ObjectiveTo observe the effects of Qingxin Jieyu granules （QXJYG） on FeCl₃-induced carotid artery thrombosis in rats and on the expression of thrombosis-related proteins tissue factor （TF） and tissue factor pathway inhibitor （TFPI） as well as the protein kinase B （Akt）/nuclear factor-κB （NF-κB） signaling pathway in EA.hy926 cells exposed to tumor necrosis factor-α （TNF-α）， thus preliminarily exploring the mechanism of QXJYG in inhibiting thrombosis. MethodsThirty-six SD rats were randomized into normal control， model， positive control （aspirin， 9 mg·kg^-1）， and low-， medium-， and high-dose （0.99， 1.98， 3.96 g·kg^-1， respectively） QXJYG groups （n=6）. The rats in the drug treatment groups were administrated with corresponding drugs， and those in the normal control group and model group were given an equal volume of distilled water. After 14 consecutive days of prophylactic gavage， the rat model of common carotid artery thrombosis was established with 45% FeCl₃ solution， and the blood vessels were collected and the wet weight of thrombus was weighed by an electronic balance （precision of 1/10 000）. The thrombosis in the common carotid artery of each group of rats was observed by hematoxylin-eosin staining. The plasma levels of von Willebrand factor （vWF）， platelet endothelial cell adhesion molecule-1 （PECAM-1）， tissue-type plasminogen activator （t-PA）， and plasminogen activator inhibitor-1 （PAI-1） were determined by enzyme-linked immunosorbent assay. An endothelial cell injury model was established by treating EA.hy926 human umbilical vein endothelial cells with TNF-α. The cell counting kit-8 method was used to screen the intervention concentrations of QXJYG. Western blot was employed to determine the protein levels of TF， TFPI， Akt， p-Akt， NF-κB p65， and p-NF-κB p65 in each group of cells. ResultsThe animal experiment showed that compared with the normal control group， the model group showed an increase in carotid artery thrombus weight （P<0.05）， with unclear vascular structure and extensive thrombosis in the lumen. In addition， the plasma levels of vWF， PECAM-1， and PAI-1 were elevated， while the t-PA level became lowered （P<0.05） in the model group. Compared with the model group， the aspirin and QXJYG groups showed reductions in the weight of FeCl₃-induced carotid artery thrombi （P<0.05） and thrombosis in the lumen， declines in plasma levels of PECAM-1 and PAI-1， and an elevation in the t-PA level （P<0.05）. Moreover， the QXJYG groups showed reductions in the plasma level of vWF （P<0.05）， which， however， had no significant difference between the aspirin group and the model group. The cell experiments indicated that 31.25， 62.5， 125， 250， 500 mg·L^-1 QXJYG had no effect on the viability of EA.hy926 cells. Therefore， 250， 500 mg·L^-1 QXJYG were selected as the intervention concentrations for subsequent experiments. Western blotting results showed that compared with the control group， the TNF-α stimulation downregulated the expression of TFPI （P<0.05）， upregulated the expression of TF， and increased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05） in EA.hy926 cells. Compared with the model group， the intervention with QXJYG upregulated the expression of TFPI （P<0.05）， inhibited the expression of TF， and decreased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05）. ConclusionQXJYG has the effect of inhibiting thrombosis and regulating the expression of TF and TFPI in endothelial cells exposed to TNF-α by suppressing the abnormal activation of the Akt/NF-κB signaling pathway.

Objective:To identify the risk factors for postoperative cognitive dysfunction (POCD) and develop the prediction model in elderly patients undergoing lumbar surgery under general anesthesia.Methods:The elderly patients undergoing elective lumbar surgery under general anesthesia in our hospital from July 2021 to July 2022 were enrolled. Cognitive function was assessed at 7 days after surgery using Mini-Mental State Examination and Montreal Cognitive Assessment. When the decrease in both scales≥ 1 standard deviation, the patients were considered as having POCD. The patients were divided into POCD group and non-POCD group according to whether POCD developed. The propensity score matching was used to balance the confounding bias between two groups. The multivariate logistic regression analysis was used to identify the risk factors for POCD. The prediction model was constructed, and a nomogram was drawn for visualization of the model. The receiver operating characteristic curve, calibration plot and decision curve analysis (DCA) were drawn to evaluate the differentiation, consistency and clinical validity of the model, respectively.Results:A total of 159 patients were enrolled in this study, and the incidence of POCD was 31.4%. There were statistically significant differences in the ratio of intraoperative blood transfusion, cumulative time of hypotension, total infusion volume and operation time between two groups ( n=32 each) after propensity score matching ( P<0.05). The results of multivariate logistic regression showed that age, educational levels, diabetes mellitus, previous two or more operations under general anesthesia, APTT and cumulative time of hypotension were independent risk factors for POCD in elderly patients undergoing lumbar surgery under general anesthesia ( P<0.05). A model was developed based on the risk factors mentioned above: LogitP=-15.878+ 0.263 × Age (years) - 0.122 × Educational Level (years)+ 1.601 × Diabetes Mellitus+ 1.468 × History of General Anesthesia for 2 or more times+ 0.608 × Cumulative Time of Hypotension(min) - 0.140 × APTT (s). The area under the receiver operating characteristic curve was 0.930 (95% CI 0.887-0.973), the sensitivity was 0.920, specificity was 0.798 and Youden index was 0.718. After visualizing the model via nomogram, the model was verified by Hosmer-Lemeshow test, P=0.403, C index was 0.930, and corrected C index was 0.914. Conclusions:Age, educational levels, diabetes mellitus, previous multiple operations under general anesthesia, APTT and cumulative time of hypotension are independent risk factors for POCD in elderly patients undergoing lumbar surgery under general anesthesia, and the established risk prediction model can effectively predict the occurrence of POCD in elderly patients undergoing lumbar surgery under general anesthesia.

Objective:To compare the effect of middle meningeal artery embolization (MMAE) versus conventional therapy for chronic subdural hematoma (CSDH).Methods:Retrospective analysis of 38 patients with 48 CSDHs treated with MMAE from May 2019 to May 2021 was performed. Comparisons were made with a conventional treatment for 126 patients with 126 CSDHs from January 2016 to May 2021. The MMAE and conventional treatment patients were matched by the propensity score matching method, and a total of 25 pairs of patients (31 pairs of CSDHs) were successfully matched. The CSDH recurrence, rescue treatment, radiographic follow-up outcome, clinical improvement and complication between the two groups were compared by t test, χ 2 test or Fisher exact probability methods. Results:The rescue treatment rate in MMAE group was significantly lower than that in conventional treatment group [0 (0/31) vs 19.4% (6/31), P=0.024] and the complete resolution rate at 6 months follow-up in MMAE group was significantly higher than that in conventional treatment group [96.8 (30/31) vs 74.2% (23/31), P=0.026]. In terms of CSDH recurrence, there was a trend of lower recurrence in the MMAE group [3.2%(1/31) vs 22.6% (7/31), P=0.053]. The complete resolution rate at 3 months follow-up was 61.3% (19/31) in MMAE group and 45.2% (14/31) in conventional treatment, clinical improvement rate was 92.0% (23/25) in MMAE group and 88.0% (22/23) in conventional treatment, good outcome rate (mRS≤2) was 92.0% (23/25) in MMAE group and 84.0% (21/25) in conventional treatment, complication rate was 0(0/25) in MMAE group and 4.0% (1/25) in conventional treatment, and there were no significant differences in all above-mentioned parameters ( P>0.05). Conclusions:The MMAE may be considered as a safe and effective treatment for CSDH, and MMAE for CSDH is associated with lower trend of recurrence, lower rescue treatment rate and better radiographic follow-up outcome than conventional therapy.

Microneedle percutaneous immunization is achieved by puncturing the stratum corneum of the skin with microneedles so that the vaccine is efficiently recognized by antigen-presenting cells to induce a specific immune response. Due to the advantages of efficient induction of immune response, low pain and easy storage, transdermal immunization by microneedles has been widely used for immunization of various vaccines in recent years. This review summarizes the materials of microneedles, application for transcutaneous immunization, as well as the challenges that need to be addressed.
Administration, Cutaneous ; Drug Delivery Systems ; Needles ; Vaccination ; Vaccines

OBJECTIVE：To study the improvement effect and mechanism of MEBO on lipopolysaccharide （LPS）-induced injury of rat skin fibroblasts. METHODS ：Skin fibroblasts of rats were divided into control group ，LPS group （5 μg/mL）， Kangfuxin solution group （positive control ，5 μg/mL LPS+1.25％ Kangfuxin solution ）and MEBO group （5 μg/mL LPS+0.6 mg/mL MEBO），with 6 wells in each group. Inflammatory injury cell model was induced by LPS （except for control group ）. After a certain period of cultivation ，the cell survival rate and cell migration rate were detected in each group. The contents of TNF-α and IL-6 in cell supernatant was detected. The localization and fluorescence intensity of IL- 6 protein were detected. The protein expression of PTEN ，p-p65，TNF-α，IL-6，PI3K and Akt in the fibroblasts were also determined. RESULTS ：Compared with control group ，survival rate of the fibroblasts was increased significantly in LPS group ，while cell migration was decreased significantly；the contents of TNF-α and IL-6 in cell supernatant as well as relative protein expression of PTEN ，p-p65，TNF-α， IL-6 and PI 3K were increased significantly （P＜0.05 or P＜0.01）；IL-6 protein mainly expressed in the cytoplasm ，and the fluorescence intensity was enhanced. Compared with LPS group ，survival rate of the fibroblasts was decreased significantly in Kangfuxin solution group and MEBO group ，while migration rate was increased significantly ；the contents of TNF-α and IL-6， relative protein expression of PTEN ，p-p65，TNF-α，IL-6（except for Kangfuxin solution group ），PI3K and Akt （except for Kangfuxin solution group ） were decreased significantly （P＜0.05 or P＜0.01），while fluorescence intensity of IL- 6 protein decreased；relative protein expression of TNF-α，IL-6，PI3K and Akt in MEBO group were significantly lower than Kangfuxin solution group （P＜0.05 or P＜0.01）. CONCLUSIONS ：MEBO can inhibit the proliferation of LPS-induced skin fibroblasts ， reduce the level of inflammatory factors and the intensity of inflammatory reaction ， which may be related to the jiang- down-regulation of PTEN/NF-κB，PI3K/Akt signaling pathway.

Objective:To investigate the potentially inappropriate medication(PIM)among elderly patients with chronic diseases in Shanghai communities and related influence factors.Method:Six community Health service Centers were choosen using stratified sampling. Total 968 elderly patients with chronic diseases who visited to the outpatient clinic of Shanghai Community Health Service Centers from July to August 2018 were included in the study. The PIM was investigated according to the 2015 Beers criteria. The χ 2 test and multivariate logistic regression model were used to analyze factors related to the PIM. Results:The survey showed that 317 elderly patients had PIM with 412 person-doses. In 134 person-doses, the PIM was unrelated to the disease; in 18 person-doses, PIM was caused by interaction of drug with disease/symptoms; in 259 person-doses PIM was related to the drugs that should be cautiously used for elderly; only in 1 person-dose the PIM was caused by the interaction between drugs. The drugs with the highest proportion of PIM were diuretics, benzodiazepines and aspirin. There were significant differences in age, kinds of diseases, kinds of drugs and times of visiting community health service centers between elderly patients with PIM and those without PIM (χ 2=42.28, 35.51, 46.47, 38.46; all P<0.05). The main PIM-related factors were age, kinds of diseases, kinds of drugs and times of visiting community health service centers. Conclusion:The study shows that the prevalence of PIM among elderly chronic diseases patients in Shanghai communities is relatively high, which is associated with the age, kinds of diseases, kinds of drugs and times of visiting community health service centers.

The fungal microbiota from self-retained soil and tongue coating of 18 patients with precancerous lesions of upper gastrointestinal (PLUG) were sequenced. The diversity of α, β in and the structure of the microbial community were analyzed, and the association of them was quantified by using the Spearman rank correlation method. The richness index (1.67±2.79) and the diversity index (0.25±0.10) of the fungal microbiota from tongue coating of PLUG patients were significantly lower than those from soil (4.00±4.69; 0.99±0.18) (all P values<0.001). The relative abundance of 11 taxa from tongue coating of these PLUG patients was positively associated with that from soil (all P values<0.05).

The fungal microbiota from self?retained soil and tongue coating of 18 patients with precancerous lesions of upper gastrointestinal (PLUG) were sequenced. The diversity of α, β in and the structure of the microbial community were analyzed, and the association of them was quantified by using the Spearman rank correlation method. The richness index (1.67±2.79) and the diversity index (0.25±0.10) of the fungal microbiota from tongue coating of PLUG patients were significantly lower than those from soil (4.00± 4.69; 0.99±0.18) (all P values<0.001). The relative abundance of 11 taxa from tongue coating of these PLUG patients was positively associated with that from soil (all P values<0.05).

The fungal microbiota from self?retained soil and tongue coating of 18 patients with precancerous lesions of upper gastrointestinal (PLUG) were sequenced. The diversity of α, β in and the structure of the microbial community were analyzed, and the association of them was quantified by using the Spearman rank correlation method. The richness index (1.67±2.79) and the diversity index (0.25±0.10) of the fungal microbiota from tongue coating of PLUG patients were significantly lower than those from soil (4.00± 4.69; 0.99±0.18) (all P values<0.001). The relative abundance of 11 taxa from tongue coating of these PLUG patients was positively associated with that from soil (all P values<0.05).

Objective To evaluate the effect of dexmedetomidine on the expression of NR1 subunit-containing NMDA receptors and GIuR2 subunit-containing AMPA receptors during hypoxic injury to rat hippocampal neurons.Methods The hippocampal neurons were isolated from Wistar rats within 24 h after birth and divided into 3 groups (n=24 each) using a random number table:control group (group C),hypoxia group (group H) and dexmedetomidine group (group D).The cells were subjected to hypoxia for 6 h to establish the model of neuronal hypoxic injury in H and D groups.In group D,0.1 μmol/L dexmedetomidine was added at 6 h of hypoxia and neurons were incubated for 3 h,and then the culture medium was replaced with a normal medium and neurons were incubated for 24 h.The neuronal viability was measured by CCK-8 assay,the leakage of LDH was detected,and the leakage rate was calculated.The expression of NR1 subunits-containing NMDA receptors and GluR2 subunits-containing AMPA receptors was detected by Western blot.The concentration of calcium ion in cytoplasm was measured using Fluo-3AM.Results Compared with group C,the neuronal viability was significantly decreased,the LDH leakage rate was increased,the expression of NR1 subunits-containing NMDA receptors in the membrane was up-regulated,the expression of GluR2 subunits-containing AMPA receptors was down-regulated,and the concentration of calcium ion in cytoplasm was increased in H and D groups (P＜0.05).Compared with group H,the neuronal viability was significantly increased,the LDH leakage rate was decreased,the expression of NR1 subunits-containing NMDA receptors in the membrane was down-regulated,the expression of GluR2 subunitscontaining AMPA receptors was up-regulated,and the concentration of calcium ion in cytoplasm was decreased in group D (P＜0.05).Conclusion The mechanism by which dexmedetomidine reduces hypoxic injury to rat hippocampal neurons may be related to inhibiting up-regulation of the expression of NR1 subunits-containing NMDA receptors in the membrane and down-regulation of the expression of GluR2 subunitscontaining AMPA receptors.