ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

ObjectiveTo decipher the mechanism of Danshenyin in regulating platelet activation in the rat model of hyperlipidemia by means of proteomics and molecular biology. MethodWistar rats were randomized into blank， model， and Danshenyin groups （n=10） according to the blood lipid level. The rats in the blank group were fed with a basic diet， and those in the model and Danshenyin groups with a high-fat diet. All the rats had free access to water and food. The treatment began at the 9th week. The rats in the Danshenyin group were administrated with Danshenyin by gavage at a crude drug dose of 3.6 g·kg^-1. The rats in the model and blank groups were administrated with an equal volume of normal saline according to body weight. At the 12th week， the tissue samples were collected for the measurement of related indicators， and the blood lipid level was measured by an automatic biochemical analyzer. The whole blood viscosity and plasma viscosity were measured by an automatic hemorheometer. The platelet proteome was determined by liquid chromatography-mass spectrometry. Western blotting was employed to determine the protein levels of platelet membrane glycoprotein 4 （CD36）， focal adhesion kinase （FAK）， phosphatidylinositol 4-phosphate 5-kinase （PIP5K）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， protein kinase B （Akt）， and phosphorylated protein kinase B （p-Akt）. ResultCompared with the model group， Danshenyin lowered the levels of total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） in the plasma （P<0.05）， elevated the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）， and reduced the platelet aggregation rate （P<0.05）. Compared with the blank group， the modeling up-regulated the expression of 44 proteins and down-regulated the expression of 12 proteins. Compared with the model group， Danshenyin up-regulated the expression of 21 proteins and down-regulated the expression of 22 proteins. Compared with the blank group， Danshenyin up-regulated the expression of 31 proteins and down-regulated the expression of 49 proteins. The gene ontology （GO） functional enrichment showed that the differentially expressed proteins were mainly involved in cholesterol transport and efflux， production of cytokines， dyslipidemia， and platelet activation. The Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment showed that the differentially expressed proteins were mainly involved in ECM-receptor interaction， peroxisome proliferators-activated receptors （PPAR）， focal adhesion， and PI3K/Akt signaling pathways. Danshenyin can significantly down-regulate the expression of CD36， FAK， PIP5K， PI3K， p-Akt （Ser473）， and p-Akt1/2/3 （Thr308）. ConclusionDanshenyin can restore the blood lipid level of hyperlipidemia rats and inhibit the platelet activation caused by abnormal lipid levels by down-regulating the CD36/PI3K/Akt signal cascade.

OBJECTIVE To explore the regulatory mechanism of Danshen decoction on dyslipidemia in hyperlipidemia model rats. METHODS The experimental rats were divided into blank group （n＝9， no modeling）， model group （n＝8， modeling）， and Danshen decoction group （n＝9， modeling）. Starting from the 9th week of feeding with the high-fat diet， rats in the Danshen decoction group were given the corresponding medication solution （3.6 g/kg） intragastrically， while blank group and model group were given equal volume of normal saline， once a day， for 4 consecutive weeks. After 4 weeks of administration， the plasma levels of triglycerides （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured in each group of rats； the pathological and morphological changes of liver tissue were observed； the differential proteins between samples were screened out by TMT quantitative proteomic analysis； the expression levels of the key differentially expressed proteins in the liver， including epoxide hydrolase 2 （EPHX2）， perilipin 2 （PLIN2）， peroxisome proliferator activated receptor γ （PPAR γ） and glycogen synthase kinase-3β （GSK-3β）were detected. RESULTS Compared with the model group， the plasma levels of TC， TG and LDL-C in the Danshen decoction group were significantly reduced （P＜0.05）， while the level of HDL-C was significantly increased （P＜0.05）. The liver tissue of rats inmodel group showed uneven staining， disordered arrangement of liver plates， disappearance of liver sinusoids， nuclearcondensation or disappearance of some cells， swelling and fusion of cytoplasm， proliferation of connective tissue， and diffuse vacuolar-like fat droplet changes. The liver tissue of Danshen decoction group showed varying degrees of improvement in the above pathological and morphological. The results of differential protein analysis showed that the total number of differential proteins was 298 between the model group and the blank group； the total number of differential proteins was 139 between the model group and Danshen decoction group. Compared with the model group， the expression levels of EPHX2 and PLIN2 proteins in the liver tissue of rats in the Danshen decoction group were significantly reduced （P＜0.01）， while the expression levels of GSK-3β and PPARγ were significantly increased （P＜0.01）. CONCLUSIONS Danshen decoction has a significant improvement effect on the plasma lipid levels and the pathological and morphological of the liver tissue in hyperlipidemia model rats. Its regulatory mechanism may be related to the up-regulation of PPARγ and GSK-3β expression and down-regulation of EPHX2 and PLIN2 expression， and the signaling pathways involved may include PPAR-γ signal pathway.

Objective To explore the application value of emergency temporal body surface positioning for single drain dual-target thalamic hematoma ventricular drainage in the treatment of thalamic hemorrhage breaking into ventricle with hydrocephalus.Methods A retrospective analysis was conducted on 223 patients with thalamic hemorrhage breaking into the ventricles with hydrocephalus,including a study group of 115 cases who underwent emergency single drain dual-target thalamic hematoma ventricular drainage surgery with temporal body surface positioning,and a control group of 108 cases who underwent emergency ventricular drainage first and then underwent stereotactic thalamic hematoma drainage surgery after the condition stabilized.Compare the differences in postoperative complications and treatment outcomes between two groups of patients,and evaluate the application value of temporal surface positioning for single drain dual-target thalamic hematoma ventricular drainage surgery in the treatment of thalamic hemorrhage breaking into the ventricle with hydrocephalus.Results The postoperative rebleeding rates,hematoma clearance and death were 5.2％,87.5％±7.3％and 13.9％in the study group and 4.7％,90.2％±8.5％and 15.7％in control group,respectively.There was no significant difference between the two groups(P＞0.05).The tube time,postoperative intracranial infection,Shunt dependent hydrocephalus,effective treatment and favorable prognosis of and the control group were(75.5±18.4)h,3.5％,19.1％,53.9％and 51.3％in the study group and(130.8±22.9)h,13.9％,35.1％,38.7％and 38.0％,respectively.The difference between the two groups was statistically significant(P＜0.05).Conclusion Body surface landmark-guided emergency single drain dual-target thalamic hematoma ventricular drainage surgery for the treatment of thalamic hemorrhage breaking into the ventricle with hydrocephalus is safe and reliable,and can improve the patient's prognosis.

Autism spectrum disorder (ASD) is one of the common neurodevelopmental disorders in children. Its etiology and pathogenesis are poorly understood. Previous studies have suggested potential changes in the complement and coagulation pathways in individuals with ASD. In this study, using multiple reactions monitoring proteomic technology, 16 of the 33 proteins involved in this pathway were identified as differentially-expressed proteins in plasma between children with ASD and controls. Among them, CFHR3, C4BPB, C4BPA, CFH, C9, SERPIND1, C8A, F9, and F11 were found to be altered in the plasma of children with ASD for the first time. SERPIND1 expression was positively correlated with the CARS score. Using the machine learning method, we obtained a panel composed of 12 differentially-expressed proteins with diagnostic potential for ASD. We also reviewed the proteins changed in this pathway in the brain and blood of patients with ASD. The complement and coagulation pathways may be activated in the peripheral blood of children with ASD and play a key role in the pathogenesis of ASD.
Child ; Humans ; Autism Spectrum Disorder/metabolism* ; Proteomics ; Brain/metabolism*

OBJECTIVE To investigate the effects and mechanism of Danshen decoction influencing platelet physiological characteristics and function in hyperlipidemia model rats based on platelet membrane glycoprotein 4 （CD36）/phosphatidylinositol 3- kinase （PI3K）/protein kinase B （Akt） signaling pathway. METHODS The hyperlipidemia model rats were induced by feeding high- fat diet， and then randomly divided into model group， simvastatin group （0.004 g/kg）， Danshen decoction high-dose and low-dose groups （3.6， 0.9 g/kg）， and blank group （fed with basic feed）， with 10 rats in each group. Rats in each administration group were intragastrically administered with corresponding drugs every day， and the other groups were intragastrically administered with equal volume of normal saline for 4 weeks. After the last administration， the contents of blood lipid biochemical indexes [total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）]， whole blood viscosity， plasma viscosity and fibrinogen （FIB）content in plasma， platelet-related parameters [platelet count （PLT）， platelet distribution width （PDW） and mean plateletvolume （MPV）] were detected. The levels of plateletphysiological characteristics and function-related factors [von Willebrand factor （vWF）， fibronectin （Fn）， phospholipase A2（PLA2）， thromboxane B2 （TXB2）， 6-keto-prostaglandin F1α （6-keto-PGF1α）， thromboxane A2 （TXA2）， prostaglandin I2 （PGI2）， cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， β-thromboglobulin （β-TG）]， platelet aggregation rate （maximum aggregation rate， 60 s aggregation rate， 180 s aggregation rate） and fibrinolytic system-related factors [tissue plasminogen activator （t-PA）， plasminogen activator inhibitor 1 （PAI-1）] and the expressions of CD36/PI3K/Akt signaling pathway-related proteins [CD36， focal adhesion kinase （FAK）， phosphatidylinositol 4-phosphate 5-kinase （PIP5K）， PI3K， phosphorylated Akt （p-Akt）， p-Akt1/2/3] in platelet were all determined. RESULTS Compared with blank group， the contents of TC， TG and LDL-C in plasma， whole blood viscosity， plasma viscosity， the plasma levels of FIB， PLT， MPV， vWF， Fn， PLA2， TXB2， TXA2， cGMP and β-TG， maximum platelet aggregation rate， 60 s aggregation rate， the expressions of PAI-1 in plasma， protein expressions of CD36， FAK， PIP5K， PI3K， p-Akt and p-Akt1/2/3 were significantly increased in the model group （P＜0.05）. The content of HDL-C and the levels of 6-keto-PGF1α， PGI2 and t-PA were significantly decreased （P＜0.05）. After the intervention of Danshen decoction， most of the above indexes were significantly reversed （P＜0.05）. CONCLUSIONS Danshen decoction can improve the physiological characteristics and function of platelets in hyperlipidemia model rats， and its mechanism may be related to the down-regulation of CD36/PI3K/Akt signaling pathway activity and the reduction of platelet activation.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

Objective:To analyze the relationship between arch index and foot kinematic parameters and their characteristics in stress fracture of lower extremity.Methods:A case-control study was performed for 108 recruits selected from a certain army unit in 2019. Before training, the recruits′ foot print images were collected by the capacitive plantar pressure measurement system to calculate their arch indices. The kinematic characteristics of the foot were analyzed by the dynamic gait posture analysis system. Spearman rank correlation analysis between arch index and foot kinematic parameters including landing elevation angle, toe-off angle, landing speed, landing varus angle, valgus amplitude and landing valgus speed were performed. Throughout the training, orthopedic physicians followed up the recruits, among whom 10 were excluded due to other types of lower extremity injuries. The arch index and foot kinematic characteristics were analyzed and compared between the remained recruits with stress fracture of lower extremity (fracture group, n=10) and those without lower extremity injury (control group, n=79). Results:(1) For the recruits, the arch index was 0.21(0.12,0.25), with landing elevation angle for (17.31±4.02)°, toe-off angle for (63.90±5.63)°, landing speed for (176.85±24.39)°/s, landing varus angle for (13.64±4.44)°, valgus amplitude for (12.16±3.42)°, and landing valgus speed for 382.50(311.05,474.80)°/s. (2) The landing varus angle ( r=0.25, P<0.01) and valgus amplitude ( r=0.14, P<0.05) were positively related to the arch index. (3) The arch index, toe-off angle and landing valgus speed were 0.20(0.07,0.24), (61.59±5.51)° and 336.00(251.02,428.67)°/s in fracture group, significantly lower than 0.23(0.17,0.26), (64.79±4.79)° and 381.20(313.63,470.92)°/s in control group ( P<0.05 or 0.01). There were no significant differences in the landing elevation angle, landing speed, landing varus angle and valgus amplitude between the two groups (all P>0.05). Conclusions:The change of the arch index can affect the landing varus angle and valgus amplitude of the foot. Recruits who suffer from stress fracture of lower extremity have the characteristics of higher arch, lower toe-off angle and lower landing valgus speed.

Objective:To evaluate the safety and effectiveness of capsule endoscopy for the diagnosis of intestinal diseases in children.Methods:Clinical data of 113 pediatric patients who received capsule endoscopy in Xi'an Children's Hospital from October 2018 to September 2020 were retrospectively analyzed. The completion rate, passage time of stomach and small intestine, lesion detection rate, adverse reactions and complications of capsule endoscopy were analyzed.Results:Among 113 pediatric patients, 78 (69.03%) were male and 35 (30.97%) were female. The age was (99.8±44.7) months (9-195 months), and 31 (27.43%) were under 7 years old. The minimum weight was 9 kg and the minimum height was 70 cm. Eighty-seven pediatric patients (76.99%) swallowed capsules orally (the oral group) with the minimum age of 4 years and 3 months. Capsules were implanted in 26 pediatric patients (23.01%) under gastroscopy (the gastroscopic group), with the maximum age of 9 years and 2 months. Unexplained abdominal pain (47.79%) and unexplained gastrointestinal bleeding (31.89%) were common in the pediatric patients. The completion rate of capsule endoscopy was 97.35% (110/113), and the detection rate of lesions in small intestine was 31.81% (35/110). The passage time of small intestine in the gastroscopic group was significantly longer than that of the oral group (461.04±129.27 min VS 288.23±107.84 min, t=5.646, P<0.01). There was no significant difference in the passage time of stomach or small intestine among different genders, different ages or different endoscopic examination results ( P>0.05). The positive results of capsule were not correlated with the method of ingestion ( P=0.401, OR=2.562, 95% CI:0.284-23.077), gender ( P=0.154, OR=2.352, 95% CI:0.726-7.616), age ( P=0.949, OR=1.007, 95% CI:0.816-1.242), examination reason ( P=0.246) or small intestine passage time ( P=0.219, OR=1.003, 95% CI:0.998-1.008). No complications such as capsule retention occurred in any pediatric patient. Conclusion:Capsule endoscopy in children is noninvasive, rapid and simple, which can improve the diagnostic rate of small intestinal diseases in children, and can be further promoted in pediatric patients.

OBJECTIVE：To investigate the effe cts of Buyang huanwu decoction on hemorheology and platelet related biological indexes of hyperlipidemia model rats. METHODS ：Male Wistar rats were randomly divided into blank control group （10 rats）and model group （40 rats）. Blank control group was given normal diet ，and model group was given high-lipid diet for 6 weeks at least to induce hypelipidemia model. After modeling ，rats were randomly divided into model control group ，positive control group （simvastatin，0.004 g/kg），Buyang huanwu decoction low-dose and medium-dose groups （3.5，14.0 g/kg，by crude drug），with 10 rats in each group. Blank control group and model control group were given normal saline intragastrically ， administration groups were given relevant drug intragastrically ，0.01 mL/g，once a day ，for consecutive 4 weeks. Thirty min after last medication ，hemorheological indexes （whole blood viscosity ，plasma viscosity ），platelet adhesion related indexes [adhesion rate，von Willebrand factor （vWF），fibronectin（FN）]，platelet release related indexes [ β-thromboglobulin（β-TG），platelet factor 4 （PF4）] and platelet fibrinolytic system related indexes [tissue plasminogen activator （t-PA），plasminogen activator inhibitor （PAI-1）]，platelet parameters （PLT，PDW，MPV，PCT，PLCR），4 kinds of coagulation parameters （APTT，TT，PT，FIB）were detected. RESULTS ：Compared with blank control group ，the whole blood viscosity （low，medium and high shear rate ），plasma viscosity，platelet adhesion rate ，the contents or levels of vWF ，FN，β-TG，PAI-1，PLT，MPV，PCT，PLCR and FIB in model control group were increased significantly （P＜0.05 or P＜0.01），and t-PA content was significantly decreased （P＜0.05）. Compared with model control group ，the whole blood viscosity （except for whole blood viscosity of high shear rate in Buyang huanwu decoction high-dose group ），plasma viscosity ，platelet adhesion rate ，the contents or levels of vWF ，FN，β-TG，PAI-1， PLT，PDW（except for Buyang huanwu decoction low-dose and high-dose groups ），MPV，PCT，PLCR（except for Byang huanwu decoction low-dose group ）and FIB were decreased significantly （P＜0.05 or P＜0.01），while t-PA content （except for positive control group ） was increased significantly （P＜0.05）. CONCLUSIONS ：Buyang huanwu decoction can significantly improve the pathological state in hyperlipidemia model rats by reducing blood viscosity and FN content ，improving platelet adhesion，enhancing fibrinolytic activity ，improving platelet aggregation ，inhibiting hypercoagulability and hyperplatelet release.