their littermate controls （Cre-ER^TM） were used， with 6 mice per group. A pressure-overload induced cardiac hypertrophy model was established via transverse aortic constriction （TAC）， with a sham-operated group （Sham） as the control. Cardiac hypertrophy was assessed by gross morphology， heart weight/body weight ratio （HW/BW）， heart weight/tibia length ratio （HW/HL）， and heart weight/lung weight ratio （HW/PW）. Cardiac function was evaluated by measuring ejection fraction （EF） and fractional shortening （FS） via echocardiography. In heart tissues， the mRNA level of atrial natriuretic peptide （ANP） and Sema3A were detected by RT-qPCR， Sema3A protein level was detected by western blot， morphological structure was detected by hematoxylin and eosin （HE） staining， level of fibrosis was detected by Masson’s trichrome staining， and angiogenesis was detected by immunohistochemical detection of CD31. For in vitro experiments， rat H9C2 cardiomyocytes were treated with angiotensin Ⅱ （Ang Ⅱ） to induce hypertrophy， with PBS-treated cells as the control. After 48 hours， the mRNA expression of ANP， B-type natriuretic peptide （BNP） and Sema3A were measured by RT-qPCR， and Sema3A protein level was assessed by western blot. ResultsAt the animal level， compared with the sham group， mice subjected to TAC showed significantly increased mRNA levels of ANP in cardiac tissue， as well as markedly elevated mRNA and protein levels of Sema3A （all P<0.05）. Compared with the Cre-ER^TM + TAC group， the Sema3A/Cre-ER^TM + TAC group exhibited more pronounced cardiac hypertrophy， greater ventricular wall thickening， higher HW/BW， HW/HL， and HW/PW ratios， more significant reductions in EF and FS， more severe cardiac fibrosis， and a significant decrease in cardiac CD31 expression levels （all P<0.05）. At the cellular level， compared with the control group， H9C2 cells treated with Ang Ⅱ displayed significantly increased mRNA levels of ANP and BNP， along with markedly elevated mRNA and protein levels of Sema3A （all P<0.05）. ConclusionSema3A promotes the progression of pressure overload-induced cardiac hypertrophy by inhibiting angiogenesis.

OBJECTIVE To investigate the mechanism of Zuogui pill in improving pancreatic β cell function in the offspring of rats with gestational diabetes mellitus （GDM）.METHODS Thirty-six pregnant rats were divided into normal group， model group， insulin glargine group （positive control）， and low-， medium- and high-dose Zuogui pill groups， with 6 rats in each group. The normal group and model group were given intragastric administration of equal-volume normal saline. The insulin glargine group was subcutaneously injected with insulin glargine at an initial dose of 1 U/kg， and the dosage was increased by 1 U per day until random blood glucose returned to normal. The low-， medium- and high-dose Zuogui pill groups were intragastrically administered with Zuogui pill solutions at 4.725， 9.45 and 18.9 g/kg once a day until the birth of offspring. On postnatal day 21 （12 offspring in each group）， body weight， fasting blood glucose （FBG） and oral glucose tolerance test were performed on the offspring. Pancreatic histopathological changes of 60-day-old offspring were observed. The insulin-positive expression area ratio in pancreatic tissue， serum levels of glycated serum protein （GSP）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C）， as well as the mRNA and protein relative expression levels of wingless-type MMTV integration site family member 7a（Wnt7a）and glycogen synthase kinase 3β（GSK-3β） in pancreatic tissue were detected.RESULTS Compared with normal group， the body weight， insulin-positive expression area ratio in pancreatic tissue， serum HDL-C level， and the mRNA and protein relative expression levels of Wnt7a in pancreatic tissue were significantly decreased of the offspring in the model group （ P ＜0.05）. Meanwhile， FBG， blood glucose levels at 60， 90 and 120 min after intragastric administration of 20% glucose solution， serum GSP and LDL-C levels， as well as the mRNA and protein relative expression levels of GSK-3β in pancreatic tissue were significantly increased （ P ＜0.05）；mild degeneration and necrosis of islet cells were observed in pancreatic tissue. Compared with the model group， the above-mentioned indexes were significantly reversed in medium- and high-dose Zuogui pill groups （ P ＜0.05）， and pancreatic pathological injury was improved to varying degrees.CONCLUSIONS Zuogui pill may restore the homeostasis of Wnt7a/GSK-3β signaling axis， so as to improve pancreatic β cell function in the offspring of GDM rats.

ObjectiveTo investigate the hemodynamic differences in cortical activation during the observation-imitation process between real-time action observation therapy (R-AOT) and video-based action observation therapy (V-AOT) in patients with stroke using functional near-infrared spectroscopy (fNIRS). MethodsA total of 29 patients with stroke in Shanxi Bethune Hospital from June to September, 2025 were enrolled. A randomized-sequence, self-controlled crossover trial design was employed. Each participant received both R-AOT and V-AOT, with a one-day interval between the two conditions to minimize potential carryover effect. fNIRS was used to simultaneously record changes in oxyhemoglobin (Oxy-Hb) concentration during the observation and imitation phases in regions of interest (ROIs), including the ipsilesional and contralesional dorsolateral prefrontal cortex (DLPFC), occipital cortex (OC), and temporal cortex (TC). ResultsAfter false discovery rate (FDR) correction across all ROIs, no significant difference was observed between R-AOT and V-AOT during either the observation or imitation phase (P_FDR > 0.05). During the observation phase, Oxy-Hb was greater under R-AOT than under V-AOT in the ipsilesional DLPFC (Z = 2.183, P_FDR = 0.045). Oxy-Hb showed an opposite directional pattern between the two conditions in the ipsilesional OC, but the difference was not statistically significant (Z = 2.321, P_FDR = 0.060). During the imitation phase, the ipsilesional TC showed greater Oxy-Hb changes under R-AOT than under V-AOT (Z = 2.724, P_FDR = 0.018). ConclusionR-AOT and V-AOT may elicit different local cortical hemodynamic responses during the observation and imitation phases in patients with stroke. The between-condition difference during the observation phase was mainly observed in the ipsilesional DLPFC, whereas during the imitation phase it was mainly observed in the ipsilesional TC.

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.

Objective To analyze the epidemiological characteristics of hand, foot, and mouth disease (HFMD) in Shanxi Province from 2012 to 2024, and predict the incidence trend for 2025, and to provide a scientific basis for the formulation of prevention and control strategies. Methods Based on the surveillance data of HFMD in Shanxi Province from 2012 to 2024, the spatial and temporal distribution characteristics and time trends of the disease were analyzed. The ARIMA model was constructed and used to predict the incidence trend in 2025. Results From 2012 to 2024, a total of 254 028 HFMD cases were reported in Shanxi Province, with an average annual incidence rate of 54.17 per 100 000 population, a severe case rate of 0.56%, and a case fatality rate (CFR) of 12.60 per 100 000 population. Joinpoint regression analysis showed that the incidence rate, severe case rate, mortality rate, and case fatality rate all presented a downward trend. The epidemic exhibited obvious seasonal distribution characteristics, with the peak period from April to November, and two incidence peaks in June-July and October-November. The male-to-female incidence ratio was 1.41:1. Children aged 1-5 years accounted for 89.24% of the total cases, among which scattered children (58.48%) and nursery children (33.54%) were the high-risk groups. Linfen City (96.06 /100 000) and Taiyuan City (88.54 /100 000) had relatively high incidence rates. After 2017, the proportion of enterovirus A71 (EV-A71) decreased, while coxsackievirus A16 (Cox-A16) and other enteroviruses became the main epidemic strains. The ARIMA(1,0,1)(0,1,1)₁₂ model predicted that the incidence of HFMD in 2025 would remain at the level of 2023-2024, and the dual-peak characteristic would continue. Conclusion From 2012 to 2024, the overall HFMD epidemic in Shanxi Province generally shows a significant downward trend. The high-risk population includes scattered children and nursery children under 5 years old, with high-incidence areas concentrated in the central and southern regions, requiring focused attention. The seasonal ARIMA model can effectively fit the evolutionary trend of HFMD incidence in Shanxi Province and possesses short-term predictive capability.

Objective To investigate the effect of Yiqi Fumai Injection combined with atorvastatin on cardiac function in elderly coronary heart disease patients with angina of Qi-Yin deficiency pat-tern.Methods A total of 122 elderly coronary heart disease patients with angina pectoris of Qi-Yin deficiency pattern admitted to our department from September 2022 to September 2023 were recruited and randomly divided into control group and observation group,with 61 cases in each group.The control group was treated with atorvastatin,and the observation group was treated with Yiqi Fumai Injection on the basis of atorvastatin.Clinical efficacy,blood lipids,B-type natri-uretic peptide level,myocardial enzymes,cardiac function,and inflammatory factors were com-pared between the two groups.Results The total effective rate was significantly higher in the observation group than the control group(95.08％vs 80.33％,x2=6.157,P＜0.05).After 4 weeks of treatment,the observation group had obviously lower levels of total cholesterol,triglyc-erides,low-density cholesterol,B-type natriuretic peptide,lactate dehydrogenase,creatine kinase,creatine kinase isoenzyme,C-reactive protein,interleukin-6 and tumor necrosis factor-α,left ven-tricular end systolic diameter,left ventricular end-diastolic diameter and left ventricular end sys-tolic volume(P＜0.05,P＜0.01),and notably higher high-density cholesterol level and left ven-tricular ejection fraction when compared with the control group(1.44±0.39 mmol/L vs 1.23±0.30 mmol/L,P=0.001;55.36±13.37％vs 50.29±10.44％,P=0.021).Conclusion Yiqi Fumai Injection combined with atorvastatin shows significantly effective in the treatment of elderly coro-nary heart disease patients with angina pectoris of Qi-Yin deficiency pattern,and can improve lipid metabolism,B-type natriuretic peptide,myocardial enzymes and cardiac function,and reduce in-flammatory factors.

OBJECTIVE: To investigate cisplatin-induced cardiovascular toxicity and explore the protective effects and potential mechanism of curcumin co-treatment. METHODS: Forty adult male Sprague-Dawley rats were numbered and randomly divided into control group, cisplatin group (7.5 mg/kg, once a week, for 2 weeks), curcumin group (200 mg/kg per day, for 2 weeks) and cisplatin+curcumin group (cisplatin 7.5 mg/kg, once a week, and curcumin 200 mg/kg per day for 2 weeks) by a random number table method, with 10 rats in each group. Cardiac and vascular morphology and functions were assessed using hematoxylin-eosin and Masson's trichrome staining, serum indexes detection, echocardiography, electrocardiogram (ECG), blood pressure monitoring, vascular ring isometric tension measurement, and left ventricular pressure evaluation. The expressions of extracellular signal-regulated kinases (ERK) and phosphorylated-ERK (p-ERK) were analyzed by immunohistochemical staining. RESULTS: Cisplatin treatment induced notable cardiac alteration, as evidenced by changes in cardiac morphology, elevated serum enzymes (P<0.05), ECG abnormalities, and increased left ventricular end-diastolic pressure (P<0.05). Meanwhile, cisplatin significantly increased arterial pulse pressure (P<0.01), primarily due to a decrease in diastolic blood pressure. Severe fibrosis was also observed in the thoracic aorta wall. In vascular ring experiments, cisplatin treatment led to a significant reduction in phenylephrine-induced contraction (P<0.05) and acetylcholine-induced relaxation (P<0.01). Notably, Curcumin co-administration significantly alleviated cisplatin-induced cardiovascular damages, as demonstrated by improvement in these parameters. Furthermore, ERK expression in the myocardium and p-ERK expression in vascular smooth muscle cells were significantly upregulated following curcumin co-treatment. CONCLUSIONS Curcumin protects the heart and vasculature from cisplatin-induced damages, likely by upregulating ERK/p-ERK expression. These findings suggest that curcumin may serve as a promising therapeutic strategy for mitigating cisplatin-associated cardiovascular toxicity during tumor chemotherapy. In vitro cell culture experiments are needed to clarify the underlying mechanism.
Animals ; Curcumin/therapeutic use* ; Cisplatin/adverse effects* ; Rats, Sprague-Dawley ; Male ; Up-Regulation/drug effects* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Phosphorylation/drug effects* ; Electrocardiography ; Blood Pressure/drug effects* ; Rats ; MAP Kinase Signaling System/drug effects*

The original version of this article (Yang et al., 2023) unfortunately contained a mistake. In Acknowledgments, the funding information for the Zhejiang Provincial Natural Science Foundation of China (No. LBY21H160001) was wrong. The correct funding should be the Zhejiang Health Science and Technology Project (No. 2022KY682), China.