ObjectiveTo explore the possible mechanisms by which ligustilide （LIG） exerts neuroprotective effects on ischemic stroke （IS） by inhibiting the release of neutrophil extracellular traps （NETs）， promoting blood-brain barrier repair， and alleviating post-ischemic neuroinflammation， thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion （MCAO） model was established in rats. The rats were divided into the sham operation （Sham） group， model （Model） group， low- and high-dose LIG groups （20， 40 mg·kg^-1）， and the NET inhibitor CI-amidine group （CI-amidine， 10 mg·kg^-1）. Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， neurological deficit scoring， and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 （H3Cit）. Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors， including interleukin-18 （IL-18） and interleukin-1β （IL-1β）. ResultsCompared with the Sham group， the Model group exhibited significant brain tissue injury （P<0.05）， significantly increased neutrophil numbers and NET expression （P<0.05）， significantly impaired blood-brain barrier permeability （P<0.05）， and significantly increased expression of inflammatory factors （P<0.05）. Compared with the Model group， both low- and high-dose LIG significantly alleviated brain tissue injury in rats （P<0.01）， inhibited neutrophil numbers and NET expression （P<0.01）， reduced blood-brain barrier damage （P<0.01）， and suppressed the expression of inflammatory factors IL-18 and IL-1β （P<0.01）， thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.

ObjectiveTo explore the possible mechanisms by which ligustilide （LIG） exerts neuroprotective effects on ischemic stroke （IS） by inhibiting the release of neutrophil extracellular traps （NETs）， promoting blood-brain barrier repair， and alleviating post-ischemic neuroinflammation， thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion （MCAO） model was established in rats. The rats were divided into the sham operation （Sham） group， model （Model） group， low- and high-dose LIG groups （20， 40 mg·kg^-1）， and the NET inhibitor CI-amidine group （CI-amidine， 10 mg·kg^-1）. Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， neurological deficit scoring， and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 （H3Cit）. Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors， including interleukin-18 （IL-18） and interleukin-1β （IL-1β）. ResultsCompared with the Sham group， the Model group exhibited significant brain tissue injury （P<0.05）， significantly increased neutrophil numbers and NET expression （P<0.05）， significantly impaired blood-brain barrier permeability （P<0.05）， and significantly increased expression of inflammatory factors （P<0.05）. Compared with the Model group， both low- and high-dose LIG significantly alleviated brain tissue injury in rats （P<0.01）， inhibited neutrophil numbers and NET expression （P<0.01）， reduced blood-brain barrier damage （P<0.01）， and suppressed the expression of inflammatory factors IL-18 and IL-1β （P<0.01）， thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.

ObjectiveThis study aimed to investigate the optimal compatibility ratio of the Chuanxiong Rhizoma-Carthami Flos （CR-CF） couplet medicines in ischemic stroke （IS） therapy and its pharmacological action mechanism， providing a scientific basis for the clinical application of CR-CF couplet medicines in IS therapy. MethodsThe chemical composition of CR-CF was analyzed using liquid chromatography mass spectrometry （LC-MS/MS）. The contents of eight characteristic chemical components in aqueous extracts of CR-CF with common clinical compatibility ratios （1∶1， 1∶2， 1∶3， 3∶2， 2∶1） were determined by ultra-high performance liquid chromatography（UHPLC）. An oxygen-glucose deprivation/reoxygenation （OGD/R）-induced mouse hippocampal neuron HT22 cell injury model was established， and cells were treated with different CR-CF compatibility ratios. The collaborative index （CI） was calculated by using CompuSyn software. A cerebral artery occlusion/reperfusion （MCAO/R） model of rats was induced by using the modified Longa suture method. The rats were divided into the sham group， model group， Chuanxiong Rhizoma （CR） group （1.3 g·kg^-1）， Carthami Flos （CF） group （3.9 g·kg^-1）， CR-CF group （5.2 g·kg^-1）， and edaravone group （5 mg·kg^-1）. Neuronal defect scores were assessed by the Longa scoring method. Cerebral infarction volume was measured by 2，3，5-triphenyltetrazolium chloride（TTC） staining. Neuronal damage was observed via hematoxylin-eosin （HE） staining. Neuronal apoptosis of rats was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） staining， and the expression of apoptosis-related proteins was analyzed by Western blot. Label-free proteomics was employed to screen differentially expressed proteins， and Western blot was used to examine the expression of phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway-related proteins. Finally， molecular docking was performed to predict the binding affinity of eight active constituents in CR-CF （1∶3） with PI3K. ResultsWhen CR-CF was combined at a 1∶3 ratio， the total content of the eight active constituents in the extract was the highest， and the synergistic protective effect on OGD/R-injured HT22 cells was the strongest （CI=0.308）. Animal experiments showed that compared with the sham group， the model group exhibited increased neuroecological score points （P<0.01）， larger cerebral infarction volumes （P<0.01）， aggravated brain tissue damage， elevated neuronal apoptosis （P<0.01）， and increased B-cell lymphoma-2（Bcl-2）-associated X protein （Bax）/Bcl-2 and cleaved Cysteinyl aspartate specific proteinase-3/Cysteinyl aspartate specific proteinase-3 （cleaved Caspase-3/Caspase-3） ratios （P<0.01）. Compared with the model group， CR-CF （1∶3） significantly reduced neurological scores （P<0.01）， significantly decreased cerebral infarction volume （P<0.01）， alleviated brain tissue damage， inhibited neuronal apoptosis （P<0.01）， and significantly lowered the Bax/Bcl-2 and cleaved Caspase-3/Caspase-3 ratios （P<0.01）. The therapeutic effect of CR-CF （1∶3） was superior to that of CR or CF alone. Proteomic analysis revealed that CR-CF （1∶3） activated the PI3K/Akt signaling pathway. Validation experiments demonstrated that compared with the sham group， the model group showed obviously reduced p-PI3K/PI3K and p-Akt/Akt （P<0.05）. Compared with the model group， p-PI3K/PI3K and p-Akt/Akt ratios （P<0.05） obviously increased. Compared with the CR-CF group， the 2-（4-morpholinyl）-8-phenyl-4H-1-benzopyran-4-one LY294002 inhibitor+CR-CF group exhibited obviously decreased p-PI3K/PI3K and p-Akt/Akt （P<0.05）. Molecular docking results indicated that the active constituents of CR-CF （1∶3） had strong binding affinity with PI3K. ConclusionThe CR-CF couplet medicines at a 1∶3 ratio exhibit optimal synergistic effects， and their anti-IS mechanism is closely related to activation of the PI3K/Akt signaling pathway and inhibition of neuronal apoptosis.

Cardiovascular diseases （CVD），a group of common diseases in clinical practice，are witnessing a steady rise in both incidence and mortality rates，posing a challenge to public health. Gualou Xiebai Banxiatang，originating from Synopsis of the Golden Chamber （《金匮要略》），was initially used to treat severe cases of chest impediment. The formula consists of Trichosanthis Fructus，Allii Macrostemonis Bulbus，Pinelliae Rhizoma，and Baijiu. It has a wide range of clinical applications，with therapeutic effects including moving Qi to relieve depression，activating Yang to dissipate mass，and expelling phlegm to alleviate chest congestion. In recent years，clinical research has confirmed that Gualou Xiebai Banxiatang，with or without modification，used alone or in combination with Western medicine，has definite effects in the treatment of CVD such as hyperlipidemia，coronary atherosclerotic heart disease，hypertension，heart failure，and arrhythmia. It can alleviate disease symptoms and reduce the risk of re-hospitalization. Basic research indicates that the mechanisms of Gualou Xiebai Banxiatang include improving endothelial functions，exhibiting anti-inflammatory properties，countering oxidative stress，preventing apoptosis，inhibiting ventricular remodeling，regulating mitochondrial functions，improving hemorheology，and modulating autophagy and neurotransmitters. This article reviews relevant articles in recent years with focuses on the compatibility，clinical application，and mechanism of Gualou Xiebai Banxiatang. This review is expected to provide a theoretical basis for the mechanism research and clinical application of this formula in treating CVD and to offer ideas and reference for in-depth research.

BACKGROUND:Electrical stimulation is an effective treatment plan for peripheral nerve injuries,but different frequencies of electrical stimulation have different mechanisms and applications for promoting peripheral nerve recovery.OBJECTIVE:To systematically sort out and summarize the roles and applications of different frequencies of electrical stimulation in the treatment of peripheral nerve injuries,and to deeply analyze the advantages and disadvantages of various methods in order to find the most beneficial treatment strategy for patients'nerve recovery.METHODS:Computer-based searches were conducted in the China National Knowledge Infrastructure(CNKI)and PubMed databases from the inception of the databases to May 2024.The search terms included"peripheral nerve injury,electrical stimulation,low frequency electrical stimulation,medium frequency electrical stimulation,high frequency electrical stimulation,TENS,interfering electricity,short wave,ultrashort wave,frequency"in both English and Chinese.Ultimately,74 relevant documents were included for analysis.RESULTS AND CONCLUSION:Peripheral nerve injury,a common clinical disease,can cause sensory and motor dysfunction in patients.Low-frequency electrical stimulation can promote cell proliferation and accelerate the expression of nerve growth factor within the cell after electrical stimulation,promote macrophage recruitment and infiltration,accelerate the clearance of myelin debris,and promote myelin regeneration of damaged axons.Medium-frequency electrical stimulation can act on deeper tissues and is better for relieving neuropathic pain.High-frequency electrical stimulation can promote the proliferation of Schwann cells and macrophages,inhibit inflammatory factors,and rapidly recruit cells to the site of nerve injury,accelerating the speed of nerve repair.Different frequencies of electrical stimulation have their own advantages in promoting the recovery of peripheral nerve injuries,but there are still some issues,such as differences in the site of electrical stimulation and the treatment plans for various disease types.

Aim To explore the effects of Kui Jie Kang(KJK)on modulating the farnesoid X receptor(FXR)pathway in the gut microbiota and bile acid metabolism in mice with ulcerative colitis(UC).Methods Mice were subjected to DSS-induced UC and randomly as-signed to the control(CON),model(MOD),and two KJK-dosed groups(KJK.H at 12.8 g·kg-1,KJK.L at 3.2 g·kg-1).Mouse body weight was recorded,and disease activity index(DAI)was scored.The his-topathological changes in colonic tissue were observed via HE staining,and the number of goblet cells and mucosal layer repair were assessed using PAS and Al-cian blue staining.Bile acid content in feces was measured using LC-MS/MS,gut microbiota composition was analyzed by 16S rRNA gene sequencing,and the expression of FXR target genes and related proteins was detected by RT-qPCR and Western blot.Results KJK significantly ameliorated colonic shortening,de-creased disease activity index in UC mice,reduced his-topathological scores,increased the number of goblet cells and mucus secretion,altered the levels of primary and secondary bile acids,and increased the relative a-bundance of beneficial bacteria such as Lactobacillus.Additionally,it significantly upregulated the expression of FXR and FGF15 mRNA and protein in colonic tissue and downregulated the expression of hepatic CYP7A1 mRNA,and the correlation analysis in this study clearly revealed a significant correlation between bile acid me-tabolism disorders and gut microbiota imbalance in UC.Conclusion KJK activates the intestinal FXR-FGF15-CYP7A1 pathway,thereby regulating bile acid metabolism and restoring gut microbiota balance,which may be key to its improvement of UC.

AIM To investigate the effects of rice wine type and wine processing method on chemical constituents and anti-coagulation effect of Angelicae sinensis Radix.METHODS Wine-washed products and wine-stir-fried products were prepared by different types and ages of rice wine,respectively,after which HPLC was adopted in the content determination of tryptophan,chlorogenic acid,vanillic acid,phthalic acid,ferulic acid,senkyunolide I,senkyunolide H,coniferyl ferulate and ligustilide,and PT,APTT,TT were detected in rabbit plasma.RESULTS Phenolic acids and volatile constituents demonstrated lower contents in the wine-stir-fried products than those in the raw product(P＜0.05),while those in the wine-washed products displayed no obvious changes(except for senkyunolide I)(P＞0.05).The contents of volatile constituents in the wine-washed products were higher than those in the wine-stir-fried products(P＜0.05).After being processed with dry rice wine,various constituents exhibited increased contents as compared with those after being processed with sweet rice wine(P＜0.05).Compared with the raw product,prolonged PT,APTT and TT were observable in the processed products prepared by 3-year semi-dry rice wine(P＜0.05).CONCLUSION The optimal rice wine type is determined to be 3-year semi-dry.Wine-washed Angelicae sinensis Radix shows high contents of ferulic acid and volatile constituents,whose activating blood and resolving stasis effect may be stronger.

Objective To clarify the network structure among stakeholders in hospital infection outbreak crisis,and provide reference for reducing conflicts of interest and promoting synergistic governance among different stakeholders.Methods Using the combination of literature analysis and social network analysis to construct the social network model of stakeholders,and analysis the overall network structure and individual network characteristics.Results The overall network density was 0.519 2,indicating that the cohesion among stakeholders in hospital infection outbreak crisis was strong.The results of network centrality analysis showed that degree centrality,betweenness centrality,closeness centrality of health administration department,public health institutions,and hospital management were all high,as well as the ability of using structural holes.Additionally,a layered structure of stakeholders was constructed which consisted of four types:authoritative stakeholders,core stakeholders,secondary stakeholders,and peripheral stakeholders.Conclusion It is suggested to explore strategies for integrating stakeholders'public interests and individual interests under the orientation of social network structure optimization,and achieve synergistic governance among different stakeholders.

AIM To compare total sugar,total protein,total phenol,total flavonoid,calycosin-7-O-β-D-glucoside,liquiritin,lobetyolin,quercetin,isoferulic acid,hesperidin,glycyrrhizic acid contents and their antioxidant activities,hypoglycemic activities of big honey pill,small honey pill,water pill,concentrated pill,granule,mixture and decoction of Buzhong Yiqi Recipe.METHODS Anthraquinone-sulfuric acid method,Coomassie brilliant blue method,Folin-phenol colorimetry method,sodium nitrite-aluminum nitrate method and HPLC were adopted in the content determination of total sugar,total protein,total phenol,total flavonoid and seven constituents,respectively,after which the scavenging capacities,reducing powers on DPPH·free radical,ABTS+free radical,hydroxyl free radical,and inhibition capacity on α-glucosidase activity were detected.Subsequently,correlation analysis was performed.RESULTS Total sugar,total protein,total phenol and total flavonoid contents demonstrated significant differences among different dosage forms(P＜0.05,P＜0.01).Calycosin-7-O-β-D-glucoside,glycyrrhizin,codonoside and quercetin displayed the highest contents in the decoction,while those of isoferulic acid,hesperidin and glycyrrhizin were observable in the mixture.The water pill exhibited the strongest antioxidant activity,while those of the concentrated pill and mixture were weak;the big honey pill exhibited the strongest hypoglycemic activity,while that of the decoction was the weakest.Total protein,total phenol,total flavonoid and liquiritin contents displayed significant positive correlations between antioxidant activity(P＜0.05,P＜0.01),while hesperidin content displayed significant negative correlation between the latter(P＜0.05);total protein,calycosin-7-O-β-D-glucoside,codonoside and quercetin contents displayed significant negative correlations between hypoglycemic activity(P＜0.05,P＜0.01).CONCLUSION Active constituent contents and their biological activities of Buzhong Yiqi Recipe with different dosage forms exist differences,total sugar,total protein,total flavonoids,calycosin-7-O-β-D-glucoside,licorice glycoside,hesperidin,codonoside and quercetin can be taken as quality control indices for this prescription.

Objective:To analyze the learning curve of TiRobot-assisted lumbar pedicle screw fixation (LPSF) by cumulative sum (CUSUM) test method.Methods:The clinical data of 50 patients who underwent TiRobot-assisted LPSF from January 2020 to December 2022 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. CUSUM analysis and learning curve fitting were performed with robot usage time as the main indicator with the time for each step refined (robot registration time, path planning time and guide wire placement time), to select the best learning curve fitting model with the R2 value closest to 1. Using the turning point of the learning curve as the boundary, the learning curve was divided into two stages as learning stage and maturity stage, and then the observation indexes were compared between the two stages. Results:All 50 patients successfully completed the surgery without perioperative complications, with a total of 244 pedicle screws implanted. The total robot usage time and robot registration time showed a gradually decreasing trend with the increase of case number, and the learning curves were successfully fitted and reached their peaks at the seventeenth and thirteenth cases respectively. The entire learning process was divided into learning stage (17 cases) and maturity stage (33 cases) based on the turning point of the learning curve of total robot usage time. The path planning time and guide wire placement time did not show significant changes with the increase in the case number. The total robot usage time, robot registration time and the intraoperative blood loss in the learning stage were significantly higher than those in the maturity stage: (35.35 ± 1.58) min vs. (30.61 ± 0.43) min, (20.83 ± 1.56) min vs. (14.94 ± 0.29) min and 400 (150, 500) ml vs. 200 (110, 300) ml, the guide wire placement time of per screw was significantly lower than that in the maturity stage: 2.00 (1.83, 2.34) min/screw vs. 2.33 (2.13, 2.69) min/screw, and there were statistical differences ( P<0.05 or <0.01). There were no statistical difference in the path planning time, path planning time of per screw, guide wire placement time and the accuracy of screw placement between two stages ( P>0.05). Conclusions:TiRobot-assisted LPSF is a new technology with safety and effectiveness, and it has a relatively short learning curve. To achieve technological maturity, at least 17 surgeries are required with accumulated experience, and the robot registration is the main step of the learning process. After reaching maturity stage, the robot usage time is significantly shortened and intraoperative trauma is significantly reduced while the relatively high screw placement accuracy is ensured.