Objective To optimize the preparation process of Swertia patens,Burk.standard decoction and establish its quality standard by using the quality by design(QbD)concept.Methods Critical Quality Attributes(CQAs)were predicted and analyzed according to the quality marker(Q-marker)theory of traditional Chinese medicine;Failure mode and effects analysis(FMEA)was used to screen critical process parameters(CPPs);The measurement method of key quality attributes was established;The extraction process was optimized by Box Behnken test after the preliminary range was determined according to the single factor test;The entropy method was used for comprehensive scoring;The design space was established and the optimal operation space for process validation was selected;Standard decoction of Swertia patens Burk in fifteen batches with different habitats were prepared with the best technology,and the quality standards for the extraction rate,extract,thin layer chromatography,fingerprint,content,and the content transfer rate were established finally.Results The key quality attributes were swertiamarin content,gentiopicrin content,and paste yield;The key process parameters were soaking time,water amount,and decocting time;The established model had statistical significance;The optimum conditions were as follows:soaking time 90 min,adding water 15 times,decocting time 30 min(second decocting 20 min);The paste yield was 21.13％-30.73％;The extract was 82.00％-88.00％;The spot of swertiamarin was clear in TLC;The similarity between each samples in 15 batches and reference atlas were＞0.85％;The content of swertiamarin was 250.64-385.21 mg·g-1,and the transfer rate was 43.76％-77.73％;The content of gentiopicrin was 0.69-2.70 mg·g-1,and the transfer rate was 56.02％-105.29％.Conclusion Based on the above methods and techniques,the preparation process of Swertia patens Burk.The standard decoction was screened,which provides a reference for the preparation development and quality control of its formula granules.

Objective:To compare the effects of intensive and standard blood pressure control on the outcomes of patients with acute ischemic stroke in the anterior circulation who have successfully recanalized after endovascular therapy (EVT).Methods:A multicenter, open-label, blinded-endpoint, randomized controlled design was used. Patients with anterior circulation stroke received EVT and successfully recanalized in Nanjing First Hospital, Nanjing Medical University and several branch hospitals from July 2020 to October 2022 were prospectively included. They were randomly divided into the intensive blood pressure control group (target systolic blood pressure [SBP] 100-120 mmHg) or the standard blood pressure control group (target SBP 121-140 mmHg). The blood pressure of both groups needs to achieve the target within 1 h and maintain for 72 h. The primary outcome endpoint was outcome at 90 d, and the good outcome was defined as a score of 0-2 on the modified Rankin Scale. Secondary outcome endpoints included early neurological improvement, symptomatic intracranial hemorrhage (sICH) within 24 h, and death and serious adverse events within 90 d.Results:A total of 120 patients were included, including 63 in the intensive blood pressure control group and 57 in the standard blood pressure control group. There was no statistically significant difference in baseline characteristics between the two groups. The SBP at 72 h after procedure was 122.7±8.1 mmHg in the intensive blood pressure control group and 130.2±7.4 mmHg in the standard blood pressure control group, respectively. There were no significantly differences in the good outcome rate (54.0% vs. 54.4%; χ2=0.002, P=0.963), the early neurological improvement rate (45.2% vs. 34.5%; χ2=1.367, P=0.242), the incidence of sICH (6.3% vs. 3.5%; P=0.682), mortality (7.9% vs. 14.0%; χ2=1.152, P=0.283) and the incidence of serious adverse events (12.7% vs. 15.8%; χ2=0.235, P=0.628) at 90 d between the intensive blood pressure control group and the standard blood pressure control group. Conclusion:In patients with anterior circulation stroke and successful revascularization of EVT, early intensive blood pressure control don’t improve clinical outcomes and reduce the incidence of sICH.

Hypertension plays a unique role in the pathogenesis and outcomes of acute ischemic stroke. Therefore, blood pressure management, especially blood pressure regulation in acute stage, is of great significance for the treatment of acute ischemic stroke. However, there is no unified antihypertensive scheme for acute stroke. This article reviews the related research progress of blood pressure management in acute ischemic stroke.

ObjectiveLipopolysaccharide （LPS）-induced zebrafish inflammation model was used to evaluate the anti-inflammatory activity of different extracts from Lianggesan （LGS） and its component Glycyrrhiza Radix et Rhizoma. MethodDifferent polar fractions of LGS and Glycyrrhiza Radix et Rhizoma were obtained by the principle of similar miscibility. For toxicity observation， the zebrafish （3 day-post-fertilization） was exposed to different concentrations of extracts for 24， 48 and 72 h. The yolk sac of the zebrafish was microinjected with 0.5 g·L^-1 LPS to establish the inflammation model， and then the embryos were soaked with different concentrations of extracts to observe their survival status at 72 h and the aggregation of neutrophils in yolk sac at 12 h after treatment. Hematoxylin-eosin staining was used to analyze the yolk sac of the zebrafish microinjected with LPS. Quantitative Real-time polymerase chain reaction （Real-time PCR） was performed to further investigate the anti-inflammatory effects and mechanisms of LGS and Glycyrrhiza Radix et Rhizoma. ResultThe toxicity of LGS and Glycyrrhiza Radix et Rhizoma was decreased with the increase of polarity， and the descending order was petroleum ether>ethyl acetate>n-butanol>water. Compared with model group， the extracts from different fractions of LGS and Glycyrrhiza Radix et Rhizoma prolonged the survival time of the zebrafish， and inhibited the recruitment and aggregation of neutrophils and decreased the infiltration of inflammatory cells in the yolk sac， among which the water fraction of LGS and the ethyl acetate fraction of Glycyrrhiza Radix et Rhizoma had the most significant effect （P<0.01）. In addition， compared with model group， the water fraction of LGS and the ethyl acetate fraction of Glycyrrhiza Radix et Rhizoma down-regulated the mRNA expression of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）， and suppressed the expression of toll like receptor 4 （TLR4） and nuclear factor kappa-B （NF-κB） in LPS-stimulated zebrafish （P<0.01）. ConclusionThe extracts from different fractions of LGS and Glycyrrhiza Radix et Rhizoma exerted protective effects in LPS-induced zebrafish by inhibiting the TLR4 and NF-κB signaling pathways. Moreover， in zebrafish model， the method of administration by soaking was applicable to the high-throughput screening of anti-inflammatory Chinese medicine， which was suitable for the evaluation of anti-LPS activity of Chinese medicine and the different extracts.

Objective:To investigate the predictive value of YKL-40 at admission on stroke-associated pneumonia (SAP) and poor outcome in patients with acute ischemic stroke (AIS).Methods:Patients with AIS admitted to Taixing People’s Hospital from February 2020 to March 2021 were enrolled prospectively. The poor outcome was defined as 3-6 points on the modified Rankin Scale at 90 d after onset. Multivariate logistic regression analysis was used to determine the independent predictors of SAP and poor outcome, and the predictive value of serum YKL-40 on SAP and poor outcome was evaluated by receiver operating characteristic (ROC) curve. Results:A total of 377 patients with AIS were enrolled. The median serum YKL-40 was 127.16 μg/L. One hundred and four patients (27.6%) had SAP, and 126 (33.4%) had poor outcomes at 90 d after onset. Multivariate logistic regression analysis showed that after adjusting for confounding factors, YKL-40 was the independent predictors of SAP (odds ratio [ OR] 1.005, 95% confidence interval [ CI] 1.003-1.008; P=0.001) and poor outcome at 90 d ( OR 1.009, 95% CI 1.006-1.011; P=0.001). The ROC curve analysis showed that the area under the curve of YKL-40 for predicting SAP was 0.769 (95% CI 0.713-0.824; P<0.001), the best cutoff value was 168.70 μg/L, and the sensitivity and specificity were 71.2% and 75.1% respectively; the area under the curve of YKL-40 for predicting poor outcome at 90 d was 0.787 (95% CI 0.735-0.840; P<0.001), the best cutoff value was 195.56 μg/L, and the sensitivity and specificity were 68.3% and 84.1% respectively. Conclusion:Higher serum YKL-40 at admission has a good predictive value for SAP and poor outcome at 90 d in patients with AIS.

The brain-gut axis is an important pathway for the interaction between the central nervous system and the gastrointestinal tract. Ischemic stroke can promote the imbalance and displacement of intestinal flora, and the intestinal flora and its metabolites in turn can affect the occurrence, development and outcome of ischemic stroke. This article reviews the related literature on ischemic stroke and intestinal flora, in order to review the relationship between the two and related mechanisms, and to prospect the stroke treatment of targeting intestinal flora.

Objective To evaluate the impact of water pollutants, water levels and meteorological factors on the Oncomelania hupensis density in Eastern Dongting Lake regions, so as to provide insights into schistosomiasis control. Methods O. hupensis snails were surveyed using a systematic sampling method in snail-infested marshlands in Eastern Dongting Lake regions from 2007 to 2014, and data pertaining to water pollutants, water levels and meteorological factors were collected. The duration of submergence and the date of the start of submergence were calculated. The snail density and its influencing factors were descriptively analyzed, and a linear mixed model was generated to examine the impacts of variables on the snail density. In addition, smooth curves were fitted to investigate the relationship between snail density and variables. Results The snail density appeared a fluctuation in Eastern Dongting Lake regions during the period from 2007 to 2014, with the highest density on October, 2010 (52.79 snails/0.1 m²) and the lowest density on January 2009 (2.15 snails/0.1 m²). Linear mixed-model analysis showed that permanganate index, total phosphorus and the date of the start of submergence affected the snail density (t = 6.386, −2.920 and −3.892, all P values < 0.01). Smooth curve analysis revealed that the associations of the snail density with the permanganate index and total phosphorus appeared an approximately quadratic curve. After the end of April, the earlier date of the start of submergence resulted in a higher snail density. Conclusion Permenganate index, total phosphorus and the date of the start of submergence affect the O. hupensis snail density in Eastern Dongting Lake regions.

Intracranial atherosclerotic lesions are a common cause of ischemic stroke. Hemodynamics plays an important role in the formation and development of atherosclerosis and the risk assessment of clinical ischemic stroke events. As an evaluation method of cerebral hemodynamics, computational fluid dynamics can intuitively obtain hemodynamic parameters and provide valuable information for clinical diagnosis and treatment. This article reviews the application progress of computational fluid dynamics in evaluating peripheral hemodynamics of intracranial atherosclerotic lesions.

Objective:To investigate the safety of the use of the intermediate catheter in the endovascular treatment (EVT) of patients with acute anterior circulation large vessel occlusive stroke and its impact on the outcomes.Methods:From May 2015 to September 2018, patients with anterior circulation large vessel occlusive stroke received EVT in Nanjing First Hospital, Nanjing Medical University were enrolled retrospectively. According to whether intermediate catheter was used during the procedure, they were divided into intermediate catheter group and non-intermediate catheter group. The demographics, clinical data and procedure related information were collected. The outcome evaluation indicators included secondary embolization, symptomatic intracranial hemorrhage, clinical outcome and death at 90 d after onset. A good outcome was defined as the modified Rankin Scale score of 0-2. Multivariate logistic regression analysis was used to determine the independent predictor of clinical outcome. Results:A total of 195 patients with anterior circulation large artery occlusive stroke received EVT were enrolled, including 161 in the intermediate catheter group and 34 in the non-intermediate catheter group. There were no significant differences in demographics and clinical characteristics between the intermediate catheter group and the non-intermediate catheter group. In terms of procedure related information, the number of mechanical thrombectomy passes in the intermediate catheter group was significantly decreased (2 [1-3] times vs. 2.5 [1.75-4] times; Z=2.218, P=0.017), the recanalization rate of one-pass thrombectomy was significantly higher (38.5% vs. 20.6%; χ2=3.943, P=0.047), and the rate of thrombus escape and secondary embolism was significantly lower (19.3% vs. 35.3%; χ2=4.202, P=0.041). In terms of clinical outcome, there were no significant differences in the incidence of symptomatic intracranial hemorrhage, mortality and good outcome at 90 d between the intermediate catheter group and the non-intermediate catheter group. Multivariate logistic regression analysis showed that the use of intermediate catheter was an independent predictor of good outcome at 90 d (odds ratio 0.430, 95% confidence interval 0.196-0.947; P=0.036). Conclusion:In EVT of patients with acute anterior circulation large vessel occlusive stroke, the use of intermediate catheter can reduce the number of mechanical thrombectomy passes, improve recanalization rate of one-pass thrombectomy, reduce the rate of thrombus escape and second embolization, and then improve the outcome of patients.

Objective To evaluate the effects of water body environments on the microbial community of Oncomelania hupensis snails in marshlands of the eastern Dongting Lake where natural extinction of O. hupensis snails are found, so as to explore the correlation between the natural extinction of O. hupensis snails and the microbial community in snails. Methods Snails were caged water bodies in the Qianliang Lake marshland (Qianliang Lake regions) where natural extinction of snails was found and in the Junshan Park marshland (Junshan Park regions) in the eastern Dongting Lake for 30 days, and then all snails were collected and identified for survival or death. DNA sequencing of the fungi and bacteria was performed in snails before and after immersion in waters, and the biodiversity and abundance were analyzed. Results The survival rates of O. hupensis snails were 28.0% (70/250) and 64.8% (162/250) in Qianliang Lake regions and Junshan Park regions 30 days after immersion in waters, respectively (χ² = 81.365, P < 0.01). The number of the fungal community and the biodiversity of the bacterial community were both greater in snails caged in Qianliang Lake regions post-immersion than pre-immersion, and there was a significant difference in the structure of the fungal and bacterial communities. The microbial community with a significant difference included Flavobacteriaceae,which was harmful to O. hupensis snails. Conclusion The water body environment affects the composition of the microbial community in O. hupensis snails in marshlands with natural snail distinction around the eastern Dongting Lake; however, further studies are required to investigate whether the natural distinction of snails is caused by water body environments-induced changes of the microbial spectrum in O. hupensis snails.