ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion （MCAO） mice by regulating the expression of neutrophil-related chemokines in exosomes， thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free （SPF） C57BL/6J mice were randomly divided into four groups： Sham-operated group， MCAO model group， Huanglian Jiedutang group （6 g·kg^-1）， and Ginaton group （21.6 mg·kg^-1）， with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·（10 g）^-1 for 7 consecutive days， while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days， MCAO surgery was performed. The distal and proximal ends of the right common carotid artery （CCA） were ligated， a small incision was made between the two ligatures， and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling， mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy， particle size analysis， and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase （MPO） in the brains of mice in each group. ResultsCompared with the sham-operated group， the model group showed decreased neurological function scores （P<0.01）， obvious cerebral infarction （P<0.01）， reduced cerebral blood flow （P<0.01）， neuronal necrosis in the brain， and decreased numbers of Nissl bodies （P<0.01）. The mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were significantly increased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were increased （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were elevated （P<0.01）. Compared with the model group， the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores （P<0.05）， reduced cerebral infarct volume （P<0.01）， restored cerebral blood flow （P<0.01）， reduced necrotic cells in the brain， and increased numbers of Nissl bodies （P<0.01）. In the Huanglian Jiedutang group， the mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were decreased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were reduced （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were decreased （P<0.01）. ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice， thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.

ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion （MCAO） mice by regulating the expression of neutrophil-related chemokines in exosomes， thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free （SPF） C57BL/6J mice were randomly divided into four groups： Sham-operated group， MCAO model group， Huanglian Jiedutang group （6 g·kg^-1）， and Ginaton group （21.6 mg·kg^-1）， with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·（10 g）^-1 for 7 consecutive days， while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days， MCAO surgery was performed. The distal and proximal ends of the right common carotid artery （CCA） were ligated， a small incision was made between the two ligatures， and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling， mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy， particle size analysis， and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase （MPO） in the brains of mice in each group. ResultsCompared with the sham-operated group， the model group showed decreased neurological function scores （P<0.01）， obvious cerebral infarction （P<0.01）， reduced cerebral blood flow （P<0.01）， neuronal necrosis in the brain， and decreased numbers of Nissl bodies （P<0.01）. The mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were significantly increased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were increased （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were elevated （P<0.01）. Compared with the model group， the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores （P<0.05）， reduced cerebral infarct volume （P<0.01）， restored cerebral blood flow （P<0.01）， reduced necrotic cells in the brain， and increased numbers of Nissl bodies （P<0.01）. In the Huanglian Jiedutang group， the mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were decreased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were reduced （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were decreased （P<0.01）. ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice， thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.

Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models. However, its therapeutic potential and mechanisms against cerebral ischemia/reperfusion (I/R) injury remain unclear. In this study, we evaluated the in vivo neuroprotective effects of indobufen through both pretreatment and posttreatment regimens in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). In vitro, human umbilical vein endothelial cells (HUVECs) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were employed to investigate the relationship between indobufen and the pyroptosis-associated NF-κB/Caspase-1/GSDMD pathway. The pharmacodynamic tests revealed that indobufen ameliorated I/R injury by decreasing the level of thromboxane B2 (TXB2), infarct size, brain edema and neurological impairment in rats and rescuing cell pyroptosis in HUVECs. The underlying mechanisms were probably related to pyroptosis suppression by regulating the NF-κB/Caspase-1/GSDMD pathway. Overall, these studies indicate that indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.

Objective To evaluate the cost–utility of lecanemab and donanemab in the treatment of early Alzheimer’s disease （AD） in China. Methods A Markov model was developed from a societal perspective to compare standard of care （SOC）, lecanemab plus SOC, and donanemab plus SOC in terms of costs, quality-adjusted life years （QALY）, and incremental cost–utility ratios （ICUR）. Deterministic and probabilistic sensitivity analyses were conducted to assess parameter uncertainty. Results Both intervention strategies increased QALY compared with SOC but were associated with substantially higher costs, and neither was cost-effective under the current willingness-to-pay threshold. Conclusion Lecanemab and donanemab may be more appropriately considered within a multi-tiered healthcare reimbursement framework in China rather than relying solely on basic medical insurance.

Objective To evaluate the cost-utility of risdiplam in the treatment of pediatric spinal muscular atrophy （SMA） and analyze changes in patients’ out-of-pocket economic burden under the medical insurance scenarios. Methods A Markov model was developed from the healthcare system perspective to compare the long-term costs and quality-adjusted life years （QALYs） of risdiplam treatment versus conventional therapy. The incremental cost-utility ratio （ICUR） was calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to assess the robustness of the model. On this basis, health insurance scenarios were simulated to evaluate patients’ individual economic burden. Results Base-case analysis showed that risdiplam treatment generated additional health benefits but substantially increased medical costs. The resulting ICUR did not demonstrate a clear cost-utility advantage under the current willingness-to-pay threshold. Sensitivity analyses indicated that the model results were relatively robust, with drug costs and key utility parameters being the main drivers of economic outcomes. Health insurance scenario analysis demonstrated that increasing reimbursement levels and reducing patient copayment rates could significantly alleviate patients’ financial burden. Conclusion Risdiplam for pediatric SMA faces economic challenges under the current health insurance payment framework in China. However, optimizing health insurance reimbursement policies and developing multi-tiered healthcare security mechanisms may improve its affordability and accessibility.

Objective To assess the situation and influencing factors of occupational burnout among the staff at the Center for Disease Control and Prevention (CDC) in Sichuan Province. Methods A total of 1 038 CDC staff members in Sichuan Province were selected as the study subjects using the stratified random sampling method. Occupational burnout of the staff was assessed using the Maslach Burnout Inventory General Survey via an online questionnaire. Results The detection rate of occupational burnout was 42.3% (439/1 038). Binary logistic regression analysis result showed that, after controlling for confounding factors such as education level and alcohol consumption, CDC staffs aged at 20-<31, 31-<41, and 41-<51 years were at higher risk of occupational burnout compared with those ≥51 years (all P<0.05). CDC staffs with 5-<10 or ≥10 years of service had higher occupational burnout risk compared with those with <5 years (both P<0.05). CDC staffs with poor or fair health status, irregular diet, and poor sleep quality had higher risk of occupational burnout compared with those healthy, have regular diet, and good sleep quality (all P<0.05). The risk of occupational burnout increased with higher overtime frequency (all P<0.05). Conclusion Occupational burnout among CDC staffs in Sichuan Province is relatively high. Age, years of service, health status, diet, sleep quality, and overtime frequency are key influencing factors.

AIM To explore the clinical effects of Heiguteng Zhuifeng Huoluo Capsules combined with warm acupuncture at musculotendinous pathological nodes on patients with knee osteoarthritis due to Cold-Dampness Obstruction and Fixed Impediment.METHODS One hundred and sixty patients were randomly assigned into control group(80 cases)for 4-week intervention of both warm acupuncture at musculotendinous pathological nodes and Celecoxib Capsules,and observation group(80 cases)for 4-week intervention of Heiguteng Zhuifeng Huoluo Capsules,warm acupuncture at musculotendinous pathological nodes and Celecoxib Capsules.The changes in clinical effects,TCM syndrome scores,WOMAC scores,Lequesne indices,pain mediators(PGE2,β-EP),growth factors(TGF-β1,IGF-1),bone metabolism indices(OPG,RANKL),TLR4/NF-κB signaling pathway and safety indices were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,WOMAC scores,Lequesne indices,PGE2,RANKLE,TLR4,NF-κB(P＜0.05),and increased β-EP,growth factors,OPG(P＜0.05),especially for the observation group(P＜0.05).No serious adverse events or reactions were observable in the two groups.CONCLUSION For the patients with knee osteoarthritis due to Cold-Dampness Obstruction and Fixed Impediment,Heiguteng Zhuifeng Huoluo Capsules combined with warm acupuncture at musculotendinous pathological nodes can safely and effectively alleviate clinical symptoms,improve knee joint pain,and enhance joint functions,whose action mechanisms may contribute to the inhibition of TLR4/NF-κB signaling pathway expression and regulations of serum TGF-β1,IGF-1,OPG,RANKL levels.

Objective To investigate the relationship between cerebral perfusion status,blood pressure variability,and prognosis in patients with moyamoya disease following cerebral revascularization.Methods A retrospective analysis was conducted on 108 patients who underwent their first combined cerebral revascularization between January 2019 and July 2022 at the Department of Neurosurgery,First Affiliated Hospital of Henan University,and Henan Provincial People's Hospital.Based on postoperative cerebral perfusion improvement,patients were categorized into a"good"group and a"general"group.Baseline characteristics,key imaging parameters,blood pressure variability,and symptom scores were compared and analyzed between the two groups.Results In this study,there were 55 cases in the good group and 53 cases in the general group.According to the comparative analysis of the postoperative indicators between the good group and the general group,Statistically significant differences were observed in symptom improvement[42(79.25%)vs.52(94.55%)],TIA[22(41.51%)vs.11(20.00%)],and cerebral infarction[6(11.32%)vs.0(0.00%)],mRS score and the Matsushima classification(P<0.05).However,there was no statistically significant difference in the BPV-related index between the two groups of patients before the operation(all P>0.05).When comparing nine blood pressure variability(BPV)-related indices including the mean of 24-hour,daytime,and nighttime systolic blood pressure,coefficient of variability(CV),and average real variability(ARV)between the two groups,no significant differences were observed in the BPV-related indices before surgery between the two groups(P>0.05).The differences in the BPV-related indices before and after surgery(postoperative index-preoperative index)between the two groups were statistically significant(P<0.05).Postoperative cerebral perfusion status was positively correlated with prognosis and negatively correlated with BPV.Conclusion Patients with good improvement in cerebral perfusion status after combined revascularization for moyamoya disease have less blood pressure variability and better prognosis.

AIM:To investigate autophagic status in ischemic stroke with Liver Yang Hyperactivity and the mechanism of Tianma Gouteng Decoction(TMGTD).METHODS:SD rats were divided into sham,model,TMGTD high/medium/low-dose(20.52/10.26/5.13 g·kg-1·d-1),and Nimodipine(30 mg·kg-1·d-1)groups.A Liver Yang Hyperactivity and cerebral ischemia-reperfusion model was es-tablished using Fuzi Decoction(2 g·kg-1·d-1)and thread-occlusion.After 21 days of Fuzi decoction pretreatment,rats received daily drug administra-tion for 12 days.Syndrome indicators(irritability,24-hour water intake,24-hour urine volume,facial temperature)were recorded,plasma NE,E,cAMP,and cGMP were measured by ELISA,neurological function was assessed using Zea Longa and mNSS methods,brain histopathology was evaluated by HE staining,protein expression of soluble/insoluble p62 and LC3B was detected by Western blot,au-tophagy-related genes were analyzed by PCR array,additionally,mRNA and protein levels of CXCR4 and CXCL12 were measured by qRT-PCR and Western blot.RESULTS:Compared to the sham group,the model group showed increased irritability,24-hours water intake,24-hours urine volume,facial temper-ature,and level of NE,E,cGMP(P＜0.01),neurologi-cal scores(P＜0.01),LC3B-Ⅱ,insoluble p62,CXCR4,CXCL12 expression(P＜0.01),but decreased soluble p62(P＜0.01).TMGTD groups exhibited reduced irri-tability,water intake,urine volume,facial tempera-ture,NE,E,cGMP(P＜0.05,P＜0.01),neurological scores(P＜0.05,P＜0.01),p62 expression(P＜0.01),alongside increased LC3B-Ⅱ(P＜0.01)and improved cortical pathology.TMGD also reversed dysregulat-ed autophagy-apoptosis genes(CXCR4,Lamp1,Tgfb1,APP,Rab24)and reduced CXCR4,CXCL12 ex-pression(P＜0.01).CONCLUSION:In the Liver Yang Hyperactivity and cerebral ischemia-reperfusion model,autophagy genes were activated but flux was impaired,and Tianma Gouteng Decoction may protect by restoring autophagic flux and inhibiting the CXCL12/CXCR4 axis.